AMGEVITA 40 mg SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the Patient

AMGEVITA 20 mg solution for injection in pre-filled syringe

AMGEVITA 40 mg solution for injection in pre-filled syringe

Adalimumab

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

• Keep this leaflet, you may need to read it again.
• Your doctor will give you a patient information card, which contains important safety information that you need to know before and during treatment with AMGEVITA. Keep this patient information card.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is AMGEVITA and what is it used for

AMGEVITA contains the active substance adalimumab.

AMGEVITA is indicated for the treatment of inflammatory diseases described below:

• Rheumatoid arthritis

• Juvenile idiopathic polyarticular arthritis

• Enthesitis-related arthritis

• Ankylosing spondylitis

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

The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the immune system (defence) and is found at high levels in the inflammatory diseases described above. By targeting TNFα, AMGEVITA reduces the inflammation process in these diseases.

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease of the joints.

AMGEVITA is used to treat rheumatoid arthritis in adults. If you have moderate to severe active rheumatoid arthritis, you may have been given other medicines that modify the disease, such as methotrexate, beforehand. If you do not respond well enough to these medicines, you will be given AMGEVITA to treat your rheumatoid arthritis.

AMGEVITA can also be used to treat severe, active, and progressive rheumatoid arthritis without prior treatment with methotrexate.

AMGEVITA reduces the damage to the cartilage and bones of the joints caused by the disease and improves physical function.

AMGEVITA is usually used in combination with methotrexate. If your doctor decides that methotrexate is not suitable for you, AMGEVITA can be given alone.

Juvenile idiopathic polyarticular arthritis and enthesitis-related arthritis

Juvenile idiopathic polyarticular arthritis and enthesitis-related arthritis are inflammatory diseases.

AMGEVITA is used to treat juvenile idiopathic polyarticular arthritis in patients from 2 years of age and enthesitis-related arthritis in patients from 6 years of age. You may have been given other disease-modifying medicines, such as methotrexate, beforehand. If you do not respond well enough to these medicines, you will be given AMGEVITA to treat your juvenile idiopathic polyarticular arthritis or enthesitis-related arthritis.

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory diseases that affect the spine.

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

Psoriatic arthritis

Psoriatic arthritis is an inflammation of the joints associated with psoriasis.

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

Plaque psoriasis in adults and children

Plaque psoriasis is a skin disease that causes red, scaly, crusty, and silvery-scaled areas. Plaque psoriasis can also affect the nails, causing them to deteriorate, thicken, and lift off the nail bed, which can be painful. It is believed that psoriasis is caused by a defect in the body's immune system that leads to an increase in skin cell production.

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 between 4 and 17 years of age who have not responded or are not candidates for topical treatment and phototherapies.

Hidradenitis suppurativa in adults and adolescents

Hidradenitis suppurativa (also known as inverse acne) is a chronic and often painful inflammatory skin disease. Symptoms can include sensitive nodules (lumps) and abscesses (boils) that can secrete pus. It usually affects specific areas of the skin, such as under the breast, armpits, inner thighs, groin, and buttocks. There can also be scarring in the affected areas.

AMGEVITA is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age. AMGEVITA can reduce the number of nodules and abscesses and the pain that is usually associated with this disease. You may have been given other medicines beforehand. If you do not respond well enough to these medicines, you will be given 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 between 6 and 17 years of age. If you have Crohn's disease, you will be treated with other medicines first. If you do not respond well enough to these medicines, you will be given 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 between 6 and 17 years of age. If you have ulcerative colitis, you may be given other medicines first. If you do not respond well to these medicines, you will be given AMGEVITA to reduce the signs and symptoms of your disease.

Non-infectious uveitis in adults and children

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

AMGEVITA is used to treat

• Adults with non-infectious uveitis with inflammation that affects the back of the eye.

• Children from 2 years of age with chronic non-infectious uveitis with inflammation that affects the front of the eye.

This inflammation can lead to a decrease in vision and/or the presence of floaters in the eye (black dots or thin lines that move along the field of vision). AMGEVITA works by reducing this inflammation.

2. What you need to know before you start using AMGEVITA

Do not use AMGEVITA

Warnings and precautions

Consult your doctor or pharmacist before starting to use AMGEVITA:

Allergic reactions

Infections

Tuberculosis

Recurrent/Travel-related infections

Hepatitis B virus

Being over 65 years old

Surgical or dental interventions

Demyelinating disease

Vaccines

Heart failure

Fever, bruising, bleeding, or paleness

Cancer

Autoimmune diseases

In order to improve the traceability of this medicine, your doctor or pharmacist should record the name and batch number of the administered medicine in your medical history. If you are asked for this information in the future, you can also take note of these details.

Children and adolescents

Using AMGEVITA with other medicines

Inform your doctor or pharmacist if you are taking or have recently taken or may need to take any other medicine.

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

Do not use AMGEVITA with medicines whose active substances are anakinra or abatacept due to an increased risk of severe infections. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

Driving and using machines

The influence of AMGEVITA on the ability to drive, ride a bicycle, or use machines is small. You may experience dizziness and vision disturbances after taking AMGEVITA.

AMGEVITA contains sodium

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

3. How to use AMGEVITA

Follow the administration instructions for this medication exactly as indicated by your doctor. In case of 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 (subcutaneously). The normal dose in adults with rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, and for 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 the use of AMGEVITA. If your doctor determines that methotrexate is inappropriate, AMGEVITA can be administered alone.

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

Children, adolescents, and adults with juvenile idiopathic polyarticular arthritis

Children and adolescents from 2 years of age with a weight of 10 kg to 30 kg

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

Children, adolescents, and adults from 2 years of age with a weight of 30 kg or more

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

Children, adolescents, and adults with arthritis associated with enthesitis

Children and adolescents from 6 years of age with a weight of 15 kg to 30 kg

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

Children, adolescents, and adults from 6 years of age with a weight of 30 kg or more

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

Adults with plaque psoriasis

The normal dosage in adults with plaque psoriasis consists of an initial dose of 80 mg (as two 40 mg injections on one day), 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 indicated. 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 with a weight of 15 kg to 30 kg

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

Children and adolescents from 4 to 17 years of age with a weight of 30 kg or more

The recommended dose of AMGEVITA is an initial dose of 40 mg, followed by 40 mg one week later. From then on, 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 (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by a dose of 80 mg (as two 40 mg injections on one day) two weeks later. After two more 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 from 12 to 17 years of age, with a weight of 30 kg or more

The recommended dose of AMGEVITA is an initial dose of 80 mg (as two 40 mg injections on one day), 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 80 mg (as two 40 mg injections on one day) initially, followed by 40 mg every other week starting two weeks later. If a faster response is required, your doctor may prescribe an initial dose of 160 mg (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (as two 40 mg injections on one day) 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 with a weight below 40 kg

The usual dosage regimen is 40 mg initially, followed by 20 mg two weeks later. If a faster response is required, your doctor may prescribe an initial dose of 80 mg (as two 40 mg injections on one day) followed by 40 mg two weeks later.

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

Children and adolescents from 6 to 17 years of age with a weight of 40 kg or more

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

From then on, 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 normal dosage of AMGEVITA in adults with ulcerative colitis is 160 mg initially (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (as two 40 mg injections on one day) 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 with a weight below 40 kg

The usual dose of AMGEVITA is 80 mg (as two 40 mg injections on one day) initially, followed by a dose of 40 mg (as one 40 mg injection) two weeks later. From then on, the usual dose is 40 mg every other week.

Patient who reach 18 years of age while receiving treatment with 40 mg every other week should continue with their prescribed dose.

Children and adolescents from 6 years of age with a weight of 40 kg or more

The usual dose of AMGEVITA is 160 mg (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days) initially, followed by a dose of 80 mg (as two 40 mg injections on one day) two weeks later. From then on, the usual dose is 80 mg every other week.

Patient who reach 18 years of age 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 (as two 40 mg injections on one day), 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 indicated.

In non-infectious uveitis, treatment with corticosteroids or other medications that affect the immune system may be continued during the use of AMGEVITA. 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 with a weight below 30 kg

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

Your pediatrician may prescribe an initial dose of 40 mg that can be administered one week before starting the usual regimen.

Children and adolescents from 2 years of age with a weight of 30 kg or more

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

Your pediatrician may prescribe an initial dose of 80 mg that can be administered one week before starting the usual regimen.

Form and route of administration

AMGEVITA is injected under the skin (subcutaneously).

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

If you use more AMGEVITA than you should

If you accidentally inject AMGEVITA more frequently than scheduled by your doctor, inform your doctor. Always carry the medicine box 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, the next dose will be administered as usual, as if you had not forgotten a dose.

If you stop treatment with AMGEVITA

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

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate. However, some can be serious and require treatment. Side effects may appear 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 allergic reaction or heart failure:

• severe rash, hives, or other signs of allergic reaction;
• swelling of the face, hands, feet;
• difficulty breathing, swallowing;
• shortness of breath when exercising or when lying down, swelling of 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 of weakness or fatigue;
• cough;
• tingling;
• numbness;
• double vision;
• weakness in arms or legs;
• signs of skin cancer such as a lump or an open sore 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 colds, 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 sepsis 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 infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• difficulty sleeping;
• sensory disturbances such as tingling, prickling, or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• vertigo (feeling of dizziness or as if the room is spinning);
• feeling of rapid heartbeat;
• high blood pressure;
• flushing;
• bruising;
• cough;
• asthma;
• difficulty breathing;
• gastrointestinal bleeding;
• indigestion (indigestion, bloating, and heartburn);
• acid reflux;
• dry eye syndrome (including dryness in eyes and mouth);
• itching;
• pruritic rash;
• bruising;
• skin inflammation (such as eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• new onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema;
• fever;
• decrease in platelet count in blood, which increases the risk of bleeding or bruising;
• wound healing problems.

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections that occur when disease resistance decreases);
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• cancer, including cancer that affects the lymphatic system (lymphoma) and melanoma (skin cancer);
• immune system disorders that can affect the lungs, skin, and lymph nodes (the most common presentation is sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy;
• stroke;
• hearing loss, tinnitus;
• feeling of irregular heartbeat like skips;
• heart problems that can cause difficulty breathing or swelling of ankles;
• heart attack;
• aneurysm (balloon in the wall of a major artery), inflammation, and clotting in a vein, blockage of a blood vessel;
• lung diseases that can cause difficulty breathing (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal fluid storage in the pleural space);
• pancreatitis (inflammation of the pancreas that causes severe abdominal and back pain);
• difficulty swallowing;
• facial edema;
• gallbladder inflammation; gallstones;
• fatty liver;
• night sweats;
• scarring;
• abnormal muscle crisis;
• systemic lupus erythematosus (including skin inflammation, heart, lungs, joints, and other organs);
• sleep disturbances;
• impotence;
• inflammations.

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

• leukemia (cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• nerve disorders (such as optic neuritis and Guillain-Barré syndrome that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring in the lung);
• intestinal perforation (hole in the intestinal wall);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B virus;
• autoimmune hepatitis (inflammation of the liver caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (potentially fatal reaction with flu-like symptoms and rash with blisters);
• facial edema associated with allergic reactions;
• erythema multiforme (inflammatory rash on the skin);
• lupus-like syndrome;
• angioedema (localized skin inflammation);
• lichenoid skin reaction (purple-red rash with itching).

Frequency not known (cannot be estimated from the 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 related to human herpesvirus 8 infection. Kaposi's sarcoma usually occurs more frequently as purple skin lesions;
• liver failure;
• worsening of a disease called dermatomyositis (seen as a skin rash accompanied by muscle weakness);
• weight gain (for most patients, weight gain was reduced).

Some side effects observed with adalimumab do not have symptoms and can only be identified through a blood test. These include:

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

• low white blood cell count;
• low red blood cell count;
• increased lipids in blood;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• high white blood cell count;
• low platelet count;
• increased uric acid 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).

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

• low counts in blood for white blood cells, red blood 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 (see details below). By reporting side effects, you can help provide more information on the safety of this medication.

Spanish Medicines for Human Use Pharmacovigilance System:

www.notificaRAM.es

5. Storage of AMGEVITA

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

Do not use this medicine after the expiry date which is stated on the label/blister and on the carton after EXP or CAD. The expiry date is the last day of the month shown.

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

Store in the original package to protect from light.

You can store a single AMGEVITA pre-filled syringe at temperatures up to a maximum of 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 no longer required. This will help protect the environment.

6. Package contents and additional information

Composition of AMGEVITA

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

Appearance and package contents of the product

AMGEVITA is a clear, colorless to slightly yellowish solution.

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

Each pack contains 1, 2, 4, or 6 single-use pre-filled syringes of 40 mg (with a blue plunger).

Marketing authorisation holder and manufacturer

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Marketing authorisation holder

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Manufacturer

Amgen Technology Ireland UC

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

You can request more information about this medicine from the local representative of the marketing authorisation holder.

Date of last revision 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.