Yuflyma

Package leaflet: Information for the patient

Yuflyma 40 mg solution for injection in pre-filled syringe

adalimumab
Please read all of this leaflet carefully before you start using this medicine, as 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, which contains important safety information you should know before and during treatment with Yuflyma. Keep the Patient Reminder Card with you during your treatment and for 4 months after your last injection of Yuflyma.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful to them.
• If you experience any adverse reactions, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Yuflyma is and what it is used for

Yuflyma contains the active substance adalimumab, a medicine that acts on your immune system (the body's defence mechanism).
Yuflyma 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
• Plaque psoriasis
• Hidradenitis suppurativa
• Crohn’s disease
• Ulcerative colitis
• Non-infectious uveitis

The active substance in Yuflyma, adalimumab, is a human 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, Yuflyma reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Yuflyma is used for the treatment of moderate to severe rheumatoid arthritis in adults. You may first be given other disease-modifying antirheumatic drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be administered to you.
Yuflyma may also be used for the treatment of severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Yuflyma can slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Yuflyma should be used with methotrexate or alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease affecting the joints.
Yuflyma is used for the treatment of polyarticular juvenile idiopathic arthritis in patients from 2 years of age. You may first be given other disease-modifying antirheumatic drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be administered to you.
Your doctor will decide whether Yuflyma should be used 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.
Yuflyma is used to treat enthesitis-related arthritis in patients aged 6 years and older. You may first be given other disease-modifying antirheumatic drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

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 diseases of the spine.
Yuflyma is used to treat severe ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease usually associated with psoriasis.
Yuflyma is used to treat psoriatic arthritis in adults. Yuflyma can slow down joint damage caused by the disease and may help you move more freely. Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Plaque psoriasis
Plaque psoriasis is a skin condition causing red, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crack, thicken, or lift from the nail bed, which can be painful.
Yuflyma is used to treat

• moderate to severe chronic plaque psoriasis in adults, and
• severe chronic plaque psoriasis in children and adolescents from 4 to 17 years of age when topical therapy and phototherapies have not worked adequately or are not suitable.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and 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.
Yuflyma is used to treat

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

Yuflyma can reduce the number of lumps and abscesses caused by the disease and the pain often associated with it. Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Crohn’s disease
Crohn’s disease is an inflammatory disease of the gastrointestinal tract. Yuflyma is used to treat

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

Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the large intestine.
Yuflyma is used to treat

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

Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Non-infectious uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. Yuflyma is used to treat

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

This inflammation can lead to reduced vision and/or the presence of floaters in the eye (black spots or thin lines moving across the visual field). Yuflyma works by reducing this inflammation.
Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

2. What you should know before using Yuflyma

Do not use Yuflyma:

• if you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, for example, 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 serious heart problems (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Yuflyma.
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or skin rash, do not take Yuflyma 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 in a specific part of the body (for example, leg ulcers), consult your doctor before starting treatment with Yuflyma. If you are in any doubt, contact your doctor.
• You may be more likely to get infections while being treated with Yuflyma. This risk may increase if you have lung problems. These infections can be serious and may include:
• tuberculosis
• infections caused by viruses, fungi, parasites or bacteria
• severe blood infection (sepsis)

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you
experience symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may instruct
you to temporarily stop taking Yuflyma.

• Inform your doctor if you live or travel in areas where fungal infections are common (for example, histoplasmosis, coccidioidomycosis or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other medical conditions that

increase the risk of infection.

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

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or if you have been in contact with someone who had tuberculosis. You must not take Yuflyma if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Yuflyma, your doctor will need to check for signs and symptoms of tuberculosis before starting treatment with Yuflyma. This will involve a detailed medical evaluation including your medical history and appropriate clinical tests (for example, a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may develop during treatment even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (for example, a persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

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

Surgery or dental procedures

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

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the protective covering of nerves, such as multiple sclerosis), your doctor will decide whether to start or continue treatment with Yuflyma. 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 may cause infections and must not be administered during treatment with Yuflyma.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Yuflyma.
• If you have taken Yuflyma during pregnancy, your child may have an increased risk of

contracting an infection for up to approximately 5 months after your last dose of Yuflyma during
pregnancy. It is important that you inform the paediatrician or other healthcare provider about your
use of Yuflyma during pregnancy so they can determine when your child should receive any
vaccinations.
Heart failure

• If you have mild heart failure and are being treated with Yuflyma, your doctor must carefully monitor your heart condition. It is important to inform your doctor if you have or have previously had serious heart problems. If new symptoms of heart failure appear or if existing symptoms worsen (for example, shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether Yuflyma can be used.

Fever, bruising, bleeding or paleness

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

Tumours

• Very rarely, certain types of tumours have been observed in patients, both children and adults, treated with Yuflyma or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumour affecting the lymphatic system) and leukaemia (a tumour affecting blood and bone marrow).
• If you are taking Yuflyma, your risk of developing lymphomas, leukaemia or other tumours may increase. In rare cases, an uncommon and serious type of lymphoma has been observed in patients treated with Yuflyma. Some of these patients were also taking azathioprine or 6-mercaptopurine.
• Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Yuflyma.
• Cases of non-melanoma skin cancer have been observed in patients taking Yuflyma.
• If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform your doctor.
• 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 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 Yuflyma may lead to the development of a lupus-like syndrome. Inform your doctor if you experience symptoms such as unexplained persistent skin rash, fever, joint pain or fatigue.

Children and adolescents

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

Other medicines and Yuflyma
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines. Do not use Yuflyma with medicines containing the following active substances due to the
increased risk of serious infections:

• anakinra
• abatacept.

Yuflyma may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (for example, sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts)
• steroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

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

Driving and using machines
Yuflyma may have a minor effect on your ability to drive, ride a bicycle or use machines.
After taking Yuflyma, you may experience vision disturbances or a sensation that your surroundings are spinning.

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

3. How to use Yuflyma

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

Method and route of administration
Yuflyma is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to administer Yuflyma are described in section 7 “Instructions for use”.
If you use more Yuflyma than you should
If you accidentally inject Yuflyma more often than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken an excess dose. Always keep the medicine carton, even if empty.
If you forget to use Yuflyma
If you forget to give an injection, inject the next dose of Yuflyma as soon as you remember. After that, continue with your regular dosing schedule.
If you stop using Yuflyma
The decision to stop using Yuflyma should be discussed with your doctor. Symptoms may return if you stop using Yuflyma.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Immediately inform your doctor if you notice any of the following reactions

• severe rash, hives or other signs of allergic reaction
• swelling of the face, hands, or feet
• difficulty breathing, difficulty swallowing
• shortness of breath during exertion or when lying down, or swollen feet

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

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

The symptoms described above may be signs of the following side effects observed with Yuflyma.

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

• injection site reactions (including pain, swelling, redness, or itching)
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal 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 cold sores)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumours
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• sicca syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• nail breakage in fingers and toes
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• oedema (fluid retention)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• impaired 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
• lymphatic system tumour
• 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 (nervous system disorder)
• stroke
• hearing loss, ringing in ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling of the ankles
• heart attack
• aneurysm (a bulge in the wall of a major artery), vein inflammation and clot, blockage of a blood vessel
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of an artery in the lung)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial oedema (swelling of the face)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukaemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scarring of the lung)
• intestinal perforation (a hole in the intestine)
• hepatitis
• 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 oedema (swelling of the face) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (itchy red-purple rash)

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

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

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

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (liver-related blood test)

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

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. 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 Yuflyma

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

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled syringe with needle safety device of Yuflyma may be stored at room temperature (up to 25°C) for a maximum period of 31 days; ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 31 days or must be 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 after which the syringe must be discarded.

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

6. Package contents and other information

What Yuflyma contains
The active substance is adalimumab.
The other components are acetic acid, sodium acetate trihydrate, glycine, polysorbate 80, and water for
injections.

Description of the appearance of Yuflyma pre-filled syringe with needle safety device and
package contents
Yuflyma 40 mg solution for injection in pre-filled syringe with needle safety device is supplied as a sterile solution containing 40 mg of adalimumab dissolved in 0.4 mL of solution.
Yuflyma pre-filled syringe consists of a solution of adalimumab contained in a glass syringe.
The pack containing 1 pre-filled syringe is supplied with 2 alcohol swabs (1 spare). In packs containing 2, 4, and 6 pre-filled syringes, each pre-filled syringe is supplied with 1 alcohol swab.
Yuflyma pre-filled syringe is a solution based on adalimumab contained in a glass syringe with a needle safety device. The pack containing 1 pre-filled syringe with needle safety device is supplied with 2 alcohol swabs (1 spare). In packs containing 2, 4, and 6 pre-filled syringes with needle safety device, each pre-filled syringe is supplied with 1 alcohol swab.
Not all pack sizes may be marketed.
Yuflyma may be available as a pre-filled syringe and/or pre-filled pen.

Marketing Authorization Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles
06410, Biot
France
Nuvisan GmbH
Wegenerstraße 13
89231 Neu-Ulm
Germany
Midas Pharma GmbH
Rheinstr. 49
55218 Ingelheim
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès
Barcelona
Spain

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

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: + 32 1528 7418 Tel.: +36 1 231 0493

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Tel.: +36 1 231 0493 Tél/Tel: + 32 1528 7418

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Hungary Kft. Mint Health Ltd.
Tlf: +36 1 231 0493 Tel: +356 2093 9800

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel.: +49 (0)30 346494150 Tel: + 31 20 888 7300
[email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tlf: +36 1 231 0493

España Österreich
Kern Pharma, S.L. Astro-Pharma GmbH
Tel: +34 93 700 2525 Tel: +43 1 97 99 860

Ελλάδα Polska
VIANEX S.A. Celltrion Healthcare Hungary Kft.
Tel: +30 210 8009111 Tel.: +36 1 231 0493

France Portugal
Celltrion Healthcare France SAS CELLTRION PORTUGAL, UNIPESSOAL LDA
Tél.: +33 (0)1 71 25 27 00 Tel: +351 21 936 8542

Hrvatska România
Oktal Pharma d.o.o. Celltrion Healthcare Hungary Kft.
Tel: +385 1 6595 777 Tel: +36 1 231 0493

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493 Tel: +36 1 231 0493

Italia Suomi/Finland
Celltrion Healthcare Italy S.r.l. Celltrion Healthcare Finland Oy.
Tel: +39 02 47927040 Puh/Tel: +358 29 170 7755

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Sweden AB
Tel: +357 22741741 [email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for use

• The following instructions explain how to perform a subcutaneous self-injection of Yuflyma using the pre-filled syringe. First, carefully read these instructions and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with instructions on the technique of self-injection.
• Do not administer the injection by yourself until you are certain you have understood how to prepare and perform the injection.
• After receiving adequate instruction, the injection may be given by you or by someone else, such as a family member or friend.
• Use each pre-filled syringe for one injection only.

Yuflyma Pre-filled Syringe

Before use                             After use
Figure A

Do not use the pre-filled syringe if:

• it is cracked or damaged.
• the expiry date has been exceeded.
• it has been dropped on a hard surface.
  Remove the needle cap only immediately before injection. Keep Yuflyma out of the sight and reach of children.

1. Prepare the materials for injection

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled syringe from the box stored in the refrigerator.

• When removing the pre-filled syringe from the box, hold it by the barrel. Do not touch the plunger. c. Make sure you have the following materials:
  • Pre-filled syringe
  • Alcohol swab Not included in the box:
  • Cotton ball or gauze pad
  • Adhesive bandage
  • Sharps disposal container

2. Inspect the pre-filled syringe

a. Make sure you have the correct medicine (Yuflyma) and the correct dosage.
b. Look at the pre-filled syringe and ensure it is not cracked or damaged.
c. Check the expiry date on the label of the pre-filled syringe.
Do not use the pre-filled syringe if:

• it is cracked or damaged
• the expiry date has passed
• it has fallen on a hard surface. Figure B

3. Inspect the medicine

a. Look at the medicine to make sure the liquid is
clear, colourless to light brown, and free of particles.

• Do not use the pre-filled syringe if the liquid is: discoloured (yellow or dark brown), cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

4. Wait 15-30 minutes

15 - 30
a. Leave the pre-filled syringe at room temperature
minutes
for 15-30 minutes so it can warm up.

• Do not heat the pre-filled syringe using heat sources such as hot water or microwave.

Figure D

5. Choose an appropriate injection site

a. You can give the injection:

• in the front of the thigh

• in the abdomen, except for the area within 5 cm of the navel

• on the outer area of the upper arm (ONLY if you are a person assisting the patient).

  • Do not give the injection in skin areas within 5 cm of your navel or in any area that is red, hard, tender, damaged, bruised, or scarred.
  • If you have psoriasis, do not give the injection on any raised, thickened, red, scaly patches or on any skin lesions.

• Do not give the injection through clothing.

b. Rotate the injection site each time you
administer an injection. Each new injection site should
be at least 3 cm away from the previous injection site.
Figure E

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol swab using a circular motion.
b. Let the skin dry before injecting.

• Do not blow on the injection site or touch it again before giving the injection.

Figure G

8. Remove the cap

a. Hold the pre-filled syringe body with one hand.
Gently pull off the cap with the other hand.

• Do not remove the cap until you are ready to administer the injection

• Do not touch the needle. This could result in a needlestick injury

• Do not re-cap the pre-filled syringe. Immediately dispose of the cap in a sharps disposal container. Figure H

• It is normal to see a few drops of liquid coming out from the needle.

9. Insert the pre-filled syringe into the injection site

a. With one hand, gently pinch the skin to create
a skin fold at the injection site.
b. Holding the pre-filled syringe by the body, insert the
needle completely into the skin fold
OR
at a 45-degree angle with a quick motion,
like throwing a dart.
Figure I

10. Administer the injection

a. Once the needle is inserted, release the pinched skin.
b. Slowly and completely push the plunger down until all the liquid is injected and the syringe is empty.

• Do not change the position of the pre-filled syringe once the injection has started.

Figure J

11. Remove the pre-filled syringe from the injection site and

take care of the injection site
a. Once the pre-filled syringe is empty, remove it from the skin using the same angle as when it was inserted.
b. Treat the injection site by gently pressing a cotton ball or gauze pad over it without rubbing. Apply a plaster if needed. Bleeding may occur.

• Do not reuse the pre-filled syringe.
• Do not touch the needle or cover it with the cap.
• Do not rub the injection site. Figure K Figure K

12. Disposal of the pre-filled syringe

• Do not recap the pre-filled syringe. a. Dispose of the used pre-filled syringe in a special container for sharp objects, as instructed by your doctor, pharmacist, or nurse. b. The alcohol swab and packaging can be disposed of in household waste.
• Always keep the pre-filled syringe and the special sharps disposal container out of sight and reach of children.

Figure L
Figure L
Yuflyma pre-filled syringe with needle safety device

Figure A

1. Prepare the injection materials

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled syringe from the box stored in the refrigerator.

• When removing the pre-filled syringe from the box, hold it by the barrel. Do not touch the plunger. c. Make sure you have the following materials:
  • Pre-filled syringe
  • Alcohol swab

Not included in the box:

• Cotton ball or gauze pad
• Adhesive bandage
• Sharps disposal container

2. Inspect the prefilled syringe

a. Make sure you have the correct medicine (Yuflyma) and correct dosage.
b. Look at the prefilled syringe and make sure it is not cracked or damaged.
c. Check the expiry date on the label of the prefilled syringe.
Do not use the prefilled syringe if:

• it is cracked or damaged
• the expiry date has passed
• it has fallen on a hard surface. Figure B

3. Inspect the medicine

a. Look at the medicine to make sure the liquid is
clear, colourless to light brown, and free from particles.

• Do not use the pre-filled syringe if the liquid is: discoloured (yellow or dark brown), cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

4. Wait 15-30 minutes

15 - 30
minutes
a. Let the prefilled syringe sit at room temperature for
15-30 minutes to allow it to warm up.

• Do not heat the prefilled syringe using heat sources such as hot water or microwave.

Figure D

5. Choose an appropriate injection site

a. You may administer the injection:

• on the front of the thigh
• on the abdomen, except for the area within 5 cm of the navel
• on the outer area of the upper arm (ONLY if you are a person assisting the patient).
  • Do not administer the injection into skin areas within 5 cm of your navel or into any area that is red, hard, tender, damaged, bruised, or scarred.
  • If you have psoriasis, do not administer the injection into any thickened, red, or scaly patches or on any skin lesions. ONLY for the person assisting the patient Self-injection and injection by b. Rotate the injection site each time an injection is administered. Each new injection site must be at least 3 cm away from the previous injection site. an assistant

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol wipe using a
circular motion.
b. Allow the skin to dry before injecting.

• Do not blow on the injection site or touch it again before administering the injection.

Figure G

8. Remove the cap

a. Hold the pre-filled syringe body with one hand. Gently pull off the cap with the other hand.

• Do not remove the cap until you are ready to administer the injection.
• Do not touch the needle. This could result in a needle-stick injury.
• Do not re-cap the pre-filled syringe. Immediately dispose of the cap in a sharps disposal container.
• It is normal to see a few drops of liquid at the needle tip. Figure H

9. Insert the pre-filled syringe into the injection site

a. With one hand, gently pinch the skin to create a skin fold at the injection site.
b. Holding the pre-filled syringe by the body, insert the needle completely into the skin fold at a 45-degree angle, using a quick, dart-like motion.
OR
Figure I

10. Administer the injection

a. Once the needle is inserted, release the
pinched skin.
b. Slowly and completely push the plunger down
until all the liquid is injected and the
syringe is empty.

• Do not change the position of the pre-filled syringe once the injection has started.

Figure J

11. Remove the prefilled syringe from the injection site and care for the injection site

a. When the prefilled syringe is empty, slowly lift your thumb from the plunger until the needle is completely covered by the needle safety device.
b. Treat the injection site by gently pressing, without rubbing, a cotton ball or gauze pad over the site and, if necessary, applying an adhesive bandage. Bleeding may occur.

• Do not reuse the prefilled syringe.
• Do not rub the injection site

Figure K

12. Disposal of the pre-filled syringe

a. Immediately dispose of the used pre-filled syringe in a special container for the disposal of sharp objects, as instructed by your doctor, nurse, or pharmacist.
b. The alcohol swab and packaging may be placed in household waste.

• Always keep the pre-filled syringe and the special container for disposal of sharp objects out of sight and reach of children.

Figure L

Patient information leaflet

Yuflyma 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 also provide you with a Patient Reminder Card containing important safety information that you must know before and during treatment with Yuflyma. Keep the Patient Reminder Card with you throughout your treatment and for 4 months after your last injection of Yuflyma.
• 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 they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Yuflyma is and what it is used for

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

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Enthesitis-related arthritis
• Ankylosing spondylitis
• Non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic evidence of ankylosing spondylitis)
• Psoriatic arthritis
• Plaque psoriasis
• Hidradenitis suppurativa
• Crohn’s disease
• Ulcerative colitis
• Non-infectious uveitis

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

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Yuflyma is used for the treatment of moderate to severe rheumatoid arthritis in adults. You may have first been treated with other disease-modifying drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be given to you.
Yuflyma may also be used for the treatment of severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Yuflyma can slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Yuflyma should be used in combination with methotrexate or alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints.
Yuflyma is used for the treatment of polyarticular juvenile idiopathic arthritis in patients aged 2 years and older. You may have first been treated with other disease-modifying drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be given to you.
Your doctor will decide whether Yuflyma should be used in combination 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.
Yuflyma is used to treat enthesitis-related arthritis in patients aged 6 years and older. You may have first been treated with other disease-modifying drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be given to you.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis are inflammatory diseases of the spine.
Yuflyma is used to treat severe ankylosing spondylitis and non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic evidence of ankylosing spondylitis) in adults. Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be given to you.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease usually associated with psoriasis.
Yuflyma is used to treat psoriatic arthritis in adults. Yuflyma can slow down joint damage caused by the disease and may help you move more freely. Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be given to you.

Plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crack, thicken, or lift from the nail bed, which can be painful.
Yuflyma is used to treat:

• moderate to severe chronic plaque psoriasis in adults, and
• severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapy have not worked optimally or are not suitable.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful lumps and abscesses (cysts) that can 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.
Yuflyma is used to treat:

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

Yuflyma can reduce the number of lumps and abscesses caused by the disease and the pain often associated with it. Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be given to you.

Crohn’s disease
Crohn’s disease is an inflammatory disease of the gastrointestinal tract. Yuflyma is used to treat:

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

Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be given to you.

Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the large intestine.
Yuflyma is used to treat:

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

Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be given to you.

Non-infectious uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. Yuflyma is used to treat:

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

This inflammation can lead to reduced vision and/or the presence of floating bodies in the eye (black spots or thin lines moving across the visual field). Yuflyma works by reducing this inflammation.
Other medicines may be used initially. If you do not respond adequately to these medicines, Yuflyma will be given to you.

2. What you should know before using Yuflyma

Do not use Yuflyma:

• if you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform 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 Yuflyma.
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not take Yuflyma 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 in a part of the body (e.g., leg ulcers), consult your doctor before starting treatment with Yuflyma. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Yuflyma. This risk may increase if you have lung problems. These infections can be serious and may include:
• tuberculosis
• infections caused by viruses, fungi, parasites, or bacteria
• severe blood infection (sepsis)

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you experience symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise you to temporarily stop taking Yuflyma.

• Inform your doctor if you live or travel to regions where fungal infections are common (e.g., histoplasmosis, coccidioidomycosis, or blastomycosis).

• Inform your doctor if you have had recurring infections or if you have other conditions that increase the risk of infection.

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

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or if you have been in contact with someone who had tuberculosis. You must not take Yuflyma if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Yuflyma, your doctor will need to check for signs and symptoms of tuberculosis before starting treatment with Yuflyma. This will involve a detailed medical evaluation including your medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may occur during treatment even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections appear during or after treatment.

Hepatitis B

• Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active hepatitis B infection, or if you think you may be at risk of contracting hepatitis B.
• Your doctor should test you for hepatitis B virus infection. In HBV carriers, taking Yuflyma may cause the virus to reactivate.
• 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 may be life-threatening.

Surgery or dental procedures

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

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the protective covering around nerves, such as multiple sclerosis), your doctor will decide whether you should start or continue treatment with Yuflyma. 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 may cause infections and must not be administered during treatment with Yuflyma.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Yuflyma.
• If you have taken Yuflyma during pregnancy, the baby may have an increased risk of infection for up to approximately 5 months after the last dose of Yuflyma received during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Yuflyma during pregnancy, so they can determine when the baby should receive any vaccinations. For further information on vaccinations, see the section "Warnings and precautions".

Heart failure

• If you have mild heart failure and are being treated with Yuflyma, your doctor should carefully monitor your heart condition. It is important to inform your doctor if you have or have had serious heart problems in the past. 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. Your doctor will decide whether Yuflyma can still be used.

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

• Very rarely, certain types of tumors have occurred in patients, both children and adults, treated with Yuflyma or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Yuflyma, your risk of developing lymphomas, leukemia, or other tumors may increase. In rare cases, a rare and serious type of lymphoma has been observed in patients treated with Yuflyma. Some of these patients were also receiving azathioprine or 6-mercaptopurine.
• Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Yuflyma.
• Cases of non-melanoma skin cancer have been observed in patients taking Yuflyma.
• If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
• Cases of tumors, other than lymphoma, have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF is appropriate.

Autoimmune disease

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

Children and adolescents

• Vaccinations: if possible, children should have received all recommended vaccinations before starting Yuflyma.

Other medicines and Yuflyma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Do not use Yuflyma with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept.

Yuflyma may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

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

Driving and using machines
Yuflyma may have a minor influence on your ability to drive, ride a bicycle, or use machinery.
After taking Yuflyma, you may experience vision disturbances or a sensation that your surroundings are spinning.
Yuflyma contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL dose, i.e., essentially “sodium-free”.

3. How to use Yuflyma

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

Method and route of administration
Yuflyma is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to administer Yuflyma are described in section 7 “Instructions for use”.
If you use more Yuflyma than you should
If you accidentally inject Yuflyma more often than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken an excess dose. Always keep the medicine packaging, even if empty.
If you forget to use Yuflyma
If you forget to give an injection, administer the next dose of Yuflyma as soon as you remember. After that, continue with your regular dosing schedule as prescribed.
If you stop using Yuflyma
The decision to discontinue treatment with Yuflyma should be discussed with your doctor. Symptoms may return if you stop using Yuflyma.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Immediately inform your doctor if you notice any of the following reactions:

• severe rash, hives, or other signs of allergic reaction
• swelling of the face, hands, or feet
• difficulty breathing, difficulty swallowing
• shortness of breath during exertion or when lying down, or swollen feet

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

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

The symptoms described above may be signs of the following side effects, which have been observed with Yuflyma.

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

• reactions at the injection site (including pain, swelling, redness, or itching)
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal 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 cold sores)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumours
• skin tumour
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• sicca syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• cracking of fingernails and toenails
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• oedema (fluid accumulation)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• impaired wound healing

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections occurring when immune defences are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• tumour
• lymphatic system tumour
• melanoma
• immune system disorders affecting lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shaking)
• neuropathy (nervous system disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling of the ankles
• heart attack
• aneurysm (a sac in the wall of a major artery), vein inflammation and clot, blockage of a blood vessel
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of an artery in the lung)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis (inflammation of the pancreas causing severe abdominal and back pain)
• difficulty swallowing
• facial oedema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukaemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scarring of the lungs)
• intestinal perforation (a hole in the intestine)
• hepatitis
• 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 oedema (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (itchy red-purple skin rash)

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

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

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

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (a liver-related blood test)

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

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. You can 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 Yuflyma

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

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled pen of Yuflyma may be stored at room temperature (up to 25°C) for a maximum of 31 days; ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pen must be used within 31 days 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 by which the pen must be discarded.

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

6. Package contents and other information

What Yuflyma contains
The active substance is adalimumab.
The other components are acetic acid, sodium acetate trihydrate, glycine, polysorbate 80, and water for
injections.

Description of the appearance of Yuflyma pre-filled pen and contents of the package
Yuflyma 40 mg solution for injection in pre-filled pen is supplied as a sterile solution containing 40 mg of
adalimumab dissolved in 0.4 mL of solution.
The Yuflyma pre-filled pen is a single-use injection system with automatic needle functions. On each side of the pen there is a viewing window through which the Yuflyma solution inside the pen can be seen.
Yuflyma pre-filled pen is available in packages containing 1, 2, 4, and 6 pre-filled pens. The package containing 1 pre-filled pen is supplied with 2 alcohol swabs (1 spare). In packages containing 2, 4, and 6 pre-filled pens, each pre-filled pen is supplied with 1 alcohol swab.
Not all pack sizes may be marketed.
Yuflyma may be available as a pre-filled syringe and/or pre-filled pen.

Marketing Authorization Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles
06410, Biot
France
Nuvisan GmbH
Wegenerstraße 13
89231 Neu-Ulm
Germany
Midas Pharma GmbH
Rheinstr. 49
55218 Ingelheim
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès
Barcelona
Spain

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

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: +32 1528 7418 Tel.: +36 1 231 0493

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Tel.: +36 1 231 0493 Tél/Tel: +32 1528 7418

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Denmark ApS Mint Health Ltd.
Tlf: +45 35352989 Tel: +356 2093 9800
[email protected]

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel.: +49 (0)30 346494150 Tel: +31 20 888 7300
[email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Norway AS
Tel: +36 1 231 0493 [email protected]

España Österreich
Kern Pharma, S.L. Astro-Pharma GmbH
Tel: +34 93 700 2525 Tel: +43 1 97 99 860

Ελλάδα Polska
VIANEX S.A. Celltrion Healthcare Hungary Kft.
Tel: +30 210 8009111 Tel.: +36 1 231 0493

France Portugal
Celltrion Healthcare France SAS CELLTRION PORTUGAL, UNIPESSOAL LDA
Tél.: +33 (0)1 71 25 27 00 Tel: +351 21 936 8542

Hrvatska România
Oktal Pharma d.o.o. Celltrion Healthcare Hungary Kft.
Tel: +385 1 6595 777 Tel: +36 1 231 0493

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493 Tel: +36 1 231 0493

Italia Suomi/Finland
Celltrion Healthcare Italy S.r.l. Celltrion Healthcare Finland Oy.
Tel: +39 02 47927040 Puh/Tel: +358 29 170 7755

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Sweden AB
Tel: +357 22741741 [email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for use

• The following instructions explain how to perform a subcutaneous self-injection of Yuflyma using the pre-filled pen. First, read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with instructions on the technique of self-injection.
• Do not administer the injection by yourself until you are certain you understand how to prepare and perform the injection.
• After proper training, the injection may be given by you or by another person, such as a family member or friend.
• Use each pre-filled pen only once.

Yuflyma Pre-filled Pen

Figure A
Do not use the pre-filled pen if:

• it is cracked or damaged.
• the expiry date has passed.
• it has been dropped on a hard surface.

Do not remove the cap until you are ready to perform the injection. Keep Yuflyma out of the
reach of children.

1. Prepare the injection materials

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled pen from the box stored in the refrigerator.
c. Make sure you have the following materials:

• Pre-filled pen
• 1 alcohol swab

Not included in the box:

• Cotton ball or gauze pad
• Adhesive bandage
• Sharps disposal container

2. Inspect the pre-filled pen

a. Make sure you have the correct medicine (Yuflyma) and correct dosage
b. Look at the pre-filled pen and make sure it is not cracked or
damaged
c. Check the expiry date on the label of the pre-filled pen

Do not use the pre-filled pen if:

• it is cracked or damaged
• the expiry date has passed
• it has fallen on a hard surface

Figure B

3. Inspect the medicine.

a. Look through the viewing window and make sure the liquid is
clear, colourless to light brown, and free from particles.

• Do not use the pre-filled pen if the liquid has changed colour (yellow or dark brown), is cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

4. Wait 15-30 minutes

15 – 30
minutes a. Let the pre-filled pen sit at room temperature for
15-30 minutes to warm up.

• Do not heat the pre-filled pen using heat sources such as hot water or microwave.

Figure D

5. Choose an appropriate injection site

a. You may administer the injection:

• in the front of the thigh.

• in the abdomen, except for the area within 5 cm around the navel.

• on the outer area of the upper arm (ONLY if you are a person assisting the patient).

  • Do not administer the injection in skin areas within 5 cm of your navel or in any area that is red, hard, tender, damaged, bruised, or scarred.
  • If you have psoriasis, do not administer the injection into any raised, thickened, red, scaly patches or skin lesions.
  • Do not administer the injection through clothing. Figure A

b. Rotate the injection site each time you administer an injection. Each new injection site should be at least 3 cm away from the previous injection site.
Figure E

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol swab using a circular motion.
b. Allow the skin to dry before injecting.

• Do not blow on the injection site or touch it again before injecting.

Figure G

8. Remove the cap

a. With one hand, hold the pre-filled pen by the body with
the cap still attached. Gently pull off the cap
using the other hand.
Cap

• Do not remove the cap until you are ready to perform the injection.

• Do not touch the needle or the needle cap. Doing so
  could result in a needlestick injury.

• Do not reattach the cap to the pre-filled pen. Immediately dispose of the cap in a sharps disposal container.

• It is normal to see a few drops of liquid Figure H leaking from the needle

9. Place the pre-filled pen at the injection site.

a. Hold the pre-filled pen so that you can see the window.
b. Without pinching or stretching the skin, place the pre-filled pen at the injection site at a 90-degree angle.
OR
Figure I

10. Administer the injection

1 a. Press the pre-filled pen firmly against the skin.
When the injection starts, you will hear a first distinct, loud click, and the
click
blue plunger will begin moving into the viewing window.
b. Continue pressing the pre-filled pen firmly against the skin until you hear a second distinct, loud click.
c. After hearing the second click, keep holding the pre-filled pen firmly against the skin and count slowly to 5 to ensure the full dose is delivered.

• Do not move the pre-filled pen once the injection has started. 2 clicks

2
click
Then, count slowly
to 5
Figure J

11. Remove the pre-filled pen from the injection site and

take care of the injection site
a. Look at the pre-filled pen and make sure that the blue plunger rod with the grey cap has fully advanced into the viewing window.
b. Remove the pre-filled pen from the skin.

• After removing the pre-filled pen from the injection site, the needle will automatically be covered. Do not re-cap the pen.
• If the viewing window has not turned completely blue or if medication is still being injected, this means you have not received a complete dose. Figure K

Contact your doctor immediately.

c. Treat the injection site by gently pressing, without rubbing, a cotton ball or gauze pad against it, and, if necessary, applying an adhesive bandage. Bleeding may occur.

• Do not reuse the pre-filled pen. Needle cap • Do not rub the injection site. needle cover

Figure L

12. Disposal of the pre-filled pen

a. Immediately dispose of the used pre-filled pen into a special container for sharp objects, as instructed by your doctor, nurse, or pharmacist.
b. The alcohol swab and packaging may be placed in household waste.

• Always keep the pre-filled pen and the special container for sharp objects out of sight and reach of children.

Figure M

Patient information leaflet

Yuflyma 80 mg solution for injection in pre-filled syringe

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

• Keep this leaflet. You may need to read it again.
• Your doctor will also provide you with a Patient Reminder Card, which contains important safety information you should know before and during treatment with Yuflyma. Keep the Patient Reminder Card with you during your treatment and for 4 months after your last injection of Yuflyma.
• 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, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Yuflyma is and what it is used for

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

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

The active substance in Yuflyma, adalimumab, is a human 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, Yuflyma reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Yuflyma is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other disease-modifying drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be administered to you.
Yuflyma may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Yuflyma can slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Yuflyma should be used with methotrexate or alone.

Plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which can be painful.
Yuflyma is used to treat moderate to severe chronic plaque psoriasis in adults.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic 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.
Yuflyma is used to treat:

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

Yuflyma can reduce the number of nodules and abscesses caused by the disease and the pain often associated with it. Other medicines may be used first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Crohn’s disease
Crohn’s disease is an inflammatory disease of the digestive tract. Yuflyma is used to treat:

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

Other medicines may be used first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the large intestine.
Yuflyma is used to treat:

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

Other medicines may be used first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Non-infectious uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. Yuflyma is used to treat:

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

This inflammation can lead to reduced vision and/or the presence of floating bodies in the eye (black spots or thin lines moving across the visual field). Yuflyma works by reducing this inflammation.
Other medicines may be used first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

2. What you should know before using Yuflyma

Do not use Yuflyma:

• if you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have active tuberculosis or other serious infections (see “Warnings and precautions”). It is important to inform 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 serious heart problems (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Yuflyma.
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not take Yuflyma 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 in one part of the body (e.g., leg ulcers), consult your doctor before starting treatment with Yuflyma. If you are in doubt, contact your doctor.
• You may be more likely to get infections while being treated with Yuflyma. This risk may increase if you have lung problems. These infections can be serious and may include:
• tuberculosis
• infections caused by viruses, fungi, parasites, or bacteria
• severe blood infection (sepsis)

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 instruct you to temporarily stop taking Yuflyma.

• Inform your doctor if you live in or travel to regions where fungal infections are common (e.g., histoplasmosis, coccidioidomycosis, or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other conditions that increase your risk of infection.
• If you are over 65 years old, you may be more prone to infections while taking Yuflyma. You and your doctor should pay special attention to signs of infection during treatment. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or if you have been in contact with someone who had tuberculosis. You must not take Yuflyma if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Yuflyma, your doctor will need to check for signs and symptoms of tuberculosis before starting treatment with Yuflyma. This will include a detailed medical evaluation including your medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may occur during treatment even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

• 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 should test you for hepatitis B virus infection. In HBV carriers, taking Yuflyma may cause reactivation of the virus.
• In rare cases, especially if the patient is also receiving other medications that suppress the immune system, reactivation of hepatitis B virus may be life-threatening.

Surgery or dental procedures

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

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the protective covering of nerves, such as multiple sclerosis), your doctor will decide whether to start or continue treatment with Yuflyma. 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 may cause infections and must not be administered during treatment with Yuflyma.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Yuflyma.
• If you have taken Yuflyma during pregnancy, the baby may have an increased risk of infection for up to approximately 5 months after the last dose received during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Yuflyma during pregnancy so they can determine when the baby should receive any vaccinations.

Heart failure

• If you have mild heart failure and are being treated with Yuflyma, your doctor must carefully monitor your heart condition. It is important to inform your doctor if you have or have had serious heart problems in the past. 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. Your doctor will decide whether Yuflyma can be used.

Fever, bruising, bleeding, or paleness

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

Tumors

• Very rarely, certain types of tumors have been observed in patients, both children and adults, treated with Yuflyma or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Yuflyma, your risk of developing lymphomas, leukemia, or other tumors may increase. In rare cases, a rare and serious type of lymphoma has been observed in patients treated with Yuflyma. Some of these patients were also receiving azathioprine or 6-mercaptopurine.
• Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Yuflyma.
• Cases of non-melanoma skin cancer have been observed in patients receiving Yuflyma.
• If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
• Cases of tumors 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 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 Yuflyma may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as persistent unexplained skin rash, fever, joint pain, or fatigue.

Children and adolescents

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

Other medicines and Yuflyma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Do not use Yuflyma with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Yuflyma may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

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

Driving and using machines
Yuflyma may have a slight effect on your ability to drive, ride a bicycle, or use machinery.
After taking Yuflyma, you may experience visual disturbances or a sensation that your surroundings are spinning.
Yuflyma contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e., essentially “sodium-free”.

3. How to use Yuflyma

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

Method and route of administration
Yuflyma is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to administer Yuflyma are described in section 7 “Instructions for use”.
If you use more Yuflyma than you should
If you accidentally inject Yuflyma more often than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken more of the medicine. Always keep the medicine packaging, even if empty.
If you forget to use Yuflyma
If you forget to give an injection, you should inject the next dose of Yuflyma as soon as you remember. After that, continue with your regular dosing schedule.
If you stop using Yuflyma
The decision to stop using Yuflyma should be discussed with your doctor. Symptoms may return if you stop using Yuflyma.
If you have any questions about the use of this medicine, ask 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 treatment. Side effects may occur up to 4 months after the last injection of Yuflyma.

Immediately inform your doctor if you notice any of the following reactions

• severe rash, hives or other signs of allergic reaction
• swelling of the face, hands, or feet
• difficulty breathing, difficulty swallowing
• shortness of breath during exertion or when lying down, or swollen feet

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

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating
• feeling weak/tired
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open sore that does not heal
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, paleness

The symptoms described above may be signs of the following side effects, which have been observed with Yuflyma.

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

• reactions at the injection site (including pain, swelling, redness, or itching)
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal 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 cold sores)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of dizziness or spinning)
• sensation of rapid heartbeat
• high blood pressure
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• cracking of fingernails and toenails
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• edema (fluid retention)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• impaired 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
• lymphatic system cancer
• melanoma
• disorders of the immune system affecting lungs, skin, and lymph nodes (commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shaking)
• neuropathy (nervous system disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling in the ankles
• heart attack
• aneurysm (a sac in the wall of a major artery), vein inflammation and clot, blood vessel blockage
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of an artery in the lung)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis (inflammation of the pancreas) causing severe abdominal and back pain
• difficulty swallowing
• facial edema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (lung scarring)
• intestinal perforation (a hole in the intestine)
• hepatitis
• 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 (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (itchy red-purple rash)

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

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

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

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (a liver-related blood test)

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

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can 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 Yuflyma

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

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled syringe with needle safety device of Yuflyma may be stored at room temperature (up to 25°C) for a maximum period of 31 days; ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 31 days or must be 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 after which the syringe must be discarded.

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

6. Package contents and other information

What Yuflyma contains
The active substance is adalimumab.
The other components are acetic acid, sodium acetate trihydrate, glycine, polysorbate 80, and water for
injections.

Description of the appearance of Yuflyma pre-filled syringe with needle safety device and
pack contents
Yuflyma 80 mg solution for injection in pre-filled syringe with needle safety device is supplied as a sterile solution containing 80 mg of adalimumab dissolved in 0.8 mL of solution.
The Yuflyma pre-filled syringe is a glass syringe containing a solution of adalimumab. The pack of 1 pre-filled syringe is supplied with 2 alcohol swabs (1 spare).
The Yuflyma pre-filled syringe is a glass syringe with needle protection containing a solution of adalimumab. The 1 pre-filled syringe with needle protection pack is supplied with 2 alcohol swabs (1 spare).
Yuflyma may be available as a pre-filled syringe and/or pre-filled pen.

Marketing Authorisation Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles
06410, Biot
France
Nuvisan GmbH
Wegenerstraße 13
89231 Neu-Ulm
Germany
Midas Pharma GmbH
Rheinstr. 49
55218 Ingelheim
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès
Barcelona
Spain

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

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: + 32 1528 7418 Tel.: +36 1 231 0493

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Teл.: +36 1 231 0493 Tél/Tel: + 32 1528 7418

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Hungary Kft. Mint Health Ltd.
Tlf: +36 1 231 0493 Tel: +356 2093 9800

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel.: +49 (0)30 346494150 Tel: + 31 20 888 7300
[email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tlf: +36 1 231 0493

España Österreich
Kern Pharma, S.L. Astro-Pharma GmbH
Tel: +34 93 700 2525 Tel: +43 1 97 99 860

Ελλάδα Polska
ΒΙΑΝΕΞ Α.Ε. Celltrion Healthcare Hungary Kft.
Τηλ: +30 210 8009111 Tel.: +36 1 231 0493

France Portugal
Celltrion Healthcare France SAS CELLTRION PORTUGAL, UNIPESSOAL LDA
Tél.: +33 (0)1 71 25 27 00 Tel: +351 21 936 8542

Hrvatska România
Oktal Pharma d.o.o. Celltrion Healthcare Hungary Kft.
Tel: +385 1 6595 777 Tel: +36 1 231 0493

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493 Tel: +36 1 231 0493

Italia Suomi/Finland
Celltrion Healthcare Italy S.r.l. Celltrion Healthcare Finland Oy.
Tel: +39 02 47927040 Puh/Tel: +358 29 170 7755

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Sweden AB
Τηλ: +357 22741741 [email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for use

• The following instructions explain how to perform a subcutaneous self-injection of Yuflyma using the pre-filled syringe. First, read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with instructions on the technique of self-injection.
• Do not administer the injection by yourself until you are sure you have understood how to prepare and perform the injection.
• After proper instruction, the injection may be given by you or by someone else, such as a family member or friend.
• Use each pre-filled syringe for only one injection.

Yuflyma Pre-filled Syringe

Before use     After use
Figure A

Do not use the pre-filled syringe if:

• it is cracked or damaged.
• the expiry date has been exceeded.
• it has fallen on a hard surface.
  Remove the needle cap only immediately before injection. Keep Yuflyma out of the sight and reach of children.

1. Prepare the injection materials

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled syringe from the box stored in the refrigerator.

• When removing the pre-filled syringe from the box, hold it by the barrel. Do not touch the plunger. c. Make sure you have the following materials:
  • Pre-filled syringe
  • Alcohol swab Not included in the package:
  • Cotton ball or gauze pad
  • Adhesive bandage
  • Sharps disposal container

2. Inspect the pre-filled syringe

a. Make sure you have the correct medicine (Yuflyma) and dose.
b. Look at the pre-filled syringe and ensure it is not cracked or damaged.
c. Check the expiry date on the label of the pre-filled syringe.

Do not use the pre-filled syringe if:

• it is cracked or damaged
• the expiry date has passed
• it has fallen onto a hard surface.

Figure B

3. Inspect the medicine

a. Look at the medicine to confirm that the liquid is
clear, colorless to light brown, and free of particles.

• Do not use the pre-filled syringe if the liquid is: discolored (yellow or dark brown), cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

4. Wait 15-30 minutes

a. Let the prefilled syringe sit at room temperature
15 - 30
for 15-30 minutes so it can warm up.
minutes

• Do not heat the prefilled syringe using heat sources such as hot water or microwave.

Figure D

5. Choose an appropriate injection site

a. You may administer the injection:

• on the front of the thigh

• on the abdomen, except for the area within 5 cm of the navel

• on the outer area of the upper arm (ONLY if you are a person assisting the patient).

  • Do not administer the injection in skin areas within 5 cm of your navel or in any area that is red, hard, tender, damaged, bruised, or scarred.
  • If you have psoriasis, do not administer the injection on any raised, thickened, red, scaly patches or on any skin lesions.
  • Do not administer the injection through clothing.

b. Rotate the injection site each time you give an injection. Each new injection site should be at least 3 cm away from the previous injection site.
Figure E

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol swab
using a circular motion.
b. Allow the skin to dry before injecting.

• Do not blow on the injection site or touch it again before administering the injection.

Figure G

8. Remove the cap

a. Hold the pre-filled syringe body with one hand.
Gently pull off the cap with the other hand.

• Do not remove the cap until you are ready to give the injection
• Do not touch the needle. This could result in a needlestick injury.
• Do not re-cap the pre-filled syringe. Immediately dispose of the cap in a sharps disposal container.
• It is normal to see a few drops of liquid coming out from the needle. Figure H

9. Insert the pre-filled syringe into the injection site

a. With one hand, gently pinch the skin to
create a skin fold at the injection site.
b. Holding the pre-filled syringe by the body,
insert the needle completely into the skin fold
at a 45-degree angle with a quick motion,
similar to throwing a dart.
OR

Figure I

10. Administer the injection

a. Once the needle is inserted, release the pinched skin.
b. Slowly and completely push the plunger down until all the liquid is injected and the syringe is empty.

• Do not change the position of the pre-filled syringe once the injection has started.

Figure J

11. Remove the prefilled syringe from the injection site

and take care of the injection site
a. Once the prefilled syringe has been emptied, remove it from the skin using the same angle as during insertion.
b. Treat the injection site by gently pressing a cotton ball or gauze pad over it without rubbing. If needed, apply an adhesive bandage. Bleeding may occur.

• Do not reuse the prefilled syringe.
• Do not touch the needle and do not cover it with the cap.
• Do not rub the injection site. Figure K

12. Disposal of the pre-filled syringe

• Do not re-cover the pre-filled syringe with the cap. a. Dispose of the used pre-filled syringe in a special sharps disposal container, as instructed by your doctor, pharmacist, or nurse. b. The alcohol swab and packaging may be placed in household waste.
• Always keep the pre-filled syringe and the sharps disposal container out of sight and reach of children.

Figure L
Yuflyma pre-filled syringe with needle safety device

Figure A

1. Prepare the injection materials

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled syringe from the box stored in the refrigerator.

• When removing the pre-filled syringe from the box, hold it by the barrel. Do not touch the plunger. c. Make sure you have the following materials:
  • Pre-filled syringe
  • Alcohol swab

Not included in the box:

• Cotton ball or gauze pad
• Adhesive bandage
• Sharps disposal container

2. Inspect the prefilled syringe

a. Make sure you have the correct medicine (Yuflyma) and dose.
b. Look at the prefilled syringe and check that it is not cracked or damaged.
c. Check the expiry date on the label of the prefilled syringe.
Do not use the prefilled syringe if:

• it is cracked or damaged
• the expiry date has passed
• it has fallen on a hard surface.

Figure B

3. Inspect the medicine

a. Look at the medicine to confirm that the liquid is
clear, colorless to light brown, and free from particles.

• Do not use the pre-filled syringe if the liquid is: discolored (yellow or dark brown), cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

15 - 30 4. Wait 15-30 minutes
minutes
a. Leave the pre-filled syringe at room temperature for
15-30 minutes to allow it to warm up.

• Do not heat the pre-filled syringe using heat sources such as hot water or a microwave.

Figure D

5. Choose an appropriate injection site

a. You may administer the injection:

• on the front of the thigh
• on the abdomen, except for the area within 5 cm of the navel
• on the outer area of the upper arm (ONLY if you are a person assisting the patient).
  • Do not administer the injection into skin areas within 5 cm of your navel or into areas that are red, hard, tender, damaged, bruised, or where scars are present.
  • If you have psoriasis, do not administer the injection into any thickened, red, or scaly patches or on any skin lesions.
  • Do not administer the injection through clothing. ONLY for the person who

b. Rotate the injection site each time
assisting the patient
administers an injection.
Self-injection and injection Each new injection site must be at least 3 cm away
by an assistant from the previous injection site used.
Figure E

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol swab, using a circular motion.
b. Allow the skin to dry before injecting.

• Do not blow on the injection site or touch it again before administering the injection.

8. Remove the cap

a. Hold the pre-filled syringe body with one hand.
Gently pull off the cap with the other hand.

• Do not remove the cap until you are ready to give the injection
• Do not touch the needle. This could result in a needle-stick injury.
• Do not re-cap the pre-filled syringe. Immediately dispose of the cap in a sharps disposal container.
• It is normal to see a few drops of liquid coming out from the needle. Figure H

9. Insert the pre-filled syringe into the injection site

a. With one hand, gently pinch the skin to create a skin fold at the injection site.
b. Holding the pre-filled syringe by the body, insert the needle completely into the skin fold at a 45-degree angle, using a quick motion, as if throwing a dart.
OR
Figure I

10. Administer the injection

a. Once the needle is inserted, release the
pinched skin.
b. Slowly and completely push the plunger down
until all the liquid is injected and the
syringe is empty.

• Do not change the position of the pre-filled syringe once the injection has started.

11. Remove the pre-filled syringe from the injection site

and take care of the injection site
a. When the pre-filled syringe is empty,
slowly lift your thumb from the
plunger until the needle is completely
covered by the needle safety device.
b. Treat the injection site by gently pressing,
without rubbing, a cotton ball or
gauze pad over the site, and, if necessary,
apply an adhesive bandage. Bleeding may occur.

• Do not reuse the pre-filled syringe.
• Do not rub the injection site Figure K

12. Disposal of the pre-filled syringe

a. Immediately dispose of the used pre-filled syringe
in a special container for the disposal of
sharps, as instructed by your doctor,
nurse or
pharmacist.
b. The alcohol swab and packaging can be
placed in household waste.

• Always keep the pre-filled syringe and the special sharps disposal container out of sight and reach of children.

Figure L

Patient information leaflet

Yuflyma 80 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 also provide you with a Patient Reminder Card, which contains important safety information you should know before and during treatment with Yuflyma. Keep the Patient Reminder Card with you throughout your treatment and for 4 months after your last injection of Yuflyma.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Yuflyma is and what it is used for

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

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

The active substance in Yuflyma, adalimumab, is a human 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, Yuflyma reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Yuflyma is used to treat moderate to severe rheumatoid arthritis in adults. You may first be given other disease-modifying drugs, such as methotrexate. If you do not respond adequately to these medicines, Yuflyma will be administered to you.
Yuflyma may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Yuflyma can slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Yuflyma should be used with methotrexate or alone.

Plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift away from the nail bed, which can be painful.
Yuflyma is used to treat moderate to severe chronic plaque psoriasis in adults.

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

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

Yuflyma can reduce the number of nodules and abscesses caused by the disease and the pain often associated with it. Other medicines may be tried first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Crohn’s disease
Crohn’s disease is an inflammatory disease of the gastrointestinal tract. Yuflyma is used to treat:

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

Other medicines may be tried first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Ulcerative colitis
Ulcerative colitis is an inflammatory disease of the large intestine.
Yuflyma is used to treat:

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

Other medicines may be tried first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

Non-infectious uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. Yuflyma is used to treat:

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

This inflammation can lead to reduced vision and/or the presence of floating bodies in the eye (black spots or thin lines moving across the visual field). Yuflyma works by reducing this inflammation.
Other medicines may be tried first. If you do not respond adequately to these medicines, Yuflyma will be administered to you.

2. What you should know before using Yuflyma

Do not use Yuflyma:

• if you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have active tuberculosis or other serious infections (see “Warnings and precautions”). It is important to inform your doctor if you have signs or symptoms of infection, for example, fever, wounds, feeling of fatigue, 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 serious heart problems (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Yuflyma.
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or skin rash, do not take Yuflyma 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 in a part of the body (for example, leg ulcers), consult your doctor before starting treatment with Yuflyma. If you have any doubts, contact your doctor.
• You may be more likely to get infections while being treated with Yuflyma. This risk may increase if you have lung problems. These infections can be serious and may include:
• tuberculosis
• infections caused by viruses, fungi, parasites or bacteria
• severe blood infection (sepsis)

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 of fatigue or dental problems. Your doctor may instruct you to temporarily stop Yuflyma.

• Inform your doctor if you live or travel in areas where fungal infections are common (for example, histoplasmosis, coccidioidomycosis or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other conditions that increase the risk of infection.
• If you are over 65 years old, you may be more prone to infections while taking Yuflyma. You and your doctor should pay particular attention to signs of infection during treatment with Yuflyma. It is important to inform your doctor if you develop symptoms of infections such as fever, wounds, feeling of fatigue or dental problems.

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or if you have been in contact with someone who had tuberculosis. You must not take Yuflyma if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Yuflyma, your doctor will check for signs or symptoms typical of tuberculosis before starting therapy with Yuflyma. This will involve a detailed medical evaluation including your medical history and appropriate clinical tests (for example, a chest X-ray and tuberculin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may occur during therapy even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (for example, persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

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

Surgery or dental procedures

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

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the insulating layer around nerves, such as multiple sclerosis), your doctor will decide whether to start or continue treatment with Yuflyma. 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 may cause infections and must not be administered during treatment with Yuflyma.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Yuflyma.
• If you have taken Yuflyma during pregnancy, your baby may have an increased risk of infection for up to approximately 5 months after your last dose of Yuflyma during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Yuflyma during pregnancy, so they can determine when your baby should receive any vaccinations.

Heart failure

• If you have mild heart failure and are being treated with Yuflyma, your doctor must carefully evaluate and monitor your heart condition. It is important to inform your doctor if you have or have had serious heart problems in the past. If new symptoms of heart failure appear or if existing symptoms worsen (for example, shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether Yuflyma can be used.

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

• Very rarely, certain types of tumors have occurred in patients, both children and adults, treated with Yuflyma or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Yuflyma, your risk of developing lymphomas, leukemia or other tumors may increase. In rare cases, a rare and serious type of lymphoma has been observed in patients treated with Yuflyma. Some of these patients were also receiving treatment with azathioprine or 6-mercaptopurine.
• Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Yuflyma.
• Cases of non-melanoma skin cancer have been observed in patients taking Yuflyma.
• If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
• There have been cases of tumors, other than lymphoma, in patients with a specific type of lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF is appropriate.

Autoimmune disease

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

Children and adolescents

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

Other medicines and Yuflyma
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Do not use Yuflyma with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Yuflyma may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (for example, sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

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

Driving and using machines
Yuflyma may have a slight effect on your ability to drive, ride a bicycle or use machinery.
After taking Yuflyma, you may experience visual disturbances or a sensation that your surroundings are spinning.
Yuflyma contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e. essentially “sodium-free”.

3. How to use Yuflyma

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

Method and route of administration
Yuflyma is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to administer Yuflyma are described in section 7 “Instructions for use”.
If you use more Yuflyma than you should
If you accidentally inject Yuflyma more often than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken an excess dose. Always keep the medicine packaging, even if it is empty.
If you forget to use Yuflyma
If you forget to give an injection, you should administer the next dose of Yuflyma as soon as you remember. After that, continue with your regular dosing schedule as prescribed.
If you stop using Yuflyma
The decision to stop using Yuflyma should be discussed with your doctor. Symptoms may return if you stop using Yuflyma.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Contact your doctor immediately if you notice any of the following reactions

• severe rash, hives or other signs of allergic reaction
• swelling of the face, hands or feet
• difficulty breathing, difficulty swallowing
• shortness of breath during exertion or when lying down, or swollen feet

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

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

The symptoms described above may be signs of the following side effects, which have been observed with Yuflyma.

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

• reactions at the injection site (including pain, swelling, redness or itching)
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal 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 cold sores)
• reproductive tract infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumours
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory disturbances such as tingling, stabbing sensations or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• nail breakage in fingers and toes
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• oedema (fluid retention)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• impaired wound healing

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections occurring when immune defences are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• cancer
• lymphatic system cancer
• melanoma
• immune system disorders affecting lungs, skin and lymph nodes (commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shaking)
• neuropathy (nervous system disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling in the ankles
• heart attack
• aneurysm (a sac in the wall of a major artery), vein inflammation and clot, blockage of a blood vessel
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of an artery in the lung)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis (inflammation causing severe abdominal and back pain)
• difficulty swallowing
• facial oedema (swelling of the face)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukaemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scarring of the lungs)
• intestinal perforation (a hole in the intestine)
• hepatitis
• 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 oedema (swelling of the face) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (itchy red-violet rash)

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

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

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

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (a blood test related to liver function)

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

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 Yuflyma

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

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled pen of Yuflyma may be stored at room temperature (up to 25°C) for a maximum period of 31 days; ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pen must be used within 31 days 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 by which the pen must be discarded.

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

6. Package contents and other information

What Yuflyma contains
The active substance is adalimumab.
The other components are acetic acid, sodium acetate trihydrate, glycine, polysorbate 80, and water for
injections.

Description of the appearance of Yuflyma pre-filled pen and contents of the pack
Yuflyma 80 mg solution for injection in pre-filled pen is supplied as a sterile solution containing 80 mg of
adalimumab dissolved in 0.8 mL of solution.
The Yuflyma pre-filled pen is a single-use injection system with automatic functions, equipped with a needle. On
each side of the pen there is a window through which the Yuflyma solution inside the pen can be seen.

The Yuflyma pre-filled pen is available in packs containing:

• 1 pre-filled pen for patient use with 2 alcohol swabs (1 spare)
• 3 pre-filled pens for patient use with 4 alcohol swabs (1 spare)

Not all pack sizes may be marketed.
Yuflyma may be available as a pre-filled syringe and/or pre-filled pen.

Marketing Authorization Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles
06410, Biot
France
Nuvisan GmbH
Wegenerstraße 13
89231 Neu-Ulm
Germany
Midas Pharma GmbH
Rheinstr. 49
55218 Ingelheim
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès
Barcelona
Spain

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

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: + 32 1528 7418 Tel.: +36 1 231 0493

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Teл.: +36 1 231 0493 Tél/Tel: + 32 1528 7418

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Denmark ApS Mint Health Ltd.
Tlf: +45 35352989 Tel: +356 2093 9800
[email protected]

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel.: +49 (0)30 346494150 Tel: + 31 20 888 7300
[email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Norway AS
Tel: +36 1 231 0493 [email protected]

España Österreich
Kern Pharma, S.L. Astro-Pharma GmbH
Tel: +34 93 700 2525 Tel: +43 1 97 99 860

Ελλάδα Polska
ΒΙΑΝΕΞ Α.Ε. Celltrion Healthcare Hungary Kft.
Τηλ: +30 210 8009111 Tel.: +36 1 231 0493

France Portugal
Celltrion Healthcare France SAS CELLTRION PORTUGAL, UNIPESSOAL LDA
Tél.: +33 (0)1 71 25 27 00 Tel: +351 21 936 8542

Hrvatska România
Oktal Pharma d.o.o. Celltrion Healthcare Hungary Kft.
Tel: +385 1 6595 777 Tel. +36 1 231 0493

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493 Tel: +36 1 231 0493

Italia Suomi/Finland
Celltrion Healthcare Italy S.r.l. Celltrion Healthcare Finland Oy.
Tel: +39 02 47927040 Puh/Tel: +358 29 170 7755

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Sweden AB
Τηλ: +357 22741741 [email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for use

• The following instructions explain how to perform a subcutaneous self-injection of Yuflyma using the pre-filled pen. First, carefully read these instructions and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with instructions on the technique of self-injection.
• Do not administer the injection by yourself until you are certain you understand how to prepare and perform the injection.
• After receiving adequate instruction, the injection may be given by you or by another person, such as a family member or friend.
• Use each pre-filled pen only once.

Yuflyma Pre-filled Pen

Figure A
Do not use the pre-filled pen if:

• it is cracked or damaged.
• the expiry date has been exceeded.
• it has fallen onto a hard surface.

Do not remove the cap until you are ready to perform the injection. Keep Yuflyma out of the reach of children.

1. Prepare the injection materials

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled pen from the box stored in the refrigerator.
c. Make sure you have the following materials:

• Pre-filled pen
• 1 alcohol swab

Not included in the box:

• Cotton ball or gauze pad
• Adhesive bandage
• Sharps disposal container

2. Inspect the prefilled pen

a. Make sure you have the correct medicine (Yuflyma) and dose
b. Look at the prefilled pen and check that it is not cracked or
damaged
c. Check the expiry date on the label of the prefilled pen

Do not use the prefilled pen if:

• it is cracked or damaged
• the expiry date has passed
• it has been dropped on a hard surface

Figure B

3. Inspect the medicine.

a. Look through the viewing window and make sure the liquid is
clear, colorless to light brown, and free from particles.

• Do not use the pre-filled pen if the liquid is discolored (yellow or dark brown), cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

4. Wait 15-30 minutes

15 – 30
minutes a. Leave the prefilled pen at room temperature for
15-30 minutes to allow it to warm up.

• Do not warm the prefilled pen using heat sources such as hot water or microwave.

Figure D

5. Choose an appropriate injection site

a. You may administer the injection:

• in the front of the thigh
• in the abdomen, except for the area within 5 cm of the navel
• on the outer area of the upper arm (ONLY if you are a person assisting the patient).
  • Do not administer the injection in skin areas within 5 cm of your navel or in areas that are red, hard, tender, damaged, bruised, or scarred.
  • If you have psoriasis, do not inject into any raised, thickened, red, scaly patches or any skin lesions.
  • Do not inject through clothing. Figure B

b. Rotate the injection site each time you
administer an injection. Each new injection site should
be at least 3 cm away from the previous injection site.
Figure E

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol swab using a circular motion.
b. Allow the skin to dry before injecting.

• Do not blow on or touch the injection site again before administering the injection.

Figure C
Figure G

8. Remove the cap

a. Hold the pre-filled pen in one hand by the body with
the cap still attached. Gently pull off the cap with the other hand.
Cap

• Do not remove the cap until you are ready copriago to perform the injection.

• Do not touch the needle or the needle cap. Doing so
  could result in a needle-stick injury.

• Do not re-cap the pre-filled pen. Immediately dispose of the cap in a sharps disposal container.

• It is normal to see a few drops of liquid Figure H leaking from the needle

9. Position the prefilled pen at the injection site.

a. Hold the prefilled pen so that you can see the
window.
b. Without pressing or pulling on the skin, place the
prefilled pen at the injection site at a 90-degree
angle.
OR
Figure I

10. Perform the injection

a. Press the pre-filled pen firmly against the skin.
When the injection starts, you will hear a first loud and clear click, and the
blue plunger will begin to move across the viewing window.
1
click

b. Continue pressing the pre-filled pen firmly against the skin until you hear a second loud and clear click.

c. After hearing the second click, keep holding the pre-filled pen firmly against the skin and slowly count to 5 to ensure the full dose is injected.
2 • Do not change the position of the pre-filled pen once the injection has started.
2
click
Then, slowly count
to 5
Figure J

11. Remove the pre-filled pen from the injection site and

attend to the injection site
a. Look at the pre-filled pen and make sure that the blue plunger rod with the grey cap completely fills the viewing window.
b. Remove the pre-filled pen from the skin.

• After removing the pre-filled pen from the injection site, the needle will automatically be covered. Do not recap the pen.
• If the viewing window has not completely turned blue or if medication is still being injected, this means you did not receive a complete dose. Contact your doctor immediately. Figure K

c. Treat the injection site by gently pressing a cotton ball or gauze pad over it—do not rub—and, if necessary, apply an adhesive bandage. Bleeding may occur.

• Do not reuse the pre-filled pen.

Needle cap • Do not rub the injection site.
Figura L

12. Dispose of the prefilled pen

a. Immediately dispose of the used prefilled pen in
a special container for sharp objects,
as instructed by your doctor, nurse, or
pharmacist.
b. The alcohol swab and packaging may
be placed in household waste.

• Always keep the prefilled pen and the special container for sharp objects out of sight and reach of children.

Figure M

Patient information leaflet

Yuflyma 20 mg solution for injection in pre-filled syringe

adalimumab
Please read this leaflet carefully before the child starts using this medicine, because
it contains important information.

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

Contents of this leaflet

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

1. What Yuflyma is and what it is used for

Yuflyma contains the active substance adalimumab.
Yuflyma 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 Yuflyma, adalimumab, is a human 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 (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Yuflyma 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.
Yuflyma 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 Yuflyma to treat polyarticular juvenile idiopathic arthritis.
Your doctor will decide whether Yuflyma should be used 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.
Yuflyma 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 Yuflyma 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 crack, thicken, or lift from the nail bed, which can be painful. Psoriasis is believed to be caused by a problem with the immune system that leads to increased production of skin cells.
Yuflyma is used to treat severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapies have not worked well or are not suitable.

Crohn’s disease in pediatric patients
Crohn’s disease is an inflammatory disease of the gastrointestinal tract. Yuflyma is used to treat moderate to severe Crohn’s disease in children and adolescents 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 Yuflyma to reduce the signs and symptoms of the disease.

Pediatric uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. Yuflyma 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 can lead to decreased vision and/or the presence of floaters in the eye (black spots or thin lines moving across the field of vision). Yuflyma 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 Yuflyma to reduce the signs and symptoms of the disease.

2. What you should know before your child uses Yuflyma

Do not use Yuflyma:

• 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 active tuberculosis or other serious infections (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 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 Yuflyma.
Allergic reactions

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

Infections

• If your child has an infection, including long-term infections or localized infections (e.g., leg ulcers), consult the doctor before starting treatment with Yuflyma. If you have any doubts, contact the doctor.
• Your child may be more likely to get infections while being treated with Yuflyma. 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, or bacteria
• severe blood infection (sepsis)

In rare cases, these infections can be life-threatening. It is important to inform the doctor if your child shows symptoms such as fever, wounds, feeling tired, or dental problems. The doctor may advise you to temporarily stop Yuflyma.

• Inform the doctor if your child lives in or travels to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.
• Inform the doctor if your child has had recurring infections or has conditions that increase the risk of infection.
• Your child and the pediatrician should pay particular attention to signs of infection while your child is being treated with Yuflyma. It is important to inform the pediatrician if symptoms of infection such as fever, wounds, feeling tired, or dental problems appear.

Tuberculosis

• Since cases of tuberculosis have occurred in patients treated with Yuflyma, the doctor will need to check whether your child shows signs or symptoms typical of tuberculosis before starting therapy with Yuflyma. This will involve a thorough medical evaluation of your child’s medical history and appropriate clinical tests (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the child’s Patient Reminder Card.
• It is very important to inform the doctor if you have ever had tuberculosis or if you have been in close contact with someone who had tuberculosis. Do not take Yuflyma if you have active tuberculosis.
• Tuberculosis may develop during treatment even if your child has received treatment to prevent tuberculosis.
• Contact the doctor immediately if symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections appear during or after treatment.

Hepatitis B

• It is very important to inform the doctor if your child is a carrier of hepatitis B virus (HBV), has an active hepatitis B virus infection, or if you think your child may be at risk of contracting hepatitis B virus.
• The doctor must test your child for hepatitis B virus infection. In HBV carriers, taking Yuflyma may cause the virus to reactivate.
• In some rare cases, especially if the patient is also taking other medicines that suppress the immune system, reactivation of hepatitis B virus can be life-threatening.

Surgery or dental procedures

• If your child is scheduled for surgery or dental procedures, inform the doctor that your child is taking Yuflyma. The doctor may recommend temporarily stopping Yuflyma.

Demyelinating diseases

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

Vaccinations

• Certain vaccines may cause infections and should not be given during treatment with Yuflyma.
• Consult the doctor before vaccinating your child.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Yuflyma.
• If a girl has taken Yuflyma during pregnancy, her baby may have an increased risk of infection for up to about 5 months after the last dose taken during pregnancy. It is important to inform the pediatrician or other healthcare provider that the girl took Yuflyma during pregnancy, so they can decide when the baby should receive any vaccinations.

Heart failure

• If your child has mild heart failure and is being treated with Yuflyma, the condition must be closely monitored by the doctor. It is important to inform the doctor about any past or current heart problems. If new symptoms of heart failure develop or existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact the doctor immediately. The doctor will decide whether your child can continue taking Yuflyma.

Fever, bruising, bleeding, or paleness

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

Tumors

• Very rare cases of certain types of tumors have been reported in patients, both children and adults, treated with Yuflyma or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If your child takes Yuflyma, the risk of developing lymphomas, leukemia, or other tumors may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with Yuflyma. Some of these patients were also taking azathioprine or 6-mercaptopurine.
• Inform the doctor if your child is taking azathioprine or 6-mercaptopurine with Yuflyma.
• Cases of non-melanoma skin cancer have been observed in patients taking Yuflyma.
• If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform the doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF. If your child has COPD or smokes heavily, discuss with the doctor whether treatment with an anti-TNF is appropriate.

Autoimmune disease

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

Other medicines and Yuflyma
Inform the doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Your child must not use Yuflyma with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Yuflyma may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• steroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult the doctor.
Pregnancy and breastfeeding

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

Driving and using machines
Yuflyma may affect, although only slightly, your child’s ability to drive, ride a bicycle, or use machinery. After taking Yuflyma, visual disturbances or a sensation that the surroundings are spinning may occur.
Yuflyma contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.2 mL dose, i.e., essentially “sodium-free”.

3. How to use Yuflyma

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

Method and route of administration
Yuflyma is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to administer Yuflyma are described in section 7 “Instructions for use”.
If you use more Yuflyma than you should
If you accidentally inject Yuflyma more often than prescribed by the doctor or pharmacist, contact your doctor or pharmacist and inform them that the child has received an excess of the medicine. Always keep the medicine carton, even if empty.
If you forget to use Yuflyma
If you forget to give the child an injection, administer the missed dose as soon as you remember. Then give the next dose at the regularly scheduled time according to the prescribed dosing schedule.
If you stop using Yuflyma
The decision to stop using Yuflyma should be discussed with your doctor. The child's symptoms may return if treatment with Yuflyma is stopped.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Immediately inform your doctor if you notice any of the following reactions:

• severe rash, hives, or other signs of allergic reaction
• swelling of the face, hands, or feet
• difficulty breathing, difficulty swallowing
• shortness of breath during exertion or when lying down, or swollen feet

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

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning during urination
• feeling weak/tired
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open sore that does not heal
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, paleness

The symptoms described above may be signs of the following side effects, which have been observed with Yuflyma.

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

• reactions at the injection site (including pain, swelling, redness, or itching)
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal 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 cold sores)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• cracking of fingernails and toenails
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• edema (fluid retention)
• fever
• reduced platelet count in blood, increasing risk of bleeding or bruising
• impaired 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)
• tumor
• lymphatic system tumor
• melanoma
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shakiness)
• neuropathy (nervous system disorder)
• stroke
• hearing loss, ringing in ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling of ankles
• heart attack
• aneurysm in the wall of a major artery, vein inflammation and clot, blood vessel blockage
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of an artery in the lung)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial edema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of skin, heart, lungs, joints, and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukemia (a blood and bone marrow cancer)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (lung scarring)
• intestinal perforation (hole in the intestine)
• hepatitis
• 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 (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (itchy red-purple skin rash)

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

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

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

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (liver blood test)

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

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

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

5. How to store Yuflyma

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

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled syringe of Yuflyma may be stored at room temperature (up to 25°C) for a maximum of 31 days; ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 31 days 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 doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Yuflyma contains
The active substance is adalimumab.
The other components are acetic acid, sodium acetate trihydrate, glycine, polysorbate 80, and water for
injections.

Description of the appearance of Yuflyma pre-filled syringe and pack contents
Yuflyma 20 mg solution for injection in pre-filled syringe is supplied as a sterile solution containing 20 mg of
adalimumab dissolved in 0.2 mL of solution.
Yuflyma pre-filled syringe consists of a solution of adalimumab contained in a glass syringe.
The pack containing 1 pre-filled syringe is supplied with 2 alcohol swabs (1 spare).
The pack containing 2 pre-filled syringes is supplied with 2 alcohol swabs.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles
06410, Biot
France
Nuvisan GmbH
Wegenerstraße 13
89231 Neu-Ulm
Germany
Midas Pharma GmbH
Rheinstr. 49
55218 Ingelheim
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès
Barcelona
Spain

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

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA Celltrion Healthcare Hungary Kft.
Tél/Tel: + 32 1528 7418 Tel.: +36 1 231 0493

България Luxembourg/Luxemburg
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Belgium BVBA
Teл.: +36 1 231 0493 Tél/Tel: + 32 1528 7418

Česká republika Magyarország
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tel.: +36 1 231 0493

Danmark Malta
Celltrion Healthcare Hungary Kft. Mint Health Ltd.
Tlf: +36 1 231 0493 Tel: +356 2093 9800

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel.: +49 (0)30 346494150 Tel: + 31 20 888 7300
[email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493 Tlf: +36 1 231 0493

España Österreich
Kern Pharma, S.L. Astro-Pharma GmbH
Tel: +34 93 700 2525 Tel: +43 1 97 99 860

Ελλάδα Polska
ΒΙΑΝΕΞ Α.Ε. Celltrion Healthcare Hungary Kft.
Τηλ: +30 210 8009111 Tel.: +36 1 231 0493

France Portugal
Celltrion Healthcare France SAS CELLTRION PORTUGAL, UNIPESSOAL LDA
Tél.: +33 (0)1 71 25 27 00 Tel: +351 21 936 8542

Hrvatska România
Oktal Pharma d.o.o. Celltrion Healthcare Hungary Kft.
Tel: +385 1 6595 777 Tel: +36 1 231 0493

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493 Tel: +36 1 231 0493

Italia Suomi/Finland
Celltrion Healthcare Italy S.r.l. Celltrion Healthcare Finland Oy.
Tel: +39 02 47927040 Puh/Tel: +358 29 170 7755

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Sweden AB
Τηλ: +357 22741741 [email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for use

• The following instructions explain how to administer a subcutaneous injection of Yuflyma to a child using the pre-filled syringe. First, read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with training on the injection administration technique.
• Do not administer the injection to the child until you are certain you understand how to prepare and give the injection.
• After proper training, the injection may be given by the child or by another person, such as a family member or friend.
• Each pre-filled syringe must be used for one injection only.

Yuflyma Pre-filled Syringe

Plunger
Flange
Barrel
Medicinal product
Needle
Cap
Before After
use use
Figure A

Do not use the pre-filled syringe if:

• it is cracked or damaged.
• the expiry date has been exceeded.
• it has been dropped on a hard surface.
  Remove the needle cap only immediately before injection. Keep Yuflyma out of the sight and reach of children.

1. Prepare the injection materials

a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
b. Remove 1 pre-filled syringe from the box stored in the refrigerator.

• When removing the pre-filled syringe from the box, hold it by the barrel. Do not touch the plunger rod or the cap. c. Make sure you have the following materials:
  • Pre-filled syringe
  • Alcohol swab Not included in the box:
  • Absorbent cotton ball or gauze
  • Adhesive bandage
  • Sharps disposal container

2. Inspect the prefilled syringe

a. Make sure you have the correct medicine (Yuflyma) and dose.
b. Look at the prefilled syringe and check that it is not cracked or
damaged.
c. Check the expiration date on the label of the prefilled
syringe.
Do not use the prefilled syringe if:

• it is cracked or damaged
• the expiration date has passed.
• it has been dropped on a hard surface. Figure B

3. Inspect the medicine

a. Look at the medicine to make sure the liquid is
clear, colourless to light brown, and free of particles.

• Do not use the pre-filled syringe if the liquid is: discoloured (yellow or dark brown), cloudy, or contains particles.
• You may see air bubbles in the liquid. This is normal.

Figure C

4. Wait 15-30 minutes

15 - 30
a . Leave the prefilled syringe at room temperature
minutes
for 15-30 minutes so it can warm up.

• Do not heat the prefilled syringe using heat sources such as hot water or microwave.

Figure D

5. Choose an appropriate injection site

a. You may administer the injection:

• on the front of the thigh

• on the abdomen, except for the area within 5 cm of the navel

• on the outer area of the upper arm (ONLY if you are a person assisting the patient).

  • Do not administer the injection in skin areas within 5 cm of your navel or in any area that is red, hard, tender, damaged, bruised, or scarred.
  • If your child has psoriasis, do not administer the injection on any raised, thickened, red, or scaly patches or on any skin lesions.

• Do not administer the injection through clothing.

b. Rotate the injection site each time you give an injection. Each new injection site should be at least 3 cm away from the
Figure E
previous injection site.

6. Wash your hands.

a. Wash your hands with water and soap and dry them
thoroughly.
Figure F

7. Clean the injection site

a. Clean the injection site with an alcohol wipe,
using a circular motion.
b. Allow the skin to dry before injecting.

• Do not blow on the injection site or touch it again before giving the injection.

Figure G

8. Remove the cap

a. Holding the pre-filled syringe body in one hand,
gently pull off the cap with the other hand.

• Never pull back the plunger

• Do not remove the cap until you are ready to perform the injection

• Do not touch the needle. This could result in a needle-stick injury.

• Do not re-cap the pre-filled syringe. Immediately dispose of the cap in a sharps disposal container. Figure H

• It is normal to see a few drops of liquid coming out from the needle.

9. Insert the pre-filled syringe at the injection site

a. With one hand, gently pinch the skin to create
a skin fold at the injection site.
b. Holding the pre-filled syringe by the body, insert
the needle completely into the skin fold at a
45-degree angle with a quick motion,
OR as if throwing a dart.
Figure I

10. Administer the injection

a. Once the needle is inserted, release the pinched skin.
b. Slowly and completely push the plunger down until all the liquid
is injected and the syringe is empty.

• Do not change the position of the pre-filled syringe once the injection has started.

Figure J

11. Remove the pre-filled syringe from the injection site and

take care of the injection site
a. Once the pre-filled syringe is empty, remove it from
the skin using the same angle as during insertion.
b. Treat the injection site by gently pressing a cotton ball
or gauze pad over it without rubbing, and, if necessary,
apply an adhesive bandage. Bleeding may occur.

• Do not reuse the pre-filled syringe.
• Do not touch the needle or cover it with the cap.
• Do not rub the injection site.

Figure K

12. Disposal of the pre-filled syringe

• Do not re-cap the pre-filled syringe.
  a. Dispose of the used pre-filled syringe in a special container for the disposal of sharp objects, as instructed by your doctor, pharmacist, or nurse.
  b. The alcohol swab and packaging may be placed in household waste.
• Always keep the pre-filled syringe and the special sharps disposal container out of the sight and reach of children.

Figure L
Figure L