Amgevita 20 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

AMGEVITA 20mg solution for injection in pre-filled syringe

AMGEVITA 40mg solution for injection in pre-filled syringe

AMGEVITA 80mg solution for injection in pre-filled syringe

adalimumab

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

• Keep this leaflet, as you may need to read it again.
• Your doctor will give you a patient information card containing important safety information you need to know before and during treatment with AMGEVITA. Keep this patient information card.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What AMGEVITA is and what it is used for

AMGEVITA contains the active substance adalimumab, a medicine that acts on the body's immune system (defence system).

AMGEVITA 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 AMGEVITA, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that target a specific structure.

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

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease affecting the joints.

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

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

AMGEVITA reduces joint damage to cartilage and bone caused by the disease and improves physical function.

AMGEVITA is usually used in combination with methotrexate. If your doctor determines that methotrexate is not appropriate, AMGEVITA may be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory joint diseases that typically first appear in childhood.

AMGEVITA is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age and enthesitis-related arthritis in patients from 6 years of age. You may have first received other disease-modifying drugs such as methotrexate. If you do not respond adequately to these medicines, you will receive AMGEVITA to treat your polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis

Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory diseases affecting the spine.

AMGEVITA is used to treat ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be treated with other medicines, and if you do not respond sufficiently to these, you will receive AMGEVITA to reduce the signs and symptoms of your disease.

Psoriatic arthritis

Psoriatic arthritis is joint inflammation associated with psoriasis.

AMGEVITA is used to treat psoriatic arthritis in adults. AMGEVITA reduces joint damage caused by the disease in cartilage and bone and improves physical function.

Plaque psoriasis in adults and children

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, or lift from the nail bed, which can be painful. Psoriasis is believed to be caused by a defect in the body's immune system leading to increased production of skin cells.

AMGEVITA is used to treat moderate to severe plaque psoriasis in adults. AMGEVITA is also used to treat severe 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 in adults and adolescents

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 typically affects specific areas of the skin such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also occur in affected areas.

AMGEVITA is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. AMGEVITA may reduce the number of nodules and abscesses and the pain usually associated with this disease. You may have received other medicines previously. If you do not respond adequately to these medicines, you will receive AMGEVITA.

Crohn’s disease in adults and children

Crohn’s disease is an inflammatory disease of the digestive tract.

AMGEVITA is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s disease, you will first be treated with other medicines. If you do not respond sufficiently to these medicines, you will receive AMGEVITA to reduce the signs and symptoms of Crohn’s disease.

Ulcerative colitis in adults and children

Ulcerative colitis is an inflammatory disease of the large intestine.

AMGEVITA is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you may first be prescribed other medicines. If you do not respond well to these medicines, AMGEVITA will be prescribed to reduce the signs and symptoms of your disease.

Non-infectious uveitis in adults and children

Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.

AMGEVITA is used to treat:

• Adults with non-infectious uveitis with inflammation affecting the posterior part of the eye.
• 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 decreased vision and/or the presence of floaters (black spots or thin lines moving across the field of vision). AMGEVITA works by reducing this inflammation.

2. What you need to know before using AMGEVITA

Do not use AMGEVITA

• if you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have a serious infection, including active tuberculosis, sepsis (blood infection), or other opportunistic infections (unusual infections associated with a weakened immune system) (see “Warnings and precautions”). If you have symptoms of any infection, for example: fever, wounds, fatigue, or dental problems, it is important to inform your doctor.
• if you have moderate or severe heart failure. It is important to tell your doctor if you have had or currently have any serious heart problems (see “Warnings and precautions”).

Warnings and precautions

Talk to your doctor or pharmacist before starting to use AMGEVITA:

Allergic reactions

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

Infections

• If you have any infection, including chronic or localized infections (for example: a leg ulcer), consult your doctor before starting treatment with AMGEVITA. If you are unsure, contact your doctor.
• While being treated with AMGEVITA, you may be more likely to get infections. 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, other opportunistic infections, and sepsis, which could, in rare cases, be life-threatening. Therefore, it is important to inform your doctor if you develop symptoms such as fever, wounds, fatigue, or dental problems. Your doctor may recommend temporarily stopping treatment with AMGEVITA.

Tuberculosis

• Cases of tuberculosis have been reported in patients treated with adalimumab. Therefore, your doctor will examine you for signs or symptoms of tuberculosis before starting treatment with AMGEVITA. 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. It is very important to inform your doctor if you have had tuberculosis or have been in contact with someone who has tuberculosis.
• Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis.
• If symptoms of tuberculosis (persistent cough, weight loss, general malaise, low-grade fever) or any other infection appear during or after treatment, contact your doctor immediately.

Recurrent infections/travel

• Inform your doctor if you live in or travel to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.
• Inform your doctor if you have a history of recurrent infections or other conditions or risk factors that increase the likelihood of infections.

Hepatitis B virus

• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have had active HBV infection, or if you think you may be at risk of contracting HBV. Your doctor should perform a test for HBV. AMGEVITA may cause reactivation of HBV in carriers of this virus. In rare cases, especially if you are taking other medicines that suppress the immune system, HBV reactivation can be life-threatening.

Over 65 years of age

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

Surgical or dental procedures

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

Demyelinating disease

• If you have or develop a demyelinating disease such as multiple sclerosis, your doctor will decide whether you should be treated or continue treatment with AMGEVITA. 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.

Vaccines

• Certain vaccines contain live but weakened bacteria or viruses that can cause diseases and lead to infections and should not be administered while being treated with AMGEVITA. Consult your doctor before receiving any type of vaccine. If possible, it is recommended that children update their vaccination schedule according to current vaccination guidelines before starting treatment with AMGEVITA.
• If you receive AMGEVITA while pregnant, your child may have an increased risk of infections for approximately 5 months after your last dose of AMGEVITA during pregnancy. It is important to inform your child’s doctor and other healthcare professionals about your use of AMGEVITA 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 AMGEVITA, your doctor should continuously monitor your heart condition. It is important to inform your doctor if you have had or currently have serious heart problems. 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 taking AMGEVITA.

Fever, bruising, bleeding, or paleness

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

Cancer

• Very rarely, certain types of cancer have been reported in children and adults treated with adalimumab or other TNF blockers. People with more severe rheumatoid arthritis and long-standing disease 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 are being treated with AMGEVITA, your risk of developing lymphoma, leukemia, and other types of cancer may increase. A specific and serious type of lymphoma has been observed, albeit rarely, in patients treated with adalimumab. Some of these patients were also receiving azathioprine or 6-mercaptopurine. Inform your doctor if you are taking azathioprine or 6-mercaptopurine with AMGEVITA.
• In addition, cases of non-melanoma skin cancer have been observed in patients using adalimumab. 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 blocker. If you have COPD or are a heavy smoker, consult your doctor to determine whether treatment with a TNF blocker is appropriate for you.

Autoimmune diseases

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

To improve traceability of this medicine, your doctor or pharmacist should record the name and batch number of the medicine administered in your medical record. If requested in the future, you may also note down these details.

Children and adolescents

• Vaccines: If possible, your child should be up to date with all recommended vaccines before using AMGEVITA.

• Do not administer AMGEVITA to children under 2 years of age with polyarticular juvenile idiopathic arthritis.

• Do not administer AMGEVITA to children under 4 years of age with plaque psoriasis.

• Do not administer AMGEVITA to children under 6 years of age with Crohn’s disease or ulcerative colitis.

Using AMGEVITA with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

AMGEVITA may be taken together with methotrexate or certain disease-modifying antirheumatic drugs (DMARDs) (sulfasalazine, hydroxychloroquine, leflunomide, and injectable gold salts), steroids, or pain medications, including non-steroidal anti-inflammatory drugs (NSAIDs).

You must not use AMGEVITA together with medicines containing anakinra or abatacept due to an increased risk of serious infections. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should consider using appropriate contraceptive methods to avoid becoming pregnant and continue using them for at least 5 months after your last dose of AMGEVITA.
• If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor about using this medicine.
• AMGEVITA should be used during pregnancy only if clearly needed.
• According to a pregnancy study, there was no increased risk of congenital malformations when mothers received AMGEVITA during pregnancy compared to mothers with the same condition who did not receive AMGEVITA.
• AMGEVITA may be used during breastfeeding.
• If you use AMGEVITA while pregnant, your child may have a higher risk of infection.
• It is important to inform your child’s pediatrician and other healthcare professionals about your use of AMGEVITA during pregnancy before your baby receives any vaccines. For more information on vaccines, see the section “Warnings and precautions”.

Driving and using machines

The effect of AMGEVITA on the ability to drive, ride a bicycle, or operate machinery is minor. Dizziness (vertigo) and vision disturbances may occur after taking AMGEVITA.

AMGEVITA contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose; hence, it is essentially “sodium-free”.

3. How to use AMGEVITA

Follow exactly the instructions for administration of this medicine as given by your doctor. If in doubt, consult your doctor again.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis

AMGEVITA is injected under the skin (subcutaneous route). The usual dose in adults with rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, and in patients with psoriatic arthritis is 40 mg administered every other week as a single dose.

In the case of rheumatoid arthritis, treatment with methotrexate is maintained during AMGEVITA use. If your doctor determines that methotrexate is inappropriate, AMGEVITA may be given alone.

If you have rheumatoid arthritis and are not receiving methotrexate during your treatment with AMGEVITA, your doctor may decide to give you 40 mg weekly or 80 mg every two weeks.

Children, adolescents and adults with polyarticular juvenile idiopathic arthritis

Children and adolescents from 2 years of age weighing 10 kg up to 30 kg

The recommended dose of AMGEVITA is 20 mg every other week.

Children, adolescents and adults from 2 years of age weighing 30 kg or more

The recommended dose of AMGEVITA is 40 mg administered every other week.

Children, adolescents and adults with enthesitis-related arthritis

Children and adolescents from 6 years of age weighing 15 kg up to 30 kg

The recommended dose of AMGEVITA is 20 mg every other week.

Children, adolescents and adults from 6 years of age weighing 30 kg or more

The recommended dose of AMGEVITA is 40 mg every other week.

Adults with plaque psoriasis

The usual dosage regimen in adults with plaque psoriasis consists of an initial dose of 80 mg, followed by 40 mg every other week starting one week after the initial dose. You should continue injecting AMGEVITA for as long as your doctor has instructed. Depending on your response, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.

Children and adolescents with plaque psoriasis

Children and adolescents from 4 to 17 years of age weighing 15 kg up to 30 kg

The recommended dose of AMGEVITA is an initial dose of 20 mg followed by 20 mg one week later. Thereafter, the usual dose is 20 mg every other week.

Children and adolescents from 4 to 17 years of age weighing 30 kg or more

The recommended dose of AMGEVITA is an initial dose of 40 mg, followed by 40 mg one week later. Thereafter, the usual dose is 40 mg every other week.

Adults with hidradenitis suppurativa

The usual dosage regimen for hidradenitis suppurativa is an initial dose of 160 mg (two injections of 80 mg on one day or one injection of 80 mg per day for two consecutive days), followed by a dose of 80 mg 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 liquid daily on the affected areas.

Adolescents with hidradenitis suppurativa aged 12 to 17 years weighing 30 kg or more

The recommended dose of AMGEVITA is an initial dose of 80 mg, followed by 40 mg every other week starting one week later. If you have an inadequate response to AMGEVITA 40 mg every other week, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.

It is recommended that you use an antiseptic liquid daily on the affected areas.

Adults with Crohn's disease

The usual dosage regimen for Crohn's disease is an initial dose of 80 mg, followed by 40 mg every other week starting two weeks later. If a more rapid response is required, your doctor may prescribe an initial dose of 160 mg (two injections of 80 mg on one day or one injection of 80 mg per day for two consecutive days), followed by 80 mg two weeks later, and then 40 mg every other week. Depending on your response, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.

Children and adolescents with Crohn's disease

Children and adolescents from 6 to 17 years of age weighing less than 40 kg

The usual dosage regimen is an initial dose of 40 mg followed by 20 mg two weeks later. If a more rapid response is required, your doctor may prescribe an initial dose of 80 mg followed by 40 mg two weeks later.

Thereafter, the usual dose is 20 mg every other week. Depending on your response, your doctor may increase the dosing frequency to 20 mg weekly.

Children and adolescents from 6 to 17 years of age weighing 40 kg or more

The usual dosage regimen is an initial dose of 80 mg followed by 40 mg two weeks later. If a more rapid response is required, your doctor may prescribe an initial dose of 160 mg (two injections of 80 mg on one day or one injection of 80 mg per day for two consecutive days) followed by 80 mg two weeks later.

Thereafter, the usual dose is 40 mg every other week. Depending on your response, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.

Adults with ulcerative colitis

The usual dosage of AMGEVITA in adults with ulcerative colitis is an initial dose of 160 mg (two injections of 80 mg on one day or one injection of 80 mg per day for two consecutive days), followed by 80 mg two weeks later, and then 40 mg every other week. Depending on your response, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.

Children and adolescents with ulcerative colitis

Children and adolescents from 6 years of age weighing less than 40 kg

The usual dose of AMGEVITA is 80 mg initially, followed by a dose of 40 mg (as a single 40 mg injection) two weeks later. Thereafter, the usual dose is 40 mg every other week.

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

Children and adolescents from 6 years of age weighing 40 kg or more

The usual dose of AMGEVITA is 160 mg (two injections of 80 mg on one day or one injection of 80 mg per day for two consecutive days) initially, followed by a dose of 80 mg two weeks later. Thereafter, the usual dose is 80 mg every other week.

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

Adults with non-infectious uveitis

The usual dose in adults with non-infectious uveitis is an initial dose of 80 mg, followed by 40 mg every other week starting one week after the initial dose. You should continue injecting AMGEVITA for as long as your doctor has instructed.

In non-infectious uveitis, treatment with corticosteroids or other medications affecting the immune system may be continued during AMGEVITA use. AMGEVITA may also be administered alone.

Children and adolescents from 2 years of age with chronic non-infectious uveitis

Children and adolescents from 2 years of age weighing less than 30 kg

The usual dose of AMGEVITA is 20 mg every other week together with methotrexate.

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

Children and adolescents from 2 years of age weighing 30 kg or more

The usual dose of AMGEVITA is 40 mg every other week together with methotrexate.

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

Method and route of administration

AMGEVITA is injected under the skin (subcutaneous route).

Detailed instructions on how to inject AMGEVITA are provided in the section “Instructions for use”.

If you use more AMGEVITA than you should

If you accidentally inject AMGEVITA more frequently than prescribed by your doctor, inform your doctor. Always carry the medicine carton with you, even if it is empty.

If you forget to use AMGEVITA

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

If you stop using AMGEVITA

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

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. Adverse effects may occur for at least up to 4 months after the last injection of AMGEVITA.

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

• severe rash, hives, or other signs of allergic reaction;
• swelling of the face, hands, feet;
• difficulty breathing or swallowing;
• shortness of breath during exercise or when lying down, 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, burning sensation when urinating;
• feeling weak or tired;
• cough;
• tingling;
• numbness;
• double vision;
• weakness in arms or legs;
• signs of skin cancer such as a lump or an 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 adverse effects listed below, which have been observed with adalimumab.

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

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

Common (may affect up to 1 in 10 people)

• serious infections (including blood poisoning and flu);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes);
• ear infection;
• oral infections (including dental infection and mouth ulcers);
• infections of the reproductive system;
• urinary tract infection;
• fungal infections;
• joint infection;
• 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);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (feeling of spinning or lightheadedness);
• sensation of rapid heartbeat;
• high blood pressure;
• flushing;
• bruising;
• cough;
• asthma;
• difficulty breathing;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, and heartburn);
• acid reflux;
• dry eye syndrome (including dry eyes and mouth);
• itching;
• itchy rash;
• bruising;
• skin inflammation (such as eczema);
• cracking or splitting of fingernails and toenails;
• increased sweating;
• hair loss;
• new-onset psoriasis or worsening of existing psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema;
• fever;
• decreased platelet count in blood, increasing the risk of bleeding or bruising;
• problems with wound healing.

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections that occur when resistance to disease is reduced);
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• cancer, including cancer affecting the lymphatic system (lymphoma) and melanoma (skin cancer);
• immune system disorders that may affect the lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy;
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause difficulty breathing or swollen ankles;
• heart attack;
• aneurysm (ballooning of a major artery wall), inflammation and clotting in a vein, blockage of a blood vessel;
• lung diseases that may cause difficulty breathing (including inflammation);
• pulmonary embolism (blockage of an artery in the lungs);
• pleural effusion (abnormal fluid accumulation in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema;
• gallbladder inflammation; gallstones;
• fatty liver;
• night sweats;
• scarring;
• abnormal muscle spasms;
• 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 1,000 people)

• leukemia (cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• nerve 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 intestinal wall);
• hepatitis (inflammation of the liver);
• 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 (a potentially life-threatening reaction with flu-like symptoms and blistering rash);
• facial edema associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized skin swelling);
• 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, an uncommon cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma usually presents more frequently as purplish skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (seen as skin rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain was minimal).

Some adverse effects observed with adalimumab do 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 count of white blood cells;
• low blood count of red blood cells;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• high blood count of white blood cells;
• low blood count of platelets;
• increased blood uric acid;
• abnormal blood sodium levels;
• low blood calcium;
• low blood phosphate;
• high blood sugar;
• high blood lactate dehydrogenase levels;
• presence of autoantibodies in blood;
• low blood potassium.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (liver function test).

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

• low blood counts of 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 included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of AMGEVITA

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

Do not use this medicine after the expiry date stated on the label/blister and outer packaging after EXP or CAD. The expiry date refers to the last day of the month indicated.

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

Keep in the original packaging to protect from light.

A single pre-filled syringe of AMGEVITA may be stored at temperatures not exceeding 25 °C for a maximum period of 14 days. The pre-filled syringe must be protected from light and must be discarded if not used within 14 days.

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

6. Contents of the pack and other information

Composition of AMGEVITA

• The active substance is adalimumab. Each pre-filled syringe contains 20 mg of adalimumab in 0.2 ml of solution, 40 mg of adalimumab in 0.4 ml of solution, or 80 mg of adalimumab in 0.8 ml of solution.
• The other components are L-lactic acid, sucrose, polysorbate 80, sodium hydroxide, and water for injections.

Nature of the product and pack contents

AMGEVITA is a clear, colourless to slightly yellowish solution.

Each pack contains 1 single-use 20 mg pre-filled syringe (with a yellow plunger).

Each pack contains 1, 2, or 6 single-use 40 mg pre-filled syringes (with a blue plunger).

Each pack contains 1, 2, or 3 single-use 80 mg pre-filled syringes (with an orange plunger).

Marketing Authorization Holder and Manufacturer

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

The Netherlands

Marketing Authorization Holder

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

The Netherlands

Manufacturer

Amgen Technology Ireland UC

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorization Holder.

Belgium/Belgium/Belgium s.a. Amgen n.v. Tel/Tel: +32 (0)2 7752711	Lithuania Amgen Switzerland AG Vilnius Branch Tel.: +370 5 219 7474
	Luxembourg/Luxembourg s.a. Amgen Belgium/Belgium Tel/Tel: +32 (0)2 7752711
Czech Republic Amgen s.r.o. Tel: +420 221 773 500	Hungary Amgen Kft. Tel.: +36 1 35 44 700
Denmark Amgen, branch of Amgen AB, Sweden Tlf: +45 39617500	Malta Amgen S.r.l. Italy Tel: +39 02 6241121
Germany Amgen GmbH Tel.: +49 89 1490960	Netherlands Amgen B.V. Tel: +31 (0)76 5732500
Estonia Amgen Switzerland AG Vilnius Branch Tel: +372 586 09553	Norway Amgen AB Tlf: +47 23308000
Greece Amgen Hellas Pharmaceutical E.P.E. Tel: +30 210 3447000	Austria Amgen GmbH Tel: +43 (0)1 50 217
Spain Amgen S.A. Tel: +34 93 600 18 60	Poland Amgen Biotechnologia Sp. z o.o. Tel.: +48 22 581 3000
France Amgen S.A.S. Tél: +33 (0)9 69 363 363	Portugal Amgen Biofarmacêutica, Lda. Tel: +351 21 4220606
Croatia Amgen d.o.o. Tel: +385 (0)1 562 57 20	Romania Amgen România SRL Tel: +4021 527 3000
Ireland Amgen Ireland Limited Tel: +353 1 8527400	Slovenia AMGEN zdravila d.o.o. Tel: +386 (0)1 585 1767
Iceland Vistor hf. Tel: +354 535 7000	Slovakia Amgen Slovakia s.r.o. Tel: +421 2 321 114 49
Italy Amgen S.r.l. Tel: +39 02 6241121	Finland Amgen AB, branch in Finland/Amgen AB, filial i Finland Puh/Tel: +358 (0)9 54900500
Cyprus C.A. Papaellinas Ltd Tel: +357 22741 741	Sweden Amgen AB Tel: +46 (0)8 6951100
Latvia Amgen Switzerland AG Riga Branch Tel: +371 257 25888

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.

INSTRUCTIONS FOR USE

Get to know your pre-filled syringe

1	Important information you need to know before AMGEVITA injection
Administration: AMGEVITA is administered in three different doses: 20 mg/0.2 ml, 40 mg/0.4 ml, 80 mg/0.8 ml. Check your prescription to ensure you have the correct dose. The color and appearance of the pre-filled syringe will differ for each dose. The amount of medication in the pre-filled syringe will also differ for each dose. For example, it is normal for the 20 mg/0.2 ml dose to contain a small amount of medication and the 80 mg/0.8 ml dose to contain a larger amount. Check the images below to see how your medication appears in the pre-filled syringe.
Use of the AMGEVITA pre-filled syringe: It is important that you do not attempt to self-administer the injection until you have read and fully understood these instructions for use and have received training from your doctor or healthcare professional. Do not use the pre-filled syringe if the carton is damaged or the seal is broken. Do not use the pre-filled syringe after the expiry date printed on the label. Do not shake the pre-filled syringe. Do not remove the needle cap from the pre-filled syringe until you are ready to inject. Do not use the pre-filled syringe if it has been frozen. Do not use the pre-filled syringe if it has been dropped on a hard surface. A component of the pre-filled syringe may be broken even if you cannot see the damage. Use a new pre-filled syringe and contact your doctor or healthcare professional. The pre-filled syringe is not made with natural rubber latex. Important: Keep the pre-filled syringe and sharps disposal containers out of sight and reach of children.

2	Preparation for AMGEVITA injection
2a	Grasp the pre-filled syringe by the barrel to remove it from the tray.
Do not grasp by the wings, plunger rod, or needle cap. Remove the number of pre-filled syringes needed for the injection. Return all unused pre-filled syringes to the refrigerator.

2b	Wait 30 minutes for the prefilled syringe to reach room temperature.
WAIT 30 minutes
Allow the prefilled syringe to warm to room temperature naturally. Do not heat it with warm water, in a microwave, or by placing it directly in sunlight. Do not shake the prefilled syringe at any time. Do not return the syringe to the refrigerator once it has reached room temperature. Using the prefilled syringe at room temperature allows for a more comfortable injection.

2c	Gather and place the injection materials on a clean, well-lit surface.
AMGEVITA pre-filled syringe (at room temperature) A sharps disposal container Alcohol wipes A bandage Cotton ball or gauze

3	Injection preparation
3a	Inspect the medication.
It should be clear and colorless to slightly yellowish. It is normal for air bubbles to appear in the pre-filled syringe. Do not use if the medication is cloudy, discolored, or contains flakes or particles. Important: If the medication is cloudy, discolored, or contains flakes or particles, contact your doctor or healthcare professional.

3b	Check the expiration date (EXP) and inspect the pre-filled syringe for any damage.

Do not use if the expiration date has passed. Do not use the pre-filled syringe if: The needle cap is missing or loose. Any component is cracked or broken. It has been dropped on a hard surface. Important: If the medication in the pre-filled syringe is damaged or has expired, contact your doctor or healthcare professional.

3c	Inject in one of these areas.
Inject in the thigh or abdomen (except for the area within 5 centimeters around the navel). Choose a different site for each injection. Wash your hands thoroughly with soap and water. Clean the injection site with an alcohol wipe. Allow the skin to dry on its own. Do not touch this area again before the injection. Important: Avoid areas with scars or stretch marks, or where the skin is tender, bruised, red, or hard.

4	AMGEVITA Injection
Important: Remove the needle cap only when you are ready to inject (within 5 minutes prior) as the medication may dry out.
4a	Pull off the needle cap while holding the body of the pre-filled syringe.
Do not twist or bend the needle cap. Do not re-cap the needle onto the syringe, as this may damage the needle. Avoid letting the needle touch anything once the cap has been removed. Do not place the uncapped pre-filled syringe on any surface once the needle cap has been removed. Do not attempt to remove air bubbles from the pre-filled syringe, as they are not a problem. It is normal for the medicine to drip slightly.

4b	Pinch the skin around the injection site before the injection.
PINCH
Pinch the skin between your thumb and index finger to create a raised area for the injection. If possible, the raised area should be about 5 centimeters wide.

4c	Insert the needle into the pinched skin.
INSERT
Insert the needle into the pinched skin at an angle between 45 and 90 degrees. Do not place your finger on the plunger while inserting the needle, as this may cause loss of medication.

4d	Slowly push the plunger to the bottom of the pre-filled syringe to inject the medication.
INJECT
Do not pull back on the plunger at any time. Do not remove the syringe until all of the medication has been administered. Important: Continue pinching the skin until the injection is complete.

5	Discontinuation and completion of AMGEVITA administration
Important: Do not recap the needle.
5a	Dispose of the used pre-filled syringe and needle cap into a sharps disposal container.
Do not recycle the prefilled syringe or dispose of it in the trash. Do not reuse the used pre-filled syringe. Do not use any remaining medicine in the used pre-filled syringe. Dispose of the used AMGEVITA syringe into a sharps disposal container immediately after use. Do not throw (discard) the syringe in the household trash. Ask your doctor or pharmacist how to properly dispose of the syringes. There may be local regulations regarding this. Do not recycle the syringe or the sharps disposal container, and do not throw them in the trash. Important: Always keep the sharps disposal container out of sight and reach of children.

5b	Examine the injection site.
Do not rub the injection site. If you see blood, press a cotton ball or gauze on the injection site. Apply a bandage if necessary.