Hulio

Package leaflet: Information for the patient

Hulio 20 mg solution for injection in pre-filled syringe

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

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

Contents of this leaflet:

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

1. What Hulio is and what it is used for

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

• Polyarticular juvenile idiopathic arthritis
• Enthesitis-related arthritis
• Pediatric plaque psoriasis
• Crohn’s disease in pediatric patients
• Pediatric uveitis

The active substance in Hulio, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target in the body.
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, Hulio reduces the inflammatory process in these diseases.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually begins during childhood.
Hulio is used to treat polyarticular juvenile idiopathic arthritis in patients aged 2 years and older. Initially, other disease-modifying drugs such as methotrexate may be given to the child. If these medicines do not work well enough, the child will be given Hulio to treat polyarticular juvenile idiopathic arthritis.
Your doctor will decide whether Hulio should be taken together with methotrexate or alone.

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

Pediatric plaque psoriasis
Plaque psoriasis is a skin condition that causes reddish, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crumble, thicken, or lift from the nail bed, which may be painful. Psoriasis is thought to be caused by a problem with the immune system that leads to an increased production of skin cells.
Hulio is used to treat severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical therapy and phototherapy have not worked well enough or are not suitable.

Crohn’s disease in pediatric patients
Crohn’s disease is an inflammation of the intestine.
Hulio is used to treat Crohn’s disease in children aged 6 to 17 years.
Other medicines may be given to the child initially. If these medicines do not work well enough, the child will be given Hulio to reduce the signs and symptoms of the disease.

Pediatric uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
Hulio is used to treat children aged 2 years and older with chronic non-infectious uveitis involving inflammation of the front part of the eye.
This inflammation may lead to decreased vision and/or the presence of floaters in the eye (black spots or thin lines moving across the field of vision). Hulio works by reducing this inflammation.
Other medicines may be given to the child initially. If these medicines do not work well enough, the child will be given Hulio to reduce the signs and symptoms of the disease.

Hulio is used for the treatment:

• of children and adolescents aged 2 to 17 years with chronic non-infectious uveitis involving inflammation of the front part of the eye.

2. What you should know before your child uses Hulio

Do not administer Hulio

• 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 active tuberculosis (see "Warnings and precautions"). It is important to tell the doctor if your child has symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• 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 Hulio.
Allergic reactions

• If your child experiences allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hulio again and contact the paediatrician immediately, as these reactions may rarely be life-threatening.

Infections

• If your child has an infection, including long-term infections or localized infections (e.g., leg ulcers), consult the paediatrician before starting treatment with Hulio. If you are in doubt, contact the paediatrician.
• Your child may be more likely to get infections while being treated with Hulio. This risk may increase if your child has lung problems. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, bacteria, or other unusual infectious organisms, and sepsis (blood poisoning).
• In rare cases, these infections may be life-threatening. It is important to inform the paediatrician if your child has symptoms such as fever, wounds, feeling tired, or dental problems. The paediatrician may instruct you to temporarily stop Hulio.
• Inform the paediatrician if your child lives in or travels to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Inform the paediatrician if your child has had recurrent infections or if your child has conditions that increase the risk of infection.
• Your child and the paediatrician should pay particular attention to signs of infection while your child is being treated with Hulio. It is important to inform the paediatrician if symptoms of infection such as fever, wounds, feeling tired, or dental problems occur.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, the paediatrician will check whether your child shows signs or symptoms typical of tuberculosis before starting therapy with Hulio. This will involve a thorough medical evaluation of your child's 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 the paediatrician if your child has ever had tuberculosis or has been in contact with someone who had tuberculosis. If your child has active tuberculosis, Hulio must not be taken.
• Tuberculosis may develop during therapy even if your child has received treatment to prevent tuberculosis.
• Contact the paediatrician immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after therapy.

Hepatitis B virus (HBV)

• Inform the paediatrician if your child is a carrier of hepatitis B virus (HBV), has an active hepatitis B infection, or if you think your child may be at risk of contracting hepatitis B virus. The paediatrician must test your child for hepatitis B virus infection. Taking adalimumab may cause reactivation of hepatitis B virus 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.

Surgery or dental procedures

• If your child is scheduled for surgery or dental procedures, inform the paediatrician that your child is taking Hulio. The paediatrician may temporarily discontinue Hulio.

Demyelinating diseases

• If your child has or develops demyelinating diseases (diseases affecting the insulating layer around nerves), such as multiple sclerosis, the paediatrician will decide whether it is appropriate to start or continue treatment with Hulio. 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.

Vaccinations

• Certain vaccines contain live but weakened bacterial or viral agents that may cause disease and must not be administered during treatment with Hulio, as they may lead to infections.
• Check with the paediatrician before your child receives any vaccine.
• It is recommended that children receive all age-appropriate scheduled vaccinations before starting treatment with Hulio, if possible.
• If you took Hulio 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 and other healthcare providers about your use of Hulio during pregnancy so they can determine when your baby should receive any vaccinations.

Heart failure

• It is important to inform the paediatrician about any past or current serious heart problems your child may have. If your child has mild heart failure and is being treated with Hulio, the doctor should 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 paediatrician immediately.

Fever, bruising, bleeding, or paleness

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

Cancer

• Very rarely, certain types of cancer have occurred in patients, both children and adults, treated with adalimumab or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a cancer affecting the lymphatic system) and leukaemia (cancers affecting blood and bone marrow). If your child takes Hulio, the risk of developing lymphomas, leukaemia, or other cancers 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 treatment with azathioprine or mercaptopurine. Inform the paediatrician if your child is taking azathioprine or mercaptopurine with Hulio.
• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform the paediatrician.
• 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-TNF medicine. If your child has COPD or is a heavy smoker, discuss with the paediatrician whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

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

Other medicines and Hulio
Inform the paediatrician or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Your child must not take Hulio together with medicines containing anakinra or abatacept as active ingredients. The combination of Hulio with 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 the paediatrician.
Hulio may 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).

Pregnancy and breastfeeding

• The girl should use adequate contraception to prevent pregnancy and continue using it for at least 5 months after the last dose of Hulio.
• If the girl is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor about taking this medicine.
• Hulio 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.
• Hulio may be used during breastfeeding.
• If the girl takes Hulio 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 Hulio during pregnancy before the baby receives any type of vaccination. For more information on vaccinations, see "Warnings and precautions".

Driving and using machines
Hulio may affect, although only slightly, the ability of adolescents to drive, ride a bicycle, or operate machinery. After taking Hulio, visual disturbances or a sensation that the surroundings are spinning may occur.

Hulio contains sodium and sorbitol
Each pre-filled syringe of Hulio contains 19.1 mg of sorbitol. Sorbitol is a source of fructose. If the paediatrician has informed you that your child has an intolerance to certain sugars or if your child has been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot metabolize fructose, inform the paediatrician before giving this medicine to your child.
In addition, this medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe, i.e., essentially 'sodium-free'.

3. How to use Hulio

Use this medicine exactly as instructed by your paediatrician or pharmacist. If you have any doubts or need clarification, consult your paediatrician or pharmacist. The doctor may prescribe a different concentration of Hulio if the child requires a different dose.

Children with juvenile idiopathic arthritis

Children and adolescents aged 2 to 17 years and weighing between 10 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 2 to 17 years and weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Children and adolescents with enthesitis-related arthritis

Children and adolescents aged 6 to 17 years and weighing between 15 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 6 to 17 years and weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Children or adolescents with plaque psoriasis

Children and adolescents aged 4 to 17 years and weighing between 15 kg and less than 30 kg
The recommended initial dose of Hulio is 20 mg, followed by another 20 mg one week later.
Subsequently, the usual dose is 20 mg every other week.

Children and adolescents aged 4 to 17 years and weighing 30 kg or more
The recommended initial dose of Hulio is 40 mg, followed by another 40 mg one week later. Then, the usual dose is 40 mg every other week.

Children and adolescents with Crohn's disease

Children and adolescents aged 6 to 17 years and weighing less than 40 kg
The usual dose is initially 40 mg (administered as two 20 mg injections on the same day), followed by 20 mg two weeks later. If a faster response is needed, the paediatrician may prescribe an initial dose of 80 mg (administered as four 20 mg injections on the same day), followed by 40 mg two weeks later.
Subsequently, the usual dose is 20 mg every other week. If this dose is not effective enough, the paediatrician may increase the frequency to 20 mg weekly.

Children and adolescents aged 6 to 17 years and weighing 40 kg or more
The usual dose is initially 80 mg (administered as four 20 mg injections on the same day), followed by 40 mg two weeks later. If a faster response is needed, the paediatrician may prescribe an initial dose of 160 mg (administered as eight 20 mg injections on the same day or four 20 mg injections per day for two consecutive days), followed by 80 mg (administered as four 20 mg injections on the same day) two weeks later.
Subsequently, the usual dose is 40 mg every other week. If this dose is not effective enough, the paediatrician may increase the frequency to 40 mg weekly or to 80 mg every other week.

Children and adolescents with paediatric uveitis

Children and adolescents aged 2 to 17 years and weighing less than 30 kg
The usual dose of Hulio is 20 mg administered every other week in combination with methotrexate.
The paediatrician may also prescribe an initial dose of 40 mg (two 20 mg injections on the same day), which may be given one week before starting the recommended usual dose. Hulio is recommended to be used in combination with methotrexate.

Children and adolescents aged 2 to 17 years and weighing 30 kg or more
The usual dose of Hulio is 40 mg administered every other week in combination with methotrexate.
The paediatrician may also prescribe an initial dose of 80 mg, which may be given one week before starting the recommended usual dose. Hulio is recommended to be used in combination with methotrexate.

Method and route of administration
Hulio is administered by subcutaneous injection (for subcutaneous use).
Detailed instructions on how to inject Hulio are provided in the Instructions for Use.

If you use more Hulio than you should
If you accidentally inject Hulio into the child more frequently than prescribed, contact the paediatrician and inform them that the child has received more medicine than intended. Always keep the medicine carton or the medicine itself, even if empty.

If you forget to use Hulio
If you forget to give the child an injection, administer the missed dose as soon as you remember. Then continue giving the next dose according to the prescribed schedule.

If the child stops treatment with Hulio
The decision to stop using Hulio should be discussed with the paediatrician. The child's symptoms may return after stopping treatment.

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

4. Possible side effects

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

Contact a doctor urgently if the child develops 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 the 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, feeling weak or tired, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision or leg weakness;
• signs of skin cancer, such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of disorders affecting the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The signs and symptoms described above may indicate the following side effects, which have been observed with adalimumab:

Very common (may affect up to 1 in 10 people)

• injection site reactions (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, throat infection and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• bone and 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;
• oral infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• mild allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• inflammation or swelling of eyes/eyelids;
• dizziness (sensation of the room spinning);
• awareness of rapid heartbeat;
• high blood pressure;
• red skin;
• hematoma (collection of blood outside blood vessels);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• indigestion, bloating, heartburn;
• acidity/acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• bruising;
• itchy rash;
• itching, skin inflammation (including eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• new onset or worsening of psoriasis (red, scaly skin);
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• edema (swelling);
• fever;
• reduced platelet count in the blood, increasing the risk of bleeding or bruising;
• slow wound healing.

Uncommon (may affect up to 1 in 100 people):

• opportunistic 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);
• tumor;
• lymphoma (tumor of the lymphatic system);
• melanoma;
• immune system disorders that may affect lungs, skin and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• irregular heartbeat;
• heart problems that may cause shortness of breath or swelling of the ankles;
• heart attack;
• 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);
• excess fluid around the lungs;
• inflammation of the pancreas;
• difficulty swallowing;
• facial swelling (facial edema);
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (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 nerve inflammation in the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, unusual sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (perforation/tear in the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash);
• facial edema (swelling of the face) associated with allergic reactions;
• inflammatory rash;
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, red-purple rash).

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

• hepatosplenic T-cell lymphoma (a rare 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 skin lesions;
• liver failure;
• worsening of rash with muscle weakness;
• weight gain (in most patients, weight gain has been low).

Reporting of side effects
If the child experiences any side effect, including those not listed in this leaflet, please contact the pediatrician or pharmacist. You may also report side effects directly via 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 Hulio

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/the carton after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), a single pre-filled syringe may be stored at room temperature (up to 25°C) for a maximum of 8 weeks – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 8 weeks or discarded, even if it is placed back into the refrigerator.
You must record the date when the syringe is first removed from the refrigerator and the date by 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Hulio contains

• The active substance is adalimumab.
• The other ingredients are monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid and water for injections (see section 2 - "Hulio contains sodium and sorbitol").

Description of the appearance of Hulio and contents of the pack
Hulio 20 mg solution for injection in pre-filled syringe is supplied as a sterile solution containing 20 mg of adalimumab dissolved in 0.4 mL of a clear or slightly opalescent solution, ranging from colourless to pale brownish-yellow.
The Hulio pre-filled syringe consists of a plastic syringe with a plunger stopper and a needle with a needle cap. Each pack contains 1 or 2 pre-filled syringes. Not all pack sizes may be marketed.
Hulio may also be available in vials for paediatric use or in a pre-filled pen.

Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36
Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
D13 R20R
Ireland

Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building, Santry Demesne
Dublin
D09 C6X8
Ireland

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

België/Belgique/Belgien Lietuva
Tél/Tel: Tel:
България Luxembourg/Luxemburg
Тел: Tél/Tel:
Česká republika Magyarország
Tel: Tel.:
Danmark Malta
Tlf: Tel.:
Deutschland Nederland
Tel: Tel:
Eesti Norge
Tel: Tlf:
Ελλάδα Österreich
Τηλ.: Tel:
España Polska
Tel: Tel: 0
France Portugal
Biocon Biologics France S.A.S
Tel: Tel:
Hrvatska România
Tel: Tel:
Ireland Slovenija
Tel: Tel:
Ísland Slovenská republika
Sími: +345 800 4316 Tel:
Italia Suomi/Finland
Tel: Puh/Tel:
Κύπρος Sverige
Τηλ: Tel:
Latvija
Tel:

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

Instructions for use
Read the instructions carefully and follow them step by step. You will receive instructions from your paediatrician, nurse or healthcare professional on how to administer an injection using a pre-filled syringe of Hulio. Ask your paediatrician or nurse if anything is unclear.
Do not allow the child to perform self-injection until you are certain they understand how to prepare and administer the injection. After adequate training, the injection may be given by the child or another person, such as a family member or nurse.
Each pre-filled syringe is for single use only and contains a 20 mg dose of adalimumab.
Do not mix other medicines with the Hulio solution.
To help you remember the days on which Hulio injections should be given, it may be helpful to mark them on a calendar or in a diary.

Before starting
Find a quiet area with a flat, clean, well-lit surface. Gather all the materials you will need to administer the injection.
The materials you need are:

• 1 pre-filled syringe
• 1 alcohol-impregnated swab (not included in the Hulio pack)
• 1 sharps container (not included in the Hulio pack)
• 1 gauze pad or cotton ball (not included in the Hulio pack)

If you do not have the necessary materials, ask your nurse or pharmacist.

Preparing the pre-filled syringe
Pre-filled syringes must be stored in the refrigerator (between 2°C and 8°C).

• Remove only one pre-filled syringe from the refrigerator at least 30 minutes before use to allow the solution to reach room temperature.
• DO NOT use other heat sources such as a microwave or hot water to warm the syringe.
• DO NOT return the syringe to the refrigerator after it has reached room temperature.
• Check the expiry date printed on the syringe.
• DO NOT use the syringe after the expiry date.
• Inspect the syringe to ensure the medicine level is at or near the fill mark (you may need to gently swirl the liquid) and that the solution is clear, colourless and free from particles.
• DO NOT use the syringe if the liquid level is below the fill mark.
• DO NOT use the syringe if the solution is cloudy, discoloured or contains particles.

Needle cap Fill mark Plunger

Medicinal product Needle safety device

Steps for injection
Follow these steps carefully for each Hulio injection using the pre-filled syringe:

Step 1 – Choose and prepare the injection site

The Hulio pre-filled syringe is for subcutaneous use. Hulio
must be injected into the thigh or abdomen.
Rotate and change injection sites, keeping them approximately 3 cm apart from the previous site.
If injecting into the abdomen, stay at least 5 cm away from the navel.

• DO NOT inject into red, hardened, bruised or painful skin.
• DO NOT inject into scars or stretch marks.
• If the child has psoriasis, DO NOT inject into raised, thick, red or scaly patches.
• DO NOT inject through clothing. Remove any clothing that may interfere with the injection.

Step 2 – Wash hands
Wash hands thoroughly with soap and water.

Step 3 – Prepare the injection site
Wipe the skin at the chosen injection site with an alcohol-impregnated swab.

• Allow the skin to dry completely; do not blow on it to dry.
• DO NOT touch this area again before the injection.

Step 4 – Remove the needle cap
Remove the needle cap from the syringe. A few small drops of liquid may leak from the needle; this is normal. It is also normal to see air bubbles.

• DO NOT remove the needle cap until you are ready to inject.
• DO NOT twist or bend the needle cap when removing it, to avoid damaging the needle.
• NEVER touch or pull the plunger.
• DO NOT recap the needle or touch the needle with fingers or allow the needle to touch any other object.
• DO NOT expel air bubbles.
• DO NOT use the pre-filled syringe if it has been dropped after removing the needle cap.

Step 5 – Pinch and hold the injection site

Gently pinch the injection site to lift up a fold of skin and hold it firmly.

Step 6 – Insert the needle

With a quick, firm motion, like throwing a dart, insert the needle at a 45° angle.
Be careful not to inject into your fingers while holding the injection site.

Step 7 – Inject Hulio
Once the needle is fully inserted, release the pinched skin.

Gently push the plunger all the way down until all the medicine has been injected and the syringe is empty.

• If the plunger is not fully depressed, the safety device will not activate to cover the needle.
• DO NOT move, shake or rotate the syringe during injection.

Step 8 – End of injection, remove the syringe
Remove the syringe from the injection site at the same angle as insertion and release your thumb from the plunger.

Each pre-filled syringe has a safety device that

retracts and covers the needle after releasing the plunger. If the needle does not retract, carefully place the used syringe into a sharps container to prevent injury.
After the injection, if slight bleeding occurs at the injection site, apply light pressure with a gauze pad or cotton ball for a few seconds – DO NOT rub the injection site. If needed, cover the injection site with a plaster.

Step 9 – Dispose of the syringe and needle cap
Dispose of the used syringe and needle cap in a sharps container.
Ask your healthcare professional for instructions on proper disposal of the full sharps container.

• DO NOT reuse the syringe.
• DO NOT recap the needle.

• DO NOT throw the sharps container into household waste.
• DO NOT recycle the used sharps container.
• Always keep the sharps container out of sight and reach of children.

Package leaflet: Information for the patient

Hulio 40 mg/0.8 mL solution for injection

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 also provide you with a patient reminder card containing important safety information you need to know before your child is given Hulio and during treatment with Hulio. Keep this patient reminder card with you or with your child, and for 4 months after the last injection of Hulio to your child.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for your child. 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 side effects, including those not listed in this leaflet, contact your paediatrician or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Hulio is and what it is used for

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

• polyarticular juvenile idiopathic arthritis in children aged 2 to 17 years;
• enthesitis-related arthritis in children aged 6 to 17 years;
• Crohn's disease in children aged 6 to 17 years;
• plaque psoriasis in children aged 4 to 17 years;
• hidradenitis suppurativa in adolescents aged 12 to 17 years;
• ulcerative colitis in children aged 6 to 17 years;
• non-infectious chronic uveitis affecting the front part of the eye in children aged 2 to 17 years.

The active substance in Hulio, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target in the body.
Adalimumab targets another 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, Hulio 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 begin during childhood.
Hulio 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.
Initially, other disease-modifying medicines, such as methotrexate, may be given to the child. If these medicines do not work well enough, the child will be given Hulio to treat polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Crohn's disease in paediatric patients
Crohn's disease is an inflammation of the intestine.
Hulio is used to treat Crohn's disease in children aged 6 to 17 years. Other medicines may be given to the child initially. If these medicines do not work well enough, Hulio will be given to the child to reduce the signs and symptoms of the disease.

Paediatric plaque psoriasis
Plaque psoriasis is an inflammatory skin condition that causes reddish, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing crumbling, thickening, and separation 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 increased production of skin cells.
Hulio is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years for whom topical medicines and UV light therapy have not worked optimally or are not suitable.

Hidradenitis suppurativa in adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic, 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 area under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Hulio is used to treat hidradenitis suppurativa in adolescents from 12 years of age. Hulio can reduce the number of nodules and abscesses you have and the pain often associated with this disease.
Initially, you may receive other medicines. If you do not respond sufficiently to these medicines, you will be given Hulio.

Ulcerative colitis in paediatric patients
Ulcerative colitis is an inflammatory disease of the large intestine. Hulio is used to treat moderate to severe ulcerative colitis in children aged 6 to 17 years. Other medicines may be given to the child initially. If these medicines do not work well enough, Hulio will be given to the child to reduce the signs and symptoms of the disease.

Non-infectious chronic uveitis affecting the front part of the eye
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. This inflammation can lead to decreased vision and/or the presence of floaters in the eye (spots or fine lines moving across the field of vision). Hulio works by reducing this inflammation.
Hulio is used to treat children and adolescents aged 2 to 17 years with non-infectious chronic uveitis with inflammation affecting the front part of the eye.

2. What you should know before your child uses Hulio

Do not administer Hulio

• 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 active tuberculosis (see "Warnings and precautions"). It is important to inform the doctor if your child has symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If your child has moderate or severe heart failure. It is important to inform the doctor if there has been or currently is a serious heart condition (see "Warnings and precautions").

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

Allergic reactions
If allergic reactions occur, with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not administer Hulio again and contact the paediatrician immediately, as these reactions may rarely be life-threatening.

Infections

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

Tuberculosis (TB)

• Cases of tuberculosis have occurred in patients treated with adalimumab. Therefore, the paediatrician should check for signs or symptoms of tuberculosis before starting Hulio treatment. This will include a thorough 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 the paediatrician if your child has ever had tuberculosis or has been in contact with someone who had tuberculosis. Tuberculosis may develop during treatment even if your child has received preventive treatment for tuberculosis. Contact the paediatrician 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 infections

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

Hepatitis B virus

• Inform the paediatrician if your child is a carrier of hepatitis B virus (HBV), has an active hepatitis B infection, or if you think your child may be at risk of contracting hepatitis B virus. The paediatrician must test your child for hepatitis B virus infection. Taking adalimumab may cause reactivation of hepatitis B virus in carriers of this virus. In 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.

Surgery or dental procedures

• If your child is scheduled for surgery or dental procedures, inform the paediatrician that your child is taking Hulio. The paediatrician may temporarily discontinue Hulio.

Demyelinating diseases
If your child has or develops demyelinating diseases (diseases affecting the protective covering around nerves), such as multiple sclerosis, the paediatrician will decide whether it is appropriate to start or continue treatment with Hulio. 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.

Vaccinations

• Certain vaccines contain live but weakened bacterial or viral agents that can cause disease and should not be given during treatment with Hulio, as they may lead to infections.
• Check with the paediatrician before your child receives any vaccine.
• It is recommended that children receive all age-appropriate vaccinations before starting treatment with Hulio, if possible.
• If you took Hulio during pregnancy, your child may have an increased risk of infection for up to about five months after your last dose during pregnancy. It is important that you inform the paediatrician and other healthcare providers about your use of Hulio during pregnancy, so they can determine when your child should receive any vaccinations.

Heart failure

• It is important to inform the paediatrician about any past or present serious heart problems in your child. If your child has mild heart failure and is being treated with Hulio, the doctor should 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 paediatrician immediately.

Fever, bruising, bleeding, or paleness

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

Cancer

• Very rare cases of certain types of cancer have been reported in patients, both children and adults, treated with adalimumab or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a cancer affecting the lymphatic system) and leukaemia (cancers affecting blood and bone marrow). If your child takes Hulio, the risk of developing lymphomas, leukaemia, or other cancers 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 paediatrician if your child is taking azathioprine or mercaptopurine with Hulio.
• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform the paediatrician.
• Cases of tumours other than lymphoma have been reported in patients with a specific lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNF medicine. If your child has COPD or is a heavy smoker, discuss with the paediatrician whether treatment with an anti-TNF medicine is appropriate.

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

Other medicines and Hulio
Inform the paediatrician or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Hulio must not be taken together with medicines containing anakinra or abatacept as active ingredients. The combination of Hulio with 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 the paediatrician.
Hulio may be taken together with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts, as well as with corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

Pregnancy and breastfeeding

• A girl should use adequate contraception to prevent pregnancy and continue using it for at least 5 months after the last dose of Hulio.
• If a girl is pregnant, suspects she might be pregnant, or is planning a pregnancy, she should consult her doctor about taking this medicine.
• Hulio should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in mothers who received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
• Hulio may be used during breastfeeding.
• If a girl takes Hulio during pregnancy, her baby may have an increased risk of infection.
• It is important that you inform the paediatrician or other healthcare provider about the use of Hulio during pregnancy before the baby receives any vaccinations. For more information on vaccinations, see "Warnings and precautions".

Driving and using machines
Hulio may affect, although only slightly, the ability of adolescents to drive, ride a bicycle, or operate machinery. After taking Hulio, visual disturbances or a sensation that the surroundings are spinning may occur.

Hulio contains sodium and sorbitol
Each vial of Hulio contains 38.2 mg of sorbitol. Sorbitol is a source of fructose. If the paediatrician has informed you that your child has an intolerance to certain sugars or if your child has been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot metabolize fructose, inform the paediatrician before giving this medicine to your child.
In addition, this medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., essentially 'sodium-free'.

3. How to use Hulio

Use this medicine exactly as instructed by your child's paediatrician or pharmacist. If you have
any doubts or need clarification, consult the paediatrician or pharmacist. The doctor may prescribe a different
concentration of Hulio if the child requires a different dose.

Children and adolescents with polyarticular juvenile idiopathic arthritis
Children and adolescents aged 2 to 17 years and weighing between 10 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 2 to 17 years and weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Children and adolescents with enthesitis-related arthritis
Children and adolescents aged 6 to 17 years and weighing between 15 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 6 to 17 years and weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Children and adolescents with Crohn's disease
Children and adolescents aged 6 to 17 years and weighing less than 40 kg
The usual dose is initially 40 mg, followed by 20 mg two weeks later. If a faster response is needed,
the paediatrician may prescribe an initial dose of 80 mg (given as two 40 mg injections on the same day),
followed by 40 mg two weeks later.

Subsequently, the usual dose is 20 mg every other week. If the response is inadequate, the paediatrician
may increase the dosing frequency to 20 mg weekly.

Children and adolescents aged 6 to 17 years and weighing 40 kg or more
The usual dose is initially 80 mg (given as two 40 mg injections on the same day), followed by 40 mg
two weeks later. If a faster response is needed, the paediatrician may prescribe an initial dose of 160 mg
(given as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days),
followed by 80 mg (given as two 40 mg injections on the same day) two weeks later.

Subsequently, the usual dose is 40 mg every other week. If the response is inadequate, the paediatrician
may increase the dosing frequency to 40 mg weekly or to 80 mg every other week.

Children and adolescents with plaque psoriasis
Children and adolescents aged 4 to 17 years and weighing between 15 kg and less than 30 kg
The recommended initial dose of Hulio is 20 mg, followed by 20 mg one week later.
Subsequently, the usual dose is 20 mg every other week.

Children and adolescents aged 4 to 17 years and weighing 30 kg or more
The recommended initial dose of Hulio is 40 mg, followed by 40 mg one week later. Then the usual dose
is 40 mg every other week.

Adolescents with hidradenitis suppurativa (aged 12 to 17 years, weighing 30 kg or more)
The recommended dose of Hulio is an initial dose of 80 mg (given as two 40 mg injections on the same day),
followed by 40 mg every other week starting one week after the initial dose. If the response is inadequate,
the paediatrician may increase the dosing frequency to 40 mg weekly or to 80 mg every other week.

It is recommended that the child use an antiseptic wash solution daily on affected areas during treatment
with Hulio.

Children and adolescents with ulcerative colitis
Children and adolescents aged 6 years and older and weighing less than 40 kg
The usual dose of Hulio is 80 mg (given as two 40 mg injections on the same day), followed by 40 mg
(given as a single 40 mg injection) two weeks later. Subsequently, the usual dose is 40 mg every other week.

Patients who turn 18 years old while receiving 40 mg every other week should continue the prescribed dose.

Children and adolescents aged 6 years and older and weighing 40 kg or more
The usual dose of Hulio is 160 mg (given as four 40 mg injections on the same day or two 40 mg injections
per day for two consecutive days), followed by 80 mg (given as two 40 mg injections on the same day)
two weeks later. Subsequently, the usual dose is 80 mg every other week.

Patients who turn 18 years old while receiving 80 mg every other week should continue the prescribed dose.

Children and adolescents with chronic non-infectious uveitis
Children and adolescents aged 2 to 17 years and weighing less than 30 kg
The usual dose of Hulio is 20 mg administered every other week in combination with methotrexate.

The paediatrician may also prescribe an initial dose of 40 mg, which may be administered one week
before starting the recommended usual dose.

Children and adolescents aged 2 to 17 years and weighing 30 kg or more
The usual dose of Hulio is 40 mg administered every other week in combination with methotrexate.

The paediatrician may also prescribe an initial dose of 80 mg, which may be administered one week
before starting the usual dose.

For patients prescribed a full dose of 40 mg of Hulio, a 40 mg pre-filled pen and a 40 mg pre-filled syringe
are available from the pharmacist.

Method and route of administration
Hulio is administered by subcutaneous injection (for subcutaneous use).
Detailed instructions on how to inject Hulio are provided in the Instructions for Use.

If you use more Hulio than you should
If you accidentally inject Hulio into the child more frequently than intended, contact the paediatrician
and inform them that the child has received more medicine than prescribed. Always keep the medicine
package or the medicine itself, even if empty.

If you forget to use Hulio
If you forget to give the child an injection, administer the next dose of Hulio as soon as you remember.
Then continue giving the child the following doses according to the regular dosing schedule.

If the child stops treatment with Hulio
The decision to stop using Hulio should be discussed with the paediatrician. The child's symptoms may
return after stopping treatment.

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

4. Possible side effects

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

Contact a doctor urgently if the child develops 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;
• paleness, dizziness, persistent fever, easy bruising or bleeding.

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, feeling weak or tired, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision or leg weakness;
• signs of skin cancer, such as swelling or an open sore that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, paleness.

The signs and symptoms described above may indicate the following side effects, which have been observed with adalimumab.

Very common (may affect up to 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, throat infection and pneumonia);
• abnormal blood test results;
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• bone and 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;
• oral infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• mild allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• inflammation or swelling of eyes/eyelids;
• dizziness (sensation of the room spinning);
• sensation of rapid heartbeat;
• high blood pressure;
• red skin;
• hematoma (collection of blood outside blood vessels);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• indigestion, bloating, heartburn;
• acidity/acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• bruising;
• itchy rash;
• itching, skin inflammation (including eczema);
• cracking of fingernails and toenails;
• increased sweating;
• hair loss;
• new onset or worsening of psoriasis (red, scaly skin);
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (swelling);
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• slow wound healing.

Uncommon (may affect up to 1 in 100 people):

• opportunistic 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);
• cancer;
• lymphoma (cancer of the lymphatic system);
• immune system disorders affecting lungs, skin and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shakiness);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• irregular heartbeat;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• excess fluid around the lungs;
• pancreatitis (inflammation of the pancreas);
• difficulty swallowing;
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (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 affecting the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• acute myocardial infarction (heart attack);
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (perforation/tearing of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome;
• facial edema (swelling of the face) associated with allergic reactions;
• inflammatory skin rash;
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, reddish-purple rash).

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

• hepatosplenic T-cell lymphoma (a rare 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 appears as purple lesions on the skin;
• liver failure;
• worsening of skin rash with muscle weakness;
• weight gain (in most patients, weight gain has been low).

Reporting of side effects
If the child experiences any side effect, including those not listed in this leaflet, talk to your pediatrician 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 Hulio

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/box after "Exp." The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not dispose of medicines 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 Hulio contains

• The active substance is adalimumab.
• The other ingredients are monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid and water for injections (see section 2 - "Hulio contains sodium and sorbitol").

Description of the appearance of Hulio and contents of the pack
Hulio 40 mg solution for injection in vials is supplied as a sterile solution containing 40 mg of
adalimumab dissolved in 0.8 mL of a clear or slightly opalescent solution, ranging from colourless to
pale brownish-yellow.
The Hulio vial is a glass vial with a rubber stopper. Hulio is supplied in packs of 1 or 2 vials. Each single pack contains 1 vial, 1 sterile injection syringe, 1 sterile needle, 1 sterile vial adapter and 2 alcohol-impregnated swabs.
Hulio may also be available in a pre-filled syringe or pre-filled pen.
Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36
Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
Ireland
D13 R20R
Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building, Santry Demesne
Dublin
D09 C6X8
Ireland
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Tél/Tel: Tel:
България Luxembourg/Luxemburg
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Tel: Tel.:
Danmark Malta
Tlf: Tel.:
Deutschland Nederland
Tel: Tel:
Eesti Norge
Tel: Tlf:
Ελλάδα Österreich
Τηλ.: Tel:
España Polska
Tel: Tel: 0
France Portugal
Biocon Biologics France S.A.S
Tel: Tel:
Hrvatska România
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Ireland Slovenija
Tel: Tel:
Ísland Slovenská republika
Sími: +345 800 4316 Tel:
Italia Suomi/Finland
.
Tel: Puh/Tel:
Κύπρος Sverige
Τηλ: Tel:
Latvija
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Other sources of information
More detailed information about this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu .
Instructions for use
Read the instructions carefully and follow them step by step. The paediatrician, nurse or healthcare professional will show you how to prepare and administer the injection to the child. They will also inform you of the prescribed amount (volume).
Do not administer the injection to the child until you are certain you understand how to prepare and give the injection. After adequate training, the injection may be given by you or another person, such as a family member or nurse.
Each vial contains a single dose of 40 mg of adalimumab.
Do not mix other medicines in the same syringe or vial with Hulio solution.
To help you remember on which days to administer the Hulio injection, it may be helpful to mark them on a calendar or in a diary.
Before starting
Ensure you know the prescribed amount. If you do not know it, DO NOT PROCEED FURTHER and consult the paediatrician.
Find a quiet area with a clean, flat, well-lit work surface and gather all the materials needed to administer the injection.
The materials you need are:

• 1 box of Hulio vial for paediatric use
• 1 sharps container (not included in the Hulio pack)
• 1 gauze pad or cotton ball (not included in the Hulio pack)

If you do not have the necessary materials, ask your nurse or pharmacist.

Preparing the Hulio injection
Each single Hulio vial contains:

• 1 syringe (1)
• 1 vial adapter (2)
• 1 vial of Hulio solution (3)
• 2 alcohol-impregnated swabs (4)
• 1 needle (5)

Hulio packs must be stored in the refrigerator (between 2°C and 8°C) until use.

• Remove only one vial box from the refrigerator at least 30 minutes before use to allow the contents to reach room temperature. If there is a second vial in the Hulio pack for the next administration, return it to the refrigerator immediately.
• DO NOT use other heat sources, such as a microwave or hot water, to warm the vial.
• DO NOT put the vial back in the refrigerator after it has reached room temperature.
• Check the expiry date printed on the vial.
• DO NOT use the vial after the expiry date.
• Check that the solution is clear, colourless and free of particles.
• DO NOT use the vial if the solution is cloudy, discoloured or contains particles.

Steps for the injection
Follow the following steps carefully for each Hulio injection:
Step 1 – Choose and prepare the injection site

Hulio is administered by subcutaneous injection. It should be
injected into the thigh or abdomen.
Rotate and change injection sites, keeping about 3 cm away from the site used previously.
If injecting into the abdomen, stay at least 5 cm away from the navel.

• DO NOT inject into red, hardened, bruised or painful skin.
• DO NOT inject into scars or stretch marks.
• If the child has psoriasis, DO NOT inject into raised, thick, red or scaly patches.
• DO NOT inject through clothing. Remove any clothing that may interfere with the injection.

Step 2 – Wash hands
Wash hands thoroughly with soap and water.
Preparing the Hulio dose for injection
Step 3 – Partially open the syringe and needle packaging
Partially open the syringe packaging from the end closest to the
white plunger. Move the transparent plastic just enough to expose
the white plunger WITHOUT removing the syringe from the
packaging.
Partially open the needle packaging from the end closest to the
yellow connector of the syringe. Move the transparent plastic just
enough to expose the yellow connector WITHOUT removing the
needle from the packaging.

Step 4 – Remove the cap from the vial and clean the vial stopper
Remove the white plastic cap from the vial to expose the vial
stopper.

Use one of the alcohol swabs to clean the stopper and then place
the vial on a flat surface.

• DO NOT touch the vial stopper after cleaning it with the swab.

Step 5 – Attach the vial adapter to the vial

Remove the cover of the vial adapter packaging WITHOUT
removing the adapter from its packaging.
With the vial adapter still in its transparent packaging, attach it
to the vial stopper by pushing it until it clicks into place.

Once you are sure the adapter is securely attached to the vial, pull
away the packaging.
Gently place the vial with the attached adapter on a flat work
surface, taking care not to let it fall.
Step 6 – Position the plunger at dose + 0.1 mL
Holding the syringe packaging, slowly pull out the white plunger
0.1 mL above the prescribed dose (for example, if the prescribed
dose is 0.5 mL, pull the plunger to 0.6 mL).
DO NOT push the white plunger completely out of the syringe.

• If the white plunger is pushed out of the syringe, discard the syringe and contact the Hulio supplier for a replacement. DO NOT attempt to reinsert the white plunger.
  Step 7 – Attach the syringe to the vial adapter and push the plunger Hold the syringe by the calibrated part and remove it from its

packaging.

• DO NOT hold the syringe by the white plunger.

Insert the tip of the syringe into the vial adapter and screw it clockwise until the syringe is securely locked in place.

• DO NOT overtighten.

Push the plunger fully in. This step is important to ensure the correct dose is drawn.
Step 8 – Position the plunger to draw up dose + 0.1 mL

Keep the plunger depressed and turn the vial and syringe upside
down.
Slowly pull the plunger to draw the Hulio solution into the
syringe. Pull the plunger 0.1 mL above the prescribed dose (for
example, if the prescribed dose is 0.5 mL, pull the plunger to
0.6 mL).
The volume will be adjusted to the prescribed dose in a later step.
If there are air bubbles in the syringe, push the plunger fully in to return the solution to the vial.

Repeat this step to draw the solution into the syringe again, pulling the plunger SLOWLY.
If air bubbles are still visible in the solution, repeat this step up to 3 times.

• DO NOT hold the syringe by the plunger.
• DO NOT shake the syringe.
• If the white plunger is pushed out of the syringe, discard the syringe and contact the Hulio supplier for a replacement. DO NOT attempt to reinsert the white plunger.
  Step 9 – Detach the syringe from the vial adapter and attach the needle

Remove the vial adapter by unscrewing it from the syringe.

• DO NOT touch the top of the syringe.
• DO NOT hold the syringe by the white plunger.

Attach the needle to the syringe by inserting the syringe tip into the yellow connector on the needle. Rotate the syringe until the needle is securely attached.

• At this point, remove the transparent needle packaging.

Preparing the dose
Step 10 – Flip down the pink needle cap and remove the needle cap

Hold the syringe with the needle pointing upwards.
Flip down the pink needle cap and remove the needle cap by pulling it off. DO NOT twist the needle cap.

• DO NOT touch the needle.
• DO NOT recap the needle after removal.

Step 11 – Check and set the prescribed dose
Hold the syringe at eye level with the needle pointing upwards to clearly see the amount of solution.
Double-check the correct prescribed dose from the doctor.
Gently push the plunger into the syringe until the syringe contains the prescribed amount of medicine. Excess solution may escape from the needle as the plunger is pressed. Be careful not to splash the solution into the eyes.
Gently place the syringe on a clean, flat work surface.

• DO NOT remove the needle or syringe.

Injecting Hulio
Step 12 – Prepare the injection site
Wipe the skin at the chosen injection site with a new alcohol-impregnated swab.

• Allow the skin to dry; do not blow on it to dry.
• DO NOT touch this area again before the injection.
  Step 13 – Pinch the injection site

Gently pinch the area already wiped with alcohol and keep it
steady.
With a quick, firm motion, insert the entire needle into the skin at a 45° angle.
Step 14 – Push the plunger to inject the solution

Release the pinched skin.
Push the white plunger to inject the Hulio solution until the syringe is empty.
Step 15 – End of injection, remove the syringe, attach the needle cap
When the syringe is empty, remove the syringe with the needle from

the skin.
After the injection, if slight bleeding occurs at the injection site, gently press a gauze pad or cotton ball over the site for a few seconds.

• DO NOT massage the injection site.

Flip the pink needle cap upwards over the needle and snap it into place. Place the syringe with the covered needle on the work surface.

• DO NOT replace the transparent cap on the needle.

Disposal of materials
Step 16 – Disposal of the syringe and needle
Each vial, syringe, vial adapter and needle is for single use only. THEY MUST NEVER BE REUSED.
After use, place the syringe, needle, vial and vial adapter into a sharps disposal container.

DO NOT dispose of the sharps container in household waste.

• DO NOT recycle the used sharps disposal container.
• Always keep the sharps disposal container out of sight and reach of children.
• Dispose of all other used materials and the empty packaging in the household waste container.

Patient information leaflet

Hulio 40 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 receiving Hulio and during treatment with Hulio. Always keep this patient reminder card with you and for 4 months after your last injection of Hulio.
• If you have any questions, 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, because it could 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 Hulio is and what it is used for
2. What you need to know before using Hulio
3. How to use Hulio
4. Possible side effects
5. How to store Hulio
6. Contents of the pack and other information
7. Instructions for use

1. What Hulio is and what it is used for

Hulio contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hulio 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,
• non-infectious chronic uveitis in adults and children.

The active substance in Hulio, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target in the body.
The target of adalimumab is another 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, Hulio reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hulio 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 you do not respond adequately to these medicines, you will be given Hulio to treat rheumatoid arthritis.
Hulio may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hulio can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hulio is generally used in combination with methotrexate. If your doctor decides that treatment with methotrexate is not appropriate, Hulio 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 begin during childhood.
Hulio 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.
You may initially be given other disease-modifying medicines such as methotrexate. If these medicines are not sufficiently effective, you will be given Hulio to treat 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.
Hulio is used to treat ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be given other medicines. If these medicines are not sufficiently effective, Hulio will be given to reduce the signs and symptoms of your disease.

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

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 separate 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.
Hulio is used to treat moderate to severe plaque psoriasis in adults. Hulio 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 adequately or are not suitable.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic, long-term inflammatory skin disease that is often painful. Symptoms may include painful lumps 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.
Hulio is used to treat hidradenitis suppuriva in adults and adolescents aged 12 years and older. Hulio can reduce the number of lumps and abscesses you have and the pain often associated with this disease. You may initially receive other medicines. If you do not respond adequately to these medicines, you will be given Hulio.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hulio 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, Hulio 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 intestine.
Hulio is used to treat ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you will first be given other medicines. If these medicines are not sufficiently effective, Hulio will be given to reduce the signs and symptoms of your disease.

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

• Adults with non-infectious uveitis with inflammation affecting the back of the eye.
• Children and adolescents aged 2 to 17 years with non-infectious chronic uveitis with inflammation affecting the front part of the eye.

2. What you should know before using Hulio

Do not use Hulio

• 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 (see “Warnings and precautions”). It is important to tell your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• 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 Hulio.

Allergic reactions
If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or skin rash, do not administer Hulio 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 infections or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hulio. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Hulio. This risk may increase if your lung function is impaired. These infections can be serious and may include tuberculosis, infections caused by viruses, fungi, parasites, bacteria, or other unusual infectious organisms, and sepsis (blood poisoning). 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 Hulio.

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 therapy with Hulio. This will involve a thorough medical evaluation of the child’s 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 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, lethargy, low-grade fever) or other infections occur during or after treatment.

Travel/recurrent infection

• Inform your doctor if you live or travel 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 (HBV)

• 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 will test you for hepatitis B virus infection. Taking adalimumab may cause reactivation of hepatitis B virus in people who are carriers of this virus. In some rare cases, especially if the patient is also taking 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 Hulio. You and your doctor should pay particular attention to signs of infection while you are being treated with Hulio. 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 surgical or dental procedure, inform your doctor that you are taking Hulio. Your doctor may recommend temporarily stopping Hulio.

Demyelinating diseases

• If you have or develop demyelinating diseases (conditions affecting the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether you should start or continue treatment with Hulio. 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.

Vaccinations

• Certain vaccines contain live but weakened bacterial or viral agents that can cause disease and must not be administered during treatment with Hulio, as they may cause infections.
• Check with your paediatrician before the child receives any vaccine.
• It is recommended that, if possible, children receive all age-appropriate scheduled vaccinations before starting treatment with Hulio.
• If you have taken Hulio during pregnancy, the baby may have an increased risk of infection for up to approximately five months after your last dose during pregnancy. It is important that you inform the paediatrician and other healthcare providers about your use of Hulio during pregnancy, so they can decide when the baby should receive any type of vaccination.

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 Hulio, 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 help 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 the treatment.

Cancer

• Very rarely, certain types of cancer have occurred in patients, both children and adults, treated with adalimumab or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a cancer affecting the lymphatic system) and leukaemia (cancers affecting blood and bone marrow). If you are taking Hulio, your risk of developing lymphomas, leukaemia, or other cancers 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 Hulio.

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

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

Autoimmune disease

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

Children and adolescents

• Do not give Hulio to children under 2 years of age with polyarticular juvenile idiopathic arthritis and non-infectious chronic uveitis.
• Do not give Hulio to children under 6 years of age with enthesitis-related arthritis and Crohn’s disease.
• Do not give Hulio to children under 4 years of age with plaque psoriasis.
• Do not give Hulio to children under 12 years of age with hidradenitis suppurativa.
• Do not use the 40 mg pre-filled syringe if doses other than 40 mg are recommended.

Other medicines and Hulio
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Hulio must not be taken together with medicines containing anakinra or abatacept as active ingredients. The combination of Hulio with 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.
Hulio may be taken together with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) (sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts), corticosteroids, or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

Pregnancy and breastfeeding

• You should consider using an appropriate contraceptive method to prevent pregnancy and continue using it for at least 5 months after the last dose of Hulio.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor about taking this medicine.
• Hulio should only be used during pregnancy 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.
• Hulio may be used during breastfeeding.
• If you take Hulio 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 Hulio during pregnancy before the baby receives any type of vaccination (for more information on vaccinations, see “Warnings and precautions”).

Driving and using machines
Hulio may affect, although only slightly, your ability to drive, ride a bicycle, or use machines. After taking Hulio, you may experience visual disturbances or a sensation that your surroundings are spinning.

Hulio contains sodium and sorbitol
Each pre-filled syringe of Hulio contains 38.2 mg of sorbitol. Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to certain sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot metabolize fructose, inform your doctor before taking or receiving this medicine (or giving it to the child).
In addition, this medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe, i.e., it is essentially ‘sodium-free’.

3. How to use Hulio

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Your doctor may prescribe a different concentration of Hulio if a different dose is required.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis
The usual dose for adults with these conditions is 40 mg of adalimumab administered every other week as a single dose.

In rheumatoid arthritis, methotrexate should be continued during treatment with Hulio. If your doctor determines that treatment with methotrexate is not appropriate, Hulio may be administered alone.

If you have rheumatoid arthritis and are not receiving methotrexate in combination with Hulio, your doctor may decide to prescribe 40 mg of adalimumab weekly or 80 mg every other week.

Children and adolescents with polyarticular juvenile idiopathic arthritis
Children and adolescents aged 2 to 17 years and weighing between 10 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 2 to 17 years and weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Children and adolescents with enthesitis-related arthritis
Children and adolescents aged 6 to 17 years and weighing between 15 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 6 to 17 years and weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Adults with psoriasis
The usual dose of Hulio for adults with psoriasis is an initial dose of 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg every other week starting the week after the initial dose. You must continue injecting Hulio for as long as your doctor has instructed. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with plaque psoriasis
Children and adolescents aged 4 to 17 years and weighing between 15 kg and less than 30 kg
The recommended initial dose of Hulio is 20 mg, followed by 20 mg one week later. The usual maintenance dose is then 20 mg every other week.

Children and adolescents aged 4 to 17 years and weighing 30 kg or more
The recommended initial dose of Hulio is 40 mg, followed by 40 mg one week later. The usual maintenance dose is then 40 mg every other week.

Adults with hidradenitis suppurativa
The usual dose for hidradenitis suppurativa is an initial dose of 160 mg (administered as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later. After another two weeks, continue with 40 mg weekly or 80 mg every other week, as prescribed by your doctor.

It is recommended to use an antiseptic wash solution daily on the affected areas.

Adolescents with hidradenitis suppurativa (aged 12 to 17 years, weighing 30 kg or more)
The recommended dose of Hulio is an initial dose of 80 mg (two 40 mg injections on one day), followed by 40 mg every other week starting one week after the initial dose. If the dose is not effective enough, your pediatrician may increase the frequency to 40 mg weekly or 80 mg every other week.

It is recommended to use an antiseptic wash solution daily on the affected areas.

Adults with Crohn’s disease
The usual dose for Crohn’s disease is initially 80 mg (administered as two 40 mg injections on one day), followed by 40 mg every other week starting after two weeks. If a more rapid effect is needed, your doctor may prescribe an initial dose of 160 mg (administered as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on one day) after two weeks, and then 40 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with Crohn’s disease
Children or adolescents aged 6 to 17 years and weighing less than 40 kg
The usual dose is initially 40 mg, followed by 20 mg after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 80 mg (administered as two 40 mg injections on one day), followed by 40 mg after two weeks.

The usual maintenance dose is then 20 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 20 mg weekly.

Children or adolescents aged 6 to 17 years and weighing 40 kg or more
The usual dose is initially 80 mg (administered as two 40 mg injections on one day), followed by 40 mg after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 160 mg (administered as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on one day) after two weeks.

The usual maintenance dose is then 40 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Patients requiring a dose lower than 40 mg should use the 20 mg pre-filled syringe formulation or the 40 mg vial formulation of Hulio.

Adults with ulcerative colitis
The usual dose of Hulio for adults with ulcerative colitis is initially 160 mg (administered as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on one day) two weeks later, and then 40 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with ulcerative colitis
Children and adolescents aged 6 years and older and weighing less than 40 kg
The usual dose of Hulio is 80 mg (administered as two 40 mg injections on one day), followed by 40 mg (administered as one 40 mg injection) two weeks later. The usual maintenance dose is then 40 mg every other week.

Patients who turn 18 years old while receiving 40 mg every other week should continue the prescribed dose.

Children and adolescents aged 6 years and older and weighing 40 kg or more
The usual dose of Hulio is 160 mg (administered as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on one day) two weeks later. The usual maintenance dose is then 80 mg every other week.

Patients who turn 18 years old while receiving 80 mg every other week should continue the prescribed dose.

Adults with non-infectious uveitis affecting the back of the eye
The usual dose for adults with non-infectious uveitis is an initial dose of 80 mg (administered as two injections on one day), followed by 40 mg every other week starting one week after the initial dose. You must continue injecting Hulio for as long as your doctor has instructed.

In non-infectious uveitis, corticosteroids or other immunosuppressive medications may be continued during treatment with Hulio. Hulio may be administered as monotherapy.

Children and adolescents with chronic non-infectious uveitis
Children and adolescents aged 2 to 17 years and weighing less than 30 kg
The usual dose of Hulio is 20 mg administered every other week in combination with methotrexate.

Your pediatrician may also prescribe an initial dose of 40 mg, which may be administered one week before starting the recommended usual dose.

Children and adolescents aged 2 to 17 years and weighing 30 kg or more
The usual dose of Hulio is 40 mg administered every other week in combination with methotrexate.

Your pediatrician may also prescribe an initial dose of 80 mg, which may be administered one week before starting the recommended usual dose.

For patients receiving a dose lower than 40 mg, the 20 mg pre-filled syringe formulation of Hulio or the 40 mg/0.8 mL vial formulation (available from the pharmacist) should be used.

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

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

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

If you stop using Hulio
The decision to stop using Hulio should be discussed with your doctor. Your symptoms may return after stopping treatment.

If you have any questions about using 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 side effects are mild to moderate in severity. However, some may be serious and require urgent treatment.
Side effects may occur up to 4 months or more after the last injection of Hulio.
Contact a doctor immediately if you develop 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 on exertion or when lying down, or swollen feet;
• paleness, dizziness, persistent fever, easy bruising or bleeding.

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, feeling weak or tired, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision or leg weakness;
• signs of skin cancer such as a lump or open sore that does not heal;
• signs and symptoms suggesting the onset of disorders affecting the haematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The signs and symptoms described above may indicate the following side effects, which have been observed with adalimumab:
Very common (may affect up to 1 in 10 people)

• injection site reactions (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, throat infection and pneumonia);
• abnormal blood test results;
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• bone and 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;
• oral infections (including dental infections and herpes simplex);
• reproductive tract infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumours;
• skin cancer;
• mild allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• inflammation or swelling of eyes/eyelids;
• dizziness (sensation of the room spinning);
• sensation of rapid heartbeat;
• high blood pressure;
• red skin;
• haematoma (collection of blood outside blood vessels);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• indigestion, bloating, heartburn;
• acidity/acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• bruising;
• itchy rash;
• itching, skin inflammation (including eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• new onset or worsening of psoriasis (red, scaly skin);
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• oedema (swelling);
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• slow wound healing.

Uncommon (may affect up to 1 in 100 people):

• opportunistic 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);
• tumour;
• lymphoma (cancer of the lymphatic system);
• immune system disorders that may affect lungs, skin and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• irregular heartbeat;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• excess fluid around the lungs;
• inflammation of the pancreas;
• difficulty swallowing;
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (including inflammation of 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 affecting the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• acute myocardial infarction (heart attack);
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (perforation/tearing of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B;
• autoimmune hepatitis (liver inflammation caused by the body’s own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome;
• facial oedema (facial swelling) associated with allergic reactions;
• inflammatory 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);
• 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 skin lesions;
• liver failure;
• worsening of rash with muscle weakness;
• weight gain (in most patients, weight gain has been low).

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 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 Hulio

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/box after "Exp.". The expiry date refers to the last day of that month.
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), the single pre-filled syringe may be stored at room temperature (up to 25°C) for a maximum of 8 weeks – ensure the medicine is protected from light.
Once removed from the refrigerator for storage at room temperature, the syringe must be used within 8 weeks or discarded, even if it is returned to the refrigerator.
You must record the date when the syringe is first removed from the refrigerator and the date by 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 in use. This will help protect the environment.

6. Package contents and other information

What Hulio contains

• The active substance is adalimumab.
• The other ingredients are monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid and water for injections (see section 2 – "Hulio contains sodium and sorbitol").

Description of the appearance of Hulio and contents of the pack
Hulio 40 mg solution for injection in pre-filled syringe is supplied as a sterile solution of 40 mg of
adalimumab dissolved in 0.8 mL of a clear or slightly opalescent solution, ranging from colourless to
pale brownish-yellow.
The pre-filled syringe of Hulio consists of a plastic syringe with a plunger stopper and a needle with a
needle cap.
Each pack contains 1, 2, 4 or 6 pre-filled syringes with 2, 2, 4 or 6 alcohol-impregnated swabs respectively.
Each pack contains 1, 2, 4 or 6 pre-filled syringes.
Not all pack sizes may be marketed.
Hulio may also be available in vials for paediatric use or in a pre-filled pen.

Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36
Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
Ireland
D13 R20R

Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building, Santry Demesne
Dublin
D09 C6X8
Ireland

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

België/Belgique/Belgien Lietuva
Tél/Tel: Tel:

България Luxembourg/Luxemburg
Тел: Tél/Tel:

Česká republika Magyarország
Tel: Tel.:

Danmark Malta
Tlf: Tel.:

Deutschland Nederland
Tel: Tel:

Eesti Norge
Tel: Tlf:

Ελλάδα Österreich
Τηλ.: Tel:

España Polska
Tel: Tel: 0

France Portugal
Biocon Biologics France S.A.S
Tel: Tel:

Hrvatska România
Tel: Tel:

Ireland Slovenija
Tel: Tel:

Ísland Slovenská republika
Sími: +345 800 4316 Tel:

Italia Suomi/Finland
.
Tel: Puh/Tel:

Κύπρος Sverige
Τηλ: Tel:

Latvija
Tel:

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

Instructions for use
Read the instructions carefully and follow them step by step. Your doctor, nurse or healthcare professional will provide instructions on how to administer an injection using a pre-filled syringe of Hulio. Ask your doctor or nurse if anything is unclear.

Do not perform self-injection until you are confident that you understand how to prepare and administer the dose. After adequate training, the injection may be administered by you or another person, such as a family member or nurse.

Each pre-filled syringe is for single use only and contains a 40 mg dose of adalimumab.

Do not mix the Hulio solution with other medicinal products.

To help you remember on which days of the week you should administer the Hulio injection, it may be helpful to mark them on a calendar or diary.

Before starting
Find a quiet area with a flat, clean, well-lit work surface. Gather all the materials you will need to administer the injection.

The materials you need are:

• 1 pre-filled syringe
• 1 alcohol-impregnated swab (not included in the Hulio pack)
• 1 sharps container (not included in the Hulio pack)
• 1 gauze pad or cotton ball (not included in the Hulio pack)

If you do not have the necessary materials, ask your nurse or pharmacist.

Preparing the pre-filled syringe
The pre-filled syringe must be stored in the refrigerator (between 2°C and 8°C).

• Remove only one pre-filled syringe from the refrigerator at least 30 minutes before use to allow the contents to reach room temperature.
• DO NOT use other heat sources, such as a microwave or hot water, to warm the syringe.
• DO NOT return the syringe to the refrigerator after it has reached room temperature.
• Check the expiry date printed on the syringe.
• DO NOT use the syringe after the expiry date.
• Inspect the syringe to ensure the medicine is at or near the fill mark (you may need to gently swirl the liquid) and that the liquid is clear, colourless and free from particles.
• DO NOT use the syringe if the liquid is not near the fill mark.
• DO NOT use the syringe if the liquid is cloudy, discoloured or contains particles.

Needle cap Fill mark Plunger

Medicinal product Needle safety device

Steps for injection
Carefully follow each of the steps below for every Hulio injection using the pre-filled syringe:

Step 1 – Choose and prepare the injection site

The Hulio pre-filled syringe is for subcutaneous use. Hulio
must be injected into the thigh or abdomen.
Rotate and change injection sites, keeping about 3 cm away from the previous injection site.
If injecting into the abdomen, inject at least 5 cm away from the navel.

• DO NOT inject into red, hardened, bruised or painful skin.
• DO NOT inject into scars or stretch marks.
• If you have psoriasis, DO NOT inject into raised, thick, red or scaly patches.
• DO NOT inject through clothing. Remove any clothing that may interfere with the injection.

Step 2 – Wash hands
Wash hands thoroughly with soap and water.

Step 3 – Prepare the injection site
Wipe the skin at the chosen injection site with an alcohol-impregnated swab.

• Allow the skin to dry. Do not blow on it to dry.
• DO NOT touch this area again before the injection.

Step 4 – Remove the needle cap
Remove the needle cap from the syringe. A few small drops of liquid may leak from the needle, which is normal. It is also normal to see air bubbles.

• DO NOT remove the needle cap until you are ready to inject.
• Do not twist or bend the needle cap when removing it to avoid damaging the needle.
• NEVER touch or pull the plunger.
• DO NOT recap the needle or touch the needle with fingers or allow the needle to touch any other object.
• DO NOT expel air bubbles.
• DO NOT use the pre-filled syringe if it has been dropped after removing the needle cap.

Step 5 – Pinch and hold the injection site

Gently pinch the injection site to lift up an area of skin and hold it firmly.

Step 6 – Insert the needle into the site

With a quick, firm motion, like a dart, insert the needle at a 45° angle.
Take care during insertion to avoid injecting into your fingers while holding the injection site.

Step 7 – Inject Hulio
Once the needle is fully inserted, release the pinched skin.

Gently push the plunger all the way down until all the medicine is injected and the syringe is empty.

• If the plunger is not fully depressed, the safety device will not activate to cover the needle.
• DO NOT move, shake or rotate the syringe during injection.

Step 8 – End of injection, remove the syringe
Remove the syringe from the injection site at the same angle as insertion and release your thumb from the plunger.

Each pre-filled syringe has a safety device that

retracts and covers the needle after releasing the plunger. If the needle does not retract, carefully place the used syringe into a sharps container to prevent injury.

After the injection, if slight bleeding occurs at the injection site, apply light pressure with a gauze pad or cotton ball for a few seconds – DO NOT rub the injection site. If needed, cover the injection site with a plaster.

Step 9 – Disposal of the syringe and needle cap
Dispose of the used syringe and needle cap in a sharps container.
Consult your healthcare professional for instructions on proper disposal of the full sharps container.

• DO NOT reuse the syringe.
• DO NOT recap the needle.

• DO NOT throw the sharps container into household waste.
• DO NOT recycle the used sharps container.
• Always keep the sharps container out of sight and reach of children.

Patient information leaflet

Hulio 40 mg solution for injection in 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 containing important safety information that you need to know before receiving Hulio and during treatment with Hulio. Keep this patient reminder card with you at all times and for 4 months after your last injection of Hulio.
• 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, because it could 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 Hulio is and what it is used for
2. What you need to know before using Hulio
3. How to use Hulio
4. Possible side effects
5. How to store Hulio
6. Contents of the pack and other information
7. Instructions for use

1. What Hulio is and what it is used for

Hulio contains the active substance adalimumab, a medicine that acts on the body's immune (defence) system.
Hulio 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,
• chronic non-infectious uveitis in adults and children.

The active substance in Hulio, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target in the body.
The target of adalimumab is another 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, Hulio reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hulio 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 you do not respond adequately to these medicines, you will be given Hulio to treat rheumatoid arthritis.
Hulio may also be used for the treatment of severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hulio can slow down the progression of joint cartilage and bone damage caused by the disease and improve physical function.
Hulio is generally used in combination with methotrexate. If your doctor decides that treatment with methotrexate is not appropriate, Hulio 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 begin during childhood.
Hulio 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.
Initially, you may be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, you will be given Hulio to treat 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 of the spine.
Hulio is used to treat ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be given other medicines. If these medicines do not work well enough, you will be given Hulio to reduce the signs and symptoms of your disease.

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

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 may be painful.
Psoriasis is thought to be caused by a problem with the body’s immune system that leads to increased production of skin cells.
Hulio is used to treat moderate to severe plaque psoriasis in adults. Hulio 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 adequately or are not suitable.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic, 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.
Hulio is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. Hulio can reduce the number of nodules and abscesses you have and the pain often associated with this disease. Initially, you may be given other medicines. If you do not respond adequately to these medicines, you will be given Hulio.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hulio 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 Hulio to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the intestine.
Hulio is used to treat ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you will first be given other medicines. If these medicines do not work well enough, you will be given Hulio to reduce the signs and symptoms of your disease.

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

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children and adolescents aged 2 to 17 years with chronic non-infectious uveitis with inflammation affecting the front part of the eye.

2. What you should know before using Hulio

Do not use Hulio

• 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 (see "Warnings and precautions"). It is important to tell your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• 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 Hulio.
Allergic reactions
If you experience allergic reactions with symptoms such as tightness in the chest, wheezing,
dizziness, swelling or skin rash, do not administer Hulio 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 infections or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hulio. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Hulio. This risk may increase if your lung function is impaired. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites, bacteria or other unusual infectious organisms, and sepsis (blood poisoning). 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 Hulio.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will check for signs or symptoms typical of tuberculosis before starting therapy with Hulio. This will involve a thorough medical evaluation of the 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 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 despite having 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 live or travel 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 acquiring hepatitis B virus. Your doctor will test you for hepatitis B virus infection. Taking adalimumab may cause reactivation of hepatitis B virus 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 Hulio. You and your doctor should pay particular attention to signs of infection while you are being treated with Hulio. 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 Hulio. Your doctor may advise temporarily stopping Hulio.

Demyelinating diseases

• 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 Hulio. 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.

Vaccinations

• Certain vaccines contain live but weakened bacteria or viruses that can cause disease and must not be given during treatment with Hulio, as they may cause infections.
• Check with your paediatrician before the child receives any vaccine.
• It is recommended that children receive all age-appropriate scheduled vaccinations before starting treatment with Hulio, if possible.
• If you have taken Hulio during pregnancy, the baby may have an increased risk of infection for up to about five months after your last dose during pregnancy. It is important that you inform the paediatrician and other healthcare providers about your use of Hulio 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 Hulio, your doctor will need to 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 help 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 the treatment.

Cancer

• Very rarely, certain types of cancer have occurred in patients, both children and adults, treated with adalimumab or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a cancer affecting the lymphatic system) and leukaemia (cancers affecting blood and bone marrow). If you are taking Hulio, your risk of developing lymphomas,
  leukaemia, or other cancers 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 being treated with azathioprine or mercaptopurine. Inform your doctor if you are taking
  azathioprine or mercaptopurine with Hulio.

• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If new areas of damaged skin appear during or after treatment, or if the appearance of existing lesions or 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-TNF medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

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

Children and adolescents

• Do not give Hulio to children under 2 years of age with polyarticular juvenile idiopathic arthritis and non-infectious chronic uveitis.
• Do not give Hulio to children under 6 years of age with enthesitis-related arthritis and Crohn’s disease.
• Do not give Hulio to children under 4 years of age with plaque psoriasis.
• Do not give Hulio to children under 12 years of age with hidradenitis suppurativa.
• Do not use the 40 mg pre-filled pen if doses other than 40 mg are recommended.

Other medicines and Hulio
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicines.
Hulio must not be taken together with medicines containing anakinra or abatacept as active ingredients. The combination of Hulio with 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.
Hulio may 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).
Pregnancy and breastfeeding

• You should consider using an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after the last dose of Hulio.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor for advice about taking this medicine.
• Hulio should only be used during pregnancy 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.
• Hulio may be used during breastfeeding.
• If you take Hulio 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 Hulio during pregnancy before the baby receives any vaccinations. For further information on vaccinations, see “Warnings and precautions”.

Driving and using machines
Hulio may affect, although only to a minor extent, your ability to drive, ride a bicycle, or
use machinery. After taking Hulio, you may experience visual disturbances or a sensation that your surroundings are spinning.
Hulio contains sodium and sorbitol
Each pre-filled pen of Hulio contains 38.2 mg of sorbitol. Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to certain sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot metabolize fructose, inform your doctor before taking or receiving this medicine (or before it is given to the child).
In addition, this medicine contains less than 1 mmol of sodium (23 mg) per pre-filled pen, i.e., essentially ‘sodium-free’.

3. How to use Hulio

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Your doctor may prescribe a different concentration of Hulio if a different dose is required.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
The usual dose for adults with these conditions is 40 mg of adalimumab administered every other week as a single dose.

In rheumatoid arthritis, methotrexate should be continued during treatment with Hulio. If your doctor determines that treatment with methotrexate is not appropriate, Hulio may be administered alone.

If you have rheumatoid arthritis and are not receiving methotrexate in combination with Hulio, your doctor may decide to prescribe 40 mg of adalimumab weekly or 80 mg every other week.

Children and adolescents with polyarticular juvenile idiopathic arthritis
Children and adolescents aged 2 to 17 years weighing between 10 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 2 to 17 years weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Children and adolescents with enthesitis-related arthritis
Children and adolescents aged 6 to 17 years weighing between 15 kg and less than 30 kg
The recommended dose of Hulio is 20 mg every other week.

Children and adolescents aged 6 to 17 years weighing 30 kg or more
The recommended dose of Hulio is 40 mg every other week.

Adults with psoriasis
The usual dose of Hulio for adults with psoriasis is an initial dose of 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg every other week, starting the week after the initial dose. You must continue injecting Hulio for as long as your doctor has instructed. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with plaque psoriasis
Children and adolescents aged 4 to 17 years weighing between 15 kg and less than 30 kg
The recommended initial dose of Hulio is 20 mg, followed by 20 mg one week later. The usual maintenance dose is then 20 mg every other week.

Children and adolescents aged 4 to 17 years weighing 30 kg or more
The recommended initial dose of Hulio is 40 mg, followed by 40 mg one week later. The usual maintenance dose is then 40 mg every other week.

Adults with hidradenitis suppurativa
The usual dose for hidradenitis suppurativa is an initial dose of 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later. After another two weeks, continue with 40 mg weekly or 80 mg every other week, as prescribed by your doctor.

It is recommended to use an antiseptic wash solution daily on the affected areas.

Adolescents with hidradenitis suppurativa aged 12 years and older, weighing 30 kg or more
The recommended dose of Hulio is an initial dose of 80 mg (two 40 mg injections on the same day), followed by 40 mg every other week starting one week after the initial dose. If the dose is not effective enough, your paediatrician may increase the frequency to 40 mg weekly or 80 mg every other week.

It is recommended to use an antiseptic wash solution daily on the affected areas.

Adults with Crohn's disease
The usual dose for Crohn's disease is initially 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg every other week starting after two weeks. If a more rapid effect is needed, your doctor may prescribe an initial dose of 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later, and then 40 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with Crohn's disease
Children or adolescents aged 6 to 17 years weighing less than 40 kg
The usual dose is initially 40 mg, followed by 20 mg after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg after two weeks.

The usual maintenance dose is then 20 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 20 mg weekly.

Children or adolescents aged 6 to 17 years weighing 40 kg or more
The usual dose is initially 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) after two weeks.

The usual maintenance dose is then 40 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Patients requiring a dose lower than 40 mg should use the 20 mg injectable solution in a pre-filled syringe or the Hulio formulation in 40 mg vials.

Adults with ulcerative colitis
The usual dose of Hulio for adults with ulcerative colitis is initially 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later, and then 40 mg every other week. If the dose is not effective enough, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with ulcerative colitis
Children and adolescents aged 6 years and older weighing less than 40 kg
The usual dose of Hulio is 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg (administered as one 40 mg injection) two weeks later. The usual maintenance dose is then 40 mg every other week.

Patients who turn 18 years old while receiving 40 mg every other week should continue the prescribed dose.

Children and adolescents aged 6 years and older weighing 40 kg or more
The usual dose of Hulio is 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later. The usual maintenance dose is then 80 mg every other week.

Patients who turn 18 years old while receiving 80 mg every other week should continue the prescribed dose.

Adults with non-infectious uveitis affecting the back of the eye
The usual dose for adults with non-infectious uveitis is an initial dose of 80 mg (administered as two injections on the same day), followed by 40 mg every other week starting one week after the initial dose. You must continue injecting Hulio for as long as your doctor has instructed.

In non-infectious uveitis, corticosteroids or other immunosuppressive medications may be continued during treatment with Hulio. Hulio may be administered as monotherapy.

Children and adolescents with chronic non-infectious uveitis
Children and adolescents aged 2 to 17 years weighing less than 30 kg
The usual dose of Hulio is 20 mg administered every other week in combination with methotrexate.

Your paediatrician may also prescribe an initial dose of 40 mg, which may be administered one week before starting the usual recommended maintenance dose.

Children and adolescents aged 2 to 17 years weighing 30 kg or more
The usual dose of Hulio is 40 mg administered every other week in combination with methotrexate.

Your paediatrician may also prescribe an initial dose of 80 mg, which may be administered one week before starting the usual recommended maintenance dose.

For patients receiving a dose lower than 40 mg, the 20 mg Hulio injectable solution in a pre-filled syringe or the 40 mg/0.8 mL injectable solution in a vial (available from the pharmacist) should be used.

Method and route of administration
Hulio is administered by subcutaneous injection (for subcutaneous use).
Detailed instructions on how to inject Hulio are provided in the Instructions for Use.

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

If you forget to use Hulio
If you forget to administer an injection, inject the next dose of Hulio as soon as you remember. Then resume your regular dosing schedule.

If you stop using Hulio
The decision to stop using Hulio should be discussed with your doctor. Your 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 urgent treatment.
Side effects may occur up to 4 months or more after the last injection of Hulio.
Contact a doctor immediately if you develop 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;
• paleness, dizziness, persistent fever, easy bruising or bleeding.

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, feeling weak or tired, or cough;
• symptoms of nerve problems such as tingling, numbness, double vision or leg weakness;
• signs of skin cancer, such as a swelling or open sore that does not heal;
• signs and symptoms suggesting the onset of disorders affecting the haematopoietic system, such as persistent fever, bruising, bleeding, paleness.

The signs and symptoms described above may be signs of the following side effects, which have been observed with adalimumab:
Very common (may affect up to 1 in 10 people)

• injection site reactions (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis, sore throat and pneumonia);
• abnormal blood test results;
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• bone and 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;
• oral infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumours;
• skin tumour;
• mild allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disturbances;
• sensory disturbances such as tingling, stabbing sensations or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• inflammation or swelling of eyes/eyelids;
• dizziness (sensation of the room spinning);
• awareness of heartbeat;
• high blood pressure;
• red skin;
• haematoma (accumulation of blood outside blood vessels);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• indigestion, bloating, heartburn;
• acidity/acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• bruising;
• itchy rash;
• itching, skin inflammation (including eczema);
• cracking or breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• new onset or worsening of psoriasis (red, scaly skin);
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• oedema (swelling);
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• slow wound healing.

Uncommon (may affect up to 1 in 100 people):

• opportunistic 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);
• tumour;
• lymphoma (cancer of the lymphatic system);
• immune system disorders affecting lungs, skin and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• irregular heartbeat;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a lung artery);
• excess fluid around the lungs;
• inflammation of the pancreas;
• difficulty swallowing;
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (including inflammation of 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 affecting the eye and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• acute myocardial infarction (heart attack);
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (perforation/laceration of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B;
• autoimmune hepatitis (liver inflammation caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome;
• facial oedema (swelling of the face) associated with allergic reactions;
• inflammatory 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);
• 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 rash with muscle weakness;
• weight gain (in most patients, weight gain was low).

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 Hulio

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/box after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer carton to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled pen of Hulio may be stored at room temperature (up to 25°C) for a maximum of 8 weeks – ensure the medicine is protected from light.
Once removed from the refrigerator for storage at room temperature, the pen must be used within 8 weeks or discarded, even if it is returned to the refrigerator.
You must record the date when the 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 Hulio contains

• The active substance is adalimumab.
• The other ingredients are monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid, and water for injections (see section 2 – "Hulio contains sodium and sorbitol").

Description of the appearance of Hulio and contents of the pack
Hulio 40 mg solution for injection in a pre-filled pen is supplied as a sterile solution containing 40 mg of adalimumab dissolved in 0.8 mL of clear or slightly opalescent solution, ranging from colourless to pale brownish-yellow.
The Hulio pre-filled pen is made of plastic with a cap and a needle with a needle cap. Each pack contains 1, 2, 4 or 6 pre-filled pens with 2, 2, 4 or 6 alcohol swabs respectively.
Each pack contains 1, 2, 4 or 6 pre-filled pens.
Not all pack sizes may be marketed.
Hulio may also be available in vials for paediatric use or in pre-filled syringes.

Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36
Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
IRELAND
D13 R20R

Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building, Santry Demesne
Dublin
D09 C6X8
IRELAND

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

België/Belgique/Belgien Lietuva
Tél/Tel: Tel:
България Luxembourg/Luxemburg
Тел: Tél/Tel:
Česká republika Magyarország
Tel: Tel.:
Danmark Malta
Tlf: Tel.:
Deutschland Nederland
Tel: Tel:
Eesti Norge
Tel: Tlf:
Ελλάδα Österreich
Τηλ.: Tel:
España Polska
Tel: Tel: 0
France Portugal
Biocon Biologics France S.A.S
Tel: Tel:
Hrvatska România
Tel: Tel:
Ireland Slovenija
Tel: Tel:
Ísland Slovenská republika
Sími: +345 800 4316 Tel:
Italia Suomi/Finland
.
Tel: Puh/Tel:
Κύπρος Sverige
Τηλ: Tel:
Latvija
Tel:

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

Instructions for use
Read the instructions carefully and follow them step by step. You will receive instructions from your doctor, nurse, or healthcare professional on how to administer an injection using the Hulio pre-filled pen. Ask your doctor or nurse if anything is unclear to you.
Do not proceed with self-injection until you are confident that you understand how to prepare and administer the injection. After proper training, the injection may be administered by you or by another person, such as a family member or nurse.
Each pre-filled pen is for single use only and contains one dose of 40 mg adalimumab.
Do not mix the Hulio solution with other medicinal products.
To help you remember the days of the week when you need to administer Hulio injections, it may be helpful to mark them on a calendar or in a diary.

Before starting
Find a quiet area with a flat, clean, and well-lit work surface. Gather all the materials you need to administer the injection.
The materials you need are:

• 1 pre-filled pen
• 1 alcohol swab (not included in the Hulio pack)
• 1 sharps disposal container (not included in the Hulio pack)
• 1 gauze pad or cotton ball (not included in the Hulio pack)

If you do not have the necessary materials, ask your nurse or pharmacist.

Preparing the pre-filled pen
Pre-filled pens must be stored in the refrigerator (between 2°C and 8°C).

• Remove only one pen from the refrigerator at least 30 minutes before use to allow the contents to reach room temperature.
  o DO NOT use other heat sources such as a microwave or hot water to warm the pen.
  o DO NOT return the pen to the refrigerator after it has reached room temperature.
• Check the expiry date printed on the pen.
  o DO NOT use the pen after the expiry date.
• Inspect the pen to ensure the medicine level is at or near the fill mark (you may need to shake it gently to see this) and that the liquid is clear, colourless, and free from particles.
  o DO NOT use the pen if the liquid level is not near the fill mark.
  o DO NOT use the pen if the liquid is cloudy, discoloured, or contains particles.

Orange activator Indicator
(needle inside) Orange medicine

Needle cap Viewing window Fill mark
Passage for injection
Carefully follow the steps below for each Hulio injection using the pre-filled pen:

Step 1 – Choose and prepare the injection site

The Hulio pre-filled pen is for subcutaneous use. It must be injected into the thigh or abdomen.
You must rotate and change injection sites, keeping them approximately 3 cm away from the previous injection site.
If injecting into the abdomen, stay at least 5 cm away from the navel.

• DO NOT inject into red, hardened, bruised, or painful skin.
• DO NOT inject into scar tissue or stretch marks.
• If you have psoriasis, DO NOT inject into raised, thick, red, or scaly patches.
• DO NOT inject through clothing. Remove any clothing that may interfere with the injection.

Step 2 – Wash hands
Wash your hands thoroughly with soap and water.

Step 3 – Prepare the injection site
Wipe the skin at the chosen injection site with an alcohol swab.

• Allow the skin to dry completely; do not blow on it to dry.
• DO NOT touch this area again before the injection.

Step 4 – Remove the needle cap from the pen
Remove the needle cap from the pen. A few small drops of liquid may leak from the needle, which is normal. It is also normal to see air bubbles.

• DO NOT remove the needle cap until you are ready to inject.

• Pull the needle cap straight off the pen, WITHOUT twisting.
• DO NOT replace the needle cap or touch the needle with your fingers or allow the needle to touch other objects.
• DO NOT touch the orange activator with your fingers (the needle emerges from this point).
• DO NOT use the pen if it has been dropped on a hard surface, as internal components may be damaged.
• DO NOT use the pen if the needle cap has been lost or is not securely attached.

Step 5 – Pinch and hold the injection site

Gently pinch the injection site to lift up a skin fold and hold it firmly.

Step 6 – Position the pen

Place the end of the orange activator of the pen flat against the injection site.
Hold the pen at a 90° angle to the injection site with the viewing window facing you.
Be careful not to inject into your fingers while holding the injection site.

Step 7 – Begin injection
Step 8 – Hold until the 2nd “CLICK” and 10 seconds

Step 7. Step 8.
Firmly press the body of the pen against the Continue holding the body of the pen pressed
injection site to activate the orange activator and against the injection site until one or all of the
start the injection. following events occur:
Continue holding the pen pressed against the • a 2nd “CLICK” is heard,
injection site after the 1st CLICK. The 1st CLICK • 10 seconds have passed,
signals the start of the injection. • the orange indicator stops and is fully blocked in
the viewing window.

In the viewing window, the orange indicator moves forward, indicating the progress of the injection.

• DO NOT move, shake, or rotate the pen during injection.

Step 9 – End of injection, remove the pen

Immediately remove the pen from the injection site.
After the injection, if slight bleeding occurs at the injection site, gently press a gauze pad or cotton ball over the site for a few seconds – DO NOT rub the injection site. If needed, cover the injection site with a plaster.

Step 10 – Dispose of the pen and needle cap
Dispose of the used pen and needle cap in a sharps disposal container.
Consult your healthcare provider for instructions on proper disposal of the full sharps container.

• DO NOT reuse the pen.

• DO NOT replace the needle cap.
• DO NOT throw the sharps container into household waste.
• DO NOT recycle the used sharps container.
• Always keep the sharps container out of sight and reach of children.