Humira 40 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Humira 40 mg solution for injection in a 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 starting and during treatment with Humira. Keep this patient information card.
• If you have any questions, ask 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, since it could harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Humira is and what it is used for

Humira contains the active substance adalimumab.

Humira is used to treat

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic 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 in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that target a specific molecule.

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

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease affecting the joints.

Humira is used to treat moderate to severe rheumatoid arthritis in adults. You may have previously received disease-modifying drugs such as methotrexate. If your response to these medications is insufficient, you will be given Humira.

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

Humira can reduce joint damage caused by the inflammatory disease and may help improve mobility.

Your doctor will decide whether Humira should be used in combination with methotrexate or as monotherapy.

Polyarticular juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis is an inflammatory joint disease.

Humira is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age.

You may have first received other disease-modifying drugs, such as methotrexate. If you do not respond adequately to these medications, you will receive Humira.

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

Enthesitis-related arthritis

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

Humira is used to treat 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 medications, you will be given Humira.

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 affecting the spine.

Humira is used to treat severe ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. You may have first received other medications. If you do not respond adequately to these medications, you will be given Humira.

Psoriatic arthritis

Psoriatic arthritis is an inflammatory joint disease that is often associated with psoriasis.

Humira is used to treat psoriatic arthritis in adults. Humira can reduce joint damage caused by the disease and may help improve mobility. You may first be treated with other medications. If you do not respond adequately to these medications, you will be given Humira.

Plaque psoriasis

Plaque psoriasis is a skin disease that causes red, scaly, crusted areas covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to deteriorate, thicken, and lift away from the nail bed, which can be painful.

Humira is used to treat

• moderate to severe chronic plaque psoriasis in adults, and
• severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years who have not responded to, or are not suitable candidates for, topical therapy and phototherapies.

Hidradenitis suppurativa

Hidradenitis suppurativa (sometimes called inverse acne) is a chronic, often painful inflammatory skin disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may discharge pus. It usually affects specific areas of skin such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also occur in affected areas.

Humira is used to treat

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

Humira can reduce the number of nodules and abscesses caused by the disease, as well as the associated pain. You may have previously received other medications. If you do not respond adequately to these medications, you will receive Humira.

Crohn's disease

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

Humira 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 previously received other medications. If you do not respond adequately to these medications, you will receive Humira.

Ulcerative colitis

Ulcerative colitis is an inflammatory disease of the large intestine.

Humira 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 previously received other medications. If you do not respond adequately to these medications, you will receive Humira.

Non-infectious uveitis

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

Humira is used to treat

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

This inflammation may lead to decreased vision and/or the presence of floaters in the eye (black spots or thin lines moving across the field of vision). Humira works by reducing this inflammation.

You may have previously received other medications. If you do not respond adequately to these medications, you will receive Humira.

2. What you need to know before using Humira

Do not use Humira:

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

• If you have active tuberculosis or other serious infections (see "Warnings and precautions"). If you have symptoms of any infection, such as 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 serious heart problems (see "Warnings and precautions").

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with Humira.

Allergic reactions

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

Infections

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

• Treatment with Humira may make you more susceptible to 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

• severe blood infection (sepsis)

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

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

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

• If you are over 65 years old, you may be more susceptible to infections while being treated with Humira. 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.

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or if you have been in close contact with someone who had tuberculosis. If you have active tuberculosis, you must not use Humira.

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

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

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

Hepatitis B

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

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

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

Surgery or dental procedures

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

Demyelinating disease

• If you have or develop a demyelinating disease (a disease affecting the protective covering around nerves, such as multiple sclerosis), your doctor will decide whether you should start or continue treatment with Humira. 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 may cause infections and should not be given while you are being treated with Humira.

• Consult your doctor before receiving any type of vaccine.

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

• If you receive Humira while pregnant, your child may have an increased risk of infections for approximately five months after your last dose of Humira during pregnancy. It is important to inform your child's doctor and other healthcare professionals about your use of Humira 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 Humira, your doctor should closely monitor your 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 (for example, difficulty breathing or swelling in the feet), contact your doctor immediately. Your doctor will decide whether you should continue taking Humira.

Fever, bruising, bleeding, or paleness

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

Cancer

• Very rarely, certain types of cancer have been reported in children and adults treated with Humira or other TNF blockers.

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

• If you are being treated with Humira, your risk of developing lymphoma, leukemia, and other cancers may increase. In rare cases, a rare and serious type of lymphoma has been observed in patients treated with Humira. Some of these patients were also receiving azathioprine or 6-mercaptopurine.

• Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Humira.

• Cases of non-melanoma skin cancer have been observed in patients using Humira.

• 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 disease

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

Children and adolescents

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

Using Humira with other medicines

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

You must not take Humira with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Humira may be taken together with:

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

If you have any questions, 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 Humira.

• If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor about using this medicine.

• Humira should be used during pregnancy only if necessary.

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

• Humira can be used during breastfeeding.

• If you use Humira 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 Humira during pregnancy before your baby receives any vaccines. For more information on vaccines, see the section "Warnings and precautions."

Driving and using machines

Humira may have a minor effect on the ability to drive, ride a bicycle, or operate machinery. Dizziness and visual disturbances may occur after using Humira.

Humira contains polysorbate

This medicine contains 0.4 mg of polysorbate 80 in each 40 mg dose. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Humira

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

The following table shows the recommended doses of Humira for each of its approved uses. Your doctor may prescribe you a different dose of Humira if needed.

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis
Age or body weight	How much and how often to take	Notes
Adults	40 mg every other week	For rheumatoid arthritis, continue methotrexate treatment during use of Humira. If your doctor determines that methotrexate is inappropriate, Humira may be given as monotherapy. If you have rheumatoid arthritis and are not receiving methotrexate with your Humira treatment, your doctor may decide to administer 40 mg of Humira weekly or 80 mg every two weeks.

Polyarticular juvenile idiopathic arthritis
Age or body weight	How much and how often to take	Notes
Children, adolescents, and adults from 2 years of age weighing 30 kg or more	40 mg every other week	Not applicable
Children and adolescents from 2 years of age weighing between 10 kg and 30 kg	20 mg every other week	Not applicable

Enthesitis-Associated Arthritis
Age or Body Weight	How Much and How Often to Take	Notes
Children, adolescents, and adults from 6 years of age weighing 30 kg or more	40 mg every other week	Not applicable
Children and adolescents from 6 years of age weighing between 15 kg and 30 kg	20 mg every other week	Not applicable

Plaque Psoriasis
Age or body weight	How much and how often to take	Notes
Adults	The initial dose is 80 mg (two 40 mg injections on the same day), followed by 40 mg every other week starting one week after the first dose.	If you achieve an inadequate response, your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.
Children and adolescents aged 4 to 17 years weighing 30 kg or more	The initial dose is 40 mg, followed by 40 mg one week later. After that, the usual dose is 40 mg every other week.	Not applicable
Children and adolescents aged 4 to 17 years weighing between 15 kg and 30 kg	The initial dose is 20 mg, followed by 20 mg one week later. After that, the usual dose is 20 mg every other week.	Not applicable

Hidradenitis suppurativa
Age or body weight	How much and how often to take	Notes
Adults	The initial dose is 160 mg (four 40-mg injections in one day or two 40-mg injections per day for two consecutive days), followed by a dose of 80 mg (two 40-mg injections in one day) two weeks later. After another two weeks, continue with a dose of 40 mg weekly or 80 mg every two weeks, as prescribed by your doctor.	It is recommended that you use an antiseptic solution daily on affected areas.
Adolescents aged 12 to 17 years, weighing 30 kg or more	The initial dose is 80 mg (two 40-mg injections in one day), followed by 40 mg every other week starting one week later.	If an inadequate response is achieved with Humira 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 solution daily on affected areas.

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

Ulcerative colitis
Age or body weight	How much and how often to take	Notes
Adults	The initial dose is 160 mg (four 40-mg injections in one day or two 40-mg injections per day for two consecutive days), followed by a dose of 80 mg (two 40-mg injections in one day) two weeks later. After that, the usual dose is 40 mg every other week.	Your doctor may increase the dose to 40 mg weekly or 80 mg every two weeks.
Children and adolescents aged 6 years and older weighing less than 40 kg	Initial dose of 80 mg (two 40-mg injections in one day), followed by 40 mg (one 40-mg injection) two weeks later. After that, the usual dose is 40 mg every other week.	You should continue using Humira at the usual dose even after turning 18 years old.
Children and adolescents aged 6 years and older weighing 40 kg or more	Initial dose of 160 mg (four 40-mg injections in one day or two 40-mg injections per day on two consecutive days), followed by 80 mg (two 40-mg injections in one day) two weeks later. After that, the usual dose is 80 mg every other week.	You should continue using Humira at the usual dose even after turning 18 years old.

Non-infectious uveitis
Age or body weight	How much and how often to take	Notes
Adults	The initial dose is 80 mg (two injections of 40 mg on the same day), followed by 40 mg every other week starting one week after the initial dose.	Treatment with corticosteroids or other immunosuppressive medications may be continued. Humira may also be administered alone.
Children and adolescents from 2 years of age weighing less than 30 kg	20 mg every other week	Your doctor may prescribe an initial dose of 40 mg, which may be given one week before starting the regular regimen of 20 mg every other week. Humira is recommended to be used in combination with methotrexate.
Children and adolescents from 2 years of age weighing at least 30 kg	40 mg every other week	Your doctor may prescribe an initial dose of 80 mg, which may be given one week before starting the regular regimen of 40 mg every other week. Humira is recommended to be used in combination with methotrexate.

Form and route of administration

Humira is injected under the skin (subcutaneous route).

Section 7, "How to inject Humira", provides detailed instructions on how to inject Humira.

If you use more Humira than you should

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

If you forget to use Humira

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

If you stop using Humira

The decision to discontinue Humira should be discussed with your doctor. Your symptoms may return if you stop using Humira.

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 gets them. Most adverse effects are mild to moderate. However, some may be serious and require treatment. Adverse effects may occur up to at least 4 months after the last Humira injection.

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

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

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

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

The symptoms described above may be signs of the adverse effects listed below, which have been observed with Humira.

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

• injection site reactions (including pain, swelling, redness, or itching)
• lower 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 cold sore)
• infections of the reproductive system
• urinary tract infection
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory disturbances such as tingling, burning, or numbness
• migraine
• nerve root compression (including lower back and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• flushing
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• 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 (swelling)
• fever
• decreased platelet count in blood, increasing the risk of bleeding or bruising
• poor wound healing

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections that occur when disease resistance is reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• cancer
• cancer affecting the lymphatic system
• melanoma
• immune system disorders that may affect the lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (feeling shaky)
• neuropathy (nervous system disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause difficulty breathing or ankle swelling
• heart attack
• aneurysm (bulge in the wall of a major artery), vein inflammation and clotting, blood vessel blockage
• lung diseases that may cause difficulty breathing (including inflammation)
• pulmonary embolism (blockage of an artery in the lung)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis (inflammation of the pancreas causing severe abdominal and back pain)
• difficulty swallowing
• facial edema (swelling of the face)
• 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 1000 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, and tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scarring of the lung)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B virus
• autoimmune hepatitis (liver inflammation caused by the body's own immune system)
• cutaneous vasculitis (inflammation of blood vessels in the skin)
• Stevens-Johnson syndrome (early symptoms include malaise, fever, headache, and rash)
• facial edema (swelling of the face) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (reddish-purple itchy 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 as purple-colored 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 in clinical trials 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 levels
• low blood phosphate levels
• high blood sugar
• high blood lactate dehydrogenase levels
• presence of autoantibodies in blood
• low blood potassium levels

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels (liver function test)

Rare (may affect up to 1 in 1000 people)

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can 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 Humira

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

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

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

Keep the pre-filled syringe in its outer packaging to protect it from light.

Alternative storage:

When necessary (for example, when travelling), a single pre-filled syringe of Humira may be stored at room temperature (up to 25°C) for a maximum of 14 days (ensure protection from light). Once the syringe has been removed from the refrigerator for storage at room temperature, it must be used within the following 14 days or discarded, even if it is returned to the refrigerator.

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

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

6. Contents of the pack and other information

Composition of Humira

The active substance is adalimumab.

The other components are: mannitol, polysorbate 80, and water for injections.

Nature of the product and pack contents

Humira 40 mg solution for injection in a pre-filled syringe is supplied as a sterile solution containing 40 mg of adalimumab dissolved in 0.4 ml of solution.

The Humira pre-filled syringe is a glass syringe containing a solution of adalimumab. Each pack contains 1, 2, 4 or 6 pre-filled syringes for patient use and 1, 2, 4 or 6 alcohol-impregnated wipes, respectively.

Only certain pack sizes may be marketed.

Humira may be available in vial, pre-filled syringe, and/or pre-filled pen presentations.

Marketing Authorization Holder

AbbVie Deutschland GmbH & Co. KG

Knollstrasse

67061 Ludwigshafen

Germany

Manufacturer

AbbVie Biotechnology GmbH

Knollstrasse

67061 Ludwigshafen

Germany

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

Belgium/Belgium/Belgium AbbVie SA Tel/Tel: +32 10 477811	Lithuania AbbVie UAB Tel: +370 5 205 3023
	Luxembourg/Luxembourg AbbVie SA Belgium/Belgium Tel/Tel: +32 10 477811
Czech Republic AbbVie s.r.o. Tel: +420 233 098 111	Hungary AbbVie Kft. Tel.: +36 1 455 8600
Denmark AbbVie A/S Tlf.: +45 72 30-20-28	Malta V.J.Salomone Pharma Limited Tel: +356 21220174
Germany AbbVie Deutschland GmbH & Co. KG Tel: 00800 222843 33 (toll-free) Tel: +49 (0) 611 / 1720-0	Netherlands AbbVie B.V. Tel: +31 (0)88 322 2843
Estonia AbbVie OÜ Tel: +372 623 1011	Norway AbbVie AS Tlf: +47 67 81 80 00
Greece AbbVie PHARMACEUTICAL CO. LTD. Tel: +30 214 4165 555	Austria AbbVie GmbH Tel: +43 1 20589-0
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France AbbVie Tél: +33 (0) 1 45 60 13 00	Portugal AbbVie, Lda. Tel: +351 (0)21 1908400
Croatia AbbVie d.o.o. Tel + 385 (0)1 5625 501	Romania AbbVie S.R.L. Tel: +40 21 529 30 35
Ireland AbbVie Limited Tel: +353 (0)1 4287900	Slovenia AbbVie Biofarmacevtska družba d.o.o. Tel: +386 (1)32 08 060
Iceland Vistor Tel: +354 535 7000	Slovakia AbbVie s.r.o. Tel: +421 2 5050 0777
Italy AbbVie S.r.l. Tel: +39 06 928921	Finland/Sweden AbbVie Oy Puh/Tel: +358 (0) 10 2411 200
Cyprus Lifepharma (Z.A.M.) Ltd Tel.: +357 22 34 74 40	Sweden AbbVie AB Tel: +46 (0)8 684 44 600
Latvia AbbVie SIA Tel: +371 67605000

Date of the most recent revision of this leaflet

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

To request a copy of this leaflet in braille, large print, or audio, please contact the local representative of the marketing authorization holder.

7. How to inject Humira

• The following instructions explain how to self-inject Humira subcutaneously using the pre-filled syringe. Please read all instructions carefully first, and then follow them step by step.

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

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

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

• Use each pre-filled syringe only once.

Humira Pre-filled Syringe

*Plunger* \ *Grip wings* \ Needle cap

Do not use the pre-filled syringe and call your doctor or pharmacist if

• the liquid is cloudy, discolored, or contains flakes or particles
• the expiry date (EXP) has passed
• the liquid has been frozen or exposed to direct sunlight
• the pre-filled syringe has been dropped or damaged

Do not remove the needle cap until immediately before injection. Keep Humira out of the sight and reach of children.

STEP 1 Take Humira out of the refrigerator. Allow Humira to reach room temperature for 15 to 30 minutes before injection. Do not remove the needle cap while allowing Humira to warm to room temperature Do not heat Humira in any other way. For example, do not heat it in a microwave or in hot water
STEP 2 Syringe Alcohol wipe	Check the expiration date (EXP). Do not use the prefilled syringe if the expiration date (EXP) has passed. On a clean, flat surface, place: 1 single-use prefilled syringe and 1 alcohol wipe Wash your hands and dry them thoroughly.
STEP 3 Injection sites Injection sites	Choose an area on your body for the injection: On the front of your thigh or On your stomach (abdomen), at least 5 cm away from the navel At least 3 cm away from your previous injection site Clean the injection site with the alcohol wipe using circular motions. Do not inject through clothing Do not inject into irritated, bruised, red, hard, scarred, stretch-marked skin, or areas with psoriatic plaques
STEP 4	Hold the prefilled syringe in one hand. Inspect the liquid in the prefilled syringe. Ensure the liquid is clear and colorless Do not use the prefilled syringe if the liquid is cloudy or contains particles Do not use the prefilled syringe if it has been dropped or damaged Carefully remove the needle cap with the other hand. Discard the needle cap and do not reuse it. Do not touch the needle with your fingers or allow it to come into contact with anything
STEP 5	Hold the prefilled syringe with the needle pointing upward. Hold the syringe at eye level with one hand to check for air bubbles Slowly push the plunger to expel air through the needle. It is normal to see a few drops of liquid come out of the needle
STEP 6	Hold the body of the prefilled syringe between your thumb and index finger with one hand, as if holding a pen. With your other hand, pinch the skin at the injection site to lift it and hold it firmly.
STEP 7	Insert the needle fully into the skin at an approximate 45-degree angle with a quick, short motion. Once the needle is under the skin, release the skin pinch Slowly push the plunger all the way down until all the liquid is injected and the prefilled syringe is empty.
STEP 8 Cotton ball	After the injection is complete, slowly remove the needle from the skin, keeping the prefilled syringe at the same angle. After completing the injection, place a cotton ball or gauze over the injection site. Do not rub the area Minor bleeding at the injection site is normal
STEP 9 Dispose of the prefilled syringe in a special medical waste container as instructed by your doctor, nurse, or pharmacist. Never recap a needle. Do not recycle or dispose of the prefilled syringe in household trash Always keep the prefilled syringe and the medical waste container out of sight and reach of children The needle cap, alcohol wipe, cotton ball or gauze, blister pack, and packaging may be disposed of in household trash.