Patient Information Leaflet

Humira 40 mg pre-filled syringe solution for injection

adalimumab

Read this 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.
• Su médico le dará unaPatient Information Card, which contains important safety information you need to know before starting and during treatment with Humira. Keep thisPatient Information Card.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Humira is and what it is used for

2.What you need to know before starting Humira treatment

3.How to use Humira

4.Possible side effects

5.Storage of Humira

6.Contents of the pack and additional information

7.How to inject Humira

Humira contains adalimumab as the active substance.

Humira is used to treat

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

The active substance of Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that attack a specific target.

The target of adalimumab is a protein called Tumor Necrosis Factor-alpha (TNFα), which is involved in the immune system (defense) and is found at elevated levels in the inflammatory diseases described above. By attacking TNFα, Humira reduces the inflammatory process in those diseases.

Rheumatoid Arthritis

Rheumatoid Arthritis is an inflammatory disease of the joints.

Humira is used to treat moderate to severe rheumatoid arthritis in adults. It may be administered before other disease-modifying medications such as methotrexate. If the response to these medications is not sufficient, Humira will be administered.

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

Humira may reduce the damage to the joints caused by the inflammatory disease and may help you move more freely.

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

Juvenile Idiopathic Polyarticular Arthritis

Juvenile Idiopathic Polyarticular Arthritis is an inflammatory disease of the joints.

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

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

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

Arthritis associated with enthesitis

Arthritis associated with enthesitis is an inflammatory disease of the joints and the places of tendon fixation in the bone.

Humira is used to treat arthritis associated with enthesitis in patients from 6 years of age. You may have received other disease-modifying medications first, such as methotrexate. If you do not respond sufficiently well to those medications, you will receive Humira.

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

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

Humira is used to treat severe ankylosing spondylitis and undifferentiated axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. You may have received other medications first. If you do not respond sufficiently well to those medications, you will receive Humira.

Psoriatic Arthritis

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

Humira is used to treat psoriatic arthritis in adults. Humira may reduce the damage caused by the disease in the joints and may help you move more freely. You may have received other medications first. If you do not respond sufficiently well to those medications, you will receive Humira.

Plaque Psoriasis

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

Humira is used to treat

• chronic plaque psoriasis of moderate to severe in adults and
• chronic plaque psoriasis of severe in children and adolescents between 4 and 17 years of age who have not responded or are not good candidates for topical therapy and phototherapy.

Hidradenitis Suppurativa

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

Humira is used to treat

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

Humira may reduce the number of nodules and abscesses caused by the disease and the pain that usually accompanies this disease. You may have received other medications previously. If you do not respond sufficiently well to those 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 received other medications previously. If you do not respond sufficiently well to those 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 received other medications previously. If you do not respond sufficiently well to those medications, you will receive Humira.

Non-infectious Uveitis

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

Humira 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 a decrease in vision and/or the presence of spots in the eye (black dots or thin lines that move across the field of vision). Humira acts by reducing this inflammation.

You may have received other medications previously. If you do not respond sufficiently well to those medications, you will receive Humira.

No use Humira:

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

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

• If you have moderate or severe heart failure. It is essential to tell your doctor if you have had or have any serious heart problems (see "Warnings and precautions").

Warnings and precautions

Consult your doctor or pharmacist before starting to use Humira.

Allergic reactions

• If you experience an allergic reaction with symptoms such as chest tightness, difficulty breathing, dizziness, swelling, or hives, interrupt the administration of Humira 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 infection in some part of the body (for example: a leg ulcer), consult your doctor before starting treatment with Humira. If you are unsure, contact your doctor.

• With Humira treatment, you may be more susceptible to infections. This risk may be higher if you have damaged lungs. These infections can be severe and include:

• tuberculosis
• infections caused by viruses, fungi, parasites, or bacteria
• severe blood infection (sepsis)

In rare cases, these infections could be life-threatening. It is essential to inform your doctor if you have symptoms such as fever, wounds, fatigue, or dental problems. Your doctor may recommend that you stop using Humira for some time.

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

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

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

Tuberculosis

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

• Since cases of tuberculosis have been described in patients treated with Humira, your doctor will examine you for signs or symptoms of tuberculosis before starting your 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 test). The performance and results of these tests should be recorded on yourpatient information card.
• Tuberculosis can develop during treatment even if you have received treatment to prevent tuberculosis.
• If you experience symptoms of tuberculosis (for example, persistent cough, weight loss, fatigue, low-grade fever) or any other infection during or after treatment, contact your doctor immediately.

Hepatitis B

• Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have had active HBV infections or if you think you may be at risk of contracting HBV.
• Your doctor should perform a test for HBV. In people who are carriers of HBV, Humira can cause the virus to become active again.
• In rare cases, especially if you are taking other medications that suppress the immune system, reactivation of HBV can be life-threatening.

Surgery or dental intervention

• Si you are to undergo surgery or dental intervention, inform your doctor that you are taking Humira. Your doctor may recommend that you temporarily interrupt your treatment with Humira.

Demyleinating disease

• Si you have or develop a demyelinating disease (a disease that affects the insulation layer around nerves, such as multiple sclerosis), your doctor will decide whether you should be treated 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 in any part of the body.

Vaccines

• Certain vaccines can cause infections and should not be administered if you are being treated with Humira.

• Consult with your doctor before administering any type of vaccine.
• If possible, it is recommended that children receive the scheduled vaccines before starting treatment with Humira.
• If you receive Humira while pregnant, your child may have a higher risk of developing infections during approximately the five months following the last dose you received of Humira during your pregnancy. It is essential 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 vaccine.

Heart failure

• If you have mild heart failure and are being treated with Humira, your doctor should continue to monitor your heart failure. It is essential to inform your doctor if you have had or have any serious heart problems. If new symptoms of heart failure appear or existing symptoms worsen (for example: difficulty breathing, or swelling of the feet), contact your doctor immediately. Your doctor will decide whether you should continue taking Humira.

Fever, hematomas, bleeding, or pale appearance

• In some patients, the body may be unable to produce a sufficient number of the type of blood cells that help the body fight infections or those that contribute to stopping bleeding. Your doctor may decide to interrupt treatment. If you have persistent fever, easy bruising, or bleed easily or are very pale, consult your doctor immediately.

Cancer

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

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

• If you are being treated with Humira, the risk of developing lymphoma, leukemia, and other types of cancer may increase. Rarely, a severe and rare type of lymphoma has been observed in patients being 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 reported in patients using Humira.
• Inform your doctor if new skin lesions appear during or after treatment or if existing lesions change appearance.

• Cancers, other than lymphoma, have been reported in patients with a certain lung disease, known as Chronic Obstructive Pulmonary Disease (COPD), treated with another TNF blocker. If you have COPD, or smoke heavily, consult your doctor if treatment with a TNF blocker is suitable for your case.

Autoimmune disease

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

Children and adolescents

• Vaccines: If possible, your child should receive all scheduled vaccines before using Humira.

Using Humira with other medications

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

You should not take Humira with medications that contain the following active ingredients due to an increased risk of severe infections:

• anakinra
• abatacept.

Humira can be taken with:

• methotrexate
• Certain disease-modifying antirheumatic drugs (such as sulfasalazine, hydroxychloroquine, leflunomide, and gold preparations)
• steroids or pain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

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

Driving and operating machines

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

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

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

Form and route of administration

Humira is administered subcutaneously (under the skin).

Instructions for injecting Humira can be found in section 7 "How to inject Humira".

Using 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 medication box with you, even if it is empty.

Missing a dose

If you forget to administer an injection, administer the next dose of Humira as soon as you remember. Then, administer the next dose as usual, as if you had not missed a dose.

Stopping treatment with Humira

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

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

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

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

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

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

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

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

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

• reactions at the injection site (including pain, swelling, redness, or itching)
• lower respiratory tract infections (including cold, cough, sinusitis, pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• pruritus
• muscle pain

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and flu)
• gastrointestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes)
• ear infection
• oral infections (including dental infection and cold sore)
• reproductive system infections
• urinary tract infections
• fungus infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergy)
• dehydration
• mood changes (including depression)
• anxiety
• difficulty sleeping
• sensory changes such as tingling, itching, or numbness
• migraine
• nerve root compression (including lower back and leg pain)
• visual changes
• eye inflammation
• eyelid inflammation and swelling of the eye
• dizziness (feeling of spinning or dizziness)
• rapid pulse
• high blood pressure
• flushing
• hematomas (accumulation of blood outside blood vessels)
• cough
• asthma
• difficulty breathing
• gastrointestinal bleeding
• indigestion, bloating, and heartburn
• acid reflux
• dry eye syndrome (including dry eyes and mouth)
• itching
• pruritus with itching
• bruises
• skin inflammation (such as eczema)
• rotting of fingernails and toenails
• excessive sweating
• hair loss
• new-onset or worsening psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• swelling
• fever
• decreased platelet count in blood, increasing 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 resistance to disease decreases)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• cancer
• cancer affecting the lymphatic system;
• melanoma
• immunological changes that can affect the lungs, skin, and lymph nodes (the most common presentation is sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (feeling shaky)
• neuropathy (disorder of the nervous system)
• stroke
• hearing loss, tinnitus
• sensation of irregular pulse like skipping
• heart problems that can cause difficulty breathing or swelling of the ankles
• heart attack
• sac in the wall of a major artery, inflammation and coagulation in a vein, blockage of a blood vessel
• lung diseases that can cause difficulty breathing (including inflammation)
• pulmonary embolism (blockage of a pulmonary artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis (inflammation of the pancreas causing severe abdominal and back pain)
• difficulty swallowing
• facial edema (swelling of the face)
• inflammation of the gallbladder; gallstones
• fat in the liver
• nocturnal sweating
• scars
• abnormal muscle crisis
• systemic lupus erythematosus (including skin inflammation, heart, lungs, joints, and other organ inflammation)
• sleep interruptions
• impotence
• inflammations

Rare(may affect up to 1 in 1000 people)

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

Frequency not known(cannot be estimated from available data)

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

Some side effects observed in clinical trials do not have symptoms and can only be identified through blood analysis. These include:

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

• low white blood cell count
• low red blood cell count
• high lipid levels in blood
• high liver enzyme levels

Common(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• high bilirubin levels (liver function test)

Rare(may affect up to 1 in 1000 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 throughthe national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

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

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

Alternative storage:

When necessary (for example when traveling), you may store an individual pre-filled syringe of Humira at room temperature (up to 25°C) for a maximum period of 14 days (ensure it is protected from light). Once removed from the refrigerator to store the syringe at room temperature,you must use it within the next 14 days or discard it, even if you return it to the refrigerator.

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

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

Composition of Humira

The active ingredient is adalimumab.

The other components are: mannitol, polisorbate 80, and water for injectable preparations.

Appearance of the product and contents of the package

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

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

Only some package sizes may be commercially available.

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

Marketing Authorization Holder

AbbVie Deutschland GmbH & Co. KG

Knollstrasse

67061 Ludwigshafen

Germany

Responsible Person

AbbVie Biotechnology GmbH

Knollstrasse

67061 Ludwigshafen

Germany

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

Last review date of this leaflet

The detailed information on this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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

7.How to inject Humira

• The following instructions explain how to inject Humira subcutaneously yourself using the pre-filled syringe. Read these instructions carefully first and then follow them step by step.

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

• Do not attempt to administer the injection yourself until you are sure you understand how to prepare and administer the injection.

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

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

Humira Pre-filled Syringe

PlungerSupporting wingsNeedle cap

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

• the liquid is cloudy, colored, or has scales or particles in it
• the expiration date (EXP) has passed
• the liquid has been frozen or exposed to direct sunlight
• the pre-filled syringe has fallen or been crushed

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