Patient Information Leaflet

Humira 80 mg pre-filled syringe

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.
• Your doctor will give you apatient information leaflet,which contains important safety information that you need to know before and during treatment with Humira. Keep thispatient information leaflet.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it 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 you start using Humira

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 its active substance.

Humira is used to treat

• Rheumatoid arthritis
• Plaque psoriasis
• Hidradenitis supurativa
• Crohn's disease
• Ulcerative colitis
• Non-infectious uveitis

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

The target of adalimumab is a protein called tumor necrosis factor (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. You may have been given other disease-modifying medications such as methotrexate beforehand. If your response to these medications is not sufficient, you will be given Humira.

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

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

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

Plaque psoriasis

Plaque psoriasis is a skin disease that causes red, scaly, crusty areas covered with silver scales. Plaque psoriasis can 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 moderate to severe plaque psoriasis in adults.

Hidradenitis supurativa

Hidradenitis supurativa (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. There may also be 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 old.

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 well enough 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 old.

You may have received other medications previously. If you do not respond well enough to those medications, you will be given 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 old.

You may have received other medications previously. If you do not respond well enough to those medications, you will be given 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 back of the eye.
• children from 2 years old with chronic non-infectious uveitis with inflammation affecting the front 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 well enough to those medications, you will be given Humira.

No use Humira:

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

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

• If you have moderate or severe heart failure. It is essential to inform 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 notice an allergic reaction with symptoms such as chest tightness, difficulty breathing, dizziness, swelling, or hives, discontinue Humira administration and contact your doctor immediately, as in rare cases, these reactions can be life-threatening.

Infections

• If you have any infection, including chronic ones, or a localized infection in some part of your body (for example, a leg ulcer), consult your doctor before starting treatment with Humira. If 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. Therefore, it is essential to inform your doctor if you have symptoms such as fever, wounds, fatigue, or dental problems. Your doctor may instruct you to stop using Humira for some time.

• Inform your doctor if you reside or travel to regions where fungal infections (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 contracting infections.

• If you are over 65 years old, you may be more prone to infections during Humira treatment. You and your doctor must pay special attention to signs of infection while receiving treatment with Humira. It is essential to inform your doctor if you have symptoms of infection, such as fever, wounds, fatigue, or dental problems.

Tuberculosis

• It is essential to inform your doctor if you have ever had tuberculosis or have been in direct contact with someone who has had it. If you have active tuberculosis, do 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 results of these tests should be recorded on yourpatient information card.
• You may develop tuberculosis during treatment, even if you have received treatment to prevent it.
• If you experience symptoms of tuberculosis (such as persistent cough, weight loss, fatigue, or low-grade fever), or any other infection during or after treatment, contact your doctor immediately.

Hepatitis B

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

• Your doctor should perform a test for HBV. In HBV carriers, Humira may reactivate the virus.
• In rare cases, especially if you are taking other medications that suppress the immune system, reactivation of HBV can be life-threatening.

Surgery or dental intervention

• If you are to undergo surgery or dental intervention, please inform your doctor that you are taking Humira. Your doctor may recommend that you temporarily discontinue Humira treatment.

Autoimmune disease

• If you have or develop an autoimmune disease (a disease that affects the protective layer around nerves, such as multiple sclerosis), your doctor will decide whether to treat 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 your body.

Vaccines

• Certain vaccines may cause infections and should not be administered while on Humira treatment.

• Consult with your doctor before administering any type of vaccine.
• If possible, it is recommended that you receive the vaccines planned for your age before starting Humira treatment.
• If you receive Humira while pregnant, your child may have a higher risk of developing infections for approximately five months after the last dose of Humira you received during pregnancy. It is essential to inform your doctor and other healthcare professionals about your use of Humira during pregnancy, so they can decide when you should receive any vaccine.

Heart failure

• If you have mild heart failure and are on Humira treatment, you may be closely monitored by your doctor. It is essential to inform your doctor if you have had or have any serious heart problems. If you develop new symptoms or worsening symptoms (difficulty breathing, or swelling of your feet), contact your doctor immediately. Your doctor will decide whether to continue taking Humira.

Fever, hematomas, bleeding, or pale appearance

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 those who have had the disease for a long time may have a higher risk than the general population of developing lymphoma (a cancer that affects the lymphatic system) and leukemia (a cancer that affects the blood and bone marrow).
• If you are on Humira treatment, the risk of developing lymphoma, leukemia, or other types of cancer may increase. Rarely, a rare and severe type of lymphoma has been observed in patients on Humira treatment. Some of these patients were also taking 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 you develop new skin lesions or if existing lesions change appearance during or after treatment.

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

Autoimmune disease

• In rare cases, Humira treatment 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 the planned vaccines before using Humira.

Using Humira with other medications

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

You should not use 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 injectable 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 Humira treatment.
• 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.
• A study on pregnancy found no increased risk ofcongenital defects when the mother had received Humira treatment during pregnancy compared to mothers with the same disease who did not receive Humira treatment.
• Humira can be used during breastfeeding.
• If you use Humira while pregnant, your child may have a higher risk ofcontracting an infection.
• It is essential to inform the pediatrician and other healthcare professionals about the use of Humira during pregnancy before the child receives any vaccine. For more information on vaccines, see the section“Warnings and precautions”.

Driving and operating machinery

The influence of Humira on the ability to drive, ride a bike, or operate machinery is small. 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. In case of doubt, consult your doctor again.

The recommended doses of Humira for each of the authorized uses are shown in the following table. Your doctor may prescribe another presentation of Humira if you need a different dose.

Form and route of administration

Humira is injected under the skin (subcutaneously).

For detailed instructions on how to inject Humira, see Section 7 “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, you should report it. Always carry the medication box with you, even if it is empty.

If you forget to use Humira

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 forgotten a dose.

If you interrupt 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 the use of this medication, ask your doctor or pharmacist.

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

Get in touch with your doctor 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

Get in touch with your doctor 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
• a lump or open wound that does not heal
• signs and symptoms of blood disorders such as persistent fever, rashes, bleeding, paleness

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)
• 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
• sensorial alterations such as tingling, itching, or numbness
• migraine
• nerve root compression (including lower back and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and swelling of the eye
• dizziness (feeling of spinning or dizziness)
• rapid pulse
• high blood pressure
• flushing
• hematomas (accumulation of blood outside of blood vessels)
• cough
• asthma
• difficulty breathing
• gastrointestinal bleeding
• indigestion, bloating, and heartburn
• acid reflux
• dry eye syndrome (including dryness in 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 of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• swelling (edema)
• fever
• decreased platelet count in blood, increasing the risk of bleeding or 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 alterations that may 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)
• cerebral hemorrhage
• loss of hearing, ringing in the ears
• sensation of irregular pulse like skipping
• heart problems that may 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 may cause difficulty breathing (including inflammation)
• pulmonary embolism (blockage of a lung artery)
• pleural effusion (abnormal fluid storage in the pleural space)
• pancreatitis 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 alterations (such as optic nerve inflammation and Guillain-Barré syndrome that may 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 (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 discomfort, fever, headache, and pruritus)
• facial edema associated with allergic reactions
• erythema multiforme (inflammatory rash on the skin)
• lupus-like syndrome
• angioedema (inflammation of localized 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 with Humira may not have symptoms and can only be identified through blood tests. These include:

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

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

Common(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• high bilirubin levels (liver function test)

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 through the 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 pen in the outer packaging to protect it from light.

Alternative storage:

When necessary (for example when traveling), you may store an individual pre-filled Humira pen 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 pen 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 pen from the refrigerator and the date after which you must discard the pen.

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

Humira Composition

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 pack

Humira 80mg injectable solution in pre-filled pen is supplied as a sterile solution of 80mg of adalimumab dissolved in 0.8ml of solution.

The pre-filled pen of Humira is a single-use, bicolor grey/plum pen that contains a glass syringe with Humira. It has two caps: one is grey and has a “1” printed on it, and the other is plum and has a “2” printed on it. It has a window on each of the faces of the pen through which you can see the Humira solution that the syringe contains.

The pre-filled pen of Humira is available in packs that contain:

• 1 pre-filled pen for patient use with 2 alcohol-impregnated wipes (1 spare)
• 3 pre-filled pens for patient use with 4 alcohol-impregnated wipes (1 spare)

Only some pack sizes may be marketed.

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

Manufacturer

AbbVie Biotechnology GmbH

Knollstrasse

67061 Ludwigshafen

Germany

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

Last update of this leaflet

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

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

7. How to inject Humira

• The following instructions explain how to inject Humira yourself using the pre-filled pen. 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-injecting.

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

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

• Use only one pre-filled pen for one injection.

Humira Pre-filled Pen

Grey cap1 White needle cap White arrow Plum cap2

Needle Inspection window Plum activator button

Do not use the pre-filled pen and contact 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 pen has fallen or been crushed

Do not remove both caps until just before the injection. Keep out of the sight and reach of children.