Yuflyma 40 mg solution for injection in pre-filled pen

Package Leaflet: Information for the User

Introduction

Package Leaflet: Patient Information

Yuflyma 40 mg Injectable Solution in Prefilled Pen

adalimumab

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• Your doctor will provide you with a Patient Information Card containing important safety information you need to know before starting and during treatment with Yuflyma. Carry this Patient Information Card with you throughout 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 pass it on to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

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 (defence).

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 target a specific site.

Adalimumab targets a protein called tumour necrosis factor (TNFα), which plays a role in the immune system (defence) and is found at elevated levels in the inflammatory diseases listed above. By targeting TNFα, Yuflyma reduces the inflammatory process in these diseases.

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease of the joints.

Yuflyma is used to treat moderate to severe rheumatoid arthritis in adults. You may have been given other disease-modifying drugs such as methotrexate first. If your response to these medicines is not sufficient, you will be given Yuflyma.

Yuflyma may also be used in the treatment of severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.

Yuflyma can reduce joint damage caused by the inflammatory disease and help you move more freely.

Your doctor will decide whether Yuflyma should be used with methotrexate or as monotherapy.

Polyarticular juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints.

Yuflyma is used to treat polyarticular juvenile idiopathic arthritis in patients from the age of 2 years. You may have been given other disease-modifying drugs such as methotrexate first. If your response to these medicines is not sufficient, you will be given Yuflyma.

Your doctor will decide whether Yuflyma should be used with methotrexate or as monotherapy.

Enthesitis-related arthritis

Enthesitis-related arthritis is an inflammatory disease affecting the joints and the sites where tendons attach to bone.

Yuflyma is used to treat enthesitis-related arthritis in patients from the age of 6 years. You may have been given other disease-modifying drugs such as methotrexate first. If your response to these medicines is not sufficient, you will be given Yuflyma.

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 affecting the spine.

Yuflyma is used to treat severe ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. You may have first received other medicines. If your response to these medicines is not sufficient, you will be given Yuflyma.

Psoriatic arthritis

Psoriatic arthritis is an inflammatory disease of the joints that is usually associated with psoriasis.

Yuflyma is used to treat psoriatic arthritis in adults. Yuflyma can reduce joint damage caused by the disease and help you move more freely. You may have first received other medicines. If your response to these medicines is not sufficient, you will be given Yuflyma.

Plaque psoriasis

Plaque psoriasis is a skin disease that causes red, scaly, crusty areas covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to deteriorate, thicken and lift away 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 who have not responded to, or are not suitable candidates for, topical treatments and phototherapies.

Hidradenitis suppurativa

Hidradenitis suppurativa (sometimes called inverse acne) is a chronic and often painful inflammatory skin disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may discharge pus. It usually affects specific skin areas such as under the breasts, under the arms, inner thighs, groin and buttocks. Scarring may also occur 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, as well as the pain usually associated with it. You may have first received other medicines. If your response to these medicines is not sufficient, you will be given Yuflyma.

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.

You may have first received other medicines. If your response to these medicines is not sufficient, you will be given Yuflyma.

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.

You may have first received other medicines. If your response to these medicines is not sufficient, you will be given Yuflyma.

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 the age of 2 years with chronic non-infectious uveitis with inflammation affecting the front of the eye.

This inflammation may lead to reduced vision or the presence of floaters (black spots or thin lines moving across the field of vision). Yuflyma works by reducing this inflammation.

You may have first received other medicines. If your response to these medicines is not sufficient, you will be given Yuflyma.

2. What you need to 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 that you inform your doctor if you have symptoms of infection, such as fever, wounds, feeling tired, or dental problems.

• If you have moderate or severe heart failure. It is important that you inform your doctor if you have had or currently have serious heart disease (see "Warnings and precautions").

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Yuflyma.

Allergic reactions

• If you experience an allergic reaction with symptoms such as chest tightness, difficulty breathing, dizziness, swelling, or rash, stop administering Yuflyma and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infections

• If you have any infection, including a chronic infection or a localized infection in any part of the body (for example: a leg ulcer), consult your doctor before starting treatment with Yuflyma. If you are unsure, contact your doctor.

• You may be more likely to get infections while receiving Yuflyma treatment. This risk may be higher if you have lung damage. These infections can be serious and include:

• tuberculosis

• infections caused by viruses, fungi, parasites, or bacteria

• severe blood infection (sepsis)

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

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

• Inform your doctor if you have had recurrent infections or other disorders that increase the risk of infections.

• If you are over 65 years old, you may be more susceptible to infections while being treated with Yuflyma. Both you and your doctor should pay special attention to the appearance of signs of infection during treatment. It is important that you inform your doctor if you have symptoms of infection such as fever, wounds, 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 close contact with someone who had tuberculosis. If you have active tuberculosis, you must not use Yuflyma.

• Since cases of tuberculosis have been reported in patients treated with Yuflyma, your doctor will examine you for signs or symptoms of tuberculosis before starting your treatment with Yuflyma. This will include a thorough medical evaluation, including your medical history and appropriate diagnostic tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in your patient information card.

• Tuberculosis may develop during treatment even if you have received treatment to prevent tuberculosis.

• If symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or any other infection appear during or after treatment, contact your doctor immediately.

Hepatitis B

• Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have had active HBV infections, or if you think you may be at risk of contracting HBV.

• Your doctor should perform a test for HBV. In people who carry HBV, Yuflyma may cause the virus to become reactivated.

• In rare cases, especially if you are taking other medicines that suppress the immune system, reactivation of HBV may be life-threatening.

Surgery or dental procedures

• If you are scheduled for surgery or a dental procedure, inform your doctor that you are taking Yuflyma. Your doctor may recommend that you temporarily stop treatment with Yuflyma.

Demyelinating disease

• 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 be treated 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 anywhere in the body.

Vaccinations

• Certain vaccines may cause infections and should not be given while you are being treated with Yuflyma.

• Consult your doctor before receiving any vaccine.

• If possible, it is recommended that children receive all age-appropriate vaccines before starting treatment with Yuflyma.

• If you received Yuflyma while pregnant, your baby may be at increased risk of infection for about five months after your last dose of Yuflyma during pregnancy. It is important to inform your child's doctors and other healthcare professionals about your use of Yuflyma during pregnancy so they can decide whether your child should receive any vaccines.

Heart failure

• If you have mild heart failure and are being treated with Yuflyma, your doctor should closely monitor your heart failure. It is important to inform your doctor if you have had or currently have serious heart disease. If new symptoms of heart failure appear or existing symptoms worsen (e.g., difficulty breathing or swelling of the feet), contact your doctor immediately. Your doctor will decide whether you should continue receiving Yuflyma.

Fever, bruising, bleeding, or pale appearance

• In some patients, the body may be unable to produce enough blood cells that help fight infections or help stop bleeding. Your doctor may decide to discontinue treatment. If you have persistent fever, easy bruising, bleed easily, or appear very pale, contact your doctor immediately.

Cancer

• Very rarely, certain types of cancer have been reported in children and adults treated with Yuflyma or other TNF-blocking agents.

• People with more severe rheumatoid arthritis and who have had the disease for a long time may have a higher than average risk of developing lymphoma (a cancer affecting the lymphatic system) and leukemia (a cancer affecting blood and bone marrow).

• If you take Yuflyma, your risk of developing lymphoma, leukemia, or other types of cancer may increase. Rarely, 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 using Yuflyma.

• Inform your doctor if new skin lesions appear during or after treatment, or if existing lesions change in appearance.

• Cancers other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD), who were treated with another TNF-blocking agent. If you have COPD or are a heavy smoker, you should consult your doctor about whether treatment with a TNF blocker is appropriate for you.

Autoimmune disease

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

Children and adolescents

• Vaccination: If possible, your child should be up to date with all vaccinations before using Yuflyma.

Using Yuflyma with other medicines

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

• anakinra
• abatacept

Yuflyma may be taken together with:

• methotrexate
• certain disease-modifying antirheumatic drugs (DMARDs) (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and injectable gold salts)
• corticosteroids or pain medicines, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should consider using effective contraception to avoid 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 plan to become pregnant, consult your doctor about using this medicine.

• Yuflyma should be used during pregnancy only if necessary.

• According to a study in pregnancy, there was no increased risk of congenital malformations when mothers received Yuflyma during pregnancy compared to mothers with the same disease who did not receive Yuflyma.

• Yuflyma can be used during breastfeeding.

• If you receive Yuflyma while pregnant, your child may have an increased risk of infection.

• It is important to inform your child's doctors and other healthcare professionals about your use of Yuflyma during pregnancy before your child receives any vaccines. For more information on vaccines, see the section "Warnings and precautions."

Driving and using machines

Yuflyma may have a minor effect on the ability to drive, ride a bicycle, or use machines. Dizziness and visual disturbances may occur after using Yuflyma.

YUFLYMA contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 ml dose; hence, it is essentially "sodium-free."

3. How to use Yuflyma

Follow exactly the administration instructions for this medicine as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The following table indicates the recommended doses of Yuflyma for each of its approved uses. Your doctor may prescribe you a different dose of Yuflyma if you require an alternative dose.

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
Age or body weight	How much and how often should it be taken?	Notes
Adults	40 mg every two weeks	In rheumatoid arthritis, continue treatment with methotrexate during Yuflyma use. If the physician determines that methotrex combustible is inappropriate, Yuflyma may be administered as monotherapy. If you have rheumatoid arthritis and are not receiving methotrexate with your Yuflyma treatment, your physician may decide to administer 40 mg of Yuflyma weekly or 80 mg every two weeks.

Juvenile idiopathic arthritis polyarticular
Age or body weight	How much and how often should it be taken?	Notes
Children, adolescents, and adults from 2 years of age weighing 30 kg or more	40 mg every two weeks	Not applicable
Children and adolescents from 2 years of age weighing from 10 kg to 30 kg	20 mg every two weeks	Not applicable

Enthesitis-related arthritis
Age or body weight	How much and how often should it be taken?	Notes
Children, adolescents, and adults aged 6 years and older weighing 30 kg or more	40 mg every two weeks	Not applicable
Children and adolescents aged 6 years and older weighing between 15 kg and 30 kg	20 mg every two weeks	Not applicable

Plaque Psoriasis
Age or body weight	How much and how often should it be taken?	Notes
Adults	The initial dose is 80 mg (two injections of 40 mg on the same day), followed by 40 mg every other week starting one week after the first dose.	If an inadequate response is obtained, the doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.
Children and adolescents from 4 to 17 years of age weighing 30 kg or more	First dose of 40 mg, followed by 40 mg one week later. From then on, the usual dose is 40 mg every two weeks.	Not applicable

Suppurative hidradenitis
Age or body weight	How much and how often should it be taken?	Notes
Adults	The initial dose is 160 mg (four 40 mg injections in one day or two 40 mg injections per day on two consecutive days), followed by a dose of 80 mg (two 40 mg injections in one day) two weeks later. After another two weeks, continue with a dose of 40 mg weekly or 80 mg every two weeks, as prescribed by your doctor.	It is recommended that you use an antiseptic daily on affected areas
Adolescents aged 12 to 17 years weighing 30 kg or more	The initial dose is 80 mg (two 40 mg injections in one day), followed by 40 mg every other week starting one week later.	If an inadequate response is obtained with Yuflyma 40 mg every two weeks, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks. It is recommended that you use an antiseptic daily on affected areas

Crohn's Disease
Age or body weight	How much and how often should it be taken?	Notes
Children, adolescents and adults from 6 years of age weighing 40 kg or more	The initial dose is 80 mg (two injections of 40 mg on the same day), followed by 40 mg two weeks later. If a more rapid response is needed, the doctor may prescribe an initial dose of 160 mg (four injections of 40 mg on one day or two injections of 40 mg per day for two consecutive days), followed by 80 mg (two injections of 40 mg on one day) two weeks later. From then on, the usual dose is 40 mg every two weeks.	The doctor may increase the dosing frequency to 40 mg weekly or 80 mg every two weeks.
Children and adolescents aged 6 to 17 years weighing less than 40 kg	The initial dose is 40 mg, followed by 20 mg two weeks later. If a more rapid response is needed, the doctor may prescribe an initial dose of 80 mg (two injections of 40 mg on one day), followed by 40 mg two weeks later. From then on, the usual dose is 20 mg every other week.	Your doctor may increase the dosing frequency to 20 mg weekly.

Ulcerative colitis
Age or body weight	How much and how often should it be taken?	Notes
Adults	The initial dose is 160 mg (four 40 mg injections in one day or two 40 mg injections per day on two consecutive days), followed by 80 mg (two 40 mg injections in one day) two weeks later. From then on, the usual dose is 40 mg every two weeks.	Your doctor may increase the dosing frequency to 40 mg weekly or 80 mg every two weeks
Children and adolescents from 6 years of age weighing less than 40 kg	Initial dose of 80 mg (two 40 mg injections in one day), followed by 40 mg (one 40 mg injection) two weeks later. From then on, the usual dose is 40 mg every other week.	You should continue using Yuflyma at the usual dose, even after turning 18 years old
Children and adolescents from 6 years of age weighing 40 kg or more	Initial dose of 160 mg (four 40 mg injections in one day or two 40 mg injections per day on two consecutive days), followed by 80 mg (two 40 mg injections in one day) two weeks later. From then on, the usual dose is 80 mg every other week.	You should continue using Yuflyma at the usual dose, even after turning 18 years old

Non-infectious uveitis
Age or body weight	How much and how often should it be taken?	Notes
Adults	The initial dose is 80 mg (two 40 mg injections on the same day), followed by 40 mg every two weeks starting one week after the first dose.	Corticosteroids or other medications affecting the immune system may continue to be taken while using Yuflyma. Yuflyma may also be administered alone.
Children and adolescents aged 2 years and older with body weight below 30 kg	20 mg every other week	Your doctor may prescribe an initial dose of 40 mg, which may be administered one week before starting the regular schedule of 20 mg every two weeks. Yuflyma is recommended for use in combination with methotrexate.
Children and adolescents aged 2 years and older with body weight below 30 kg	40 mg every two weeks	Your doctor may prescribe an initial dose of 80 mg, which will be administered one week before starting the regular schedule of 40 mg every two weeks. Yuflyma is recommended for use in combination with methotrexate.

Form and route of administration

Yuflyma is administered by injection under the skin (subcutaneous injection).

Section 7 "Instructions for use" provides detailed instructions on how to inject Yuflyma.

If you use more Yuflyma than you should

If Yuflyma is accidentally injected more frequently than prescribed by your doctor or pharmacist, inform your doctor or pharmacist. Always carry the outer packaging of the medicine with you, even if it is empty.

If you forget to use Yuflyma

If you forget to administer an injection, you should inject the next dose of Yuflyma as soon as you remember. Then, administer the following dose as usual, as if no dose had been missed.

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 further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

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

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

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

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

• signs of infection, such as fever, nausea, wounds, dental problems, or burning sensation when urinating
• feeling weak or tired
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• a lump or open wound that does not heal
• signs and symptoms of blood disorders such as persistent fever, bruising, bleeding, and 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)

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

Common (may affect up to 1 in 10 people)

• serious infections (including blood poisoning and influenza)
• intestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes)
• ear infections
• oral infections (including dental infection and mouth sores)
• reproductive system infections
• urinary tract infection
• 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, burning, or numbness
• migraine
• nerve root compression (including lower back and leg pain)
• vision disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• flushing
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, and burning)
• acid reflux
• dry eye syndrome (including dry eyes and mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• nail breakage in hands and feet
• increased sweating
• hair loss
• new-onset psoriasis or worsening of existing psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• edema (swelling)
• fever
• decreased 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 disease resistance is reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• cancer
• cancer affecting the lymphatic system
• melanoma**
• immune disorders that may affect the lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (feeling shaky)
• neuropathy (nervous system disorder)
• stroke
• hearing loss, tinnitus
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or ankle swelling
• heart attack
• aneurysm (bulge in the wall of a major artery), venous inflammation and clotting, blood vessel blockage
• lung diseases that may cause difficulty breathing (including inflammation)
• pulmonary embolism (blockage of a lung artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis (inflammation of the pancreas) causing severe abdominal and back pain
• difficulty swallowing
• facial edema (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)
• sleep disturbances
• impotence
• inflammations

Rare (may affect up to 1 in 1000 people)

• leukemia (cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• nervous system disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, and tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scarring of the lung)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B virus
• autoimmune hepatitis (liver inflammation caused by the body's own immune system)
• cutaneous vasculitis (inflammation of blood vessels in the skin)
• Stevens-Johnson syndrome (early symptoms include malaise, fever, headache, and rash)
• facial edema (swelling of the face) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (itchy, reddish-purple rash)

Frequency not known (cannot be estimated from available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer)
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma usually appears as purplish lesions on the skin.
• liver failure
• worsening of a condition called dermatomyositis (seen as skin rash accompanied by muscle weakness)
• Weight gain (for most patients, weight gain was minimal)

Some adverse effects observed with Yuflyma may not cause symptoms and can only be detected through blood tests. These include:

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (liver function blood test)

Rare (may affect up to 1 in 1000 people)

• low blood counts for white blood cells, red blood cells, and platelets

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Yuflyma

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the container after “EXP”.

Store in a refrigerator (between 2 °C - 8 °C). Do not freeze.

Keep the prefilled pen in the outer packaging to protect it from light.

Alternative storage:

When necessary (e.g. when travelling), a single prefilled pen of Yuflyma with needle cover may be stored at room temperature (up to 25 °C) for a maximum of 31 days (ensure protection from light). Once the pen has been removed from the refrigerator for storage at room temperature, it must be used within the next 31 days or discarded, even if it is returned to the refrigerator.

You should record the date on which the pen was removed from the refrigerator, and the date after which the pen must be discarded.

Medicines should not be disposed of via wastewater or household waste. Ask your doctor how to dispose of medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Yuflyma

The active substance is adalimumab.

The other components are acetic acid, sodium acetate trihydrate, glycine, polysorbate 80, and water for injections.

Appearance of the Yuflyma pre-filled pen and contents of the pack

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, disposable injection system with automated features. There is a viewing window on each side of the pen through which you can see the Yuflyma solution inside the pen.

The Yuflyma pre-filled pen is available in packs containing 1, 2, 4, and 6 pre-filled pens.

Each pre-filled pen pack contains 2 alcohol-impregnated wipes (1 spare). Each pack contains 2, 4, or 6 pre-filled pens, and each pre-filled pen is supplied with 1 alcohol-impregnated wipe.

Only certain pack sizes may be marketed.

Yuflyma may be available as a pre-filled syringe or pre-filled pen.

Marketing Authorization Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B tower

Hungary

Manufacturer responsible

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

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium Celltrion Healthcare Belgium BVBA Tel/Tel: + 32 1528 7418	Lithuania Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493
Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493	Luxembourg/Luxembourg Celltrion Healthcare Belgium BVBA Tel/Tel: + 32 1528 7418
Czech Republic Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493	Hungary Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493
Denmark Celltrion Healthcare Denmark ApS Tlf: +45 35352989 [email protected]	Malta Mint Health Ltd. Tel: +356 2093 9800
Germany Celltrion Healthcare Deutschland GmbH Tel.: +49 (0)30 346494150 [email protected]	Netherlands Celltrion Healthcare Netherlands B.V. Tel: + 31 20 888 7300
Estonia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493	Norway Celltrion Healthcare Norway AS [email protected]
Spain Kern Pharma, S.L. Tel: +34 93 700 2525	Austria Astro-Pharma GmbH Tel: +43 1 97 99 860
Greece BIANEX S.A. Tel: +30 210 8009111 - 120	Poland Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493
France Celltrion Healthcare France SAS Tél.: +33 (0)1 71 25 27 00	Portugal CELLTRION PORTUGAL, UNIPESSOAL LDA Tel: +351 21 936 8542
Croatia Oktal Pharma d.o.o. Tel: +385 1 6595 777	Romania Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
Ireland Celltrion Healthcare Ireland Limited Tel: +353 1 223 4026	Slovenia OPH Oktal Pharma d.o.o. Tel.: +386 1 519 29 22
Iceland Celltrion Healthcare Hungary Kft. Sími: +36 1 231 0493	Slovakia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
Italy Celltrion Healthcare Italy S.r.l. Tel: +39 0247927040	Finland/Sweden Celltrion Healthcare Finland Oy. Puh/Tel: +358 29 170 7755
Cyprus C.A. Papaellinas Ltd Tel: +357 22741741	Sweden Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493 [email protected]
Latvia Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu

1. Instructions for use

• The following instructions explain how to administer a subcutaneous injection of Yuflyma using the pre-filled pen. First, read the instructions carefully and then follow them step by step.

• Your doctor, nurse, or pharmacist will show you the technique for self-injection.

• Do not attempt to give yourself the injection until you are certain that you understand how to prepare and administer it.

• After proper training, either you or another person, such as a family member or friend, may administer the injection.

• Use each pre-filled pen for only one injection.

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 inject. Keep Yuflyma out of the reach of children.

Gather injection supplies Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. Remove 1 prefilled pen from the refrigerator box. Make sure you have the following supplies: Prefilled pen 1 alcohol wipe Not included in the box: Cotton ball or gauze Adhesive bandage Sharps disposal container
Figure B	Inspect the prefilled pen Make sure you have the correct medication (Yuflyma) and dose. Examine the prefilled pen to ensure it is not cracked or damaged. Check the expiration date on the pen label. Do not use the prefilled pen if: it is cracked or damaged. the expiration date has passed. it has fallen on a hard surface.
Figure C	Inspect the medication. Look through the viewing window and make sure the liquid is clear, colorless to light brown, and free of particles. Do not use the prefilled pen if: the liquid has changed color (yellow or dark brown), is cloudy, or contains particles. Air bubbles in the liquid may be visible. This is normal.
Figure D	Wait 15 to 30 minutes Allow the prefilled pen to warm to room temperature for 15 to 30 minutes. Do not warm the prefilled pen using heat sources such as hot water or a microwave oven.
Figure E	Choose an appropriate injection site Injections can be given in: the front of the thighs. the abdomen, except within 5 cm (2 inches) around the navel. the outer side of the upper arm (ONLY if you are a caregiver). Do not inject into skin within 5 cm (2 inches) of the navel, or into skin that is red, hard, irritated, bruised, or scarred. If you have psoriasis, do not inject directly into any raised, thick, red, or scaly patches or skin lesions. Do not administer the injection through clothing. Change the injection site each time you give an injection. Each new injection site should be at least 3 cm (1.2 inches) away from the previous injection site.
Figure F	Wash your hands. Wash your hands with soap and water and dry them thoroughly.
Figure G	Clean the injection site Clean the injection site with an alcohol wipe using circular motions. Allow the skin to dry before administering the injection. Do not blow on or touch the injection site again before administering the injection.
Figure H	Remove the cap. Hold the prefilled pen by the body of the injector with one hand. Remove the cap straight off with the other hand. Do not remove the cap until you are ready to inject. Do not touch the needle or needle shield. Doing so may result in a needlestick injury. Do not recap the prefilled pen. Immediately discard the cap into a sharps disposal container. It is normal to see a few drops of liquid coming from the needle.
Figure I	Position the prefilled pen at the injection site. Hold the prefilled pen so you can see the viewing window. Without pinching or stretching the skin, place the prefilled pen at the injection site at a 90-degree angle.
Figure J	Administer the injection Press the prefilled pen firmly against the skin. When the injection starts, you will hear the first loud click and the blue plunger rod will begin to fill the viewing window. Hold the prefilled pen firmly against the skin and listen for the second loud click. After hearing the second loud click, continue holding the prefilled pen firmly against the skin and count slowly to 5 to ensure the full dose is delivered. Do not change the position of the prefilled pen after starting the injection.
Figure K Figure L	Remove the prefilled pen from the injection site and clean the injection site Look at the prefilled pen and make sure the blue plunger rod with the gray top has completely filled the viewing window. Remove the prefilled pen from the skin. After removing the prefilled pen from the injection site, the needle will automatically be covered. Do not recap the pen. If the viewing window has not turned completely blue or if medication is still being injected, this means a full dose was not delivered. Contact your doctor immediately. Gently press, do not rub, the injection site with a cotton ball or gauze and apply an adhesive bandage if needed. Bleeding may occasionally occur. Do not reuse the prefilled pen. Do not rub the injection site.
Figure M	Dispose of the prefilled pen Place the used prefilled pen in a special sharps disposal container as instructed by your doctor, nurse, or pharmacist. The alcohol wipe and packaging may be disposed of in household trash. Always keep the prefilled pen and sharps disposal container out of sight and reach of children.