Prospect: information for the patient

Yuflyma 40 mg injectable solution in pre-filled pen

adalimumab

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• Your doctor will give you apatient information leaflet, which contains important safety information that you need to know before starting to use and during treatment with Yuflyma. Carry thispatient information leafletwith you during treatment and the 4 months after your last Yuflyma injection.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

Yuflyma contains the active ingredient adalimumab, a medication that acts on your immune system (defense).

Yuflyma is indicated for the treatment of the following inflammatory diseases:

• Rheumatoid Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Arthritis associated with enthesitis
• Ankylosing Spondylitis
• Undifferentiated Axial Spondyloarthritis without radiographic evidence of ankylosing spondylitis
• Psoriatic Arthritis
• Plaque Psoriasis
• Hidradenitis Suppurativa
• Crohn's Disease
• Ulcerative Colitis
• Non-infectious Uveitis

The active ingredient in Yuflyma, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that target a specific target.

The target of adalimumab is a protein called Tumor Necrosis Factor-alpha (TNFa), which is involved in the immune system (defense) and is found at elevated levels in the aforementioned inflammatory diseases. By targeting TNFa, Yuflyma reduces the inflammatory process in those 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 received other disease-modifying medications such as methotrexate first. If the response to these medications is not sufficient, Yuflyma will be administered.

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

Yuflyma may reduce the damage to the joints 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 2 years of age. You may have received other disease-modifying medications such as methotrexate first. If the response to these medications is not sufficient, Yuflyma will be administered.

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

Arthritis associated with enthesitis

Arthritis associated with enthesitis is an inflammatory disease of the joints and the places where tendons attach to bone.

Yuflyma is used to treat arthritis associated with enthesitis in patients from 6 years of age. You may have received other disease-modifying medications such as methotrexate first. If the response to these medications is not sufficient, Yuflyma will be administered.

Ankylosing Spondylitis and Undifferentiated Axial Spondyloarthritis without radiographic evidence of ankylosing spondylitis

Ankylosing Spondylitis and Undifferentiated Axial Spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory diseases that affect the spine.

Yuflyma is used to treat severe ankylosing spondylitis and undifferentiated axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. You may have received other medications first. If the response to these medications is not sufficient, Yuflyma will be administered.

Psoriatic Arthritis

Psoriatic Arthritis is an inflammatory disease of the joints that often occurs with psoriasis.

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

Plaque Psoriasis

Plaque Psoriasis is a skin disease that causes red, scaly, crusty, and silvery patches. Plaque Psoriasis may also affect the nails, causing them to deteriorate, thicken, and 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 between 4 and 17 years of age who have not responded or are not good candidates for topical and phototherapy treatments.

Hidradenitis Suppurativa

Hidradenitis Suppurativa (also known as inverse acne) is a chronic and often painful inflammatory skin disease. Symptoms may include sensitive nodules (bumps) and abscesses (boils) that may secrete pus. It usually affects specific areas of the skin, such as under the chest, armpits, inner thighs, groin, and buttocks. It may also leave scars in the affected areas.

Yuflyma is used to treat

• moderate to severe hidradenitis suppurativa in adults and
• moderate to severe hidradenitis suppurativa in adolescents from 12 to 17 years of age.

Yuflyma may reduce the number of nodules and abscesses caused by the disease and the pain that usually accompanies this disease. You may have received other medications first. If the response to these medications is not sufficient, Yuflyma will be administered.

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 from 6 to 17 years of age.

You may have received other medications first. If the response to these medications is not sufficient, Yuflyma will be administered.

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 from 6 to 17 years of age.

You may have received other medications first. If the response to these medications is not sufficient, Yuflyma will be administered.

Non-infectious Uveitis

Non-infectious Uveitis is an inflammatory disease that affects certain parts of the eye. Yuflyma is used to treat

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

This inflammation may lead to a decrease in vision or the presence of spots in the eye (black dots or thin lines that move across the field of vision). Yuflyma acts by reducing this inflammation.

You may have received other medications first. If the response to these medications is not sufficient, Yuflyma will be administered.

Do not use Yuflyma:

• If you are allergic to adalimumab or any of the other components of this medication (listed in section 6).

• If you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is essential to inform your doctor if you have symptoms of infection, such as fever, wounds, fatigue, or dental problems.

• If you have moderate or severe heart failure. It is essential to inform your doctor if you have had or have a severe heart disease (see "Warnings and precautions").

Warnings and precautions

Consult 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 hives, discontinue Yuflyma administration and contact your doctor immediately, as these reactions can be life-threatening in rare cases.

Infections

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

• You may be more susceptible to infections while receiving Yuflyma treatment. This risk may be higher if you have damaged lungs. These infections can be severe 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 essential to inform your doctor if you have symptoms such as fever, wounds, fatigue, or dental problems. Your doctor may recommend discontinuing Yuflyma treatment for a period.

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

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

• If you are over 65 years old, you may be more susceptible to infections while receiving Yuflyma treatment. Both you and your doctor should pay special attention to the appearance of infection symptoms while you are being treated with Yuflyma. It is essential to inform your doctor if you have symptoms of infections such as fever, wounds, fatigue, or dental problems.

Tuberculosis

• It is essential to inform your doctor if you have had tuberculosis at any time or have been in direct contact with someone who has had tuberculosis. If you have active tuberculosis, do 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 test). The results of these tests should be recorded on yourpatient information card.
• Tuberculosis can develop during treatment, even if you have received preventive treatment for tuberculosis.
• If you experience symptoms of tuberculosis (e.g., persistent cough, weight loss, fatigue, or low-grade fever) or any other infection 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 are carriers of HBV, Yuflyma can cause the virus to become active again.
• In rare cases, especially if you are taking other medications that suppress the immune system, reactivation of HBV can be life-threatening.

Surgery or dental intervention

• If you are scheduled for surgery or dental intervention, inform your doctor that you are taking Yuflyma. Your doctor may recommend temporarily discontinuing Yuflyma treatment.

Demyelinating disease

• If you have or develop a demyelinating disease (a disease that affects the insulation layer around nerves, such as multiple sclerosis), your doctor will decide whether to treat 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 can cause infections and should not be administered while taking Yuflyma.

• Consult your doctor before receiving any vaccine.
• If possible, it is recommended that children receive scheduled vaccinations before starting Yuflyma treatment.
• If you received Yuflyma during pregnancy, your child may be at higher risk of contracting an infection for approximately five months after the last dose of Yuflyma you received during pregnancy. It is essential 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 vaccine.

Heart failure

• If you have mild heart failure and are being treated with Yuflyma, your doctor should closely monitor your heart failure. It is essential to inform your doctor if you have had or have severe 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 receive Yuflyma.

Fever, hematomas, bleeding, or pale appearance

• In some patients, the body may be unable to produce sufficient blood cells that help the body fight infections or contribute to stopping bleeding. Your doctor may decide to suspend treatment. If you experience persistent fever, minor hematomas, easy bleeding, or pale appearance, consult your doctor immediately.

Cancer

• In rare cases, certain types of cancer have been reported in children and adults treated with Yuflyma or other TNF blockers.

• People with severe rheumatoid arthritis and a long history of the disease may have a higher risk than average of developing lymphoma (a cancer that affects the lymphatic system) and leukemia (a cancer that affects the blood and bone marrow).
• Using Yuflyma may increase the risk of developing lymphoma, leukemia, or other types of cancer. Rare cases of a rare and severe type of lymphoma have 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 reported in patients using Yuflyma.
• Inform your doctor if new skin lesions appear during or after treatment or if existing lesions change 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 blocker. If you have COPD or smoke heavily, consult your doctor about whether treatment with a TNF blocker is suitable for you.

Autoimmune disease

• In rare cases, treatment with Yuflyma may lead to a condition similar to lupus. Contact your doctor if you experience symptoms such as persistent rash without explanation, fever, joint pain, or fatigue.

Children and adolescents

• Vaccination: If possible, your child should receive all scheduled vaccinations before starting Yuflyma treatment.

Using Yuflyma with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. Do not take Yuflyma with medications that contain the following active ingredients due to an increased risk of severe infections:

• anakinra
• abatacept.

Yuflyma can be taken with:

• methotrexate
• certain disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and injectable gold preparations)
• corticosteroids or pain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs).

Consult your doctor if you have any doubts.

Pregnancy and breastfeeding

• Consider using effective birth control methods to avoid pregnancy and continue using them for at least 5 months after the last Yuflyma treatment.
• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor about using this medication.
• Yuflyma should only be used during pregnancy if necessary.
• A study on pregnancy found no increased risk of congenital defects when the mother received Yuflyma during pregnancy compared to mothers with the same disease who did not receive Yuflyma.
• Yuflyma can be used during breastfeeding.
• If you received Yuflyma during pregnancy, your child may be at higher risk of contracting an infection.
• It is essential to inform your child's doctors and other healthcare professionals about your use of Yuflyma during pregnancy before your child receives any vaccine. For more information on vaccines, see the "Warnings and precautions" section.

Driving and using machines

Yuflyma may have a small effect on your ability to drive, ride a bike, or use machines. You may experience a sensation of the room spinning and visual disturbances after using Yuflyma.

YUFLYMA contains sodium

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

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of 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 another dose of Yuflyma if you need a different dose.

Form and Route of Administration

Yuflyma is injected under the skin (subcutaneously).

Instructions for Use

See the section 7 “Instructions for Use” for detailed instructions on how to inject Yuflyma.

Using more Yuflyma than prescribed

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

Missing a dose

If you forget to administer an injection, you should inject the next dose of Yuflyma as soon as you remember. Then, administer the next dose as usual, as if you had not forgotten a dose.

Stopping treatment with 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 other questions about the use of this medication, ask your doctor or pharmacist.

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

Seek medical attention immediately if you notice any of the following side effects

• severe rash, urticaria, or other signs of allergic reaction
• swelling of face, hands, feet
• difficulty breathing, swallowing
• shortness of breath with physical activity or lying down, or swelling of feet.

Seek medical attention as soon as possible if you notice any of the following side effects

• signs of infection, such as fever, nausea, wounds, dental problems, burning sensation while urinating
• feeling of weakness or fatigue
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• open sore or lump that does not heal
• signs and symptoms of blood abnormalities such as persistent fever, rashes, bleeding, and pallor

The symptoms described above may be signs of the side effects mentioned below, 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, cough, sinusitis, pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• skin rash
• musculoskeletal pain

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and flu)
• gastrointestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes)
• ear infections
• oral infections (including dental infection and ulcers)
• reproductive system infections
• urinary tract infections
• fungus infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergy)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory changes such as tingling, itching, or numbness
• migraine
• nerve root compression (including lower back and leg pain)
• vision changes
• eye inflammation
• eyelid inflammation and swelling of the eye
• dizziness (feeling of spinning or dizziness)
• rapid pulse
• high blood pressure
• flushing
• hematomas (accumulation of blood outside of blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• indigestion, bloating, and heartburn
• acid reflux
• dry eye syndrome (including dry eyes and mouth)
• itching
• hives with itching
• hematomas
• skin inflammation (such as eczema)
• rotting of fingernails and toenails
• excessive sweating
• hair loss
• new onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• swelling (edema)
• fever
• decreased platelet count in blood, increasing the risk of bleeding or hematomas
• Impaired wound healing

Uncommon(may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections that occur when resistance to disease decreases)
• 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 system disorders that can affect the lungs, skin, and lymph nodes (the most common presentation is sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (feeling shaky)
• neuropathy (disorder of the nervous system)
• stroke
• loss of hearing, ringing in the ears
• sensation of irregular pulse like skipping
• heart problems that can cause difficulty breathing or swelling of ankles
• heart attack
• sac in the wall of a major artery, inflammation and coagulation in a vein, blockage of a blood vessel
• lung diseases that can cause difficulty breathing (including inflammation)
• pulmonary embolism (blockage of a lung artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial edema (swelling of the face)
• inflammation of the gallbladder, gallstones in the gallbladder
• steatosis (fatty liver)
• nocturnal sweating
• scarring
• abnormal muscle decomposition
• systemic lupus erythematosus (including skin, heart, lung, joint, and other organ inflammation)
• sleep interruptions
• impotence
• inflammations

Rare(may affect up to 1 in 1000 people)

• leukemia (cancer affecting the blood and bone marrow)
• severe allergic reaction with anaphylaxis
• multiple sclerosis
• neurological changes (such as optic nerve inflammation and Guillain-Barré syndrome that can cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scar tissue in 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 (initial symptoms include discomfort, fever, headache, and hives)
• facial edema associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized skin swelling)
• lichenoid reaction in the skin (red-purple hives with itching)

Frequency not known(cannot be estimated from available data)

• hepatosplenic lymphoma of T lymphocytes (rare blood cancer often fatal)
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi's sarcoma, a rare cancer related to human herpesvirus 8 infection. Kaposi's sarcoma usually appears as purple lesions on the skin.
• liver insufficiency
• worsening of a disease called dermatomyositis (seen as skin rash accompanied by muscle weakness)
• Weight gain (for most patients, weight gain was reduced)

Some side effects observed with Yuflyma may not have symptoms and can only be identified 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
• high levels of lipids in blood
• high levels of liver enzymes

Common(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• high bilirubin levels (liver function test in blood)

Rare(may affect up to 1 in 1000 people)

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after “CAD”.

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

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

Alternative storage:

When necessary (for example when traveling), you may store a preloaded Yuflyma pen with needle guard at room temperature (up to 25 °C) for a maximum period of 31 days (ensure it is protected from light). Once you have removed the pen from the refrigerator to store it at room temperature,you must use it within the next 31 days or discard it, even if you return it to the refrigerator.

You must note the date when you removed the pen from the refrigerator, and the date after which you must discard the pen.

Medicines should not be disposed of through drains or in the trash. Ask your doctor how to dispose of the medication that you no longer need. This will help protect the environment.

Composition of Yuflyma

The active ingredient is adalimumab.

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

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

Yuflyma 40 mg injectable solution in pre-filled syringe is supplied as a sterile solution of 40 mg of adalimumab dissolved in 0.4 ml of solution.

The pre-filled syringe of Yuflyma is a single-use disposable auto-injector system with a needle. There is a viewer on each side of the syringe through which you can see the Yuflyma solution inside the syringe.

The pre-filled syringe of Yuflyma is available in packs containing 1, 2, 4, and 6 pre-filled syringes.

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

Only some pack sizes may be marketed.

Yuflyma may be available in the form of a pre-filled syringe or a pre-filled pen.

Marketing Authorization Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B torony

Hungary

Manufacturer

Millmount Healthcare Ltd.

Block 7

City North Business Campus

Stamullen, Co. Meath K32 YD60

Ireland

Nuvisan GmbH

Wegenerstraße 13,

89231 Neu Ulm,

Germany

Nuvisan France SARL

2400, Route des Colles,

06410, Biot,

France

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicine 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 using the pre-filled syringe. First, read the instructions carefully and then follow them step by step.

• The doctor, nurse, or pharmacist will instruct you on the technique for self-administering the injection.

• Do notattempt to administer the injection yourself until you are sure you understand how to prepare and administer the injection.

• After you have been correctly instructed, you or another person, such as a family member or friend, can administer the injection.

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

Pre-filled syringe of Yuflyma

Figure A

Do not use the pre-filled syringe if:

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

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