Hefiya

Package leaflet: Information for the patient

Hefiya 20 mg solution for injection in pre-filled syringe

adalimumab
20 mg/0.4 mL
Please read this leaflet carefully before your child uses
this medicine because it contains important information.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before your child starts treatment with Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you or your child during treatment and for 4 months after your child’s last injection of Hefiya.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for your child only. Do not give it to others, even if their symptoms are the same as your child’s, because it could be harmful.
• If your child experiences any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before your child uses Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• polyarticular juvenile idiopathic arthritis,
• enthesitis-related arthritis,
• paediatric plaque psoriasis,
• paediatric Crohn’s disease,
• paediatric non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its activity and reduces the inflammatory process in these diseases.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory joint diseases that usually first appear during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years.
At diagnosis, other disease-modifying drugs such as methotrexate may be given.
If these medicines do not work satisfactorily, patients will be given Hefiya for the treatment of polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Paediatric plaque psoriasis
Plaque psoriasis is an inflammatory skin condition that causes reddish, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken, or lift from the nail bed, which can be painful. Psoriasis is believed to be caused by a problem with the body’s immune system leading to an increased production of skin cells.
Hefiya is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical medications and UV light therapy have not worked adequately or are not suitable.

Paediatric Crohn’s disease
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.
Your child may first be given other medicines. If these medicines do not work satisfactorily, your child will be given Hefiya to reduce the typical symptoms of the disease.

Paediatric non-infectious uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters in the eye (black spots or thin lines moving across the field of vision). Hefiya works by reducing this inflammation.
Hefiya is used to treat children from 2 years of age with chronic non-infectious uveitis involving inflammation of the front part of the eye.
Your child may first be given other medicines. If these medicines do not work satisfactorily, your child will be given Hefiya to reduce the typical symptoms of the disease.

2. What you should know before your child uses Hefiya

Do not use Hefiya

• If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If your child has a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell the doctor if your child has signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If your child has moderate or severe heart failure. It is important to inform the doctor if your child has had or currently has a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.

Allergic reaction

• If allergic reactions occur, with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hefiya again and contact the doctor immediately, as in rare cases these reactions can be life-threatening.

Infection

• If your child has an infection, including long-term or localized infections (e.g., leg ulcers), consult the doctor before starting treatment with Hefiya. If you are unsure, contact the doctor.
• Your child may be more likely to get infections while being treated with Hefiya. This risk may increase if your child has reduced lung function. These infections can be serious and may include tuberculosis, viral, fungal, parasitic, or bacterial infections, other unusual infectious organisms, or sepsis (septicaemia).
• In rare cases, these infections can be life-threatening. It is important to inform the doctor if your child has symptoms such as fever, wounds, feeling tired, or dental problems. The doctor may advise temporarily stopping Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, the doctor will need to check whether your child has signs or symptoms typical of tuberculosis before starting treatment with Hefiya. This will involve a detailed medical evaluation including your child’s medical history and clinical examinations (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in your child’s Patient Reminder Card. It is very important to inform the doctor if your child has ever had tuberculosis or has been in close contact with someone who has tuberculosis. Tuberculosis can develop during treatment even if your child has received preventive treatment for tuberculosis. Contact the doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections appear during or after treatment.

Travel/recurrent infection

• Inform the doctor if your child has lived in or traveled to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform the doctor if your child has had recurring infections or has conditions that increase the risk of infection.

Hepatitis B virus

• Inform the doctor if your child is a carrier of the hepatitis B virus (HBV), has an active hepatitis B virus infection, or if you think your child may be at risk of contracting hepatitis B virus. The doctor must test your child for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in people who are carriers of this virus. In rare cases, especially if your child is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening.

Surgery or dental procedures

• Before any surgery or dental procedures, inform the doctor that your child is taking Hefiya. The doctor may advise temporarily stopping Hefiya.

Demyelinating disease

• If your child has or develops demyelinating diseases (diseases affecting the protective covering of nerves), such as multiple sclerosis, the doctor will decide whether to start or continue treatment with Hefiya. Inform the doctor immediately if your child develops symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and should not be given during treatment with Hefiya, as they may cause infections. Consult the doctor before vaccinating your child. In children, it is recommended, if possible, to administer age-appropriate vaccinations before starting Hefiya therapy.
• If your daughter takes Hefiya during pregnancy, the baby may have an increased risk of infection for up to about 5 months after the last dose your daughter received during pregnancy. It is important that you inform your daughter’s paediatrician or other healthcare provider about your daughter’s use of Hefiya during pregnancy, so they can determine when the baby should receive any vaccinations.

Heart failure

• It is important to inform the doctor about any past or current heart problems. If your child has mild heart failure and is being treated with Hefiya, the doctor will need to carefully monitor your child’s heart condition. If new symptoms of heart failure appear or existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact the doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If your child has persistent fever, bruising, easy bleeding, or paleness, contact the doctor immediately. The doctor may decide to stop the treatment.

Tumours

• Very rare cases of certain types of tumours have been observed in children and adults treated with Hefiya or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukaemia (cancers affecting blood cells and bone marrow). If your child takes Hefiya, the risk of developing lymphoma, leukaemia, or other tumours may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also receiving azathioprine or mercaptopurine. Inform the doctor if your child is taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment, or if the appearance of existing marks or damaged areas changes, inform the doctor.
• Cases of cancers other than lymphoma have been reported in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If your child has COPD or smokes heavily, discuss with the doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform the doctor if symptoms such as unexplained persistent rash, fever, joint pain, or fatigue occur.

Other medicines and Hefiya
Inform the doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Hefiya can be taken with methotrexate and other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF agents and anakinra or abatacept is not recommended because of the possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult the doctor.

Pregnancy and breastfeeding

• Your daughter should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after the last dose of Hefiya.
• If your daughter is pregnant, suspects she may be pregnant, or is planning a pregnancy, consult her doctor about taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed when mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding with breast milk.
• If your daughter takes Hefiya during pregnancy, the baby may have an increased risk of infection.
• It is important that you inform your daughter’s paediatrician or other healthcare provider about her use of Hefiya during pregnancy before the baby receives any vaccinations (for more information on vaccines, see section “Warnings and precautions”).

Driving and using machines
Hefiya may affect, although only to a minor extent, the ability to drive, ride a bicycle, or use machines. After taking Hefiya, vision disturbances or dizziness (a sensation that the surroundings are spinning) may occur.

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Hefiya is available in 40 mg pens and 20 mg and 40 mg pre-filled syringes for
administration of a complete dose of 20 mg or 40 mg to patients.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If Hefiya is accidentally injected more frequently than intended, contact your child’s doctor or pharmacist and inform them that your child has received more medication than prescribed. Always keep the medicine packaging, even if empty.

If you forget to use Hefiya
If you forget to give your child an injection, administer the next dose of Hefiya as soon as you remember. Then continue with your child’s regular dosing schedule as prescribed.

If you stop treatment with Hefiya
The decision to discontinue the use of Hefiya should be discussed with your child’s doctor. Symptoms may return after stopping treatment.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attention if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning during urination, fatigue or weakness, or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a lump or open sore that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with Hefiya:

Very common (may affect more than 1 in 10 people)

• injection site reactions (including pain, swelling, redness, or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• severe infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of spinning room);
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• hematoma (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dryness syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• cracking or breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid accumulation in the body, causing swelling of affected tissues);
• fever;
• reduced platelet count in the blood, increasing the risk of bleeding or bruising;
• impaired wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including lymphatic system tumors (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling in the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• pancreatitis (inflammation of the pancreas) causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and a blistering rash);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (pruritic red-purple rash).

Not known (frequency cannot be estimated from available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (characterized by rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain was low).

Some of the side effects observed with adalimumab may be asymptomatic and can only be detected through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased blood uric acid;
• altered blood sodium;
• reduced blood calcium;
• reduced blood phosphorus;
• increased blood sugar;
• increased blood lactate dehydrogenase;
• presence of autoantibodies in the blood;
• reduced blood potassium.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in the blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in its outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 21 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 21 days or discarded, even if it is subsequently returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which it must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 20 mg of adalimumab in 0.4 mL of solution.
• The excipients are adipic acid, monohydrate citric acid, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2, “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 20 mg solution for injection in pre-filled syringe for paediatric use is supplied as 0.4 mL of solution, from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use transparent type I glass syringe with a 29-gauge stainless steel needle, a needle safety device with finger grip, a rubber needle cap (thermoplastic elastomer) and a plastic plunger, containing 0.4 mL of solution.
The pack contains 2 pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Terapia S.A.
Tél: +33 1 49 64 48 00 Tel: +40 264 50 15 00

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Tel: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare professional must show you how to properly prepare and inject Hefiya using the
pre-filled syringe before you use the medicine for the first time. If you have any doubts, consult
your healthcare professional.
Single-use pre-filled syringe of Hefiya with needle safety device and additional finger grip

Figure A: pre-filled syringe of Hefiya with needle safety device and additional finger grip
It is important that you:

• Do not open the outer carton until you are ready to use the syringe;
• Do not use the syringe if the blister seals are broken, as use may not be safe;
• Never leave the syringe unattended where it could be tampered with by others;
• Do not use the syringe if it has been dropped and appears damaged or if it was dropped after removing the needle cap;
• Do not remove the needle cap until the time of injection;
• Be careful not to touch the wings of the needle safety device before use. Doing so may activate the needle safety device too early. Do not remove the finger grip before injection;
• Inject Hefiya 15–30 minutes after removing it from the refrigerator for a more comfortable injection;
• Immediately dispose of the used syringe after use. Do not reuse the syringe. See “4. Disposal of Used Syringes” at the end of these Instructions for Use.

How should Hefiya be stored?

• Store the syringe carton in the refrigerator at a temperature between 2°C and 8°C.
• When necessary (e.g., when traveling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 21 days—ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 21 days or discarded, even if later returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which it must be discarded.
• Keep syringes in their original packaging until ready to use, to protect the medicine from light.
• Do not store syringes at extremely hot or cold temperatures.
• Do not freeze the syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Pre-filled syringe(s) of Hefiya (see Figure A). Each syringe contains 20 mg/0.4 mL of Hefiya.

The package does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container.

Figure B: items not included in the package
See “4. Disposal of Used Syringes” at the end of these Instructions for Use.
Before the injection

Figure C: needle safety device not activated – Figure D: needle safety device activated – do not use
the syringe is ready for use

• In this configuration, the needle safety device is NOT ACTIVATED.
• The syringe is ready for use (see Figure C).
• In this configuration, the needle safety device is ACTIVATED.
• DO NOT USE the syringe (see Figure D).

Preparing the syringe

• For a more comfortable injection, remove the blister containing the syringe from the refrigerator and leave it closed on the work surface for about 15–30 minutes to reach room temperature.
• Remove the syringe from the blister.
• Look through the viewing window. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you see particles and/or changes in color. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance.
• Do not use the syringe if it is damaged or if the needle safety device is activated. Return the syringe and its packaging to the pharmacy.
• Check the expiration date (Exp.) on the syringe. Do not use the syringe if the expiration date has passed.

Contact your pharmacist if the syringe fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the front of the

thighs. You may also use the lower abdomen,
but not the area within 5 cm around the navel (see
Figure E).

• Choose a different site each time you administer an injection.
• Do not inject the medicine into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, DO NOT inject the medicine directly into areas with psoriatic plaques. Figure E: How to choose the injection site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure F).
• Do not touch the cleaned area before the injection.

Figure F: how to clean the injection site

3. Administering the injection:

• Carefully pull off the needle cap from the

syringe (see Figure G).

• Discard the needle cap.
• You may see a drop of liquid at the tip of the needle. This is normal.

Figure G: How to remove the needle cap

• Gently create a skin fold at the injection site

(see Figure H).

• Insert the needle into the skin as shown.
• Push the entire needle under the skin to ensure that the full dose of medicine is delivered.

Figure H: How to insert the needle

• Hold the syringe as shown (see Figure I).
• Slowly push the plunger all the way down until it stops, so that the plunger head is completely between the wings of the needle safety device.
• While holding the syringe in place, keep the plunger fully depressed for 5 seconds.

Figure I: How to hold the syringe

• Keep the plunger fully depressed while

carefully withdrawing the needle from the injection site, then release the skin (see Figure J).
Figure J: How to withdraw the needle

• Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle

(see Figure K).

• You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad against the injection site and hold it for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a small adhesive bandage.
  Figure K: How to slowly release the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container
  (puncture-resistant, closable container) as shown in the image below:

For your safety and the safety of others, needles and syringes must never be reused.

• Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to properly dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

If you have any questions, consult a doctor, pharmacist, or nurse familiar with Hefiya.

Patient information leaflet

Hefiya 20 mg solution for injection in pre-filled syringe

adalimumab
20 mg/0.2 mL
Please read this leaflet carefully before your child uses this medicine, as it contains
important information.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before your child starts treatment with Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you or your child during treatment and for 4 months after your child’s last injection of Hefiya.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for your child only. Do not give it to other people, even if their symptoms are the same as your child’s, as it may be harmful.
• If your child experiences any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before your child uses Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• polyarticular juvenile idiopathic arthritis,
• enthesitis-related arthritis,
• paediatric plaque psoriasis,
• paediatric Crohn’s disease,
• non-infectious paediatric uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the inflammatory process in these diseases.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years. At diagnosis, other disease-modifying drugs such as methotrexate may be given. If these drugs do not work satisfactorily, Hefiya will be administered to treat polyarticular juvenile idiopathic arthritis.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the sites where tendons attach to bones.
Hefiya is used to treat enthesitis-related arthritis in children and adolescents aged 6 to 17 years.
Initially, other disease-modifying medicines such as methotrexate may be given. If these medicines do not work well enough, Hefiya will be administered to treat enthesitis-related arthritis.

Paediatric plaque psoriasis
Plaque psoriasis is an inflammatory skin condition causing reddish, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken, or lift from the nail bed, which may be painful. Psoriasis is believed to be caused by a problem with the body’s immune system leading to increased production of skin cells.
Hefiya is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical medications and UV light therapy have not worked adequately or are not suitable.

Paediatric Crohn’s disease
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.
Your child may first be given other medicines. If these medicines do not work satisfactorily, your child will be given Hefiya to reduce the typical symptoms of the disease.

Non-infectious paediatric uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters in the eye (black spots or fine lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used to treat children from the age of 2 years with chronic non-infectious uveitis affecting the front part of the eye.
Your child may first be given other medicines. If these medicines do not work satisfactorily, your child will be given Hefiya to reduce the typical symptoms of the disease.

2. What you should know before your child uses Hefiya

Do not use Hefiya

• If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If your child has a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to inform the doctor if your child has signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If your child has moderate or severe heart failure. It is important to inform the doctor if there has been or is a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.

Allergic reaction

• If allergic reactions occur with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hefiya again and contact the doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

• If your child has an infection, including long-term or localized infections (e.g., leg ulcers), consult the doctor before starting treatment with Hefiya. If you have any doubts, contact the doctor.
• Your child may be more likely to get infections while being treated with Hefiya. This risk may increase if your child has reduced lung function. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, or bacteria, or other unusual infectious organisms, and sepsis (septicaemia).
• In rare cases, these infections may be life-threatening. It is important to inform the doctor if your child has symptoms such as fever, wounds, feeling tired, or dental problems. The doctor may advise temporarily stopping Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, the doctor will need to check whether your child has signs or symptoms typical of tuberculosis before starting treatment with Hefiya. This will involve a detailed medical assessment, including your child’s medical history and clinical examinations (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in your child’s Patient Reminder Card. It is very important to inform the doctor if your child has ever had tuberculosis or has been in close contact with people who have tuberculosis. Tuberculosis may develop during treatment even if your child has received preventive treatment for tuberculosis. Contact the doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections appear during or after treatment.

Travel/recurrent infection

• Inform the doctor if your child has lived in or traveled to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform the doctor if your child has had recurrent infections or has conditions that increase the risk of infection.

Hepatitis B virus

• Inform the doctor if your child is a carrier of hepatitis B virus (HBV), has an active hepatitis B virus infection, or if you think your child may be at risk of contracting hepatitis B virus. The doctor must test your child for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in carriers of this virus. In some rare cases, especially if your child is also receiving treatment with other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Surgery or dental procedures

• Before any surgery or dental procedures, inform the doctor that your child is taking Hefiya. The doctor may advise temporarily stopping Hefiya.

Demyelinating disease

• If your child has or develops demyelinating diseases (diseases affecting the insulating layer around nerves), such as multiple sclerosis, the doctor will decide whether to start or continue treatment with Hefiya. Inform the doctor immediately if your child develops symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be given during treatment with Hefiya, as they may cause infections. Consult the doctor before vaccinating your child. In children, it is recommended, if possible, to administer age-appropriate vaccinations before starting Hefiya therapy.
• If your daughter takes Hefiya during pregnancy, the baby may have an increased risk of infection for up to about 5 months after the last dose your daughter received during pregnancy. It is important that you inform your daughter’s paediatrician or other healthcare provider about your daughter’s use of Hefiya during pregnancy, so they can decide when the baby should receive any vaccinations.

Heart failure

• It is important to inform the doctor about any past or present heart problems. If your child has mild heart failure and is being treated with Hefiya, the doctor will need to carefully monitor your child’s heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact the doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If your child has persistent fever, bruising, easy bleeding, or paleness, contact the doctor immediately. The doctor may decide to stop the treatment.

Tumours

• Very rare cases of certain types of tumours have been observed in children and adults treated with Hefiya or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukaemia (cancers affecting blood cells and bone marrow). If your child is taking Hefiya, the risk of developing lymphomas, leukaemia, or other tumours may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also receiving azathioprine or mercaptopurine. Inform the doctor if your child is taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If areas of damaged skin appear during or after treatment, or if the appearance of existing marks or damaged areas changes, inform the doctor.
• Cases of cancers other than lymphoma have been reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If your child has COPD or is a heavy smoker, discuss with the doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform the doctor if symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue occur.

Other medicines and Hefiya
Inform the doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Hefiya may be taken together with methotrexate and other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other TNF inhibitors, anakinra, or abatacept is not recommended because of the possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult the doctor.

Pregnancy and breastfeeding

• Your daughter should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after the last dose of Hefiya.
• If your daughter is pregnant, suspects she may be pregnant, or is planning a pregnancy, consult her doctor about taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed when mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding with breast milk.
• If your daughter takes Hefiya during pregnancy, the baby may have an increased risk of infection.
• It is important that you inform your daughter’s paediatrician or other healthcare provider about her use of Hefiya during pregnancy before the baby receives any vaccinations (for more information on vaccines, see section “Warnings and precautions”).

Driving and using machines
Hefiya may have a minor influence on the ability to drive, ride a bicycle, or use machines. After taking Hefiya, vision disturbances or dizziness (a sensation that the surroundings are spinning) may occur.

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.2 mL dose, i.e., essentially ‘sodium-free’.

3. How to use Hefiya

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Hefiyia for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hefiya if the child requires
a different dose.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than prescribed, contact your doctor or pharmacist and inform them that your child has received more medication than intended. Always keep the medicine packaging, even if empty.

If you forget to use Hefiya
If you forget to give your child an injection, administer the missed dose of Hefiya as soon as you remember. After that, resume your child's regular dosing schedule as prescribed.

If you stop treatment with Hefiya
The decision to discontinue Hefiya should be discussed with your child's doctor. Symptoms may return after stopping treatment.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical advice if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, trouble swallowing;
• shortness of breath during physical activity or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning during urination, fatigue or weakness, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a growing bump or open sore that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with Hefiya:

Very common (may affect more than 1 in 10 people)

• injection site reactions (including pain, swelling, redness, or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of spinning);
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• bruising (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• sicca syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• contusion;
• skin inflammation (such as eczema);
• cracking or breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid accumulation in the body causing swelling of affected tissues);
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) occurring when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling of the ankles;
• acute myocardial infarction;
• formation of an aneurysm in the wall of a major artery, vein inflammation and clot, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• pancreatitis (inflammation of the pancreas) causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (an immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and blistering skin rash);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (pruritic red-purple skin rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi’s sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly appears as purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (characterized by skin rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain was low).

Some of the side effects observed with adalimumab may be asymptomatic and detectable only through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• decreased platelet count;
• increased blood uric acid;
• sodium imbalance in blood;
• decreased blood calcium;
• decreased blood phosphorus;
• increased blood glucose;
• increased blood lactate dehydrogenase;
• presence of autoantibodies in blood;
• decreased blood potassium.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly through the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 42 days or discarded, even if it is subsequently returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which the syringe must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 20 mg of adalimumab in 0.2 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 20 mg solution for injection in pre-filled syringe for paediatric use is supplied as 0.2 mL of solution, from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is provided in a single-use, transparent type I glass syringe with a 29-gauge stainless steel needle, finger grip, needle rubber cap (thermoplastic elastomer) and plastic plunger, containing 0.2 mL of solution.
The multiple pack contains 2 (2 packs of 1) pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen presentations.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Tel: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare professional must show you how to properly prepare and inject Hefiya using the
single-dose pre-filled syringe before you use the medicine for the first time. If you have any doubts, consult
your healthcare professional.
Single-use pre-filled syringe of Hefiya

Figure A: pre-filled syringe of Hefiya
It is important that you:

• do not use the pre-filled syringe if the seal on the outer case is broken, as it may not be safe to use;
• do not open the inner case until you are ready to use the pre-filled syringe of Hefiya;
• never leave the pre-filled syringe unattended where it could be tampered with by others;
• if you drop the syringe, do not use it if it appears damaged or if it was dropped after removing the needle cap;
• do not remove the needle cap until just before injection;
• inject Hefiya 15–30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the syringe. See “4. Disposal of Used Syringes” at the end of these Instructions for Use;
• consult your doctor or nurse for advice on the appropriate injection site and technique if you are underweight or if administering the injection to a child.

How should you store the single-dose pre-filled syringe of Hefiya?

• Store the Hefiya single-dose syringe in its original packaging to protect the medicine from light.
• Store the outer packaging of the pre-filled syringes in the refrigerator, at a temperature between 2°C and 8°C.
• If necessary (e.g., when traveling), you may store the pre-filled syringe at room temperature up to 25°C for a maximum of 42 days.
• After 42 days, discard the pre-filled syringe that has been stored at room temperature.
• You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which it must be discarded.
• Do not store the pre-filled syringe at extremely hot or cold temperatures.
• Do not freeze the pre-filled syringe.
• Do not use the pre-filled syringe after the expiry date stated on the outer case or on the syringe label. If the expiry date has passed, return the entire pack to the pharmacy.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The pre-filled syringe pack contains:

• Pre-filled syringe of Hefiya (see Figure A). Each pre-filled syringe contains 20 mg/0.2 mL of adalimumab.

The pre-filled syringe pack of Hefiya does not contain (see Figure B ):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “4. Disposal of Used Syringes” at the end of these Instructions for Use.
• Adhesive bandage.

Figure B: items not included in the pack
Preparing the pre-filled syringe

• For a more comfortable injection, remove the case containing the pre-filled syringe from the refrigerator and leave it closed on the work surface for about 15–30 minutes to allow it to reach room temperature.
• Remove the pre-filled syringe from the box and inspect it. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you notice particles and/or changes in color. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance.
• Do not use the pre-filled syringe if it is damaged. Return the entire product pack to the pharmacy.
• Check the expiry date (Exp.) of the pre-filled syringe. Do not use the pre-filled syringe if the expiry date has passed.

Consult your pharmacist if the pre-filled syringe fails any of the checks listed above.

1. Choosing the injection site:

The injection site is the location on the body where you will administer
the injection using the Hefiya pre-filled syringe.

• The recommended injection site is the front of the thighs. The lower abdomen may also be used, but not within 5 cm of the navel (see Figure C ).
• Choose a different site each time you give an injection.
• Do not inject the medicine into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. Figure C : how to choose the injection site If you have psoriasis, do not inject the medicine directly into areas affected by psoriatic plaques.

2. Cleaning the injection site:

• When ready to use the pre-filled syringe, wash your hands thoroughly with water and soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure D).

• Do not touch this area again before giving the injection. Let the skin dry completely before injection. Do not wave or blow air onto the cleaned area. Figure D: How to clean the injection site

3. Injection Administration:

• Carefully pull off the needle cap
  
  from the syringe (see Figure E).

• Discard (dispose of) the needle cap.

• You may see a drop of liquid at the tip of the needle. This is normal.

Figure E: How to remove the needle cap

• Gently create a skin fold at the injection site
  
  (see Figure F).

• Insert the needle into the skin at a 45° angle, as shown (see Figure F).

Figure F: How to insert the needle

• Hold the prefilled single-dose syringe as shown
  
  (see Figure G).

• Slowly push the plunger all the way down until it stops.

• While holding the syringe in place, keep the plunger fully depressed for 5 seconds.

• Carefully withdraw the needle from the injection site, then release the skin. You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad against the injection site and hold pressure for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a small adhesive bandage.

Figure G: How to push the plunger

4. Disposal of used pre-filled syringes:

• Dispose of the used syringe in a sharps disposal
  container (a puncture-resistant, closable
  container). For your safety and the safety of
  others, needles and syringes must never be
  reused.

• Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste derived from such medicine must be disposed of in accordance with local regulations.

Figure H: how to dispose of the used
pre-filled syringe
If you have any questions, consult a doctor, pharmacist, or nurse familiar with
Hefiya.

Patient information leaflet: information for the patient

Hefiya 40 mg solution for injection in pre-filled syringe

adalimumab
40 mg/0.8 mL
Please read this leaflet carefully before using this medicine, as it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information that you need to know before receiving Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you during treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before using Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• enthesitis-related arthritis,
• ankylosing spondylitis,
• non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic evidence of ankylosing spondylitis),
• psoriatic arthritis,
• psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis, and
• non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs such as methotrexate may be used first. If these drugs do not work satisfactorily, you will be given Hefiya to treat rheumatoid arthritis.
Hefiya may also be used for the treatment of severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hefiya can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hefiya is generally used in combination with methotrexate. If your doctor considers that treatment with methotrexate is not appropriate, Hefiya may be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory joint diseases that usually first appear during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years.
At diagnosis, other disease-modifying drugs such as methotrexate may be given. If these drugs do not work satisfactorily, patients will be given Hefiya for the treatment of polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis are inflammatory conditions of the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be given other medicines. If these medicines do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.

Plaque psoriasis in adults and children
Plaque psoriasis is an inflammatory skin condition causing red, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which can be painful. Psoriasis is thought to be caused by a problem with the body’s immune system leading to an increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical medications and UV light therapy have not worked adequately or are not suitable.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya can slow down the joint cartilage and bone damage caused by the disease and improve physical function.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term inflammatory skin disease that is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus.
It most commonly affects specific areas of the skin, such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Hefiya is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. Hefiya can reduce the number of nodules and abscesses you have and the pain often associated with this disease. You may first be given other medicines. If these medicines do not work satisfactorily, you will be given Hefiya.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s disease, you will first be given other medicines. If you do not respond adequately to these medicines, you will be given Hefiya to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Hefiya is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you may first take other medicines. If these medicines do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters (black spots or fine lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye

2. What you should know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.

Allergic reaction

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hefiya again and contact your doctor immediately, as these reactions may rarely be life-threatening.

Infection

• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hefiya. If you are in doubt, contact your doctor.
• You may be more likely to get infections while being treated with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, bacteria, or other unusual infectious organisms, and sepsis (septicaemia).
• Rarely, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise temporarily stopping Hefiya.

Tuberculosis (TB)

• Cases of tuberculosis have occurred in patients treated with adalimumab. Therefore, your doctor will check for signs and symptoms of tuberculosis before starting Hefiya treatment. This will include a detailed medical assessment including your medical history and clinical examinations (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or have been in close contact with someone who has tuberculosis. Tuberculosis may occur during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if you develop symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Travel/recurrent infection

• Inform your doctor if you have lived in or traveled to areas where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor must test you for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in carriers of this virus. In rare cases, especially if the patient is also receiving treatment with other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Age over 65 years

• If you are over 65 years old, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection during treatment. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Hefiya. Your doctor may advise temporarily stopping Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases affecting the protective covering of nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of your body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be administered during treatment with Hefiya, as they may cause infections. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to administer age-appropriate vaccinations before starting Hefiya therapy. If you take Hefiya during pregnancy, your baby may have an increased risk of infection for up to approximately 5 months after your last dose. It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy so they can determine when your baby should receive any vaccinations.

Heart failure

• It is important to inform your doctor about any heart problems, past or present. If you have mild heart failure and are being treated with Hefiya, your doctor should carefully monitor your heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.

Tumours

• Very rare cases of certain types of tumours have been observed in children and adults treated with Hefiya or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukaemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, your risk of developing lymphomas, leukaemia, or other tumours may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also receiving azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hefiya.

• Cases of non-melanoma skin cancer have been observed in patients treated with adalimumab. If you notice damaged skin areas during or after treatment, or if the appearance of existing marks or damaged areas changes, inform your doctor.

• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If you have COPD or are a heavy smoker, discuss with your doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as persistent unexplained skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: If possible, children should have received all age-appropriate vaccinations before starting Hefiya.
• Do not give Hefiya to children under 2 years of age with polyarticular juvenile idiopathic arthritis.

Other medicines and Hefiya
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hefiya may be taken with methotrexate and other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF agents and anakinra or abatacept is not recommended because of the possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should consider using an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after your last dose of Hefiya.
• If you are pregnant, think you might be pregnant, or are planning to become pregnant, ask your doctor for advice regarding the use of this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed when mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding.
• If you take Hefiya during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy before your baby receives any vaccinations (for more information on vaccines, see the section "Warnings and precautions").

Driving and using machines
Hefiya may affect your ability to drive, ride a bicycle, or use machines, although only to a minor extent. After taking Hefiya, you may experience vision disturbances or a sensation that your surroundings are spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Hefiya is available in 40 mg pens and in 20 mg and 40 mg prefilled syringes for
administration of a complete dose of 20 mg or 40 mg to patients.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist and inform them that you have taken more medicine than required. Always keep the medicine carton, even if empty.

If you forget to use Hefiya
If you forget to make an injection, administer the next dose of Hefiya as soon as you remember. After that, resume your regular dosing schedule as prescribed.

If you stop using Hefiya
The decision to discontinue the use of Hefiya should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Most of the side effects are mild to moderate in severity. However, some may be serious and require treatment.
Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical advice if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating, fatigue or weakness, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a swelling or open sore that does not heal;
• signs and symptoms suggesting disorders of the haematopoietic system, such as persistent fever, bruising, bleeding, or pallor.

The following side effects have been observed with Hefiya:

Very common (may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness, or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumours;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of spinning);
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• haematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• cracking or breaking of fingernails or toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• oedema (fluid accumulation in the body, causing swelling of affected tissues);
• fever;
• reduced platelet count in the blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defences are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumours, including tumours of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that may affect the lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling of the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, vein inflammation and clot, or blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal fluid accumulation in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial oedema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (an immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• disrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukaemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and blistering skin rash);
• facial oedema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy red-purple rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (characterized by skin rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain was low).

Some of the side effects observed with adalimumab may be asymptomatic and may only be detected through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• altered sodium levels in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased blood sugar;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in the blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister pack/box following the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in its outer packaging to protect from light.

Alternative storage conditions:
When necessary (e.g., when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 21 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 21 days or discarded, even if subsequently returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date by which it must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 40 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, citric acid monohydrate, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 40 mg solution for injection in pre-filled syringe is supplied as 0.8 mL of solution, from clear to
slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use, transparent type I glass syringe with a 29-gauge stainless steel needle, a needle safety device with finger grip, a rubber needle cap (thermoplastic elastomer), and a plastic plunger, containing 0.8 mL of solution.
Pack sizes contain 1 and 2 pre-filled syringes of Hefiya.
Multiple pack sizes contain 6 (3 packs of 2) pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Terapia S.A.
Tél: +33 1 49 64 48 00 Tel: +40 264 50 15 00

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Τηλ: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare professional must show you how to properly prepare and inject Hefiya using the
pre-filled syringe before you use the medicine for the first time. If you have any doubts, consult
your healthcare professional.
Single-use pre-filled syringe of Hefiya with needle safety device and additional finger grip

Figure A: Pre-filled syringe of Hefiya with needle safety device and additional finger grip
It is important that you:

• Do not open the outer box until you are ready to use the syringe;
• Do not use the syringe if the blister seals are broken, as use may not be safe;
• Never leave the syringe unattended where it could be tampered with by others;
• If you drop the syringe, do not use it if it appears damaged or if it has been dropped after removing the needle cap;
• Do not remove the needle cap until the moment of injection;
• Be careful not to touch the wings of the needle safety device before use. If you do, the needle safety device might activate too early. Do not remove the finger grip before injection;
• Inject Hefiya 15–30 minutes after removing it from the refrigerator for a more comfortable injection;
• Dispose of the used syringe immediately after use. Do not reuse the syringe. See “4. Disposal of Used Syringes” at the end of these Instructions for Use.

How should Hefiya be stored?

• Store the outer packaging of the syringes in the refrigerator at a temperature between 2°C and 8°C.
• When necessary (e.g., when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 21 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 21 days or discarded, even if subsequently returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which it must be discarded.
• Keep syringes in their original packaging until ready to use, to protect the medicine from light.
• Do not store syringes at extremely hot or cold temperatures.
• Do not freeze the syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Pre-filled syringe(s) of Hefiya (see Figure A). Each syringe contains 40 mg/0.8 mL of Hefiya.

The package does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container.

Figure B: Items not included in the package
See “4. Disposal of Used Syringes” at the end of these Instructions for Use.
Before Injection

Figure C: Needle safety device not activated – Figure D: Needle safety device activated –
the syringe is ready for use do not use
o In this configuration, the o In this configuration, the
needle safety device is NOT ACTIVATED. needle safety device is ACTIVATED.
o The syringe is ready for use (see o DO NOT USE the syringe (see
Figure C). Figure D).
Preparing the syringe

• For a more comfortable injection, remove the blister containing the syringe from the refrigerator and leave it closed on the work surface for approximately 15–30 minutes to reach room temperature.
• Remove the syringe from the blister.
• Look through the viewing window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you see particles or changes in colour. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance.
• Do not use the syringe if it is damaged or if the needle safety device is activated. Return the syringe and packaging to the pharmacy.
• Check the expiry date (Exp.) of the syringe. Do not use the syringe if the expiry date has passed.

Contact your pharmacist if the syringe fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the front of the

thighs. You may also use the lower abdomen,
but not the area within 5 cm around the navel (see
Figure E).

• Choose a different site each time you give an injection.
• Do not inject the medicine into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, DO NOT inject the medicine directly into areas affected by psoriatic plaques. Figure E: How to choose the injection site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure F).
• Do not touch the cleaned area before the injection.

Figure F: How to clean the injection site

3. Administering the injection:

• Carefully pull off the needle cap from the

syringe (see Figure G).

• Discard the needle cap.
• You may see a drop of liquid at the tip of the needle. This is normal.

Figure G: How to remove the needle cap

• Gently create a skin fold at the injection site (see

Figure H).

• Insert the needle into the skin as shown.
• Push the entire needle under the skin to ensure that the full dose of medicine is delivered.

Figure H: How to insert the needle

• Hold the syringe as shown (see Figure I).

• Slowly push the plunger all the way down until it stops, ensuring that the plunger head moves completely between the wings of the needle safety device.
• While holding the syringe in place, keep the plunger fully depressed for 5 seconds.

Figure I: How to hold the syringe

• Keep the plunger fully depressed while

carefully withdrawing the needle from the injection site, then release the skin (see Figure J).
Figure J: How to withdraw the needle

• Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle
  (see Figure K).

• You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad over the injection site and hold for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a small adhesive bandage.
  Figure K: How to slowly release the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container (a puncture-resistant, closable container). For your safety and health, and that of others, needles and syringes must never be reused.

• Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste derived from this medicine must be disposed of in accordance with local applicable regulations.

If you have any questions, consult a doctor, pharmacist, or nurse familiar with Hefiya.

Patient information leaflet

Hefiya 40 mg solution for injection in pre-filled pen

adalimumab
40 mg/0.8 mL
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card, which contains important safety information you need to know before receiving Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you throughout the treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before using Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• enthesitis-related arthritis,
• ankylosing spondylitis,
• non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,
• psoriatic arthritis,
• psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis, and
• non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, you may initially be given other disease-modifying drugs, such as methotrexate. If these medicines do not work satisfactorily, you will be given Hefiya to treat rheumatoid arthritis.
Hefiya may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hefiya can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hefiya is generally used in combination with methotrexate. If your doctor considers methotrexate treatment inappropriate, Hefiya may be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory joint diseases that typically first appear during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years.
At diagnosis, other disease-modifying drugs such as methotrexate may be given. If these medicines do not work satisfactorily, patients will be given Hefiya for the treatment of polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory conditions affecting the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first be given other medicines. If these medicines do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.

Plaque psoriasis in adults and children
Plaque psoriasis is an inflammatory skin condition causing red, scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which can be painful. Psoriasis is believed to be caused by a problem with the body’s immune system leading to an increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical medications and UV light therapy have not worked adequately or are not suitable.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya can slow down joint cartilage and bone damage caused by the disease and improve physical function.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term inflammatory skin disease that is often painful. Symptoms may include painful nodules and abscesses (cysts) that can drain pus. It most commonly affects specific skin areas such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Hefiya is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. Hefiya can reduce the number of nodules and abscesses you have, as well as the pain often associated with this disease. You may initially receive other medicines. If these do not work satisfactorily, you will be given Hefiya.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s disease, you will first be given other medicines. If you do not respond adequately to these medicines, Hefiya will be given to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Hefiya is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you may first take other medicines. If these medicines do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters in the eye (black spots or thin lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not administer Hefiya again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infection

• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hefiya. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, or bacteria, or other unusual infectious organisms, and sepsis (septicaemia).
• In rare cases, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise temporarily stopping Hefiya.

Tuberculosis (TB)

• Cases of tuberculosis have occurred in patients treated with adalimumab. Therefore, your doctor will check for signs or symptoms of tuberculosis before starting treatment with Hefiya. This will include a detailed medical evaluation including your medical history and clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or if you have been in close contact with someone who has tuberculosis. Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after treatment.

Travel/recurrent infection

• Inform your doctor if you have lived in or traveled to areas where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus.
  Your doctor must test you for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in carriers of this virus. In some rare cases, especially if the patient is also receiving other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if symptoms of infection such as fever, wounds, feeling tired, or dental problems occur.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Hefiya. Your doctor may advise temporarily stopping Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases affecting the protective covering of nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be given during treatment with Hefiya, as they may cause infections. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to complete age-appropriate vaccinations before starting Hefiya therapy. If you have taken Hefiya during pregnancy, your baby may have an increased risk of infection for up to approximately 5 months after your last dose during pregnancy. It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy so they can decide when the baby should receive any vaccinations.

Heart failure

• It is important to inform your doctor about any past or current heart problems. If you have mild heart failure and are being treated with Hefiya, your doctor should carefully monitor your heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.

Tumours

• Very rare cases of certain types of tumours have been observed in children and adults treated with adalimumab or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher-than-average risk of developing lymphoma and leukaemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, your risk of developing lymphomas, leukaemia, or other tumours may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also receiving azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hefiya.

• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If areas of damaged skin appear during or after treatment, or if the appearance of moles or damaged areas changes, inform your doctor.

• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα medicine. If you have COPD or are a heavy smoker, discuss with your doctor whether treatment with an anti-TNFα medicine is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as persistent unexplained skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: If possible, children should have completed all recommended vaccinations before starting Hefiya.
• Do not give Hefiya to children under 2 years of age with polyarticular juvenile idiopathic arthritis.

Other medicines and Hefiya
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hefiya may be taken with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) (such as sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF medicines, anakinra, or abatacept is not recommended because of the possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an appropriate method of contraception to prevent pregnancy and continue using it for at least 5 months after your last dose of Hefiya.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor about taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding.
• If you take Hefiya during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy before the baby receives any vaccinations (for more information on vaccines, see section "Warnings and precautions").

Driving and using machines
Hefiya may have a minor influence on your ability to drive, ride a bicycle, or use machines. After taking Hefiya, you may experience visual disturbances or a sensation that your surroundings are spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as prescribed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Hefiya is available in 40 mg pens and 20 mg and 40 mg pre-filled syringes for
administration of a complete dose of 20 mg or 40 mg to patients.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist and inform them that you have taken more medicine than required. Always keep the medicine packaging, even if empty.

If you forget to use Hefiya
If you forget to give an injection, administer the next dose of Hefiya as soon as you remember. Then continue with your regular dosing schedule.

If you stop using Hefiya
The decision to stop using Hefiya should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild to moderate in severity. However, some may be serious and require treatment.
Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical advice if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating; fatigue or weakness or cough;
• symptoms of nerve problems such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a swelling or open sore that does not heal;
• signs and symptoms suggesting disorders of the haematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with Hefiya:
Very common (may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness, or itching);
• respiratory tract infections (including colds, rhinorrhoea, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumours;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (feeling that the room is spinning);
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• haematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• cracking or breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• oedema (fluid accumulation in the body, causing swelling of affected tissues);
• fever;
• reduced platelet count in the blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defences are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumours, including tumours of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• disorders of the immune system that may affect lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling in the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial oedema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (an immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• disrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukaemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and a blistering rash);
• facial oedema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, red-purple rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which presents as a rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain has been low).

Some of the side effects observed with adalimumab may be asymptomatic and can only be detected through blood tests. These include:
Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• altered sodium levels in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased blood sugar;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in the blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell count, low red blood cell count, and low platelet count.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.
You may also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box after the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 21 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 21 days or discarded, even if it is later returned to the refrigerator. You must record the date when the pre-filled pen is first removed from the refrigerator and the date after which the pen must be discarded.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled pen contains 40 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, monohydrate citric acid, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 40 mg solution for injection in pre-filled pen is supplied as 0.8 mL of solution, from clear to slightly opalescent, from colourless to slightly yellowish.
Hefiya is supplied in a single-use pre-filled syringe assembled into a triangular-shaped pen with a transparent window and label. The syringe inside the pen is made of type I glass with a 29-gauge stainless steel needle, an inner needle rubber cap (thermoplastic elastomer) and a rubber stopper, containing 0.8 mL of solution.
The packs contain 1 and 2 pre-filled pens of Hefiya.
Multiple packs contain 6 (3 packs of 2) pre-filled pens of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and in pre-filled pen.
Marketing Authorization Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria
Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037
България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97
Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890
Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126
Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600
Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000
Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00
España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00
France România
Sandoz SAS Terapia S.A.
Tél: +33 1 49 64 48 00 Tel: +40 264 50 15 00
Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02
Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600
Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400
Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Τηλ: +30 216 600 5000
Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure correct use of the medicine, it is important that
you follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare professional must show you how to properly prepare and inject Hefiya using the
pre-filled pen before you use the medicine for the first time. If you have any doubts, consult your
healthcare professional.
Single-use pre-filled pen of Hefiya

Figure A: Parts of the Hefiya pen
In Figure A, the pen is shown without the cap. Do not remove the cap until you are ready to
administer the injection.
It is important that you:

• do not open the outer packaging until you are ready to use the pen;
• do not use the pen if the outer packaging seal or the pen’s security seal is broken;
• never leave the pen unattended where it could be tampered with by others;
• if the pen is dropped, do not use it if it appears damaged or if it was dropped after removing the cap;
• inject Hefiya 15–30 minutes after removing it from the refrigerator for a more comfortable injection;
• dispose of the used pen immediately after use. Do not reuse the pen. See “4. Disposal of Used Pens” at the end of these Instructions for Use.

How should you store the pen?

• Store the pen in its packaging in the refrigerator at a temperature between 2°C and 8°C.
• When necessary (e.g., when traveling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 21 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 21 days or discarded, even if subsequently returned to the refrigerator. You must record the date when the pre-filled pen is first removed from the refrigerator and the date after which it must be discarded.
• Keep the pen in its original packaging until you are ready to use it, to protect the medicine from light.
• Do not store the pen at extremely hot or cold temperatures.
• Do not freeze the pen.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Pre-filled pen(s) of Hefiya (see Figure A). Each pen contains 40 mg/0.8 mL of Hefiya. The package does not contain (see Figure B):
• Alcohol swab.
• Cotton ball or gauze pad.
• Sharps disposal container.

Figure B: Items not included in the package
See “4. Disposal of Used Pens” at the end of these Instructions for Use.
Before the injection
Preparing the pen

• For a more comfortable injection, remove the pen from the refrigerator approximately 15–30 minutes before injection to allow it to reach room temperature.
• Look through the viewing window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not use the pen if you notice particles and/or changes in colour. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance.

Figure C: Safety checks before injection

• Check the pen’s expiration date (Exp.). Do not use the pen if the expiration date has passed.
• Do not use the pen if the security seal is broken.

Contact your pharmacist if the pen fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the front of the
  thighs. You may also use the lower stomach area,
  but avoid the 5 cm area around the navel (see
  Figure D).

• Always choose a different site each time you give an injection.

• Do not inject the medicine into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, DO NOT inject the medicine directly into areas affected by psoriatic plaques.
  Figure D: How to choose the injection site

2. Cleaning the injection site:

• Wash your hands thoroughly with soap and water.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure E).
• Do not touch the cleaned area before the injection.

Figure E: How to clean the injection site

3. Removing the pen cap:

• Remove the cap only when you are ready to use the pen.

• Rotate the cap in the direction of the arrows (see Figure F).
• Once removed, discard the cap. Never attempt to reattach the cap.
• Use the pen within 5 minutes after removing the cap.
• You may notice a few drops of liquid coming out from the needle. This is normal.
  Figure F: How to remove the cap

4. How to hold the pen:

• Hold the pen at a 90-degree angle to the injection site

clean (see Figure G).

Correct Incorrect
Figure G: How to hold the pen

Injection
Read before administering the injection

During the injection, you will hear two clicks:

• The first click indicates that the injection has started.
• A moment later, a second click indicates that the injection is almost complete.
  You must keep the pen firmly pressed against the skin until you see a green indicator
  fill the viewing window and stop moving.

5. Starting the injection:

• Press the pen firmly against the skin to start the injection (see Figure H).

• The first click indicates that the injection has started.
• Continue to press the pen firmly against the skin.
• The green indicator shows the progress of the injection.

Figure H: How to start the injection

6. Completing the injection:

• Pay attention to the second click, which indicates that

the injection is almost complete.

• Check that the green indicator has filled the viewing window and has stopped moving (see Figure I).
• You may now remove the pen.

Figure I: How to complete
the injection
After the injection

7. Check that the green indicator fills the viewing window (see Figure J):
   • This means the medicine has been delivered. Contact your doctor if the green indicator is not visible.

• You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad against the injection site and hold it for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a small adhesive bandage. Figure J: How to check the green indicator

8. Disposal of used pens:

• Dispose of the used pen in a sharps disposal container (a puncture-resistant, closable container). For your safety and the safety of others, used pens must never be reused.

• Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer in use. This will help protect the environment. Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

If you have any questions, consult a doctor, pharmacist, or nurse who is familiar with Hefiya.

Patient information leaflet

Hefiya 40 mg solution for injection in pre-filled syringe

adalimumab
40 mg/0.4 mL
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before administration of Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you during treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before using Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• enthesitis-related arthritis,
• ankylosing spondylitis,
• non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic evidence of ankylosing spondylitis),
• psoriatic arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis,
• non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind specifically to a target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its activity and reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs such as methotrexate may be prescribed first. If these medicines do not work satisfactorily, you will be given Hefiya to treat your rheumatoid arthritis.
Hefiya may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hefiya can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hefiya is usually used in combination with methotrexate. If your doctor considers methotrexate treatment inappropriate, Hefiya may be given alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years. At diagnosis, other disease-modifying drugs such as methotrexate may be prescribed. If these medicines do not work satisfactorily, patients will be given Hefiya.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the areas where tendons attach to bones. Hefiya is used to treat enthesitis-related arthritis in patients aged 6 years and older.
Initially, other disease-modifying drugs such as methotrexate may be used. If these medicines are not effective enough, patients will be given Hefiya.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis are inflammatory conditions affecting the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be treated with other medicines. If these medicines do not work satisfactorily, you will be given Hefiya to reduce the signs and symptoms of the disease.

Plaque psoriasis in adults and children
Plaque psoriasis is an inflammatory skin condition causing red, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crack, thicken or lift from the nail bed, which may be painful. Psoriasis is thought to be caused by a problem with the body’s immune system leading to increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical medications and UV light therapy have not worked well enough or are not suitable.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya can slow down the damage to joint cartilage and bones caused by the disease and improve physical function.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic, often painful inflammatory skin disease. Symptoms may include painful nodules and abscesses (cysts) that may drain pus.
It most commonly affects specific skin areas such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Hefiya is used to treat:

• moderate to severe hidradenitis suppurativa in adults, and
• moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hefiya can reduce the number of nodules and abscesses you have and the pain often associated with this disease. You may initially receive other medicines. If these do not work satisfactorily, you will be given Hefiya.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat:

• moderate to severe Crohn’s disease in adults, and
• moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.

If you have Crohn’s disease, you will first be given other medicines. If you do not respond adequately to these medicines, Hefiya will be given to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Hefiya is used to treat:

• moderate to severe ulcerative colitis in adults, and
• moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

If you have ulcerative colitis, you may first be prescribed other medicines. If these do not work satisfactorily, you will be given Hefiya to reduce the signs and symptoms of ulcerative colitis.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters (dark spots or fine lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used for the treatment of:

• adults with non-infectious uveitis with inflammation affecting the back of the eye, and
• children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front of the eye.

Initially, other medicines may be used. If the response to these medicines is not adequate, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.

Allergic reaction

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hefiya again and contact your doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hefiya. If you are in doubt, contact your doctor.
• You may be more likely to get infections while being treated with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, bacteria, or other unusual infectious organisms, and sepsis (septicaemia).
• In rare cases, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise you to temporarily stop taking Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will check whether you have signs or symptoms typical of tuberculosis before starting treatment with Hefiya. This will involve a detailed medical assessment, including your medical history and clinical examinations (e.g., a chest X-ray and tuberculin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or if you have been in close contact with people who have tuberculosis. Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after treatment.

Travel/recurrent infection

• Inform your doctor if you have lived in or travelled to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus (HBV)

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor must test you for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in people who are carriers of this virus. In rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Age over 65

• If you are over 65 years old, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop taking Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases affecting the protective covering around nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of your body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be given during treatment with Hefiya, as they may cause infections. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to complete age-appropriate vaccinations before starting Hefiya therapy. If you take Hefiya during pregnancy, your baby may have an increased risk of infection for up to about 5 months after your last dose during pregnancy. It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy, so they can decide when your baby should receive any vaccinations.

Heart failure

• It is important to inform your doctor about any past or current heart problems. If you have mild heart failure and are being treated with Hefiya, your doctor should carefully monitor your heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.

Tumours

• Very rare cases of certain types of tumours have been observed in children and adults treated with Hefiya or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukaemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, your risk of developing lymphomas, leukaemia, or other tumours may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If you notice damaged areas of skin during or after treatment, or if the appearance of moles or damaged areas changes, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNFα medicine is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as unexplained persistent rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Hefiya.

Other medicines and Hefiya
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hefiya can be taken with methotrexate and other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF agents, anakinra, or abatacept is not recommended due to a possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after your last dose of Hefiya.
• If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor about taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy before your baby receives any vaccinations (for more information on vaccines, see section "Warnings and precautions").

Driving and using machines
Hefiya may affect your ability to drive, ride a bicycle, or use machines, although only to a minor extent. After taking Hefiya, you may experience vision disturbances or a sensation that your surroundings are spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya for each approved indication are listed in the table below. Your doctor may prescribe a different concentration of Hefiya if you require a different dose.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist and inform them that you have taken more medicine than required. Always keep the medicine packaging, even if empty.

If you forget to use Hefiya
If you forget to administer an injection, inject the missed dose as soon as you remember. After that, resume your regular dosing schedule as prescribed.

If you stop using Hefiya
The decision to discontinue treatment with Hefiya should be discussed with your doctor. Symptoms may return after stopping the treatment.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity. However, some can be serious and require treatment. Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical advice if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning during urination, fatigue or weakness, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a swelling or open sore that does not heal;
• signs and symptoms suggesting disorders of the haematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with adalimumab:

Very common (may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness, or itching);
• respiratory tract infections (including colds, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumours;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of the room spinning);
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• haematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• cracking or breaking of fingernails or toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• oedema (fluid accumulation in the body, causing swelling of affected tissue);
• fever;
• reduced platelet count in the blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) occurring when immune defences are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumours, including tumours of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• disorders of the immune system that may affect the lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling of the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial oedema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukaemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and a blistering rash);
• facial oedema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy red-violet rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi’s sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly appears as purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which presents as a rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain has been low).

Some of the side effects observed with adalimumab may be asymptomatic and may only be detected through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• changes in blood sodium levels;
• reduced blood calcium;
• reduced blood phosphorus;
• increased blood sugar;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced blood potassium.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in the blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell count, low red blood cell count, and low platelet count.

Reporting of side effects

If you get any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box after the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum period of 42 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 42 days or discarded, even if subsequently returned to the refrigerator. You must record the date on which the pre-filled syringe is first removed from the refrigerator and the date by which it must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 40 mg of adalimumab in 0.4 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 40 mg solution for injection in pre-filled syringe is supplied as 0.4 mL of solution, from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use, transparent type I glass syringe with a 29-gauge stainless steel needle, needle safety device with finger grip, rubber needle cap (thermoplastic elastomer) and plastic plunger, containing 0.4 mL of solution.
The packs contain 1 and 2 pre-filled syringes of Hefiya.
Multiple packs contain 6 (3 packs of 2) pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Tel: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare professional must show you how to properly prepare and inject Hefiya using the
single-dose pre-filled syringe before you use the medicine for the first time. If you have any doubts, consult
your healthcare professional.
Single-dose pre-filled syringe of Hefiya with needle safety device and additional finger grip

Figure A: Pre-filled syringe of Hefiya with needle safety device and finger grip
It is important that you:

• Do not use the pre-filled syringe if the blister seals are broken, as use may not be safe;
• Do not open the outer box until you are ready to use the pre-filled syringe;
• Never leave the pre-filled syringe unattended where it could be tampered with by others;
• If you drop the syringe, do not use it if it appears damaged or if it was dropped after removing the needle cap;
• Do not remove the needle cap until the time of injection;
• Be careful not to touch the wings of the needle safety device before use. Doing so may cause the needle safety device to activate prematurely.
• Do not remove the finger grip before injection;
• Inject Hefiya 15–30 minutes after removing it from the refrigerator for a more comfortable injection;
• Dispose of the used syringe immediately after use. Do not reuse the pre-filled syringe. See “4. Disposal of used pre-filled syringes” at the end of these Instructions for Use.

How should you store the single-dose pre-filled syringe of Hefiya?

• Store the pre-filled syringe packaging in the refrigerator at a temperature between 2°C and 8°C.
• When necessary (e.g., when traveling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 42 days or discarded, even if subsequently returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which it must be discarded.
• Keep the pre-filled syringes in their original packaging until ready to use, to protect the medicine from light.
• Do not store the pre-filled syringes at extremely hot or cold temperatures.
• Do not freeze the pre-filled syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The pre-filled syringe package contains:

• Pre-filled syringe(s) of Hefiya ( see Figure A ). Each pre-filled syringe contains 40 mg/0.4 mL of adalimumab.

The Hefiya pre-filled syringe package does not contain ( see Figure B ):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “4. Disposal of used syringes” at the end of these Instructions for Use.
• Adhesive bandage.

Figure B: Items not included in the package
Before the injection

Figure C: the needle safety device is not Figure D: the needle safety device is
activated – the syringe is ready for use activated – do not use
o In this configuration, the needle safety o In this configuration, the needle safety
device is NOT ACTIVATED. device is ACTIVATED.
o The syringe is ready for use (see o DO NOT USE the syringe (see
Figure C ). Figure D ).
Preparing the syringe

• For a more comfortable injection, remove the syringe’s carton from the refrigerator and let it remain closed on the work surface for about 15–30 minutes to reach room temperature.
• Remove the pre-filled syringe from the blister.
• Look through the viewing window. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you see particles and/or changes in color. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance.
• Do not use the pre-filled syringe if it is damaged or if the needle safety device is activated. Return the pre-filled syringe and its packaging to the pharmacy.
• Check the expiry date (Exp.) of the pre-filled syringe. Do not use the pre-filled syringe if the expiry date has passed.

Consult your pharmacist if the syringe fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the front of the thighs. The lower stomach area may also be used, but not within 5 cm of the navel (see Figure E).

• Always choose a different site each time you give an injection.

• Do not inject the medicine into areas where the skin is tender, bruised, red, flaky, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, Figure E: How to choose the injection site, do not inject the medicine directly into areas affected by psoriatic plaques.

2. Cleaning the injection site:

• Wash your hands thoroughly with water and

soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure F).
• Do not touch the cleaned area before the injection.

Figure F: How to clean the injection site

3. Administering the injection:

• Carefully pull off the needle cap from the pre-filled syringe (see Figure G).
• Discard the needle cap.
• You may see a drop of liquid at the tip of the needle. This is normal.

Figure G: How to remove the needle cap

• Gently create a skin fold at the injection site (see Figure H).
• Insert the needle into the skin as shown.
• Push the entire needle into the skin to ensure the full dose of medicine is delivered.
• Use the syringe within 5 minutes after removing the needle cap.

Figure H: How to insert the needle

• Hold the pre-filled syringe as shown (see Figure I).
• Slowly push the plunger all the way down until it stops, so that the plunger head is completely between the safety device wings.
• While keeping the syringe in place, hold the plunger fully depressed for 5 seconds.

Figure I: How to hold the syringe

• Keep the plunger fully depressed while carefully withdrawing the needle from the injection site, then release the skin (see Figure J).

Figure J: How to withdraw the needle

• Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle (see Figure K).
• You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad over the injection site and hold pressure for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a small adhesive bandage.
  Figure K: How to slowly release the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container (a puncture-resistant, closable container, see Figure L). For your safety and health and that of others, needles and used syringes must never be reused.

• Do not dispose of any medicines in wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicines and waste materials derived from such medicines must be disposed of in accordance with local regulations.

Figure L: how to dispose of the used pre-filled syringe
If you have any doubts, consult a doctor, pharmacist, or nurse familiar with
Hefiya.

Patient information leaflet

Hefiya 40 mg solution for injection in a pre-filled pen

adalimumab
40 mg/0.4 mL
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before receiving Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you throughout treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before using Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• enthesitis-related arthritis,
• ankylosing spondylitis,
• non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic evidence of ankylosing spondylitis),
• psoriatic arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis,
• non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind specifically to a target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs such as methotrexate may be tried first. If these medicines do not work satisfactorily, you will be given Hefiya to treat rheumatoid arthritis.
Hefiya may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hefiya can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hefiya is usually used in combination with methotrexate. If your doctor considers methotrexate treatment inappropriate, Hefiya may be given alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory joint disease that typically first appears during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years. Other disease-modifying drugs such as methotrexate may be given at diagnosis. If these medicines do not work satisfactorily, patients will be given Hefiya.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the sites where tendons attach to bones. Hefiya is used to treat enthesitis-related arthritis in patients aged 6 years and older.
Other disease-modifying drugs such as methotrexate may be tried first. If these medicines do not work well enough, patients will be given Hefiya.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis are inflammatory conditions of the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be given other medicines. If these do not work satisfactorily, you will be given Hefiya to reduce the signs and symptoms of the disease.

Plaque psoriasis in adults and children
Plaque psoriasis is an inflammatory skin condition causing red, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which can be painful. Psoriasis is thought to be caused by a problem with the body’s immune system leading to increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical medicines and UV light therapy have not worked well enough or are not suitable.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya can slow down the joint cartilage and bone damage caused by the disease and improve physical function.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus. It most commonly affects specific skin areas such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Hefiya is used to treat:

• moderate to severe hidradenitis suppurativa in adults, and
• moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hefiya can reduce the number of nodules and abscesses you have and the pain often associated with this disease. You may first be given other medicines. If these do not work satisfactorily, you will be given Hefiya.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat:

• moderate to severe Crohn’s disease in adults, and
• moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.

If you have Crohn’s disease, you will first be given other medicines. If you do not respond adequately to these, you will be given Hefiya to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Hefiya is used to treat:

• moderate to severe ulcerative colitis in adults, and
• moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

If you have ulcerative colitis, you may first take other medicines. If these do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of ulcerative colitis.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters (black spots or fine lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used for the treatment of:

• adults with non-infectious uveitis with inflammation affecting the back of the eye,
• children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye.

Other medicines may be used first. If the response to these medicines is not adequate, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not administer Hefiya again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hefiya. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, or bacteria, or other unusual infectious organisms, and sepsis (septicaemia).
• In rare cases, these infections may be life-threatening. It is important to inform your doctor if you experience symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise you to temporarily stop taking Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will check for signs or symptoms of tuberculosis before starting Hefiya therapy. This will include a detailed medical evaluation, including your medical history and clinical examinations (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or if you have had close contact with people who have tuberculosis. Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after treatment.

Travel/recurrent infection

• Inform your doctor if you have lived in or traveled to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor must test you for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in carriers of this virus. In some rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if symptoms of infection such as fever, wounds, feeling tired, or dental problems occur.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop taking Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases affecting the protective covering of nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of your body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be given during treatment with Hefiya, as they may cause infections. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to complete all age-appropriate vaccinations before starting Hefiya therapy.
  If you have taken Hefiya during pregnancy, the baby may have an increased risk of infection for up to approximately 5 months after your last dose during pregnancy. It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy, so they can determine when the baby should receive any vaccinations.

Heart failure

• It is important to inform your doctor about any past or present heart problems. If you have mild heart failure and are being treated with Hefiya, your doctor should carefully monitor your heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to discontinue treatment.

Tumours

• Very rarely, certain types of tumours have been observed in children and adults treated with adalimumab or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukaemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, your risk of developing lymphomas, leukaemia, or other tumours may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If you notice damaged areas of skin during or after treatment, or if the appearance of moles or damaged areas changes, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNFα medicine is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as a persistent unexplained skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Hefiya.

Other medicines and Hefiya
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hefiya may be taken with methotrexate and other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF agents, anakinra, or abatacept is not recommended because of the possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after your last dose of Hefiya.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed when mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding.
• If you take Hefiya during pregnancy, the baby may have an increased risk of infection.
• It is important that you inform the paediatrician or other healthcare provider about your use of Hefiya during pregnancy before the baby receives any vaccinations (for more information on vaccines, see section "Warnings and precautions").

Driving and using machines
Hefiya may affect your ability to drive, ride a bicycle, or operate machinery, although only to a minor extent. After taking Hefiya, you may experience vision disturbances or a sensation that your surroundings are spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hefiya if you require a different
dose.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist and inform them that you have taken more medicine than intended. Always keep the medicine packaging, even if empty.

If you forget to use Hefiya
If you forget to give an injection, administer the next dose of Hefiya as soon as you remember. Then continue with your regular dosing schedule.

If you stop using Hefiya
The decision to stop using Hefiya should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attention if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning during urination; fatigue or weakness, or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a lump or open sore that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with Hefiya:

Very common (may affect more than 1 in 10 people)

• injection site reactions (including pain, swelling, redness, or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and Herpes Zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of spinning room);
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• hematoma (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• sicca syndrome (including dry eyes and dry mouth/throat);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• nail breakage in fingers and toes;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid accumulation in the body, causing swelling of affected tissues);
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling in the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal fluid accumulation in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and blistering rash);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (pruritic red-purple rash).

Not known (frequency cannot be estimated from available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (manifesting as skin rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain has been low).

Some of the side effects observed with adalimumab may be asymptomatic and detectable only through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in blood;
• altered sodium levels in blood;
• reduced calcium in blood;
• reduced phosphorus in blood;
• increased blood glucose;
• increased lactate dehydrogenase in blood;
• presence of autoantibodies in blood;
• reduced potassium in blood.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell count, low red blood cell count, and low platelet count.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box after the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 42 days or discarded, even if it is later returned to the refrigerator. You must record the date when the pre-filled pen is first removed from the refrigerator and the date after which the pen must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled pen contains 40 mg of adalimumab in 0.4 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 40 mg solution for injection in pre-filled pen is supplied as 0.4 mL of solution from clear
to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use pre-filled syringe assembled into a triangular-shaped pen with
a transparent viewing window and label. The syringe inside the pen is made of Type I glass with a
29-gauge stainless steel needle, an inner needle rubber cap (thermoplastic elastomer) and a rubber
plunger stopper, containing 0.4 mL of solution.
Pack sizes contain 1, 2 and 4 pre-filled pens of Hefiya.
Multiple pack sizes contain 6 (3 packs of 2) pre-filled pens of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Tel: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure that you use Hefiya correctly, it is important that you
follow these instructions.
Be sure to read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare provider must show you how to properly prepare and inject Hefiya using the Hefiya
single-dose pre-filled pen before you use the medicine for the first time. If you have any doubts,
consult your healthcare provider.
Single-use pre-filled pen of Hefiya

Figure A: parts of the Hefiya pen
In Figure A, the pen is shown without the cap. Do not remove the cap until you are ready to administer
the injection.
It is important that you:

• do not use the pen if the outer packaging seal or the pen’s security seal is broken;
• keep the pen in its sealed outer packaging until you are ready to use it;
• never leave the pen unattended where it could be tampered with by others;
• do not use the pen if it has been dropped, appears damaged, or has been dropped after removing the cap;
• inject Hefiya 15–30 minutes after removing it from the refrigerator for a more comfortable injection;
• dispose of the used pen immediately after use. Do not reuse the pen. See “4. Disposal of Used Pens” at the end of these Instructions for Use.

How should you store the pen?

• Store the pen’s packaging in the refrigerator at a temperature between 2°C and 8°C.
• When necessary, for example when traveling, Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure that the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 42 days or discarded, even if it is later returned to the refrigerator.
• You must record the date when the pre-filled pen is first removed from the refrigerator and the date after which it must be discarded.
• Keep the pen in its original packaging until you are ready to use it, to protect the medicine from light.
• Do not store the pen at extremely hot or cold temperatures.
• Do not freeze the pen.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Pre-filled pen(s) of Hefiya (see Figure B). Each pen contains 40 mg/0.4 mL of adalimumab.

The pen’s packaging does not contain (see Figure B ):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “8. Disposal of Used Pens” at the end of these Instructions for Use.
• Adhesive bandage.

Figure B: items not included in the package
Preparing the pen
Before the injection

• For a more comfortable injection, remove the pen from the refrigerator approximately 15–30 minutes

before the injection so that it can reach
room temperature.

• Look through the viewing window. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the pen if you notice particles and/or changes in color. You may see small air bubbles. This is normal. If you have doubts about the appearance of the solution, see Figure C: safety check before injection, consult your pharmacist for assistance.
• Check the expiration date (Exp.) of the pen (see Figure C). Do not use the pen if the expiration date has passed.
• Do not use the pen if the security seal is broken.

Consult your pharmacist if the pen fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the
  front of the thighs.

The lower area of the stomach can also be used, but not within 5 cm around the navel (see Figure D).

• Always choose a different site each time you administer an injection.
• Do not inject the medicine into areas where the skin is tender, bruised, red, flaky, or hardened. Avoid areas with scars or stretch marks. If you have psoriasis, DO NOT inject the medicine directly into areas affected by psoriatic plaques.
  Figure D: How to choose the injection site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and

soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure E).
• Do not touch the cleaned area before the injection. Figure E: How to clean the injection site

3. Removing the cap from your pen:

• Remove the cap only when you are ready to use the pen.
  
  (see Figure F).
• Twist the cap in the direction of the arrows (see Figure F).
• Once the cap has been removed, discard it. Never try to reattach the cap.
• Use the pen within 5 minutes after removing the cap.
• You may notice a few drops of liquid coming out from the needle. This is normal. Figure F: How to remove the cap

4. How to hold the pen:

• Hold the pen at a 90-degree angle to the clean injection site (see Figure G ).

Correct Incorrect
Figure G: How to hold the pen
Injection
Read before administering the injection
During the injection, you will hear 2 clicks:
o The first click indicates that the injection has started.
o A moment later, a second click indicates that the injection is almost complete.
You must keep the pen firmly pressed against the skin until you see a green indicator
fill the viewing window and stop moving.

5. Starting the injection:

• Press the pen firmly against the

skin to start the injection (see
Figure H).

• The first click indicates that the injection has started.
• Keep pressing the pen firmly against the skin.
• The green indicator shows the progress of the injection. Figure H: how to start the injection

6. Completing the injection:

• Pay attention to the second click, which

indicates that the injection is nearly complete.

• Check that the green indicator has filled the viewing window and has stopped moving (see Figure I).
• Now you may remove the pen.

Figure I: How to complete the injection
After the injection

7. Check that the green indicator

fills the viewing window (see Figure J ):

• This means that the medicine has been

administered. Contact your doctor if
the green indicator is not visible.

• You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad against the injection site and hold it in place for 10 seconds. Do not rub the injection site. If needed, you may cover the Figure J : how to check the green indicator injection site with a small adhesive bandage.

8. Disposal of used pens:

• Dispose of the used pen in a sharps disposal container
  (puncture-resistant, closable container, see
  Figure K ). For your safety and the safety of others,
  used pens must never be reused.

• Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer in use. This will help protect the environment. Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

Figure K: how to dispose of the used pen
If you have any doubts, consult a doctor, pharmacist, or nurse familiar with
Hefiya.

Patient information leaflet

Hefiya 80 mg solution for injection in pre-filled syringe

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information that you need to know before starting treatment with Hefiya and during treatment. Keep this Patient Reminder Card with you throughout your treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms appear to be the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before using Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• rheumatoid arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis,
• non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs such as methotrexate may initially be prescribed. If these medicines do not work satisfactorily, you will be given Hefiya to treat rheumatoid arthritis.
Hefiya may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hefiya can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hefiya is generally used in combination with methotrexate. If your doctor considers methotrexate treatment inappropriate, Hefiya may be given alone.

Plaque psoriasis
Plaque psoriasis is an inflammatory skin condition that causes red, scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift away from the nail bed, which can be painful. Psoriasis is thought to be caused by a problem with the body’s immune system leading to an increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus.
It most commonly affects specific areas of the skin, such as the under-breast area, armpits, inner thighs, groin and buttocks. Scarring may also develop in affected areas.
Hefiya is used to treat:

• moderate to severe hidradenitis suppurativa in adults, and
• moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hefiya can reduce the number of nodules and abscesses you have and the pain often associated with this disease. You may initially be given other medicines. If these do not work satisfactorily, you will be given Hefiya.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat:

• moderate to severe Crohn’s disease in adults, and
• Crohn’s disease in children and adolescents aged 6 to 17 years.

If you have Crohn’s disease, you will first be given other medicines. If you do not respond adequately to these medicines, Hefiya will be given to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Hefiya is used to treat:

• moderate to severe ulcerative colitis in adults, and
• moderate to severe ulcerative colitis in children aged 6 to 17 years.

If you have ulcerative colitis, you may first take other medicines. If these do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of ulcerative colitis.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters in the eye (black spots or thin lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used for the treatment of:

• adults with non-infectious uveitis with inflammation affecting the back of the eye,
• children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye.

You may first be given other medicines. If you do not respond satisfactorily to these medicines, Hefiya will be given.

2. What you should know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not administer Hefiya again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hefiya. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, or bacteria, or other unusual infectious organisms, and sepsis (septicemia).
• In rare cases, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise temporarily stopping Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will check for signs or symptoms of tuberculosis before starting Hefiya therapy. This will involve a detailed medical evaluation including your medical history and clinical examinations (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or if you have been in close contact with someone who has tuberculosis. Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections appear during or after treatment.

Travel/recurrent infection

• Inform your doctor if you have lived in or traveled to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor must test you for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in people who are carriers of this virus. In some rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Age over 65 years

• If you are over 65 years old, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection during treatment with Hefiya. It is important to inform your doctor if symptoms of infection such as fever, wounds, feeling tired, or dental problems occur.

Surgery or dental procedures

• Before any surgery or dental procedures, inform your doctor that you are taking Hefiya. Your doctor may advise temporarily stopping Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases affecting the protective covering of nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of your body.

Vaccination

• Some vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be given during treatment with Hefiya, as they may cause infections. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to complete all age-appropriate vaccinations before starting Hefiya therapy. If you take Hefiya during pregnancy, your baby may have an increased risk of infection for up to about 5 months after your last dose during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Hefiya during pregnancy, so they can determine when your baby should receive any vaccinations.

Heart failure

• It is important to inform your doctor about any past or present heart problems. If you have mild heart failure and are being treated with Hefiya, your doctor will need to carefully monitor your heart condition. If new symptoms of heart failure appear or existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.

Tumors

• Very rare cases of certain types of tumors have been reported in children and adults treated with Hefiya or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, your risk of developing lymphomas, leukemia, or other tumors may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If you notice damaged skin areas during or after treatment, or if the appearance of moles or damaged areas changes, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα medicine. If you have COPD or are a heavy smoker, discuss with your doctor whether treatment with an anti-TNFα medicine is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all age-appropriate vaccinations before starting Hefiya.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hefiya may be taken with methotrexate and other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF agents and anakinra or abatacept is not recommended because of the possible increased risk of infections, including serious infections, and other potential drug interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should consider using an appropriate contraceptive method to prevent pregnancy and continue using it for at least 5 months after your last dose of Hefiya.
• If you are pregnant, think you may be pregnant, or are planning a pregnancy, consult your doctor about taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding.
• If you take Hefiya during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Hefiya during pregnancy before your baby receives any vaccinations (for more information on vaccines, see section "Warnings and precautions").

Driving and using machines
Hefiya may affect your ability to drive, ride a bicycle, or use machines, although only to a minor extent. After taking Hefiya, you may experience vision disturbances or a sensation that your surroundings are spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hefiya if the child requires
a different dose.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more often than you should, contact your doctor or pharmacist and inform them that you have taken more medicine than required. Always keep the medicine carton, even if empty.

If you forget to use Hefiya
If you forget to make an injection, you should inject the next dose of Hefiya as soon as you remember. After that, continue with your regular dosing schedule as prescribed.

If you stop using Hefiya
The decision to discontinue treatment with Hefiya should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most of the side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months or more after the last injection of Hefiya.

Contact a doctor urgently if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during physical activity or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning sensation when urinating, fatigue or weakness, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a lump or open sore that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with Hefiya:

Very common (may affect more than 1 in 10 people)

• injection site reactions (including pain, swelling, redness, or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain (stomach pain);
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of spinning);
• awareness of heartbeat (palpitations);
• high blood pressure;
• hot flushes;
• hematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• sicca syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• nail breakage in fingers and toes;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid accumulation in the body, causing swelling of affected tissues);
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) occurring when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling in the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, blood clot in a vein, or blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a lung artery);
• pleural effusion (abnormal fluid buildup in the pleural space);
• pancreatitis (inflammation of the pancreas causing severe abdominal and back pain);
• difficulty swallowing;
• facial edema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (an immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, and tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (pruritic red-purple rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi’s sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly appears as purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which presents as a rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain was low).

Some of the side effects observed with adalimumab may be asymptomatic and can only be detected through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in blood;
• changes in blood sodium levels;
• reduced calcium in blood;
• reduced phosphorus in blood;
• increased blood sugar;
• increased lactate dehydrogenase in blood;
• presence of autoantibodies in blood;
• reduced potassium in blood.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 42 days or discarded, even if it is subsequently returned to the refrigerator. You must record the date when the pre-filled syringe is first removed from the refrigerator and the date after which the syringe must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 80 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 80 mg solution for injection in pre-filled syringe is supplied as a solution from clear to slightly opalescent, colourless or slightly yellowish, in a volume of 0.8 mL.
Hefiya is supplied in a single-use, transparent type I glass syringe with a 29-gauge stainless steel needle, needle safety device with finger grip, needle rubber cap (thermoplastic elastomer) and plastic plunger, containing 0.8 mL of solution.
Pack sizes contain 1 and 2 pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Greece) Tel: +43 5338 2000
Tel: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure correct use of the medicine, it is important that
you follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare professional must show you how to properly prepare and inject Hefiya using the
single-use pre-filled syringe before you use the medicine for the first time. If you have any doubts, consult your healthcare provider.
Single-use pre-filled Hefiya syringe with needle safety device and additional finger grip

Figure A: Pre-filled Hefiya syringe with needle safety device and finger grip
It is important that you:

• do not use the syringe if the blister seals are broken, as use may not be safe;
• do not open the outer box until you are ready to use the pre-filled syringe;
• never leave the pre-filled syringe unattended where it could be tampered with by others;
• do not use the syringe if it has been dropped and appears damaged or if it was dropped after removing the needle cap;
• do not remove the needle cap until just before injection;
• take care not to touch the wings of the needle safety device before use. Doing so may activate the needle safety device prematurely.
• do not remove the finger grip before injection;
• inject Hefiya 15–30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the pre-filled syringe. See “4. Disposal of used pre-filled syringes” at the end of these Instructions for Use.

How should you store the single-dose pre-filled Hefiya syringe?

• Store the pre-filled syringe packaging in the refrigerator at a temperature between 2°C and 8°C.
• When necessary (e.g., when traveling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days—ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled syringe must be used within 42 days or discarded, even if subsequently returned to the refrigerator. You must record the date when the pre-filled syringe was first removed from the refrigerator and the date after which it must be discarded.
• Keep pre-filled syringes in their original packaging until ready to use, to protect the medicine from light.
• Do not store pre-filled syringes at extremely hot or cold temperatures.
• Do not freeze pre-filled syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The pre-filled syringe packaging contains:

• Pre-filled syringe(s) of Hefiya (see Figure A). Each pre-filled syringe contains 80 mg/0.8 mL of adalimumab.

The Hefiya pre-filled syringe packaging does not contain (see Figure B ):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “4. Disposal of used syringes” at the end of these Instructions for Use.
• Adhesive bandage.

Figure B: Items not included in the packaging
Before the injection

Figure C: needle safety device is Figure D: needle safety device is
not activated – the single-dose pre-filled activated – do not use
syringe is ready for use
o In this configuration, the needle safety o In this configuration, the needle safety
device is not activated. device of the pre-filled syringe is activated.
o The syringe is ready for use (see o do not use the syringe (see Figure D).
Figure C).
Preparing the syringe

• For a more comfortable injection, remove the packaging containing the pre-filled syringe from the refrigerator and let it sit closed on the work surface for approximately 15–30 minutes to reach room temperature.
• Remove the pre-filled syringe from the blister pack.
• Look through the viewing window. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you observe particles and/or changes in color. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance.
• Do not use the pre-filled syringe if it is damaged or if the needle safety device is activated. Return the pre-filled syringe and its packaging to the pharmacy.
• Check the expiration date (Exp.) of the pre-filled syringe. Do not use the pre-filled syringe if the expiration date has passed.

Contact your pharmacist if the syringe fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the front of the

thighs. The lower stomach area may also be used,
but not the area within 5 cm around the navel (see
Figure E ).

• Choose a different site each time you give an injection.
• Do not inject the medicine into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, do NOT inject the medicine directly into areas with psoriasis plaques. Figure E : How to choose the injection site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure F).
• Do not touch the cleaned area before the injection.

Figure F: how to clean the injection site

3. Administration of the injection:

• Carefully pull off the needle cap from the pre-filled syringe (see Figure G).
• Discard the needle cap.
• You may see a drop of liquid at the tip of the needle. This is normal.

Figure G: How to remove the needle cap

• Gently create a skin fold at the injection site (see Figure H).
• Insert the needle into the skin as shown.
• Push the entire needle into the skin to ensure that the full dose of medicine is delivered.
• Use the syringe within 5 minutes after removing the needle cap.

Figure H: How to insert the needle

• Hold the pre-filled syringe as shown (see Figure I).
• Slowly push the plunger all the way down until it stops, so that the plunger head is completely between the safety device flanges.
• While keeping the syringe in place, continue to fully press the plunger for 5 seconds.

Figure I: How to hold the syringe

• Keep the plunger fully pressed while carefully withdrawing the needle from the injection site, then release the skin (see Figure J).

Figure J: How to withdraw the needle

• Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle (see Figure K).
• You may notice a small amount of blood at the injection site. You may apply a cotton ball or gauze pad to the injection site and press for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a small adhesive bandage.
  Figure K: How to slowly release the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container
  (puncture-resistant, closable container, see
  Figure L ). For your safety and health and that of others,
  needles and syringes must never be reused.

• Do not dispose of medicines via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer in use. This will help protect the environment. Unused medicine and waste material from such medicine must be disposed of in accordance with local regulations.

Figure L: how to dispose of the
pre-filled syringe after use
If you have any questions, consult a doctor, pharmacist, or nurse familiar with
Hefiya.

Patient information leaflet

Hefiya 80 mg solution for injection in a pre-filled pen

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card, which contains important safety information you need to know before receiving Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you throughout your treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Hefiya is and what it is used for
2. What you need to know before using Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hefiya is indicated for the treatment of the following inflammatory diseases:

• Rheumatoid arthritis,
• Plaque psoriasis,
• Hidradenitis suppurativa,
• Crohn’s disease,
• Ulcerative colitis,
• Non-infectious uveitis.

The active substance in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, you may initially be given other disease-modifying drugs, such as methotrexate. If these medicines do not work satisfactorily, you will be given Hefiya to treat rheumatoid arthritis.
Hefiya may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hefiya can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hefiya is generally used in combination with methotrexate. If your doctor considers that treatment with methotrexate is not appropriate, Hefiya may be given alone.

Plaque psoriasis
Plaque psoriasis is an inflammatory skin condition that causes red, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crack, thicken or lift from the nail bed, which can be painful. Psoriasis is thought to be caused by a problem with the body’s immune system that leads to an increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a long-term inflammatory skin disease and is often painful. Symptoms may include painful lumps and abscesses (cysts) that may drain pus.
It most commonly affects specific areas of skin such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in the affected areas.
Hefiya is used to treat:

• Moderate to severe hidradenitis suppurativa in adults, and
• Moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hefiya can reduce the number of lumps and abscesses you have, as well as the pain often associated with this disease. You may initially be given other medicines. If these do not work satisfactorily, you will be given Hefiya.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat:

• Moderate to severe Crohn’s disease in adults, and
• Moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.

If you have Crohn’s disease, you will first be given other medicines. If you do not respond adequately to these, Hefiya will be given to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Hefiya is used to treat:

• Moderate to severe ulcerative colitis in adults, and
• Moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

If you have ulcerative colitis, you may first take other medicines. If these do not work satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
The inflammation leads to reduced vision and/or the presence of floaters in the eye (black spots or thin lines moving across the visual field). Hefiya works by reducing this inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye,
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye.

You may first be given other medicines. If you do not respond satisfactorily to these, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems (see "Warnings and precautions").
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hefiya again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hefiya. If in doubt, contact your doctor.
• You may be more likely to get infections while being treated with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, or bacteria, or other unusual infectious organisms, and sepsis (septicemia).
• In rare cases, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check for signs or symptoms of tuberculosis before starting treatment with Hefiya. This will include a detailed medical evaluation including your medical history and clinical tests (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or if you have been in close contact with someone who has tuberculosis. Tuberculosis may occur during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if you develop symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Travel/recurrent infection

• Inform your doctor if you have lived in or traveled to areas where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor must test you for hepatitis B virus infection. Taking adalimumab may reactivate hepatitis B virus infection in people who are carriers of this virus. In some rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus infection may be life-threatening.

Age over 65 years

• If you are over 65 years old, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases affecting the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of your body.

Vaccination

• Some vaccines contain live but weakened forms of bacteria or viruses that cause disease and must not be given during treatment with Hefiya, as they may cause infections. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to administer all age-appropriate vaccinations before starting Hefiya therapy. If you have taken Hefiya during pregnancy, the baby may have an increased risk of infection for up to approximately 5 months after your last dose during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Hefiya during pregnancy so they can determine when the baby should receive any vaccinations.

Heart failure

• It is important to inform your doctor about any past or current heart problems. If you have mild heart failure and are being treated with Hefiya, your doctor should carefully monitor your heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.

Tumors

• Very rarely, certain types of tumors have occurred in children and adults treated with adalimumab or other anti-TNFα medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, your risk of developing lymphoma, leukemia, or other tumors may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If you notice damaged skin areas during or after treatment, or if the appearance of existing marks or damaged areas changes, inform your doctor.
• Cases of cancers other than lymphoma have occurred in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNFα medicine is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to a lupus-like syndrome. Inform your doctor if you develop symptoms such as persistent unexplained skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Hefiya.

Other medicines and Hefiya
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hefiya can be taken together with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) (such as sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. The combination of adalimumab with other anti-TNF medicines, anakinra, or abatacept is not recommended due to the possible increased risk of infections, including serious infections, and other potential pharmacological interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after your last dose of Hefiya.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor about taking this medicine.
• Hefiya should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hefiya may be used during breastfeeding.
• If you take Hefiya during pregnancy, the baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Hefiya during pregnancy before the baby receives any vaccinations (for more information on vaccines, see section "Warnings and precautions").

Driving and using machines
Hefiya may have a minor influence on your ability to drive, ride a bicycle, or use machines. After taking Hefiya, you may experience vision disturbances or a sensation that your surroundings are spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e., essentially 'sodium-free'.

3. How to use Hefiya

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hefiya if the child requires
a different dose.

Method and route of administration
Hefiya is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist and inform them that you have taken more medication than required. Always keep the medicine carton, even if empty.

If you forget to use Hefiya
If you forget to give an injection, administer the next dose of Hefiya as soon as you remember. After that, resume your regular dosing schedule as prescribed.

If you stop using Hefiya
The decision to stop using Hefiya should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attention if you notice any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during physical activity or while lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning sensation when urinating; fatigue or weakness; or cough;
• symptoms of nerve problems such as tingling, numbness, double vision, or weakness in the arms or legs;
• signs of skin cancer such as a lump or open sore that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The following side effects have been observed with Hefiya:

Very common (may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness, or itching);
• respiratory tract infections (including colds, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• muscle pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (sensation of spinning);
• awareness of heartbeat (palpitations);
• high blood pressure;
• hot flushes;
• hematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• cracking or breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• edema (fluid accumulation in the body causing swelling of affected tissues);
• fever;
• reduced platelet count in the blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) occurring when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• disorders of the immune system that may affect lungs, skin, and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling of the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema (swelling);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare (may affect up to 1 in 1,000 people)

• leukemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (lung scarring);
• intestinal perforation (a hole in the intestinal wall);
• hepatitis (liver inflammation);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy red-purple rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (characterized by skin rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain was low).

Some of the side effects observed with adalimumab may be asymptomatic and detectable only through blood tests. These include:

Very common (may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased blood uric acid;
• altered blood sodium;
• reduced blood calcium;
• reduced blood phosphorus;
• increased blood glucose;
• increased blood lactate dehydrogenase;
• presence of autoantibodies in the blood;
• reduced blood potassium.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in the blood (liver blood test).

Rare (may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box after the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 42 days or discarded, even if it is subsequently returned to the refrigerator. You must record the date on which the pre-filled pen was first removed from the refrigerator and the date after which the pen must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled pen contains 80 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2, “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 80 mg solution for injection in pre-filled pen is supplied as 0.8 mL of solution, from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use pre-filled syringe assembled into a triangular-shaped pen with a transparent viewing window and label. The syringe inside the pen is made of Type I glass with a 29-gauge stainless steel needle, an inner needle rubber cap (thermoplastic elastomer), and a rubber stopper, containing 0.8 mL of solution.
Pack sizes contain 1, 2 and 3 pre-filled pens of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf./Sími/Tel: +45 63 95 10 00 Tel: +356 99644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH
(Ελλάδα) Tel: +43 5338 2000
Τηλ: +30 216 600 5000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure you use Hefiya correctly, it is important that you
follow these instructions.
Make sure you read, understand, and follow these Instructions for Use before injecting Hefiya.
A healthcare provider must show you how to properly prepare and inject Hefiya using the
single-dose pre-filled pen of Hefiya before you use the medicine for the first time. If you have any doubts,
consult your healthcare provider.
Single-use pre-filled pen of Hefiya

Figure A: Parts of the Hefiya pen
In Figure A, the pen is shown without the cap. Do not remove the cap until you are ready to administer
the injection.
It is important that you:

• Do not use the pen if the outer packaging seal or the pen’s safety seal is broken;
• Keep the pen in its sealed outer packaging until you are ready to use it;
• Never leave the pen unattended where it could be tampered with by others;
• Do not use the pen if it has been dropped, appears damaged, or if it was dropped after removing the cap;
• Inject Hefiya 15–30 minutes after removing it from the refrigerator for a more comfortable injection;
• Immediately dispose of the used pen after use. Do not reuse the pen. See “4. Disposal of Used Pens” at the end of these Instructions for Use.

How should you store the pen?

• Store the pen in its packaging in the refrigerator at a temperature between 2°C and 8°C.
• When necessary, for example when traveling, Hefiya may be stored at room temperature (up to 25°C) for a maximum of 42 days – ensure you protect the medicine from light. Once removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 42 days or discarded, even if it is later returned to the refrigerator.
• You must record the date when the pre-filled pen is first removed from the refrigerator and the date after which it must be discarded.
• Keep the pen in its original packaging until you are ready to use it, to protect the medicine from light.
• Do not store the pen at extremely hot or cold temperatures.
• Do not freeze the pen.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Pre-filled pen(s) of Hefiya (see Figure B). Each pen contains 80 mg/0.8 mL of adalimumab.

The pen package does not contain (see Figure B ):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “8. Disposal of Used Pens” at the end of these Instructions for Use.
• Adhesive bandage.

Figure B: Items not included in the package
Before the injection
Preparing the pen

• For a more comfortable injection, remove the pen from the refrigerator approximately 15–30 minutes before

the injection so it can reach room temperature.

• Look through the viewing window. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the pen if you notice particles and/or changes in color. You may see small air bubbles. This is normal. If you have any doubts about the appearance of the solution, consult your pharmacist for assistance. See Figure C: Safety checks before injection.
• Check the expiration date (Exp.) of the pen (see Figure C). Do not use the pen if the expiration date has passed.
• Do not use the pen if the safety seal is broken.

Consult your pharmacist if the pen fails any of the checks listed above.

1. Choosing the injection site:

• The recommended injection site is the
  front of the thighs.

The lower abdominal area may also be used,
but not within 5 cm of the navel (see Figure D).

• Always choose a different site each time you administer an injection.
• Do not inject the medicine into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, Figure D: how to choose the injection site DO NOT inject the medicine directly into areas with psoriasis plaques.

2. Cleaning the injection site:

• Wash your hands thoroughly with water and

soap.

• Using a circular motion, clean the injection site with an alcohol swab. Allow it to dry before administering the injection (see Figure E).
• Do not touch the cleaned area before the injection.

Figure E: How to clean the injection site

3. Removing the pen cap:

• Remove the cap only when you are ready to use the

pen.

• Rotate the cap in the direction of the arrows (see Figure F).
• Once the cap has been removed, discard it. Never attempt to reattach the cap.
• Use the pen within 5 minutes after removing the cap.
• You may notice a few drops of liquid coming out. This is normal. Figure F: How to remove the needle cap.

4. How to hold the pen:

• Hold the pen at a 90-degree angle to the injection site,
  clean (see Figure G ).

Correct Incorrect
Figure G: how to hold the pen
Injection
Read before administering the injection
During the injection, you will hear 2 clicks:
o The first click indicates that the injection has started.
o A moment later, a second click indicates that the injection is almost complete.
You must keep the pen firmly pressed against the skin until you see a green
indicator fill the viewing window and stop moving.

5. Starting the injection:

• Press the pen firmly against the skin to

start the injection (see Figure H).

• The first click indicates that the injection has started.
• Keep pressing the pen firmly against the skin.
• The green indicator shows the progress of the injection.

Figure H: How to start the injection

6. Completing the injection:

• Pay attention to the second click, which indicates

that the injection is almost complete.

• Check that the green indicator has completely filled the viewing window and has stopped moving (see Figure I).
• You may now remove the pen.

Figure I: How to complete the injection
After the injection

7. Check that the green indicator

fills the viewing window (see Figure J ):

• This means that the medicine has been

administered. Contact your doctor if
the green indicator is not visible.

• You may notice a small amount of blood at the injection site. You may press a cotton ball or gauze pad against the injection site and hold it in place for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site Figure J: how to check the green indicator with a small adhesive bandage.

8. Disposal of used pens:

• Dispose of the used pen in a sharps disposal
  container (puncture-resistant, closable container,
  see Figure K). For your safety and the safety of
  others, used pens must never be reused.

• Do not dispose of any medicine via wastewater or
  household waste. Ask your doctor or pharmacist
  how to dispose of medicines you no longer use.
  This will help protect the environment. Unused
  medicine and waste derived from this medicine
  must be disposed of in accordance with local
  regulations.

Figure K: How to dispose of the used pen

If you have any questions, consult a doctor, pharmacist, or nurse familiar with Hefiya.