Humira

Package leaflet: Information for the patient

Humira 20 mg solution for injection in pre-filled syringe

adalimumab
Please read this leaflet carefully before your child starts using this medicine because it contains important information.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before your child starts taking Humira and during treatment with Humira. You or your child should keep this Patient Reminder Card.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for your child only. Do not give it to others, even if their symptoms are the same as your child's, as it may be harmful.
• If your child experiences any side effects, including those not listed in this leaflet, speak to your paediatrician or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Humira and what is it used for

Humira contains the active substance adalimumab.
Humira is indicated for the treatment of the following inflammatory diseases:

• Polyarticular juvenile idiopathic arthritis
• Enthesitis-related arthritis
• Pediatric plaque psoriasis
• Crohn’s disease in pediatric patients
• Pediatric uveitis

The active substance in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Humira reduces the inflammatory process in these diseases.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually begins during childhood.
Humira is used to treat polyarticular juvenile idiopathic arthritis in patients aged 2 years and older. Initially, other disease-modifying drugs such as methotrexate may be given to the child. If these medicines do not work well enough, the child will be given Humira to treat polyarticular juvenile idiopathic arthritis.
Your doctor will decide whether Humira should be taken with methotrexate or on its own.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease of the joints and of the sites where tendons attach to bones.
Humira is used to treat enthesitis-related arthritis in patients aged 6 years and older. Initially, other disease-modifying drugs such as methotrexate may be given to the child. If these medicines do not work well enough, the child will be given Humira to treat enthesitis-related arthritis.

Pediatric plaque psoriasis
Plaque psoriasis is a skin condition that causes reddish, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crumble, thicken, or lift from the nail bed, which can be painful. Psoriasis is believed to be caused by a problem with the immune system that leads to increased production of skin cells.
Humira is used to treat chronic severe plaque psoriasis in children and adolescents aged between 4 and 17 years for whom topical therapy and phototherapies have not worked adequately or are not suitable.

Crohn’s disease in pediatric patients
Crohn’s disease is an inflammatory disease of the digestive tract.
Humira is used to treat moderate to severe Crohn’s disease in children and adolescents aged between 6 and 17 years.
Other medicines may be given to the child initially. If these medicines do not work well enough, the child will be given Humira to reduce the signs and symptoms of the disease.

Pediatric uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
Humira is used to treat children with chronic non-infectious uveitis aged 2 years and older who have inflammation affecting the front part 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.
Other medicines may be given to the child initially. If these medicines do not work well enough, the child will be given Humira to reduce the signs and symptoms of the disease.

2. What you need to know before your child uses Humira

Do not use Humira

• If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If your child has active tuberculosis or other serious infections (see “Warnings and precautions”). It is important to tell the doctor if your child has symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If your child has moderate or severe heart failure. It is important to inform the doctor if your child has had or currently has serious heart problems (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Humira.
Allergic reactions

• If your child experiences allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Humira again and contact the doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

• If your child has an infection, including long-term infections or localized infections (e.g., leg ulcers), consult the doctor before starting treatment with Humira. If you are unsure, contact the doctor.
• Your child may be more likely to get infections while being treated with Humira. This risk may increase if your child has lung problems. These infections can be serious and may include:
  • tuberculosis
  • infections caused by viruses, fungi, parasites, or bacteria
  • severe blood infections (sepsis)

In rare cases, these infections can be life-threatening. It is important to inform the doctor if your child has symptoms such as fever, wounds, feeling tired, or dental problems. The doctor may instruct you to temporarily stop Humira.

• Inform the doctor if your child lives in or travels to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.
• Inform the doctor if your child has had recurring infections or has conditions that increase the risk of infection.
• Your child and the paediatrician should pay particular attention to signs of infection while your child is on Humira treatment. It is important to inform the paediatrician if symptoms of infection such as fever, wounds, feeling tired, or dental problems occur.

Tuberculosis

• Cases of tuberculosis have occurred in patients treated with Humira. Therefore, the doctor will check whether your child shows signs or symptoms of tuberculosis before starting Humira therapy. This will involve a thorough medical evaluation of your child’s medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the child’s Patient Reminder Card.
• It is very important to inform the doctor if your child has ever had tuberculosis or has been in contact with someone who had tuberculosis. If your child has active tuberculosis, Humira must not be used.
• Tuberculosis may develop during treatment even if your child has received preventive treatment for tuberculosis.
• Contact the doctor immediately if symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections appear during or after treatment.

Hepatitis B

• It is very important to inform the doctor if your child is a carrier of hepatitis B virus (HBV), has an active hepatitis B infection, or if you think your child may be at risk of contracting hepatitis B virus.
• The doctor should test your child for hepatitis B virus infection. In individuals who are carriers of HBV, Humira may cause reactivation of the virus.
• In rare cases, especially if the patient is also receiving other medicines that suppress the immune system, reactivation of hepatitis B virus may be life-threatening.

Surgery or dental procedures

• If your child is scheduled for surgery or dental procedures, inform the doctor that your child is taking Humira. The doctor may recommend temporarily stopping Humira.

Demyelinating diseases

• If your child has or develops a demyelinating disease (a disease affecting the insulating layer around nerves, such as multiple sclerosis), the doctor will decide whether it is appropriate to start or continue Humira treatment. Inform the doctor immediately if your child experiences symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccinations

• Certain vaccines may cause infections and must not be given during treatment with Humira.
• Consult the doctor before vaccinating your child.
• It is recommended, if possible, to ensure that children receive all age-appropriate vaccinations before starting Humira treatment.
• If a woman used Humira during pregnancy, her baby may have an increased risk of infection for up to approximately 5 months after the last dose received during pregnancy. It is important to inform the paediatrician or other healthcare provider that the mother used Humira during pregnancy, so they can determine when the baby should receive any vaccinations.

Heart failure

• If your child has mild heart failure and is being treated with Humira, the doctor must closely monitor the condition of the heart failure. It is important to inform the doctor about any past or current heart problems. If new symptoms of heart failure develop or existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact the doctor immediately. The doctor will decide whether your child can continue taking Humira.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not produce enough blood cells to fight infections or stop bleeding. The doctor may decide to stop treatment. If your child has persistent fever, develops easy bruising or bleeding, or appears pale, contact the doctor immediately.

Tumours

• Very rarely, certain types of tumours have been observed in patients, both children and adults, treated with Humira or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumour affecting the lymphatic system) and leukaemia (a tumour affecting blood and bone marrow).
• If your child takes Humira, the risk of developing lymphoma, leukaemia, or other tumours may increase. In rare cases, a specific 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 the doctor if your child is taking azathioprine or 6-mercaptopurine with Humira.
• Cases of non-melanoma skin cancer have been observed in patients taking Humira.
• If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform the doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If your child has COPD or is a heavy smoker, discuss with the doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

• Rarely, treatment with Humira may lead to the development of a lupus-like syndrome. Inform the doctor if symptoms such as persistent unexplained skin rash, fever, joint pain, or fatigue occur.

Other medicines and Humira
Inform the doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Your child must not use Humira with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Humira may be used with:

• methotrexate
• other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult the doctor.

Pregnancy and breastfeeding

• A woman should use an appropriate contraceptive method to prevent pregnancy and continue using it for at least 5 months after the last dose of Humira.
• If a woman is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor about using this medicine.
• Humira should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy, compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If a woman used Humira during pregnancy, her baby may have an increased risk of infection.
• It is important to inform the paediatrician and other healthcare providers that Humira was used during pregnancy, before the baby receives any vaccinations. For more information on vaccinations, see the section “Warnings and precautions”.

Driving and using machines
Humira may affect, although only slightly, your child’s ability to drive, ride a bicycle, or use machinery. After taking Humira, vision disturbances or a sensation that the surroundings are spinning may occur.

3. How to use Humira

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts or need clarification, consult your doctor or pharmacist.
The recommended doses of Humira for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Humira if the child requires
a different dose.

Method and route of administration
Humira is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions for Humira injection are provided in section 7, “Injection of Humira”.
If you use more Humira than you should
If you accidentally inject Humira more frequently than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that the child has received more medicine. Always keep the medicine carton, even if empty.
If you forget to use Humira
If you forget to give the child an injection, administer the missed dose as soon as you remember. Then continue giving the next dose regularly according to the prescribed dosing schedule.
If you stop treatment with Humira
The decision to discontinue Humira should be discussed with your doctor. The child's symptoms may return if treatment with Humira is stopped.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

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

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

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

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning during urination
• fatigue or weakness
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open sore that does not heal
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness

The symptoms described above may be signs of the following side effects 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, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal pain

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza)
• intestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes zoster infection)
• ear infections
• oral infections (including dental infections and herpes simplex)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• sleep disorders
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (sensation of spinning or lightheadedness)
• sensation of rapid heartbeat
• high blood pressure
• hot flashes
• bruising (hematoma – blood accumulation outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• contusion
• skin inflammation (such as eczema)
• nail breakage in fingers and toes
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• edema (swelling)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• delayed wound healing

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections occurring when immune defenses are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• tumors
• lymphatic system tumors
• melanoma
• immune system disorders affecting lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shakiness)
• neuropathy (nerve disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling in the ankles
• acute myocardial infarction
• formation of a sac in the wall of a major artery, vein inflammation and clot, or blockage of a blood vessel
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of a pulmonary artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial edema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological 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 (lung scarring)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B
• 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 (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (pruritic red-purple rash)

Not known (frequency cannot be determined from available data)

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal)
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma typically presents with purple skin lesions
• liver failure
• worsening of a condition called dermatomyositis (presenting as skin rash accompanied by muscle weakness)
• Weight gain (in most patients, weight gain has been low)

Some of the side effects observed with Humira may be asymptomatic and detectable only 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
• increased blood lipids
• increased liver enzymes

Common (may affect up to 1 in 10 people)

• increased white blood cell count
• reduced platelet count
• increased uric acid in blood
• altered blood sodium levels
• reduced blood calcium
• reduced blood phosphorus
• increased blood sugar
• increased lactate dehydrogenase in blood
• presence of autoantibodies in blood
• reduced blood potassium

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test)

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

• low white blood cell, red blood cell, and platelet counts

Reporting of side effects
If the child experiences any side effect, including those not listed in this leaflet, please consult the pediatrician or pharmacist. You may also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. while travelling), a single pre-filled syringe may be stored at room temperature (up to 25 °C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date on which the syringe was first removed from the refrigerator and the date after which the syringe must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, polysorbate 80 and water for injections.

Description of the appearance of Humira pre-filled syringe and contents of the package
Humira 20 mg solution for injection in pre-filled syringe for paediatric use is supplied as a sterile solution containing 20 mg of adalimumab dissolved in 0.2 ml of solution.
The Humira pre-filled syringe is a single-use glass syringe containing a solution of adalimumab.
The Humira pre-filled syringe is available in a pack containing 2 pre-filled syringes with 2 alcohol swabs.
Humira may be available in vial, pre-filled syringe and/or pre-filled pen.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.: +36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ.: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

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

To listen to or request a copy of this leaflet in , or , please contact the local representative of the Marketing Authorisation Holder.

7. Humira Injection

• The following instructions explain how to administer a subcutaneous injection of Humira to a child using the prefilled syringe. Please read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with training on the proper technique for administering the injection.
• Do not administer the injection to the child until you are confident you understand how to prepare and give the injection correctly.
• After proper training, the injection may be given by the child or by another person, such as a family member or friend.
• Use each prefilled syringe only once for a single injection.

Humira Prefilled Syringe
Plunger Finger Grip Needle Cap

Do not use the prefilled syringe and contact your doctor or pharmacist if:

• the solution appears cloudy, has changed color, or contains flakes or particles
• the expiration date (Exp.) has passed
• the solution has been frozen or exposed to direct sunlight
• the prefilled syringe has been dropped or damaged

Remove the needle cap only immediately before injection. Keep Humira out of the
sight and reach of children.
STEP 1
Remove Humira from the refrigerator.
Before administering the injection, allow Humira to reach room temperature for 15–30 minutes.

• Do not remove the needle cap while waiting for Humira to warm to room temperature
• Do not heat Humira by any other method. For example, do not heat in a microwave or in warm water.
  STEP 2 Check the expiration date (Exp.). Do not use the prefilled syringe if the expiration date (Exp.) has passed.
  Syringe Gather the following items on a clean, flat surface:
• 1 single-use prefilled syringe
• 1 alcohol swab

Wash and dry your hands.
Swab
STEP 3 Choose an injection site:
Injection Sites • On the front of the child’s thigh, or

• On the child’s abdomen (belly), at least 5 cm away from the navel
• At least 3 cm away from the child’s previous injection site

Clean the injection site with circular motions using the alcohol swab.

• Do not inject through clothing
• Do not inject into areas where the skin appears red or hardened, or where bruises, ulcers, scars, stretch marks, or plaque psoriasis are present

Injection Sites
STEP 4 Hold the prefilled syringe in one hand.
Inspect the liquid in the syringe.

• Make sure 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

Gently remove the needle cap with the other hand. Discard the cap. Do not reuse the cap.

• Do not touch the needle with your fingers, and ensure the needle does not come into contact with anything

STEP 5 Hold the prefilled syringe with the needle pointing

upward.

• Hold the prefilled syringe at eye level with one hand so you can see any air bubbles in the syringe

Slowly push the plunger to expel air through the needle.

• It is normal to see a small drop of liquid at the tip of the needle

STEP 6 Hold the prefilled syringe like a pencil, between your thumb and index finger, in one hand.
With the other hand, pinch the skin at the injection site to lift and firmly hold it.

STEP 7 Insert the needle completely into the skin at an angle of approximately 45° with a quick, firm motion.

• Once the needle is inserted, release the skin.

Push the plunger completely until all the liquid has been injected and the prefilled syringe is empty.
STEP 8 When the syringe is empty, slowly remove the needle from the skin, maintaining the same angle used during insertion.
After the injection, apply cotton wool or gauze gently over the injection site.

• Do not rub the area
• Mild bleeding at the injection site is normal

Cotton wool
STEP 9
Dispose of the used prefilled syringe in a special sharps container, as instructed by your doctor, nurse, or pharmacist. Never recap the needle.

• Do not recycle or dispose of the prefilled syringe in household waste
• Always keep the prefilled syringe and the sharps container out of the sight and reach of children

The needle cap, alcohol swab, cotton wool or gauze, blister pack, and outer packaging may be disposed of in household waste.

Patient information leaflet

Humira 40 mg/0.8 ml solution for injection

adalimumab
Please read this leaflet carefully before the child starts using this medicine because
it contains important information

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information that you need to know before the child is given Humira and during treatment with Humira. You or the child should keep this Patient Reminder Card.
• If you have any doubts, consult the doctor or pharmacist.
• This medicine has been prescribed for the child only. Do not give it to others, even if their symptoms are the same as the child's, as it could be harmful.
• If the child experiences any adverse reaction, including those not listed in this leaflet, contact the paediatrician or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Humira is and what it is used for

Humira contains the active substance adalimumab.
Humira is indicated for the treatment of the following inflammatory diseases:

• Juvenile polyarticular idiopathic arthritis
• Enthesitis-related arthritis
• Pediatric plaque psoriasis
• Hidradenitis suppurativa in adolescents
• Crohn’s disease in pediatric patients
• Ulcerative colitis in pediatric patients
• Pediatric uveitis

The active substance in Humira, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind specifically to a target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Humira reduces the inflammatory process in these diseases.

Juvenile polyarticular idiopathic arthritis and enthesitis-related arthritis
Juvenile polyarticular idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases.
Humira is used to treat juvenile polyarticular idiopathic arthritis and enthesitis-related arthritis.
Initially, other disease-modifying medicines, such as methotrexate, may be given to the child. If these medicines do not work well enough, the child will be given Humira to treat juvenile polyarticular idiopathic arthritis or enthesitis-related arthritis.

Pediatric plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crumble, thicken, or lift from the nail bed, which can be painful. Psoriasis is believed to be caused by a problem with the body’s immune system that leads to an increased production of skin cells.
Humira is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapy have not worked adequately or are not suitable.

Hidradenitis suppurativa in adolescents
Hidradenitis suppurativa (sometimes called inverse acne) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that can drain pus. It most commonly affects specific skin areas such as the under-breast region, armpits, inner thighs, groin, and buttocks. Scarring may also develop in the affected areas.
Humira is used to treat hidradenitis suppurativa in adolescents aged 12 years and older. Humira can reduce the number of nodules and abscesses you have, as well as the pain often associated with this disease.
Initially, you may be given other medicines. If you do not respond adequately to these medicines, you will be given Humira.

Crohn’s disease in pediatric patients
Crohn’s disease is an inflammatory disease of the digestive tract. Humira is indicated for the treatment of Crohn’s disease in children aged 6 to 17 years.
Other medicines may be given to the child initially. If these medicines do not work well enough, the child will be given Humira to reduce the signs and symptoms of the disease.

Ulcerative colitis in pediatric patients
Ulcerative colitis is an inflammatory disease of the large intestine. Humira is used to treat moderate to severe ulcerative colitis in children aged 6 to 17 years. Other medicines may be given to the child initially. If these medicines do not work well enough, the child will be given Humira to reduce the signs and symptoms of the disease.

Pediatric uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
Humira is used to treat children from 2 years of age with chronic non-infectious uveitis involving inflammation of the front part of the eye. This inflammation can lead to decreased vision and/or the presence of floating bodies in the eye (black spots or thin lines moving across the visual field). Humira works by reducing this inflammation.

2. What you should know before your child uses Humira

Do not use Humira

• If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If your child has a serious infection, including active tuberculosis (see "Warnings and precautions"). It is important to inform the doctor if your child has symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If your child has moderate or severe heart failure. It is important to inform the doctor if there has been or currently is a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your paediatrician or pharmacist before using Humira.

• If allergic reactions occur, with symptoms such as chest tightness, wheezing, dizziness, swelling or rash, do not administer Humira again and contact the doctor immediately, as in rare cases these reactions may be life-threatening.
• If your child has an infection, including long-term or localized infections (for example, leg ulcers), consult the doctor before starting treatment with Humira. If you have any doubts, contact the doctor.
• Your child may be more likely to get infections while being treated with Humira. This risk may increase if your child's lung function is impaired. These infections can be serious and may include tuberculosis, viral, fungal, parasitic or bacterial infections, other opportunistic infections, and sepsis, which in rare cases may be life-threatening. It is important to inform the doctor if your child has symptoms such as fever, wounds, feeling tired, or dental problems. The doctor may recommend temporarily stopping Humira.
• Cases of tuberculosis have occurred in patients treated with Humira. Therefore, the doctor should check whether your child shows signs or symptoms typical of tuberculosis before starting treatment with Humira. This will involve a detailed medical evaluation including your child’s medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform the doctor if your child has ever had tuberculosis or has been in close contact with someone who has tuberculosis. Tuberculosis may develop during treatment even if your child has received preventive treatment for tuberculosis. Contact the doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after treatment.
• Inform the doctor if your child lives in or travels to regions where fungal infections such as histoplasmosis, coccidioidomycosis or blastomycosis are endemic.
• Inform the doctor if your child has had recurring infections or if there are conditions that increase the risk of infection.
• Inform the doctor if your child is a carrier of hepatitis B virus (HBV), has an active hepatitis B infection, or if you think your child may be at risk of contracting hepatitis B virus. The doctor must test your child for hepatitis B virus infection. Taking Humira may cause reactivation of hepatitis B virus in carriers of this virus. In rare cases, especially if the patient is also taking other medicines that suppress the immune system, hepatitis B reactivation may be life-threatening.
• It is important to inform the paediatrician if symptoms of infection such as fever, wounds, feeling tired or dental problems occur.
• Before any surgery or dental procedures, inform the doctor that your child is taking Humira. The doctor may recommend temporarily stopping treatment.
• If your child has or develops demyelinating diseases such as multiple sclerosis, the doctor will decide whether to start or continue treatment with Humira. Inform the doctor immediately if your child develops symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.
• Certain vaccines may cause infections and should not be given during treatment with Humira. Consult the doctor before vaccinating your child. In children, it is recommended, if possible, to complete the routine vaccination schedule according to current vaccination guidelines before starting Humira therapy. If you took Humira during pregnancy, your child may have an increased risk of infection for up to approximately 5 months after your last dose during pregnancy. It is important that you inform the paediatrician or other healthcare provider about your use of Humira during pregnancy so they can determine when your child should receive any vaccinations.
• If your child has mild heart failure and is being treated with Humira, the doctor should carefully monitor your child’s heart condition. It is important to inform the doctor about any past or current heart problems. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact the doctor immediately. The doctor will decide whether your child can continue taking Humira.
• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If your child has persistent fever, bruising, bleeding easily or paleness, contact the doctor immediately. The doctor may decide to stop treatment.
• Very rarely, certain types of cancer have been observed in patients, both children and adults, treated with Humira or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a cancer affecting the lymphatic system) and leukaemia (a cancer affecting blood and bone marrow). If your child takes Humira, the risk of developing lymphoma, leukaemia or other cancers may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with Humira. Some of these patients were also taking azathioprine or 6-mercaptopurine. Inform the doctor if your child is taking azathioprine or 6-mercaptopurine with Humira. In addition, cases of non-melanoma skin cancer have been reported in patients taking Humira. If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform the doctor.
• Cases of 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 anti-TNF medicine. If your child has COPD or is a heavy smoker, discuss with the doctor whether treatment with an anti-TNF medicine is appropriate.
• Rarely, treatment with Humira may cause a lupus-like syndrome. Inform the doctor if symptoms such as unexplained persistent rash, fever, joint pain or fatigue occur.

Other medicines and Humira
Inform the paediatrician or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Humira may be taken together with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts, corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Humira must not be taken together with medicines containing anakinra or abatacept as active ingredients due to an increased risk of serious infections. If you have any doubts, consult the doctor.

Pregnancy and breastfeeding

• Girls should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after the last dose of Humira.
• If a girl is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor about taking this medicine.
• Humira should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If a girl takes Humira during pregnancy, her baby may have an increased risk of infection.
• It is important that you inform the paediatrician or other healthcare provider about your use of Humira during pregnancy before the baby receives any vaccinations. For more information on vaccinations, please refer to the section "Warnings and precautions".

Driving and using machines
Humira may affect, although only to a minor extent, the ability to drive, ride a bicycle or use machinery. After taking Humira, vision disturbances or a sensation that the surroundings are spinning may occur.

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

3. How to use Humira

Use this medicine exactly as instructed by the paediatrician or pharmacist. If you have
any doubts or need clarification, consult the paediatrician or pharmacist. The doctor may prescribe a
different concentration of Humira if the child requires a different dose.

Children and adolescents with polyarticular juvenile idiopathic arthritis
Children and adolescents aged 2 years and older, weighing between 10 kg and less than 30 kg
The recommended dose of Humira is 20 mg every other week.

Children and adolescents aged 2 years and older, weighing 30 kg or more
The recommended dose of Humira is 40 mg every other week.

Children, adolescents, and adults with enthesitis-related arthritis
Children and adolescents aged 6 years and older, weighing between 15 kg and less than 30 kg
The recommended dose of Humira is 20 mg every other week.

Children, adolescents, and adults aged 6 years and older, weighing 30 kg or more
The recommended dose of Humira is 40 mg every other week.

Children and adolescents with psoriasis
Children and adolescents aged between 4 and 17 years, weighing between 15 kg and less than 30 kg
The recommended dose of Humira is an initial dose of 20 mg, followed by a second dose of 20 mg the
following week. Afterwards, the usual dose is 20 mg every other week.

Children and adolescents aged between 4 and 17 years, weighing 30 kg or more
The recommended dose of Humira is an initial dose of 40 mg, followed by a second dose of 40 mg the
following week. Afterwards, the usual dose is 40 mg every other week.

Adolescents with hidradenitis suppurativa, aged between 12 and 17 years, weighing 30 kg or more
The recommended dose of Humira is an initial dose of 80 mg (administered as two 40 mg injections on the
same day), followed by 40 mg every other week starting one week after the initial dose. If there is an inadequate response to 40 mg of Humira every other week, the doctor may increase the dose to 40 mg weekly or 80 mg every other week.
It is recommended to use an antiseptic wash solution daily on the affected areas.

Children and adolescents with Crohn’s disease
Children and adolescents aged between 6 and 17 years, weighing less than 40 kg
The usual dose is initially 40 mg, followed by 20 mg two weeks later. If a more rapid response is needed, the paediatrician may prescribe an initial dose of 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg two weeks later.
Subsequently, the usual dose is 20 mg every other week. Depending on the child’s response, the paediatrician may increase the dosing frequency to 20 mg weekly.

Children and adolescents aged between 6 and 17 years, weighing 40 kg or more
The usual dose is initially 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg two weeks later. If a more rapid response is needed, the paediatrician may prescribe an initial dose of 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later.
Subsequently, the usual dose is 40 mg every other week. Depending on the child’s response, the paediatrician may increase the dose to 40 mg weekly or 80 mg every other week.

Children and adolescents with ulcerative colitis
Children and adolescents aged 6 years and older, weighing less than 40 kg
The usual dose of Humira is 80 mg (administered as two 40 mg injections on the same day), followed by 40 mg (administered as a single 40 mg injection) two weeks later. Subsequently, the usual dose is 40 mg every other week.
Patients who turn 18 years old while receiving 40 mg every other week should continue the prescribed dose.

Children and adolescents aged 6 years and older, weighing 40 kg or more
The usual dose of Humira is 160 mg (administered as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (administered as two 40 mg injections on the same day) two weeks later. Subsequently, the usual dose is 80 mg every other week.
Patients who turn 18 years old while receiving 80 mg every other week should continue the prescribed dose.

Children and adolescents with chronic non-infectious uveitis, aged 2 years and older
Children and adolescents aged 2 years and older, weighing less than 30 kg
The usual dose of Humira is 20 mg administered every other week in combination with methotrexate.
The paediatrician may also prescribe an initial dose of 40 mg, which may be administered one week before starting the usual dose.

Children and adolescents aged 2 years and older, weighing 30 kg or more
The usual dose of Humira is 40 mg administered every other week in combination with methotrexate.
The paediatrician may also prescribe an initial dose of 80 mg, which may be administered one week before starting the usual dose.

Method and route of administration
Humira is administered by subcutaneous injection (under the skin).

Instructions for preparing and injecting Humira
The following instructions explain how to inject Humira. Read the instructions carefully and follow them step by step. You will receive guidance from the doctor or their assistant on the administration technique and the amount to administer to the child. Do not proceed with the injection until you are certain you understand how to prepare and administer it. After proper training, the injection may be given by you or another person, such as a family member or friend.
Failure to follow these instructions as described may result in contamination, which could in turn cause infections in the child.
The contents of the syringe must not be mixed with other medicines in the same syringe or vial.

1) Preparation

• Make sure you know the correct amount (volume) required for the dose. If you do not know the amount, STOP and contact the doctor for further instructions.
• You will need a special waste container, such as a sharps container, or as advised by the nurse, doctor, or pharmacist. Place the container on your work surface.
• Wash your hands thoroughly.
• Remove from the kit one box containing a syringe, a vial adapter, a vial, two alcohol swabs, and a needle. If there is a second box in the kit for the next administration, return it to the refrigerator immediately.
• Check the expiration date on the box. DO NOT use any of the items in the box after the expiration date.
• Arrange the following items on a clean surface, WITHOUT removing them from their packaging yet:

o A 1 ml syringe (1)
o A vial adapter (2)
o A paediatric-use vial of Humira injectable solution (3)
o Two alcohol swabs (4)
o A needle (5)

• Humira is a clear, colourless liquid. DO NOT use it if the liquid is cloudy, discoloured, or contains flakes or particles.

2) Preparing the Humira dose for injection
General instructions: DO NOT discard any items until the injection is completed.

• Prepare the needle by partially opening the packaging from the end closest to the yellow connector of the syringe. Open the packaging just enough to expose the yellow connector of the syringe. Place the packaging with the clear side facing upwards.

• Remove the plastic cap from the vial until you see the top of the vial stopper.

• Use one of the alcohol swabs to clean the vial stopper. DO NOT touch the vial stopper after cleaning it with the swab.
• Remove the cover of the vial adapter packaging without removing the adapter from its packaging.

• Hold the vial with the stopper facing upwards.
• While the vial adapter is still in its transparent packaging, attach it to the vial stopper by pushing it down until it clicks into place.
• Once you are sure the adapter is securely attached to the vial, remove the packaging from the adapter.
• Gently place the vial and adapter on a clean work surface, taking care not to let them fall. DO NOT touch the adapter.

• Prepare the syringe by partially opening the packaging from the end closest to the white plunger.
• Open the transparent packaging just enough to expose the white plunger without removing the syringe from its packaging.
• While holding the syringe packaging, slowly pull the white plunger out by 0.1 ml above the prescribed dose (for example, if the prescribed dose is 0.5 ml, pull the plunger to 0.6 ml). Never exceed the 0.9 ml mark regardless of the prescribed dose.
• The volume will be adjusted to the prescribed dose in a later step.
• DO NOT push the white plunger completely out of the syringe.

NOTE:
If the white plunger is pushed completely out of the syringe, discard the syringe and contact the Humira supplier for a replacement. DO NOT attempt to reinsert the white plunger.

Dose + 0.1 mL

• DO NOT use the white plunger to remove the syringe from its packaging. Hold the syringe by the barrel and pull it out of the packaging. DO NOT place the syringe down at any time.
• Holding the adapter steady, insert the tip of the syringe into the adapter and turn the syringe clockwise with one hand until it is secure. DO NOT overtighten.

• Holding the vial, push the white plunger all the way in. This step is important to draw up the correct dose. Keep the plunger inside and invert the vial and syringe.

• Slowly pull the white plunger up to 0.1 ml above the prescribed dose. This is important to ensure the correct dose is drawn. The equivalent volume to the prescribed dose will be set at step 4, Dose Preparation. If the prescribed dose is 0.5 ml, pull the plunger to 0.6 ml. The liquid will transfer from the vial to the syringe.

• Push the white plunger back in fully to return the liquid to the vial. Again, slowly pull the white plunger up to 0.1 ml above the prescribed dose; this is important to ensure the correct dose is drawn and to prevent air bubbles or empty spaces in the liquid. The equivalent volume to the prescribed dose will be set at step 4, Dose Preparation.

• If air bubbles or empty spaces remain in the syringe, repeat this process up to three times. DO NOT shake the syringe.

NOTE:
If the white plunger is pushed completely out of the syringe, discard the syringe and contact the Humira supplier for a replacement. DO NOT attempt to reinsert the white plunger.

• While holding the syringe upright by the barrel, unscrew and remove the adapter with the vial using the other hand. Make sure to remove the adapter and vial from the syringe. DO NOT touch the tip of the syringe.

• If a large air bubble or empty space is visible near the tip of the syringe, slowly push the white plunger into the syringe until fluid begins to enter the tip. DO NOT push the white plunger beyond the mark corresponding to the prescribed dose.
• For example, if the prescribed dose is 0.5 ml, DO NOT push the white plunger beyond the 0.5 ml mark.
• Check that the fluid remaining in the syringe is at least equal to the prescribed dose. If it is less, DO NOT use the syringe and contact your healthcare provider.
• With your free hand, pick up the needle packaging with the yellow syringe connector facing downwards.
• While keeping the syringe upright, insert the tip of the syringe into the yellow connector and rotate the syringe as indicated by the arrow in the figure until it stops. The needle is now attached to the syringe.

• Pull the needle out of its packaging, but DO NOT remove the transparent needle cap yet.
• Place the syringe on a clean work surface. Proceed immediately to the next steps: injection site selection and dose preparation.

3) Choosing and preparing an injection site

• Choose a spot on the thigh or abdomen: DO NOT use the same site used for the last injection.
• The new injection should be administered at least 3 cm away from the previous injection site.

• DO NOT administer the injection in areas where the skin appears red, bruised, or hardened. This could indicate infection; contact the doctor if this occurs.
• To reduce the risk of infection, clean the injection site with the other alcohol swab. DO NOT touch the area again before the injection.

4) Preparing the dose

• Pick up the syringe with the needle pointing upwards.
• Use your other hand to turn the pink needle cap towards the syringe.

• Remove the transparent needle cap by pulling it upwards with the other hand.

• The needle is clean.
• DO NOT touch the needle.
• DO NOT point the syringe downwards after removing the transparent needle cap.
• DO NOT attempt to re-sheath the transparent needle cap.
• Hold the syringe at eye level with the needle pointing upwards to clearly see the amount of liquid. Be careful not to spray the medicine into your eyes.
• Check the amount of medicine drawn up again.
• Gently push the white plunger into the syringe until the syringe contains the prescribed amount of medicine. Excess liquid may escape from the needle as the plunger is pressed. DO NOT remove the needle or syringe.

5) Injecting Humira

• With your free hand, gently pinch the area already cleaned with alcohol and hold it steady.
• With the other hand, hold the syringe at a 45° angle to the injection site.
• With a firm, quick motion, push the entire needle into the skin.
• Release the skin with your hand.
• Push the white plunger to inject the medicine until the syringe is empty.
• When the syringe is empty, remove the needle from the skin by pulling it out at the same angle as insertion.

• Gently turn the pink needle cap upwards over the needle and click it into place, then place the syringe with the needle on the work surface. DO NOT re-sheath the transparent needle cap.

• Using a piece of gauze, apply pressure to the injection site for 10 seconds. Minor bleeding may occur. DO NOT massage the injection site. You may apply a plaster if desired.

6) Disposal of materials

• You will need a special waste container, such as a sharps container, or as instructed by the nurse, doctor, or pharmacist.
• Place the syringe with the needle, vial, and adapter into a special sharps container. DO NOT dispose of these items in household waste.
• The syringe, needle, vial, and adapter MUST NEVER be reused.
• Always keep this container out of sight and reach of children.
• Dispose of all other used materials in the household waste container.

If you use more Humira than you should
If you accidentally inject more Humira than prescribed, or inject it more frequently than directed by the doctor, contact the doctor and inform them that the child has received more medicine.
Always keep the medicine box or vial, even if empty.

If you use less Humira than you should
If you accidentally inject less Humira than prescribed, or inject it less frequently than directed by the paediatrician or pharmacist, contact the paediatrician or pharmacist and inform them that the child has received less medicine. Always keep the medicine box or vial, even if empty.

If you forget to use Humira
If you forget to give a Humira injection to the child, administer the missed dose as soon as you remember. Then give the next dose according to the regular schedule.

If the child stops treatment with Humira
The decision to stop using Humira should be discussed with the paediatrician. The child’s symptoms may return after stopping treatment.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most of the side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months after the last Humira injection.
Inform your doctor immediately if you notice any of the following reactions:

• severe rash, hives, or other signs of allergic reaction;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning sensation when urinating;
• fatigue or weakness;
• cough;
• tingling;
• numbness;
• double vision;
• weakness in arms or legs;
• swelling or open wound that does not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The symptoms described above may be signs of the following side effects, 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);
• respiratory tract infections (including colds, rhinorrhea, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• musculoskeletal pain.

Common (may affect up to 1 in 10 people):

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• oral infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness;
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• bruising;
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry eye syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• contusion;
• skin inflammation (such as eczema);
• breakage of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema;
• fever;
• reduced platelet count in blood, increasing the risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people):

• opportunistic infections (including tuberculosis and other infections occurring when immune defenses are reduced);
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors;
• lymphatic system tumors;
• melanoma;
• disorders of the immune system affecting lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• stroke;
• neuropathy;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling in the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, vein inflammation and clot, or blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal fluid accumulation in the pleural space);
• pancreatitis causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema;
• gallbladder inflammation, gallstones;
• fatty liver;
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

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

• leukemia (a blood and bone marrow cancer);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (lung scarring);
• intestinal perforation;
• hepatitis;
• reactivation of hepatitis B;
• 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 associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized skin swelling);
• lichenoid skin reaction (pruritic red-purple rash).

Not known (frequency cannot be estimated from the available data):

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi’s sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly presents with purple skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (presenting as rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain has been low).

Some of the side effects observed with Humira may be asymptomatic and can only be detected 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;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people):

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in blood;
• altered sodium levels in blood;
• reduced calcium in blood;
• reduced phosphorus in blood;
• increased blood sugar;
• increased lactate dehydrogenase in blood;
• presence of autoantibodies in blood;
• reduced potassium in blood.

Uncommon (may affect up to 1 in 100 people):

• elevated bilirubin levels in blood (liver blood test).

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

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If the child experiences any side effect, including those not listed in this leaflet, please contact the pediatrician or pharmacist. You may also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humira contains

• The active substance is adalimumab.
• The excipients are mannitol, monohydrate citric acid, sodium citrate, disodium phosphate dihydrate, monosodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide, and water for injections.

Description of the appearance of Humira vials and package contents
Humira 40 mg solution for injection in vials is supplied as a sterile solution containing 40 mg of
adalimumab dissolved in 0.8 ml of solution.
Humira vials consist of a solution of adalimumab contained in a glass vial. A package contains 2 cartons, each containing 1 vial, 1 empty sterile syringe, 1 needle, 1 vial adapter, and 2 alcohol swabs.
Humira may also be available in vials, pre-filled syringes, and/or pre-filled pens.

Marketing Authorization Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

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More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/ .

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Patient information leaflet

Humira 40 mg solution for injection in pre-filled syringe

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before starting Humira and during treatment with Humira. Keep this Patient Reminder Card.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Humira is and what it is used for

Humira contains the active substance adalimumab.
Humira is indicated for the treatment of the following inflammatory diseases:

• Rheumatoid arthritis,
• Polyarticular juvenile idiopathic arthritis,
• Enthesitis-related arthritis,
• Ankylosing spondylitis,
• Non-radiographic axial spondyloarthritis (axial spondyloarthritis without radiographic evidence of ankylosing spondylitis),
• Psoriatic arthritis,
• Psoriasis,
• Hidradenitis suppurativa,
• Crohn’s disease,
• Ulcerative colitis, and
• Non-infectious uveitis

The active substance in Humira, adalimumab, is a human monoclonal antibody.
Monoclonal antibodies are proteins that bind specifically to a particular target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to 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 rheumatoid arthritis in adults.
If you have moderate to severe rheumatoid arthritis, you may initially be given other disease-modifying drugs, such as methotrexate. If your response to these drugs is not satisfactory, you will be given Humira to treat rheumatoid arthritis.
Humira may also be used for the treatment of severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Humira has been shown to slow down the progression of joint cartilage and bone damage caused by the disease and to improve physical function.
Humira is generally used in combination with methotrexate. If your doctor decides that treatment with methotrexate is not appropriate, Humira may be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases.
Humira is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years.
At diagnosis, other disease-modifying drugs such as methotrexate may be administered. If your response to these drugs is inadequate, you will be given Humira for the treatment of polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis are inflammatory conditions of the spine.
Humira is used to treat ankylosing spondylitis and non-radiographic axial spondyloarthritis in adults. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be given other medications. If you do not achieve an adequate response with these medications, you will take Humira to reduce the signs and symptoms of the disease.

Psoriatic arthritis
Psoriatic arthritis is joint inflammation associated with psoriasis.
Humira is used to treat psoriatic arthritis in adults. Humira has been shown to slow down joint cartilage and bone damage caused by the disease and to improve physical function.

Plaque psoriasis in adults and children
Plaque psoriasis is a skin condition that causes red, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which may be painful. Psoriasis is believed to be caused by a problem with the body’s immune system that leads to an increased production of skin cells.
Humira is used to treat moderate to severe plaque psoriasis in adults. Humira is also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapy have not worked well or are not suitable.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful lumps and abscesses (cysts) that may drain pus. It most commonly affects specific skin areas such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Humira is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. Humira can reduce the number of lumps and abscesses you have, as well as the pain often associated with this disease. Initially, you may receive other medicines. If you do not respond adequately to these medicines, you will be given Humira.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the gastrointestinal tract.
Humira is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s disease, you will first be given other medications. If you do not respond adequately to these medications, Humira will be given to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine (colon).
Humira is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you may initially take other medications. If you do not achieve an adequate response with these medications, you will take Humira to reduce the signs and symptoms of the disease.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
Humira is used for the treatment of:

• Adults with non-infectious uveitis involving posterior segment inflammation of the eye
• Children from 2 years of age with chronic non-infectious uveitis involving anterior segment inflammation of the eye

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

2. What you should know before using Humira

Do not use Humira

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a serious infection, including active tuberculosis (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If you have moderate or severe heart failure. It is important to inform 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 using Humira

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not administer Humira again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.
• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Humira. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Humira. This risk may increase if your lung function is impaired. These infections can be serious and may include tuberculosis, viral, fungal, parasitic, or bacterial infections, other opportunistic infections, and sepsis, which in rare cases may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may advise temporarily stopping Humira.
• Since cases of tuberculosis have occurred in patients treated with Humira, your doctor will check for signs or symptoms of tuberculosis before starting therapy with Humira. This will include a thorough medical evaluation including your medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or have been in close contact with someone who has tuberculosis. Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after treatment.
• Inform your doctor if you live in or travel to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.
• Inform your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.
• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor must test you for hepatitis B virus infection. Taking Humira may cause reactivation of hepatitis B virus in carriers of this virus. In rare cases, especially if the patient is also receiving other medications that suppress the immune system, hepatitis B virus reactivation may be life-threatening.
• If you are over 65 years old, you may be more susceptible to infections while taking Humira. You and your doctor should pay particular attention to signs of infection during treatment. It is important to inform your doctor if symptoms of infection such as fever, wounds, feeling tired, or dental problems occur.
• Before any surgery or dental procedures, inform your doctor that you are taking Humira. Your doctor may recommend temporarily stopping treatment.
• If you have or develop demyelinating diseases such as multiple sclerosis, your doctor will decide whether to 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 affecting any part of your body.
• Certain vaccines may cause infections and should not be given during treatment with Humira. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to complete the routine vaccination schedule according to current vaccination guidelines before starting Humira therapy. If you have taken Humira during pregnancy, the baby may have an increased risk of infection for up to about 5 months after your last dose during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy so they can determine when the baby should receive any vaccinations.
• If you have mild heart failure and are being treated with Humira, your doctor should carefully monitor your heart condition. It is important to inform your doctor about any past or present heart problems. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether you can continue taking Humira.
• In some patients, the body may not produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.
• Very rarely, certain types of tumors have been observed in patients, both children and adults, treated with Humira or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis 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 take Humira, your risk of developing lymphoma, leukemia, or other cancers may increase. In rare cases, a specific 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. In addition, cases of non-melanoma skin cancer have been observed in patients taking Humira. If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.
• Rarely, treatment with Humira may cause a lupus-like syndrome. Inform your doctor if you develop symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Humira.
• Do not give Humira to children under 2 years of age with polyarticular juvenile idiopathic arthritis.

Other medicines and Humira

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

Humira may be taken together with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts, as well as corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Humira must not be used in combination with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after your last dose of Humira.
• If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor about using this medicine.
• Humira should be used during pregnancy only if clearly needed.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If you take Humira during pregnancy, the baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy before the baby receives any vaccinations (for more information on vaccinations, see the section "Warnings and precautions").

Driving and using machines
Humira may affect your ability to drive, ride a bicycle, or use machinery, although only to a minor extent. After taking Humira, you may experience vision disturbances or a sensation that your surroundings are spinning.

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

3. How to use Humira

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Your doctor may prescribe a different concentration of Humira if a different dose is required.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis
Humira is injected under the skin (subcutaneous use). The usual dose for adults with rheumatoid arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, or psoriatic arthritis is 40 mg of adalimumab every other week, administered as a single dose.

In rheumatoid arthritis, methotrexate is continued during treatment with Humira. If your doctor decides that methotrexate is not appropriate, Humira may be given alone.

If you have rheumatoid arthritis and are not receiving methotrexate in combination with Humira, your doctor may decide to prescribe 40 mg of adalimumab weekly or 80 mg every other week.

Children, adolescents, and adults with polyarticular juvenile idiopathic arthritis
Children and adolescents aged 2 years and older, weighing between 10 kg and less than 30 kg
The recommended dose of Humira is 20 mg every other week.

Children, adolescents, and adults aged 2 years and older, weighing 30 kg or more
The recommended dose of Humira is 40 mg every other week.

Children, adolescents, and adults with enthesitis-related arthritis
Children and adolescents aged 6 years and older, weighing between 15 kg and less than 30 kg
The recommended dose of Humira is 20 mg every other week.

Children, adolescents, and adults aged 6 years and older, weighing 30 kg or more
The recommended dose of Humira is 40 mg every other week.

Adults with psoriasis
The usual dose of Humira for adults with psoriasis is an initial dose of 80 mg (via two 40 mg injections on the same day), followed by 40 mg every other week, starting from the week following the initial dose. You must continue Humira treatment for the duration prescribed by your doctor. Depending on clinical response, your doctor may increase the dose to 40 mg weekly or 80 mg every other week.

Children and adolescents with plaque psoriasis
Children and adolescents aged 4 to 17 years, weighing between 15 kg and less than 30 kg
The recommended dose of Humira is an initial dose of 20 mg, followed by a 20 mg dose the following week. Subsequently, the usual dose is 20 mg every other week.

Children and adolescents aged 4 to 17 years, weighing 30 kg or more
The recommended dose of Humira is an initial dose of 40 mg, followed by a 40 mg dose the following week. Subsequently, the usual dose is 40 mg every other week.

Adults with hidradenitis suppurativa
The usual dose for hidradenitis suppurativa is an initial dose of 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) two weeks later. After another two weeks, continue with 40 mg weekly or 80 mg every other week, as prescribed by your doctor. It is recommended to use an antiseptic wash solution daily on affected areas.

Adolescents with hidradenitis suppurativa aged 12 to 17 years, weighing 30 kg or more
The recommended dose of Humira is an initial dose of 80 mg (via two 40 mg injections on the same day), followed by 40 mg every other week starting one week after the initial dose. If there is an inadequate response to 40 mg of Humira every other week, your doctor may increase the dose to 40 mg weekly or 80 mg every other week.

It is recommended to use an antiseptic wash solution daily on affected areas.

Adults with Crohn’s disease
The usual dose for Crohn’s disease is initially 80 mg (via two 40 mg injections on the same day), followed by 40 mg every other week after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) after two weeks, and subsequently 40 mg every other week. Depending on clinical response, your doctor may increase the dose to 40 mg weekly or 80 mg every other week.

Children and adolescents with Crohn’s disease
Children and adolescents aged 6 to 17 years, weighing less than 40 kg
The usual dose is initially 40 mg, followed by 20 mg after two weeks. If a more rapid response is required, your doctor may prescribe an initial dose of 80 mg (via two 40 mg injections on the same day), followed by 40 mg after two weeks. Subsequently, the usual dose is 20 mg every other week. Depending on clinical response, your doctor may increase the frequency to 20 mg weekly.

Children and adolescents aged 6 to 17 years, weighing 40 kg or more
The usual dose is initially 80 mg (via two 40 mg injections on the same day), followed by 40 mg after two weeks. If a more rapid response is required, your doctor may prescribe an initial dose of 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) after two weeks. Subsequently, the usual dose is 40 mg every other week. Depending on clinical response, your doctor may increase the dose to 40 mg weekly or 80 mg every other week.

Adults with ulcerative colitis
The usual dose of Humira for adults with ulcerative colitis is 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days) at week 0, 80 mg (via two 40 mg injections on the same day) at week 2, and subsequently 40 mg every other week. Depending on clinical response, your doctor may increase the dose to 40 mg weekly or 80 mg every other week.

Children and adolescents with ulcerative colitis
Children and adolescents aged 6 years and older, weighing less than 40 kg
The usual dose of Humira is 80 mg (via two 40 mg injections on the same day), followed by 40 mg (via one 40 mg injection) two weeks later. Subsequently, the usual dose is 40 mg every other week.

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

Children and adolescents aged 6 years and older, weighing 40 kg or more
The usual dose of Humira is 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) two weeks later. Subsequently, the usual dose is 80 mg every other week.

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

Adults with non-infectious uveitis
The usual dose for adults with non-infectious uveitis is an initial dose of 80 mg (via two injections on the same day), followed by 40 mg every other week starting one week after the initial dose. You must continue injecting Humira for the entire duration prescribed by your doctor. In non-infectious uveitis, corticosteroids or other immunosuppressive medications may be continued during treatment with Humira. Humira may be administered as monotherapy.

Children and adolescents with chronic non-infectious uveitis, aged 2 years and older
Children and adolescents aged 2 years and older, weighing less than 30 kg
The usual dose of Humira is 20 mg every other week, administered with methotrexate.

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

Children and adolescents aged 2 years and older, weighing 30 kg or more
The usual dose of Humira is 40 mg every other week, administered with methotrexate.

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

Method and route of administration
Humira is administered by subcutaneous injection (under the skin).

Instructions for preparing and injecting Humira
The following instructions explain how to inject Humira. Read the instructions carefully and follow them step by step. You will receive training from your doctor or their assistant on the technique of self-administration. Do not perform the injection yourself until you are certain you understand how to prepare and administer the dose. After proper instruction, the injection may be given by you or another person, such as a family member or friend.

The contents of the syringe must not be mixed with other medicines in the same syringe or vial.

1) Preparation

• Wash your hands thoroughly.
• Place the following items on a clean surface:
  • One pre-filled syringe of Humira injectable solution
  • One alcohol swab

• Check the expiration date on the syringe. Do not use the product after the month and year indicated.

2) Choosing and preparing an injection site

• Choose a site on the thigh or abdomen.

• Each new injection should be administered at least 3 cm away from the previous injection site.
• Do not inject in areas where the skin appears red, bruised, or hardened. This could indicate infection.
• Clean the injection site with the alcohol swab using a circular motion.
• Do not touch the area again before the injection.

3) Injecting Humira

• DO NOT shake the syringe.
• Remove the needle cap from the syringe, taking care not to touch the needle or let it touch any surface.
• With one hand, gently pinch the area cleaned with alcohol and hold it steady.

• With the other hand, hold the syringe (with the fluted part facing upward) at a 45° angle to the injection site.
• With a firm, quick motion, push the entire needle into the skin.
• Release the skin with your first hand.
• Push the plunger to inject the solution – it may take 2 to 5 seconds to empty the syringe.
• When the syringe is empty, remove the needle from the skin, maintaining the same angle as insertion.
• Using your thumb or a piece of gauze, apply pressure to the injection site for 10 seconds. Minor bleeding may occur. Do not massage the injection site. You may apply a bandage if desired.

4) Disposal of materials

• NEVER reuse the Humira syringe. NEVER recap the needle.
• After injecting Humira, immediately dispose of the used syringe in a special container as instructed by your doctor, nurse, or pharmacist.
• Keep the container out of sight and reach of children.

Instructions for preparing and injecting Humira
The following instructions explain how to inject Humira. Read the instructions carefully and follow them step by step. You will receive training from your doctor or their assistant on the technique of self-administration. Do not perform self-injection until you are certain you understand how to prepare and administer the dose. After proper instruction, the injection may be given by you or another person, such as a family member or friend.
The contents of the syringe must not be mixed with other medicines in the same syringe.

1) Preparation

• Wash your hands thoroughly.
• Place the following items on a clean surface:
  • One pre-filled syringe of Humira injectable solution
  • One alcohol swab

• Check the expiration date on the syringe. Do not use the product after the month and year indicated.

2) Choosing and preparing an injection site

• Choose a site on the thigh or abdomen.

• Each new injection should be administered at least 3 cm away from the previous injection site.
• Do not inject in areas where the skin is red, bruised, or hardened. This could indicate infection.
• Clean the injection site with the alcohol swab using a circular motion.
• Do not touch the area again before the injection.

3) Injecting Humira

• DO NOT shake the syringe.
• Remove the needle cap from the syringe, taking care not to touch the needle or let it touch any surface.
• With one hand, gently pinch the area cleaned with alcohol and hold it steady.

• With the other hand, hold the syringe with the fluted part facing upward, at a 45° angle to the injection site.
• With a firm, quick motion, push the entire needle into the skin.
• Release the skin with your first hand.
• Push the plunger to inject the solution – it may take 2 to 5 seconds to empty the syringe.
• When the syringe is empty, remove the needle from the skin, maintaining the same angle as insertion.
• Hold the syringe with one hand and use the other hand to slide the protective needle cover over the exposed needle until it locks into place.
• Using your thumb or a piece of gauze, apply pressure to the injection site for 10 seconds. Minor bleeding may occur. Do not massage the injection site. You may apply a bandage if desired.

4) Disposal of materials

• NEVER reuse the Humira syringe. NEVER recap the needle.
• After injecting Humira, immediately dispose of the used syringe in a special container as instructed by your doctor, nurse, or pharmacist. Keep this medicine out of sight and reach of children.

If you use more Humira than you should
If you accidentally inject Humira more frequently than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken more medicine than required. Always keep the medicine packaging, even if empty.

If you forget to use Humira
If you forget to give an injection, administer the next dose of Humira as soon as you remember. Then resume your regular dosing schedule.

If you stop using Humira
The decision to stop using Humira should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild to moderate in severity. However, some may be serious and require treatment.
Side effects may occur up to 4 months after the last Humira injection.
Immediately inform your doctor if you notice any of the following reactions:

• severe rash, hives, or other signs of allergic reaction;
• swelling of the face, hands, or feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath on exertion or when lying down, or swollen feet.

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning during urination;
• fatigue or weakness;
• cough;
• tingling;
• numbness;
• double vision;
• weakness in arms or legs;
• swelling or a sore that does not heal;
• signs and symptoms suggesting disorders of the haematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The symptoms described above may be signs of the following side effects, 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);
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• musculoskeletal pain.

Common (may affect up to 1 in 10 people):

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• oral infections (including dental infections and herpes simplex);
• genital infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumours;
• skin tumours;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness;
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• bruising;
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• contusion;
• skin inflammation (such as eczema);
• cracking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• oedema;
• fever;
• reduced 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 occurring when immune defences are reduced);
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumours;
• lymphatic system tumours;
• melanoma;
• immune system disorders affecting lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy;
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling of the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, vein inflammation and clot, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• pancreatitis causing severe abdominal and back pain;
• difficulty swallowing;
• facial oedema;
• gallbladder inflammation, gallstones;
• fatty liver;
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

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

• leukaemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (lung scarring);
• intestinal perforation;
• hepatitis;
• reactivation of hepatitis B;
• 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 oedema associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, red-purple rash).

Not known (frequency cannot be estimated from the available data):

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma typically presents with purple skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• Weight gain (in most patients, weight gain has been low).

Some of the side effects observed with Humira may be asymptomatic and detectable only 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;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people):

• increased white blood cell count;
• reduced platelet count;
• increased blood uric acid;
• altered blood sodium;
• reduced blood calcium;
• reduced blood phosphorus;
• increased blood glucose;
• increased blood lactate dehydrogenase;
• presence of autoantibodies in blood;
• reduced blood potassium.

Uncommon (may affect up to 1 in 100 people):

• elevated bilirubin levels in blood (liver blood test).

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

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.
You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister pack/box following the word "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), a single ready-to-use syringe may be stored at room temperature (up to 25°C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date when the syringe is first removed from the refrigerator and the date after which the syringe must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, monohydrate citric acid, sodium citrate, monobasic sodium phosphate
dihydrate, dibasic sodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for
injections.

Description of the appearance of Humira pre-filled syringe and contents of the pack
Humira 40 mg solution for injection in pre-filled syringes is supplied as a sterile solution containing 40 mg of
adalimumab dissolved in 0.8 ml of solution.
The Humira pre-filled syringe consists of a solution of adalimumab contained in a glass syringe.
Each pack contains 1, 2, 4 or 6 pre-filled syringes with respectively 1, 2, 4 or 6 alcohol-impregnated swabs. Not all pack sizes may be marketed.
Humira may be available in vial, pre-filled syringe and/or pre-filled pen.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.: +36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ.: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

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

To listen to or request a copy of this summary of product characteristics in , or , please contact the local representative of the Marketing Authorisation Holder.

Patient Information Leaflet

Humira 40 mg solution for injection in pre-filled pen

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before administration of Humira and during treatment with Humira. Keep this Patient Reminder Card.
• 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 their symptoms are the same as yours, because it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Humira is and what it is used for

Humira contains the active substance adalimumab.
Humira is indicated for the treatment of the following inflammatory diseases:

• Rheumatoid arthritis,
• Polyarticular juvenile idiopathic arthritis,
• Enthesitis-related arthritis,
• Ankylosing spondylitis,
• Non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,
• Psoriatic arthritis,
• Psoriasis,
• Hidradenitis suppurativa,
• Crohn’s disease,
• Ulcerative colitis, and
• Non-infectious uveitis

The active substance in Humira, adalimumab, is a human monoclonal antibody.
Monoclonal antibodies are proteins that bind to a specific target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the (defensive) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to 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 rheumatoid arthritis in adults.
If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs such as methotrexate may initially be prescribed. If your response to these drugs is not satisfactory, you will be given Humira to treat rheumatoid arthritis.
Humira may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Humira has been shown to slow the progression of joint cartilage and bone damage caused by the disease and to improve physical function.
Humira is generally used in combination with methotrexate. If your doctor decides that treatment with methotrexate is not appropriate, Humira may be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis
Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases.
Humira is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years, and enthesitis-related arthritis in children and adolescents aged 6 to 17 years.
Other disease-modifying drugs, such as methotrexate, may be given at diagnosis. If your response to these drugs is inadequate, Humira will be administered to treat polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory conditions of the spine.
Humira is used to treat ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. If you have ankylosing spondylitis or non-radiographic axial spondyloarthritis, you will first be treated with other drugs. If you do not achieve an adequate response with these drugs, you will take Humira to reduce the signs and symptoms of the disease.

Psoriatic arthritis
Psoriatic arthritis is a joint inflammation associated with psoriasis.
Humira is used to treat psoriatic arthritis in adults.
Humira has been shown to slow down joint cartilage and bone damage caused by the disease and to improve physical function.

Plaque psoriasis in adults and children
Plaque psoriasis is a skin condition that causes red, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken, or lift from the nail bed, which can be painful. Psoriasis is thought to be caused by a problem with the body’s immune system that leads to an increased production of skin cells.
Humira is used to treat moderate to severe plaque psoriasis in adults. Humira is also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapies have not worked well or are not suitable.

Hidradenitis suppurativa in adults and adolescents
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus. It most commonly affects specific skin areas such as the under-breast area, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Humira is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. Humira can reduce the number of nodules and abscesses you have and the pain often associated with this disease. Initially, you may receive other medications. If you do not respond adequately to these medications, you will be given Humira.

Crohn’s disease in adults and children
Crohn’s disease is an inflammation of the digestive tract.
Humira is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If you have Crohn’s disease, you will first be given other drugs. If you do not respond adequately to these drugs, Humira will be administered to reduce the typical symptoms of Crohn’s disease.

Ulcerative colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine.
Humira is used to treat moderate to severe ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis, you may initially take other drugs. If you do not achieve an adequate response with these drugs, you will take Humira to reduce the signs and symptoms of the disease.

Non-infectious uveitis in adults and children
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
Humira is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye

This inflammation can lead to reduced vision and/or the presence of floating bodies in the eye (black spots or fine lines moving across the visual field). Humira works by reducing this inflammation.

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 ingredients of this medicine (listed in section 6).
• If you have a serious infection, including active tuberculosis (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If you have moderate or severe heart failure. It is important to inform 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 using Humira

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not administer Humira again and contact your doctor immediately, as these reactions may, in rare cases, be life-threatening.
• If you have an infection, including long-term or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Humira. If you are in doubt, contact your doctor.
• You may be more likely to get infections while being treated with Humira. This risk may increase if your lung function is impaired. These infections can be serious and may include tuberculosis, viral, fungal, parasitic, or bacterial infections, or other opportunistic infections and sepsis, which may, in rare cases, be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may recommend temporarily stopping Humira.
• Cases of tuberculosis have occurred in patients treated with Humira. Therefore, your doctor will check for signs or symptoms of tuberculosis before starting Humira therapy. This will involve a detailed medical evaluation including your medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to inform your doctor if you have ever had tuberculosis or have been in close contact with someone who has tuberculosis. Tuberculosis may develop during treatment even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if you develop symptoms of tuberculosis (persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.
• Inform your doctor if you live in or travel to areas where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.
• Inform your doctor if you have had recurring infections or if you have conditions that increase your risk of infection.
• Inform your doctor if you are a carrier of hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting hepatitis B virus. Your doctor should test you for hepatitis B virus infection. Taking Humira may cause reactivation of hepatitis B virus in carriers of this virus. In some rare cases, especially if the patient is also receiving other medicines that suppress the immune system, reactivation of hepatitis B virus may be life-threatening.
• If you are over 65 years old, you may be more susceptible to infections while taking Humira. You and your doctor should pay particular attention to signs of infection while you are being treated with Humira. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.
• Before undergoing surgery or dental procedures, inform your doctor that you are taking Humira. Your doctor may recommend temporarily stopping treatment.
• If you have or develop demyelinating diseases such as multiple sclerosis, your doctor will decide whether or not to 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 in any part of the body.
• Certain vaccines may cause infections and should not be administered during treatment with Humira. Consult your doctor before receiving any vaccinations. In children, it is recommended, if possible, to complete the vaccination schedule according to current vaccination guidelines before starting Humira therapy. If you have taken Humira during pregnancy, your baby may have an increased risk of infection for up to about 5 months after your last dose during pregnancy. It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy so they can decide when your baby should receive any vaccinations.
• If you have mild heart failure and are being treated with Humira, your doctor will need to carefully monitor your heart condition. It is important to inform your doctor about any past or present heart problems. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether Humira can be used.
• In some patients, the body may not be able to produce enough blood cells to help fight infections or stop bleeding. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately. Your doctor may decide to stop treatment.
• Very rare cases of certain types of tumors have been reported in patients, both children and adults, treated with Humira or other anti-TNF medicines. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow). If you are taking Humira, your risk of developing lymphoma, leukemia, or other tumors may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with Humira. Some of these patients were also being treated with azathioprine or 6-mercaptopurine. Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Humira. In addition, cases of non-melanoma skin cancer have been observed in patients taking Humira. If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
• Cases of tumors other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.
• Rarely, treatment with Humira may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: If possible, children should have completed all recommended vaccinations before starting Humira.
• Do not give Humira to children under 2 years of age with polyarticular juvenile idiopathic arthritis.

Other medicines and Humira
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Humira may be taken together with methotrexate and other disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts, as well as corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Humira must not be taken together with medicines containing the active substances anakinra or abatacept due to an increased risk of serious infections. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after your last dose of Humira.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor for advice before taking this medicine.
• Humira should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy, compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If you take Humira during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy before your baby receives any vaccinations. For more information on vaccinations, see the section "Warnings and precautions".

Driving and using machines
Humira may affect your ability to drive, ride a bicycle, or use machines, although only to a minor extent. After taking Humira, you may experience visual disturbances or a sensation that your surroundings are spinning.

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

3. How to use Humira

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Your doctor may prescribe a different concentration of Humira if a different dose is required.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis
Humira is injected under the skin (subcutaneous use). The usual dose for adults with rheumatoid arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, or psoriatic arthritis is 40 mg of adalimumab every other week, administered as a single dose.

In rheumatoid arthritis, methotrexate is continued during treatment with Humira. If your doctor decides that methotrexate is not appropriate, Humira may be given alone.

If you have rheumatoid arthritis and are not receiving methotrexate in combination with Humira, your doctor may decide to prescribe 40 mg of adalimumab weekly or 80 mg every other week.

Children, adolescents, and adults with polyarticular juvenile idiopathic arthritis
Children and adolescents aged 2 years and older, weighing between 10 kg and less than 30 kg
The recommended dose of Humira is 20 mg every other week.

Children, adolescents, and adults aged 2 years and older, weighing 30 kg or more
The recommended dose of Humira is 40 mg every other week.

Children, adolescents, and adults with enthesitis-related arthritis
Children and adolescents aged 6 years and older, weighing between 15 kg and less than 30 kg
The recommended dose of Humira is 20 mg every other week.

Children, adolescents, and adults aged 6 years and older, weighing 30 kg or more
The recommended dose of Humira is 40 mg every other week.

Adults with psoriasis
The usual dose of Humira for adults with psoriasis is an initial dose of 80 mg (via two 40 mg injections on the same day), followed by 40 mg every other week, starting the week after the initial dose. You must continue Humira treatment for the duration specified by your doctor. Depending on your clinical response, your doctor may increase the dosage to 40 mg weekly or 80 mg every other week.

Children and adolescents with plaque psoriasis
Children and adolescents aged 4 to 17 years, weighing between 15 kg and less than 30 kg
The recommended dose of Humira is an initial dose of 20 mg, followed by a dose of 20 mg the following week. Thereafter, the usual dose is 20 mg every other week.

Children and adolescents aged 4 to 17 years, weighing 30 kg or more
The recommended dose of Humira is an initial dose of 40 mg, followed by a dose of 40 mg the following week. Thereafter, the usual dose is 40 mg every other week.

Adults with hidradenitis suppurativa
The usual dose for hidradenitis suppurativa is an initial dose of 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) two weeks later. After another two weeks, continue with 40 mg weekly or 80 mg every other week, as prescribed by your doctor. Daily use of an antiseptic wash solution on affected areas is recommended.

Adolescents with hidradenitis suppurativa, aged 12 to 17 years, weighing 30 kg or more
The recommended dose of Humira is an initial dose of 80 mg (via two 40 mg injections on the same day), followed by 40 mg every other week starting one week after the initial dose. If the response to 40 mg of Humira every other week is inadequate, your doctor may increase the dosage to 40 mg weekly or 80 mg every other week.

Daily use of an antiseptic wash solution on affected areas is recommended.

Adults with Crohn’s disease
The usual dose for Crohn’s disease is initially 80 mg (via two 40 mg injections on the same day), followed by 40 mg every other week after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) after two weeks, and then 40 mg every other week. Depending on clinical response, your doctor may increase the dosage to 40 mg weekly or 80 mg every other week.

Children and adolescents with Crohn’s disease
Children and adolescents aged 6 to 17 years, weighing less than 40 kg
The usual dose is initially 40 mg, followed by 20 mg after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 80 mg (via two 40 mg injections on the same day), followed by 40 mg after two weeks.
Thereafter, the usual dose is 20 mg every other week. Depending on clinical response, your doctor may increase the frequency to 20 mg weekly.

Children and adolescents aged 6 to 17 years, weighing 40 kg or more
The usual dose is initially 80 mg (via two 40 mg injections on the same day), followed by 40 mg after two weeks. If a more rapid response is needed, your doctor may prescribe an initial dose of 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) after two weeks.
Thereafter, the usual dose is 40 mg every other week. Depending on clinical response, your doctor may increase the dosage to 40 mg weekly or 80 mg every other week.

Adults with ulcerative colitis
The usual dose of Humira for adults with ulcerative colitis is 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days) at week 0, followed by 80 mg (via two 40 mg injections on the same day) at week 2, and then 40 mg every other week. Depending on clinical response, your doctor may increase the dosage to 40 mg weekly or 80 mg every other week.

Children and adolescents with ulcerative colitis
Children and adolescents aged 6 years and older, weighing less than 40 kg
The usual dose of Humira is 80 mg (via two 40 mg injections on the same day), followed by 40 mg (via a single 40 mg injection) after two weeks. Thereafter, the usual dose is 40 mg every other week.
Patients who turn 18 years old while receiving 40 mg every other week should continue the prescribed dose.

Children and adolescents aged 6 years and older, weighing 40 kg or more
The usual dose of Humira is 160 mg (via four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (via two 40 mg injections on the same day) after two weeks. Thereafter, the usual dose is 80 mg every other week.
Patients who turn 18 years old while receiving 80 mg every other week should continue the prescribed dose.

Adults with non-infectious uveitis
The usual dose for adults with non-infectious uveitis is an initial dose of 80 mg (via two injections on the same day), followed by 40 mg every other week starting one week after the initial dose. You must continue injecting Humira for the duration specified by your doctor.
In non-infectious uveitis, corticosteroids or other immunosuppressive medications may be continued during Humira treatment. Humira may be administered as monotherapy.

Children and adolescents with chronic non-infectious uveitis, aged 2 years and older
Children and adolescents aged 2 years and older, weighing less than 30 kg
The usual dose of Humira is 20 mg every other week, administered with methotrexate.
Your doctor may also prescribe an initial dose of 40 mg, which may be administered one week before starting the usual dose.

Children and adolescents aged 2 years and older, weighing 30 kg or more
The usual dose of Humira is 40 mg every other week, administered with methotrexate.
Your doctor may also prescribe an initial dose of 80 mg, which may be administered one week before starting the usual dose.

Method and route of administration
Humira is administered by subcutaneous injection (under the skin).

How to self-inject Humira using the pre-filled pen
The following instructions explain how to self-inject Humira using the pre-filled pen. Read the instructions carefully and follow them step by step. You will receive training from your doctor or their assistant on the self-administration technique. Do not attempt self-injection until you are certain you understand how to prepare and administer the injection. After proper training, the injection may be performed by you or by others, such as a family member or friend.

What procedure should be followed before self-injecting Humira subcutaneously?

1. Wash your hands thoroughly.
2. Remove the single-dose container containing the pre-filled pen of Humira from the refrigerator.
3. Do not shake or drop the pre-filled pen.
4. Place the following items on a clean surface:
   • one pre-filled pen of Humira
   • one alcohol swab

Swab
Window

5. Check the expiration date printed on the label of the pre-filled pen (Exp.). Do not use the product if the date (of self-injection) has passed the month and year indicated on the label.
6. Hold the pre-filled pen with the grey cap (marked with the number ‘1’) facing upwards. Check the Humira solution through the viewing window on the side of the pre-filled pen to assess its appearance. The solution should appear clear and colourless. If the solution appears cloudy, has changed colour, or contains visible particles or impurities, do not use it. Do not use a pre-filled pen that has been frozen or exposed to direct sunlight. Remove both the grey cap and the purple cap only immediately before injection.

Window
Clear liquid in syringe

Where should the injection be administered?

1. Choose either the upper thigh or the stomach area (excluding the area around the navel) as the injection site.

2. Change the injection site each time to avoid irritation or soreness. Each injection should be administered at least 3 centimetres away from the previous injection site.
3. Do not inject into areas where the skin appears red, bruised, or hardened. The presence of these signs may indicate an infection.

How should the injection be performed?

1. Clean the skin thoroughly using the alcohol swab provided in the package, using a circular motion. Avoid touching the area again before administering the injection.
2. Remove both the grey cap and the purple cap only immediately before injection. Hold the grey body of the pre-filled pen in one hand, placing your hand in the middle of the pen so that neither the grey cap (1) nor the purple cap (2) is covered. Hold the pre-filled pen with the grey cap (1) facing upwards. With the other hand, pull the grey cap (1) outward. Check that the black needle cover has been removed along with the cap, then discard it. If small drops of liquid appear at the needle tip, this is normal. The white needle guard will now be exposed. Do not touch the needle inside the syringe barrel. DO NOT REPLACE THE CAP, as this may damage the needle inside.

3. Remove the purple safety cap (marked with the number ‘2’) to expose the purple activation button. The pre-filled pen is now ready for use. Do not press the purple activation button until the syringe is correctly positioned, as this may cause the medicine to be expelled. DO NOT REPLACE THE CAP, as this may cause the medicine to leak from the pen.

How to inject the medicine

1. With your free hand, gently pinch a firm area of skin at the chosen and sterilized injection site and hold it firmly (see the figure below).
2. Position the white end of the pre-filled pen at a right angle (90 degrees) to the skin, ensuring you can see the viewing window on the pen. The presence of one or more air bubbles in the window is normal.
3. While holding the barrel of the pre-filled pen, apply gentle pressure against the injection site (keeping the pen firmly in place without moving it).
4. When ready to inject, press the purple button on the top end of the pen with your index finger or thumb (see the figure below). At this moment, you will hear a loud ‘click’ and feel a slight prick as the needle penetrates the skin.
5. Continue holding the button down and keep the pre-filled pen in place, applying constant pressure for approximately 10 seconds to ensure the injection is complete. Do not remove the pre-filled pen while injecting the solution.

6. During the injection, you will see a yellow indicator moving within the viewing window (on the side of the pen). The injection is complete when the yellow indicator stops moving. The yellow indicator is part of the plunger in the pre-filled syringe. If the yellow indicator does not appear in the window, the plunger has not been fully depressed, and the injection is incomplete.
7. Remove the pre-filled pen from the injection site. The white protective sheath covering the needle will slide over the needle and lock in place, covering the tip. Do not touch the needle. The white sheath protects you from contact with the needle.

¿
White protective
needle sheath Window
Yellow indicator
visible

8. You may notice a small drop of blood at the injection site. If so, apply light pressure with a cotton ball or gauze for 10 seconds. Do not rub the injection site. You may apply a bandage if desired.

How to dispose of the pen

• Use each pre-filled pen for one injection only. Do not replace any of the caps on the pre-filled pen.
• After injecting Humira, immediately dispose of the used pre-filled pen in a special container as instructed by your doctor, nurse, or pharmacist.
• Keep this container out of sight and reach of children.

If you use more Humira than you should
If you accidentally inject Humira more frequently than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken more medicine than directed. Always keep the medicine box or the pre-filled pen, even if 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 resume your regular dosing schedule.

If you stop using Humira
The decision to stop using Humira should be discussed with your doctor. Symptoms may return after stopping treatment.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months after the last Humira injection.

Contact your doctor immediately if you notice any of the following reactions:

• severe rash, hives, or other signs of allergic reaction;
• swelling of the face, hands, or feet;
• difficulty breathing, trouble swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

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

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning during urination;
• fatigue or weakness;
• cough;
• tingling;
• numbness;
• double vision;
• weakness in arms or legs;
• swelling or open sores that do not heal;
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, or paleness.

The symptoms described above may be signs of the following side effects, 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);
• respiratory tract infections (including colds, runny nose, sinusitis, and pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;
• rash;
• musculoskeletal pain.

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster);
• ear infections;
• oral infections (including dental infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations, or numbness;
• migraine;
• nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness;
• sensation of rapid heartbeat;
• high blood pressure;
• hot flushes;
• bruising;
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux disorder;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• contusion;
• skin inflammation (such as eczema);
• cracking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema;
• fever;
• reduced platelet count in blood, increasing risk of bleeding or bruising;
• delayed wound healing.

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections occurring when immune defenses are reduced);
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors;
• lymphatic system tumors;
• melanoma;
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy;
• stroke;
• hearing loss, ringing in the ears;
• sensation of irregular heartbeat such as palpitations;
• heart problems that may cause shortness of breath or swelling of the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal fluid accumulation in the pleural space);
• pancreatitis causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema;
• gallbladder inflammation, gallstones;
• fatty liver;
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs);
• interrupted sleep;
• impotence;
• inflammations.

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

• leukemia (a cancer affecting blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (lung scarring);
• intestinal perforation;
• hepatitis;
• reactivation of hepatitis B;
• 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 associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (pruritic red-violet rash).

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare and often fatal blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma typically presents with purple skin lesions;
• liver failure;
• worsening of a condition called dermatomyositis (which presents as a skin rash accompanied by muscle weakness);
• weight gain (in most patients, weight gain has been low).

Some of the side effects observed with Humira may be asymptomatic and detectable only 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;
• increased blood lipids;
• increased liver enzymes.

Common (may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased blood uric acid;
• altered blood sodium;
• reduced blood calcium;
• reduced blood phosphorus;
• increased blood glucose;
• increased blood lactate dehydrogenase;
• presence of autoantibodies in blood;
• reduced blood potassium.

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test).

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

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in its outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), a single pre-filled pen may be stored at room temperature (up to 25°C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator and stored at room temperature, the pen must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date on which the pen was first removed from the refrigerator and the date after which the pen must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, monohydrate citric acid, sodium citrate, disodium phosphate dihydrate,
disodium hydrogen phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and water for
injections.

Description of the appearance of Humira pre-filled pen and contents of the pack
Humira 40 mg solution for injection in pre-filled pens is supplied as a sterile solution containing 40 mg of
adalimumab dissolved in 0.8 ml of solution.
The Humira pre-filled pen is a single-use pen in grey and purple containing a glass syringe filled with Humira. The pen has two caps – one grey marked with the number '1' and the other purple marked with the number '2'. On each side of the pen there is a viewing window through which the Humira solution inside the syringe can be seen.
The Humira pre-filled pen is available in packs containing 1, 2, 4 and 6 pre-filled pens.
The pack containing 1 pre-filled pen includes 2 alcohol swabs (1 spare). Packs containing 2, 4 and 6 pre-filled pens are supplied with 1 alcohol swab for each pre-filled pen.
Not all pack sizes may be marketed.
Humira may be available in vials, pre-filled syringes and/or pre-filled pens.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information about this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.: +36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ.: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

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

To listen to or request a copy of this package leaflet in , or , contact the local representative of the Marketing Authorisation Holder.

Patient Information Leaflet

Humira 40 mg solution for injection in pre-filled syringe

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before receiving Humira and during treatment with Humira. Keep this Patient Reminder Card.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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. Injection of 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
• Non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis
• Hidradenitis suppurativa
• Crohn’s disease
• Ulcerative colitis
• Non-infectious uveitis

The active substance in Humira, adalimumab, is a human monoclonal antibody.
Monoclonal antibodies are proteins that bind specifically to a particular target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to 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.
Other disease-modifying drugs, such as methotrexate, may initially be used. If the response to these drugs is not satisfactory, 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 slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Humira should be taken with methotrexate or alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory joint disease.
Humira is used to treat polyarticular juvenile idiopathic arthritis in patients aged 2 years and older.
Other disease-modifying drugs, such as methotrexate, may initially be used. If the response to these drugs is not adequate, you will be given Humira.
Your doctor will decide whether Humira should be taken with methotrexate or alone.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the sites where tendons attach to bones.
Humira is used to treat enthesitis-related arthritis in patients aged 6 years and older.
Other disease-modifying drugs, such as methotrexate, may initially be used. If the response to these drugs is not adequate, you will be given Humira.

Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
Ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory conditions affecting the spine.
Humira is used to treat severe ankylosing spondylitis and non-radiographic axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease usually associated with psoriasis.
Humira is used to treat psoriatic arthritis in adults. Humira can slow down joint damage caused by the disease and may help you move more freely.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Plaque psoriasis
Plaque psoriasis is a skin condition causing reddish, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crack, thicken, or lift from the nail bed, which may 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 when topical therapy and phototherapies have not worked optimally or are not suitable.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus. It most commonly affects specific skin areas such as the under-breast region, armpits, inner thighs, groin, and buttocks. Scarring may also develop 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. Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Crohn’s disease
Crohn’s disease is an inflammation of the gastrointestinal 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 aged 6 to 17 years.

Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Ulcerative colitis
Ulcerative colitis is an inflammation of the large intestine (colon).
Humira is used to treat

• moderate to severe ulcerative colitis in adults, and
• moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

Other medications may be used initially. If the response to these drugs is not adequate, you will be given 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,
• children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front of the eye.

This inflammation may lead to reduced vision and/or the presence of floaters in the eye (black spots or fine lines moving across the visual field). Humira works by reducing this inflammation.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

2. What you should know before using Humira

Do not use Humira

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Humira.
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not take Humira again and contact your doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

• If you have an infection, including long-term infections or localized infections in a part of the body (e.g., leg ulcers), consult your doctor before starting treatment with Humira. If you are in doubt, contact your doctor.
• You may be more likely to get infections while being treated with Humira. This risk may increase if you have lung problems. These infections can be serious and may include:
• tuberculosis
• infections caused by viruses, fungi, parasites, or bacteria
• serious blood infections (sepsis)

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may instruct you to temporarily stop taking Humira.

• Inform your doctor if you live or travel to areas where fungal infections are common (e.g., histoplasmosis, coccidioidomycosis, or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other conditions that increase your risk of infection.
• If you are over 65 years old, you may be more likely to get infections while taking Humira. You and your doctor should pay particular attention to signs of infection during treatment. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or have been in close contact with someone who had tuberculosis. You must not take Humira if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Humira, your doctor will need to check for signs and symptoms of tuberculosis before starting Humira treatment. This will involve a detailed medical evaluation including your medical history and appropriate clinical tests (e.g., chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may develop during treatment even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

• Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active hepatitis B infection, or if you think you may be at risk of contracting hepatitis B virus.
• Your doctor should test you for hepatitis B virus infection. In HBV carriers, taking Humira may cause reactivation of the virus.
• In rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus may be life-threatening.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Humira. Your doctor may recommend temporarily stopping Humira.

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the insulating layer 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 in any part of the body.

Vaccinations

• Certain vaccines may cause infections and should not be administered during treatment with Humira.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting Humira treatment.
• If you took Humira during pregnancy, your child may have an increased risk of infection for up to approximately 5 months after your last Humira dose. It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy, so they can determine when the child should receive any vaccinations.

Heart failure

• If you have mild heart failure and are being treated with Humira, your doctor will need to carefully monitor your heart condition. It is important to inform your doctor about any past or current heart problems. If new symptoms of heart failure appear or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether Humira can be continued.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. Your doctor may decide to stop treatment. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately.

Tumors

• Very rarely, certain types of tumors have occurred in patients, both children and adults, treated with Humira or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Humira, your risk of developing lymphomas, leukemia, or other tumors 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 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 taking Humira.
• If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific type of lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

• Rarely, treatment with Humira may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Humira.

Other medicines and Humira
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use Humira with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Humira may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

• You should consider using an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after your last dose of Humira.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor about taking this medicine.
• Humira should be used during pregnancy only if clearly needed.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If you take Humira during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy before the baby receives any vaccinations. For further information on vaccinations, see the section "Warnings and precautions".

Driving and using machines
Humira may have a minor influence on your ability to drive, ride a bicycle, or use machines. After taking Humira, you may experience visual disturbances or a sensation that your surroundings are spinning.

3. How to use Humira

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Humira for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Humira if a different dose is required.

Method and route of administration
Humira is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to administer Humira are described in section 7 ‘Injection of Humira’.
If you use more Humira than you should
If you accidentally inject Humira more often than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken an excess dose. Always keep the medicine packaging, even if empty.
If you forget to use Humira
If you forget to give an injection, you should administer the next dose of Humira as soon as you remember. After that, resume your regular dosing schedule as prescribed.
If you stop using Humira
The decision to stop using Humira should be discussed with your doctor. Symptoms may return if you stop using Humira.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Contact your doctor immediately if you notice any of the following reactions:

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

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

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning during urination
• fatigue or weakness
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open wound that does not heal
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, paleness

The symptoms described above may be signs of the following side effects, 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)
• respiratory tract infections (including colds, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• skin rash
• musculoskeletal pain

Common (may affect up to 1 in 10 people):

• serious infections (including sepsis and influenza)
• intestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes zoster infection)
• ear infections
• oral infections (including dental infections and herpes simplex)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• sleep disorders
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain 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
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy skin rash
• contusion
• skin inflammation (such as eczema)
• nail breakage of fingers and toes
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• edema (fluid accumulation)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• delayed wound healing

Uncommon (may affect up to 1 in 100 people):

• opportunistic infections (including tuberculosis and other infections occurring when immune defenses are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• tumors
• lymphatic system tumors
• melanoma
• immune system disorders that may affect lungs, skin, and lymph nodes (commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shaking)
• neuropathy (nervous system disorders)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling in ankles
• acute myocardial infarction
• formation of a sac in the wall of a major artery, vein inflammation and clot, blood vessel blockage
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of a pulmonary artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial edema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of skin, heart, lungs, joints, and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (lung scarring)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B
• 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 skin rash)
• facial edema (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (pruritic red-violet skin rash)

Not known (frequency cannot be estimated from available data):

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal)
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma typically presents with purple skin lesions
• liver failure
• worsening of a condition called dermatomyositis (characterized by skin rash accompanied by muscle weakness)
• weight gain (in most patients, weight gain has been minimal)

Some of the side effects observed with Humira may be asymptomatic and can only be detected 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
• increased blood lipids
• increased liver enzymes

Common (may affect up to 1 in 10 people):

• increased white blood cell count
• reduced platelet count
• increased uric acid in blood
• altered blood sodium levels
• reduced blood calcium
• reduced blood phosphorus
• increased blood sugar
• increased lactate dehydrogenase in blood
• presence of autoantibodies in blood
• reduced blood potassium

Uncommon (may affect up to 1 in 100 people):

• elevated bilirubin levels in blood (liver blood test).

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

• low white blood cell, red blood cell, and platelet counts.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist.
You may also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled syringe may be stored at room temperature (up to 25 °C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date when the syringe is first removed from the refrigerator and the date after which the syringe must be discarded.

Do not dispose of medicines via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, polysorbate 80 and water for injections.

Description of the appearance of Humira pre-filled syringe and contents of the pack
Humira 40 mg solution for injection in pre-filled syringes is supplied as a sterile solution containing 40 mg of adalimumab dissolved in 0.4 ml of solution.
Humira pre-filled syringe consists of a solution of adalimumab contained in a glass syringe.
Each pack contains 1, 2, 4 or 6 pre-filled syringes with respectively 1, 2, 4 or 6 alcohol swabs.
Not all pack sizes may be marketed.
Humira may be available in vials, pre-filled syringes and/or pre-filled pens.

Marketing Authorization Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien                       Lietuva
AbbVie SA                                                 AbbVie UAB
Tél/Tel: +32 10 477811                              Tel: +370 5 205 3023

България                                             Luxembourg/Luxemburg
АбВи ЕООД                                             AbbVie SA
Тел.: +359 2 90 30 430                             Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika                                 Magyarország
AbbVie s.r.o.                                            AbbVie Kft.
Tel: +420 233 098 111                             Tel.: +36 1 455 8600

Danmark                                             Malta
AbbVie A/S                                             V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28                               Tel: +356 21220174

Deutschland                                      Nederland
AbbVie Deutschland GmbH & Co. KG         AbbVie B.V.
Tel: 00800 222843 33 (toll-free)                 Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti                                                 Norge
AbbVie OÜ                                             AbbVie AS
Tel: +372 623 1011                                 Tlf: +47 67 81 80 00

Ελλάδα                                             Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.                 AbbVie GmbH
Τηλ: +30 214 4165 555                            Tel: +43 1 20589-0

España                                             Polska
AbbVie Spain, S.L.U.                             AbbVie Sp. z o.o.
Tel: +34 91 384 09 10                            Tel.: +48 22 372 78 00

France                                              Portugal
AbbVie                                                 AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00                      Tel: +351 (0)21 1908400

Hrvatska                                          România
AbbVie d.o.o.                                         AbbVie S.R.L.
Tel: +385 (0)1 5625 501                         Tel: +40 21 529 30 35

Ireland                                             Slovenija
AbbVie Limited                                     AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900                           Tel: +386 (1)32 08 060

Ísland                                              Slovenská republika
Vistor hf.                                              AbbVie s.r.o.
Tel: +354 535 7000                                Tel: +421 2 5050 0777

Italia                                                Suomi/Finland
AbbVie S.r.l.                                          AbbVie Oy
Tel: +39 06 928921                                 Puh/Tel: +358 (0)10 2411 200

Κύπρος                                             Sverige
Lifepharma (Z.A.M.) Ltd                         AbbVie AB
Τηλ.: +357 22 34 74 40                           Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/ .

To listen to or request a copy of this summary in , or , contact the local representative of the Marketing Authorization Holder.

7. Humira Injection

• The following instructions explain how to perform a subcutaneous self-injection of Humira using the pre-filled syringe. First, carefully read these instructions and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with training on the technique of self-administration.
• Do not perform the injection on your own until you are confident that you fully understand how to prepare and administer the injection.
• After proper training, the injection may be given by you or by someone else, such as a family member or friend.
• Use each pre-filled syringe for only one injection.

Humira Pre-filled Syringe
Plunger Finger Grip Needle Cap

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

• the solution appears cloudy, has changed color, or contains flakes or particles
• the expiration date (Exp.) has passed
• the solution has been frozen or exposed to direct sunlight
• the pre-filled syringe has been dropped or damaged

Remove the needle cap only immediately before injection. Keep Humira out of the
sight and reach of children.
STEP 1
Remove Humira from the refrigerator.
Before injecting, allow Humira to reach room temperature for 15–30 minutes.

• Do not remove the needle cap while waiting for Humira to warm to room temperature
• Do not heat Humira by other means. For example, do not heat it in a microwave or in hot water. STEP 2 Check the expiration date (Exp.). Do not use the pre-filled syringe if the expiration date (Exp.) has passed. Syringe Arrange the following items on a clean, flat surface

• 1 single-use pre-filled syringe ~' • 1 alcohol swab ~ Wash and dry your hands.  ~~~ ~

Alcohol Swab
STEP 3 Choose an injection site:
Injection Sites • On the front of the thigh or

• On the abdomen (belly), at least 5 cm away from the navel
• At least 3 cm away from the previous injection site

Clean the injection site using the alcohol swab with circular motions.

• Do not inject through clothing
• Do not inject into areas where the skin appears red, hardened, bruised, ulcerated, scarred, or has stretch marks, or areas affected by plaque psoriasis

Injection Sites
STEP 4 Hold the pre-filled syringe in one hand.
Inspect the liquid in the pre-filled syringe.

• Ensure the liquid is clear and colorless
• Do not use the pre-filled syringe if the liquid is cloudy or contains particles
• Do not use the pre-filled syringe if it has been dropped or crushed

Gently remove the needle cap with the other hand. Discard the cap. Do not reuse the cap.

• Do not touch the needle with your fingers, and ensure the needle does not come into contact with anything STEP 5 Hold the pre-filled syringe with the needle pointing upward.

• Hold the pre-filled syringe at eye level with one hand so you can see any air bubbles in the syringe

Slowly push the plunger to expel air through the needle.

• It is normal to see a drop of liquid at the tip of the needle

STEP 6 Hold the pre-filled syringe in one hand between your thumb and index finger, like a pencil.

With the other hand, pinch the skin at the injection site and hold it firmly
STEP 7 Insert the needle completely into the skin at an angle of approximately 45° with a quick, firm motion.

• Once the needle is inserted, release the skin.

Push the plunger all the way down until all the liquid has been injected and the pre-filled syringe is empty.

STEP 8 When the syringe is empty, slowly remove the needle from the skin, maintaining the same angle used during insertion.

After completing the injection, apply gentle pressure to the injection site with a cotton ball or gauze.

• Do not rub the area
• Mild bleeding at the injection site is normal

Cotton Ball
STEP 9
Dispose of the used pre-filled syringe in a special sharps container according to instructions from your doctor, nurse, or pharmacist. Never recap the needle.

• Do not recycle or dispose of the pre-filled syringe in household waste
• Always keep the pre-filled syringe and the sharps container out of the sight and reach of children.

The needle cap, alcohol swab, cotton ball or gauze, blister pack, and outer packaging may be disposed of in household waste.

Package leaflet: information for the patient

Humira 40 mg solution for injection in pre-filled pen

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card, which contains important safety information you need to know before starting Humira and during treatment with Humira. Keep this Patient Reminder Card.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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. Injection of 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 bind specifically to a target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to 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.
Other disease-modifying drugs, such as methotrexate, may initially be used. If the response to these drugs is not satisfactory, 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 slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Humira should be taken with methotrexate or alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease affecting the joints.
Humira is used to treat polyarticular juvenile idiopathic arthritis in patients aged 2 years and older.
Other disease-modifying drugs, such as methotrexate, may initially be used. If the response to these drugs is not adequate, you will be given Humira.
Your doctor will decide whether Humira should be taken with methotrexate or alone.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the sites where tendons attach to bones.
Humira is used to treat enthesitis-related arthritis in patients aged 6 years and older.
Other disease-modifying drugs, such as methotrexate, may initially be used. If the response to these drugs is not adequate, 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 conditions of the spine.
Humira is used to treat severe ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory joint disease usually associated with psoriasis.
Humira is used to treat psoriatic arthritis in adults. Humira can slow down joint damage caused by the disease and may help you move more freely.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Plaque psoriasis
Plaque psoriasis is a skin condition causing reddish, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crack, thicken, or separate 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 when topical therapy and phototherapy have not worked well or are not suitable.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease that is often painful. Symptoms may include painful lumps and abscesses (cysts) that may drain pus. It most commonly affects specific areas of skin such as under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop 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 lumps and abscesses caused by the disease, as well as the pain often associated with it.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Crohn’s disease
Crohn’s disease is an inflammation of the gastrointestinal 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 aged 6 to 17 years.

Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

Ulcerative colitis
Ulcerative colitis is an inflammation of the large intestine (colon).
Humira is used to treat:

• Moderate to severe ulcerative colitis in adults, and
• Moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

Other medications may be used initially. If the response to these drugs is not adequate, you will be given 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
• Children aged 2 years and older with chronic non-infectious uveitis with inflammation affecting the front of the eye

This inflammation can lead to decreased vision and/or the presence of floaters in the eye (black spots or thin lines moving across the visual field). Humira works by reducing this inflammation.
Other medications may be used initially. If the response to these drugs is not adequate, you will be given Humira.

2. What you should know before using Humira

Do not use Humira:

• if you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• if you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• if you have moderate or severe heart failure. It is important to inform 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 using Humira.
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not take Humira again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infections

• If you have an infection, including long-term infections or localized infections in a part of the body (for example, leg ulcers), consult your doctor before starting treatment with Humira. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Humira. This risk may increase if you have lung problems. These infections can be serious and include:
• tuberculosis
• infections caused by viruses, fungi, parasites, or bacteria
• severe blood infections (sepsis)

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you develop symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may tell you to stop taking Humira temporarily.

• Inform your doctor if you live or travel in areas where fungal infections are common (for example, histoplasmosis, coccidioidomycosis, or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other medical conditions that increase your risk of infection.
• If you are over 65 years old, you may be more likely to get infections while taking Humira. You and your doctor should pay particular attention to signs of infection during treatment with Humira. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or if you have been in contact with someone who had tuberculosis. You must not take Humira if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Humira, your doctor will need to check for signs and symptoms of tuberculosis before starting Humira therapy. This will involve a thorough medical evaluation of your medical history and appropriate clinical tests (for example, a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may occur during treatment even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (for example, persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

• Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting the hepatitis B virus.
• Your doctor must test you for hepatitis B virus infection. In carriers of HBV, taking Humira may cause the virus to reactivate.
• In some rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of the hepatitis B virus may be life-threatening.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Humira. Your doctor may advise you to temporarily stop taking Humira.

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the insulating layer 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 in any part of your body.

Vaccinations

• Certain vaccines may cause infections and must not be administered during treatment with Humira.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Humira.
• If you have taken Humira during pregnancy, your baby may have an increased risk of infection for up to about 5 months after your last dose of Humira. It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy so they can decide when your baby should receive any vaccinations.

Heart failure

• If you have mild heart failure and are being treated with Humira, your heart failure condition must be closely monitored by your doctor. It is important to inform your doctor if you have had or currently have serious heart problems. If you develop new symptoms of heart failure or if existing symptoms worsen (for example, shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether you can continue taking Humira.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. Your doctor may decide to stop treatment. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately.

Tumors

• Very rarely, certain types of tumors have been observed in patients, both children and adults, treated with Humira or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Humira, your risk of developing lymphomas, leukemia, or other tumors 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 taking Humira.
• If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

• Rarely, treatment with Humira may lead to the development of a syndrome such as lupus. Inform your doctor if you develop symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Humira.

Other medicines and Humira
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use Humira with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Humira may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (DMARDs) (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

• You should use an appropriate contraceptive method to prevent pregnancy, and continue using it for at least 5 months after your last dose of Humira.
• If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor about taking this medicine.
• Humira should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy compared to babies whose mothers had the same condition but did not receive Humira.
• Humira may be used during breastfeeding.
• If you take Humira during pregnancy, your baby may have an increased risk of infection.
• It is important to inform the pediatrician or other healthcare provider about your use of Humira during pregnancy before your baby receives any vaccinations. For further information on vaccinations, see the section "Warnings and precautions".

Driving and using machines
Humira may have a minor influence on your ability to drive, ride a bicycle, or use machines. After taking Humira, you may experience vision disturbances or a sensation that your surroundings are spinning.

3. How to use Humira

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended doses of Humira for each approved indication are listed in the following table. Your doctor may prescribe a different concentration of Humira if a different dose is required.

Method and route of administration
Humira is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions on how to administer Humira are described in section 7 ‘Injection of Humira’.
If you use more Humira than you should
If you accidentally inject Humira more frequently than instructed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken an excess dose. Always keep the medicine carton, even if empty.
If you forget to use Humira
If you forget to give an injection, you should administer the next dose of Humira as soon as you remember. After that, resume your regular dosing schedule as prescribed.
If you stop using Humira
The decision to discontinue the use of Humira should be discussed with your doctor. Symptoms may return if you stop using Humira.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months after the last injection of Humira.

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

• severe rash, hives or other signs of allergic reaction
• swelling of the face, hands or feet
• difficulty breathing, trouble swallowing
• shortness of breath on exertion or when lying down, or swollen feet

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

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating
• fatigue or weakness
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open sore that does not heal
• signs and symptoms suggesting disorders of the haematopoietic system, such as persistent fever, bruising, bleeding, paleness

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

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

• injection site reactions (including pain, swelling, redness or itching)
• respiratory tract infections (including colds, runny nose, sinusitis and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• rash
• musculoskeletal pain

Common (may occur in up to 1 in 10 people)

• serious infections (including sepsis and influenza)
• intestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes zoster infection)
• ear infections
• oral infections (including dental infections and herpes simplex)
• genital infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumours
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• sleep disorders
• sensory disturbances such as tingling, stabbing sensations or numbness
• migraine
• nerve root compression (including lower back pain 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
• hot flushes
• haematoma (collection of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• bruising
• skin inflammation (such as eczema)
• cracking of fingernails and toenails
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• oedema (fluid retention)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• delayed wound healing

Uncommon (may occur in up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections that occur when immune defences are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• tumours
• lymphatic system tumours
• melanoma
• immune system disorders that may affect lungs, skin and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor (shaking)
• neuropathy (nervous system disorders)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling of the ankles
• acute myocardial infarction
• formation of a sac in the wall of a major artery, vein inflammation and clotting, blockage of a blood vessel
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of a pulmonary artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial oedema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints and other organs)
• disrupted sleep
• impotence
• inflammations

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

• leukaemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (lung scarring)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B
• 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 oedema (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized swelling of the skin)
• lichenoid skin reaction (pruritic red-purple rash)

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal)
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi’s sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly presents with purple skin lesions
• liver failure
• worsening of a condition called dermatomyositis (which presents as a rash accompanied by muscle weakness)
• Weight gain (in most patients, weight gain has been low)

Some of the side effects observed with Humira may be asymptomatic and may only be detected through blood tests.
These include:

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

• low white blood cell count
• low red blood cell count
• increased blood lipids
• increased liver enzymes

Common (may occur in up to 1 in 10 people)

• increased white blood cell count
• decreased platelet count
• increased blood uric acid
• altered blood sodium levels
• decreased blood calcium
• decreased blood phosphorus
• increased blood glucose
• increased lactate dehydrogenase in blood
• presence of autoantibodies in blood
• decreased blood potassium

Uncommon (may occur in up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test)

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

• low white blood cell, red blood cell and platelet counts

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box following the word "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g., when travelling), a single pre-filled pen may be stored at room temperature (up to 25°C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pen must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date when the pen is first removed from the refrigerator and the date by which the pen must be discarded.

Do not dispose of medicines via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, polysorbate 80, and water for injection.

Description of the appearance of Humira pre-filled pen and package contents
Humira 40 mg solution for injection in pre-filled pen is supplied as a sterile solution containing 40 mg of adalimumab dissolved in 0.4 mL of solution.
The Humira pre-filled pen is a single-use, grey and purple pen containing a glass syringe filled with Humira. The pen has two caps – one grey cap marked with the number '1' and one purple cap marked with the number '2'. On each side of the pen there is a viewing window through which the solution inside the syringe can be seen.
The Humira pre-filled pen is available in packages containing 1, 2, 4, and 6 pre-filled pens.
The pack containing 1 pre-filled pen includes 2 alcohol swabs (1 spare). Packs containing 2, 4, and 6 pre-filled pens are supplied with 1 alcohol swab per pre-filled pen. Not all pack sizes may be marketed.
Humira may also be available in vials, pre-filled syringes, and/or pre-filled pens.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.:+359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.:+36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ.: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/ .

To listen to or request a copy of this package leaflet in , or , please contact the local representative of the Marketing Authorisation Holder.

7. Humira Injection

• The following instructions explain how to perform a subcutaneous self-injection of Humira using the pre-filled pen. First, read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with training on the technique of self-administration.
• Do not administer the injection by yourself until you are certain you have understood how to prepare and perform the injection.
• After proper instruction, the injection may be given by you or by another person, such as a family member or friend.
• Use each pre-filled pen only once for a single injection.

Humira Pre-filled Pen
Gray cap 1 White protective sleeve
covering the needle White arrow Purple cap 2

Needle Inspection window Purple activation button

Do not use the pre-filled pen and contact your doctor or pharmacist if

• the solution appears cloudy, has changed color, or contains flakes or particles
• the expiration date (Exp.) has passed
• the solution has been frozen or exposed to direct sunlight
• the pre-filled pen has been dropped or damaged

Remove the cap only immediately before injection. Keep Humira out of sight and
out of reach of children.
STEP 1
Take Humira out of the refrigerator.
Before injection, allow Humira to reach room temperature for 15–30 minutes.

• Do not remove the gray cap and purple cap while Humira is reaching room temperature
• Do not heat Humira in any other way. For example, do not heat Humira in a microwave or in warm water
  STEP 2 Check the expiration date (Exp.). Do not use the pre-filled pen if the expiration date has passed.

Place the following items on a clean, flat surface:

• 1 single-use pre-filled pen
• 1 alcohol swab

Wash and dry your hands.
Alcohol swab
STEP 3
Choose an injection site:
Injection sites

On the front of the thigh or

• On the abdomen (abdominal area), at least 5 cm away from the navel
• At least 3 cm away from the previous injection site

Clean the injection site thoroughly with circular motions using the alcohol swab.

• Do not inject through clothing
• Do not inject into damaged, bruised, red, hardened skin, or areas with scars, stretch marks, or plaque psoriasis

Injection sites
STEP 4
Hold the pre-filled pen with the gray cap (1) facing

upwards.
Look through the inspection window.

• It is normal to see one or more small air bubbles in the window
• Ensure the solution is clear and colorless
• Do not use the pre-filled pen if the solution appears cloudy or contains particles
• Do not use the pre-filled pen if it has been dropped or damaged

STEP 5
Remove the gray cap (1). Discard the cap. Do not replace the
Cap 1 cap.

Check that the black protective cover over the needle has been removed together with the cap.

• It is normal for a few small drops of liquid to appear at the needle tip

Remove the purple cap (2). Discard the cap. Do not replace the cap.
The pre-filled pen is now ready for use.
Rotate the pre-filled pen so that the white arrow points toward the injection site.
Cap 2
STEP 6
With your other hand, pinch the skin at the injection site to create a raised skin fold and hold it firmly until the injection is complete.
Position the white arrow toward the injection site (thigh or abdomen).
Position the white protective sleeve covering the needle at a right angle (90° angle) to the injection site.

Hold the pre-filled pen so that you can see the inspection window.
Do not press the purple activation button until you are ready to administer the injection.
STEP 7
Firmly press the pre-filled pen against the injection site before starting the injection.

Continue to press firmly to prevent the pre-filled pen from moving away from the skin during injection.
Press the purple activation button and slowly count to
10 seconds.

• A distinct “click” will signal the start of the injection
• Continue to hold the pre-filled pen firmly against the injection site until the injection is complete. ♦ The injection is complete when the yellow indicator stops moving.

STEP 8
After the injection is complete, slowly withdraw the

pre-filled pen from the skin. The white protective sleeve covering the needle will automatically cover the needle tip.

• A small amount of liquid at the injection site is normal

If more than a few drops are present at the injection site, contact your doctor, nurse, or pharmacist.
After completing the injection, apply a cotton ball or gauze pad to the skin at the injection site.

• Do not rub the area
• Mild bleeding at the injection site is normal
  STEP 9

Dispose of the used pre-filled pen in a special container according to instructions provided by your doctor,
nurse, or pharmacist.

• Do not reuse or dispose of the pre-filled pen in household waste
• Always keep the pre-filled pen and the special disposal container out of sight and out of reach of children

The caps, alcohol swabs, cotton ball or gauze, blister pack, and packaging may be disposed of in household waste.

Patient information leaflet

Humira 80 mg solution for injection in pre-filled syringe

adalimumab
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card containing important safety information you need to know before starting Humira and during treatment with Humira. Keep this Patient Reminder Card.
• 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 their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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. Injection of Humira

1. What Humira is and what it is used for

Humira contains the active substance adalimumab.
Humira is used to treat:

• Rheumatoid 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 bind to a specific target.
The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to 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.
Initially, other disease-modifying drugs such as methotrexate may be used. If the response to these drugs is not satisfactory, 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 slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Humira should be taken with methotrexate or on its own.

Plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which can be painful.
Humira is used to treat chronic moderate to severe plaque psoriasis in adults.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus. It most commonly affects specific areas of skin such as the area under the breasts, armpits, inner thighs, groin, and buttocks. Scarring may also develop in the 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 and the pain often associated with it. Other medicines may be used first. If the response to these medicines is not adequate, you will be given Humira.

Crohn’s disease
Crohn’s disease is an inflammation of the gastrointestinal 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 aged 6 to 17 years.

Other medicines may be used first. If the response to these medicines is not adequate, you will be given Humira to treat Crohn’s disease.

Ulcerative colitis
Ulcerative colitis is an inflammation of the large intestine (colon).
Humira is used to treat:

• Moderate to severe ulcerative colitis in adults, and
• Moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

Other medicines may be used first. If the response to these medicines is not adequate, you will be given 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 reduced 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 will first be given other medicines. If you do not respond adequately to these medicines, Humira will be administered.

2. What you should know before using Humira

Do not use Humira:

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have active tuberculosis or other serious infections (see “Warnings and precautions”). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Humira
Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or rash, do not take Humira again and contact your doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

• If you have an infection, including long-term infections or an infection in a specific part of your body (e.g., leg ulcers), consult your doctor before starting treatment with Humira. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Humira. This risk may be higher if you have lung problems. These infections can be serious and may include:
• tuberculosis,
• infections caused by viruses, fungi, parasites, or bacteria,
• serious blood infections (sepsis).

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you develop symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may instruct you to temporarily stop taking Humira.

• Inform your doctor if you live or travel in areas where fungal infections are common (e.g., histoplasmosis, coccidioidomycosis, or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other medical conditions that increase your risk of infection.
• If you are over 65 years old, you may be more likely to get infections while taking Humira. You and your doctor should pay particular attention to signs of infection during treatment. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, 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. You must not take Humira if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Humira, your doctor will check for signs and symptoms of tuberculosis before starting Humira therapy. This will involve a thorough medical evaluation of your medical history and appropriate clinical tests (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may occur during treatment even if you have received preventive treatment for tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

• Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active hepatitis B infection, or if you think you may be at risk of contracting hepatitis B virus.
• Your doctor should test you for hepatitis B virus infection. In HBV carriers, taking Humira may cause reactivation of the virus.
• In rare cases, especially if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus may be life-threatening.

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Humira. Your doctor may advise you to temporarily stop taking Humira.

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the protective covering of nerves, such as multiple sclerosis), your doctor will decide whether to start or continue Humira treatment. 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.

Vaccinations

• Certain vaccines may cause infections and must not be administered during treatment with Humira.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting Humira treatment.
• If you have taken Humira during pregnancy, your baby may have an increased risk of infection for up to approximately 5 months after your last dose of Humira. It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy, so they can determine when your baby should receive any vaccinations.

Heart failure

• If you have mild heart failure and are being treated with Humira, your condition should be closely monitored by your doctor. It is important to inform your doctor if you have had or currently have a serious heart condition. If you develop new symptoms of heart failure or if existing symptoms worsen (e.g., shortness of breath or swelling of 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 not be able to produce enough blood cells to fight infections or stop bleeding. Your doctor may decide to stop treatment. If you have persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately.

Tumors

• Very rarely, certain types of tumors have occurred in patients, both children and adults, treated with Humira or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Humira, your risk of developing lymphomas, leukemia, or other tumors 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 taking Humira.
• If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine.

If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.
Autoimmune disease

• Rarely, treatment with Humira may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as persistent unexplained skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Humira.

Other medicines and Humira
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use Humira with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept.

Humira may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

• You should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after your last dose of Humira.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor about using this medicine.
• Humira should be used during pregnancy only if necessary.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If you take Humira during pregnancy, your baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy before your baby receives any vaccinations. For more information on vaccinations, see the section “Warnings and precautions”.

Driving and using machines
Humira may affect your ability to drive, ride a bicycle, or use machines, although only to a minor extent. After taking Humira, you may experience vision disturbances or a sensation that your surroundings are spinning.

3. How to use Humira

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Humira for each of the approved uses are shown in the table below.
Your doctor may prescribe a different dosage of Humira if needed.

Method and route of administration
Humira is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions for Humira injection are provided in section 7 “Injection of Humira”.
If you use more Humira than you should
If you accidentally inject Humira more frequently than instructed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken more of the medicine. Always keep the medicine carton, even if it is empty.
If you forget to use Humira
If you forget to give an injection, you should inject the next dose of Humira as soon as you remember. After that, continue with your regular dosing schedule as prescribed.
If you stop using Humira
The decision to stop using Humira should be discussed with your doctor. Symptoms may return if you stop taking Humira.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Most of the side effects are mild to moderate in severity. However, some may be serious and require treatment.
Side effects may occur up to 4 months after the last Humira injection.

Immediately inform your doctor if you notice any of the following reactions:

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

Inform your doctor as soon as possible if you notice any of the following reactions:

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning sensation when urinating
• fatigue or weakness
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open sore that does not heal
• signs and symptoms suggesting disorders of the hematopoietic system, such as persistent fever, bruising, bleeding, paleness

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

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

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

Common (may occur in up to 1 in 10 people)

• serious infections (including sepsis and influenza)
• intestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes zoster infection)
• ear infections
• oral infections (including dental infections and herpes simplex)
• reproductive tract infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• sleep disorders
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain 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
• hot flushes
• bruising (hematoma – blood accumulation outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy rash
• contusion
• skin inflammation (such as eczema)
• nail breakage of fingers and toes
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in the urine
• kidney problems
• chest pain
• edema (swelling)
• fever
• reduced platelet count in the blood, increasing the risk of bleeding or bruising
• poor wound healing

Uncommon (may occur in up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections occurring when immune defenses are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• tumors
• lymphatic system tumors
• melanoma
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor
• neuropathy (nerve disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling in the ankles
• acute myocardial infarction
• formation of a sac in the wall of a major artery, vein inflammation and clot, blood vessel blockage
• lung disease causing shortness of breath (including inflammation)
• pulmonary embolism (blockage of a pulmonary artery)
• pleural effusion (abnormal fluid accumulation in the pleural space)
• pancreatitis causing severe abdominal and back pain
• difficulty swallowing
• facial edema (facial swelling)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs)
• interrupted sleep
• impotence
• inflammations

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

• leukemia (a blood and bone marrow cancer)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (lung scarring)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B
• autoimmune hepatitis (liver inflammation caused by the body's own immune system)
• cutaneous vasculitis (inflammation of skin blood vessels)
• Stevens-Johnson syndrome (early symptoms include malaise, fever, headache, and rash)
• facial edema (facial swelling) associated with allergic reactions
• erythema multiforme (inflammatory skin rash)
• lupus-like syndrome
• angioedema (localized skin swelling)
• lichenoid skin reaction (itchy red-purple rash)

Not known (frequency 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, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple skin lesions
• liver failure
• worsening of a condition called dermatomyositis (presenting as skin rash accompanied by muscle weakness)
• weight gain (in most patients, weight gain has been low)

Some of the side effects observed with Humira may be asymptomatic and detectable only through blood tests.
These include:

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

• low white blood cell count
• low red blood cell count
• increased blood lipids
• increased liver enzymes

Common (may occur in up to 1 in 10 people)

• increased white blood cell count
• reduced platelet count
• increased blood uric acid
• altered blood sodium levels
• reduced blood calcium
• reduced blood phosphorus
• increased blood sugar
• increased blood lactate dehydrogenase
• presence of autoantibodies in the blood
• reduced blood potassium

Uncommon (may occur in up to 1 in 100 people)

• elevated bilirubin levels in the blood (liver blood test)

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

• low white blood cell, red blood cell, and platelet counts

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box after the word "Exp".
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (e.g. when travelling), a single pre-filled syringe may be stored at room temperature (up to 25°C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the syringe must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date when the syringe is first removed from the refrigerator and the date after which the syringe must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, polysorbate 80 and water for injectable preparations.

Description of the appearance of Humira pre-filled syringe and contents of the pack
Humira 80 mg solution for injection in pre-filled syringes is supplied as a sterile solution containing 80 mg of adalimumab dissolved in 0.8 ml of solution.
The Humira pre-filled syringe consists of a solution of adalimumab contained in a glass syringe.
The Humira pre-filled syringe is available in a pack containing 1 pre-filled syringe for patient use with an alcohol swab.
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

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.:+359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.:+36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ.: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

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

To listen to or request a copy of this package leaflet in , or , please contact the local representative of the Marketing Authorization Holder.

7. Humira Injection

• The following instructions explain how to perform a subcutaneous self-injection of Humira using the pre-filled syringe. First, read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with training on the technique of self-administration.
• Do not perform the injection on your own until you are confident that you fully understand how to prepare and administer the injection.
• After proper training, the injection may be administered by you or by another person, such as a family member or friend.
• Use each pre-filled syringe for only one injection.

Humira Pre-filled Syringe
Plunger Finger Grip Needle Cap

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

• the solution appears cloudy, has changed color, or contains flakes or particles
• the expiration date (Exp.) has passed
• the solution has been frozen or exposed to direct sunlight
• the pre-filled syringe has been dropped or damaged

Remove the needle cap only immediately before injection. Keep Humira out of the
sight and reach of children.
STEP 1
Remove Humira from the refrigerator.
Before administering the injection, allow Humira to reach room temperature for 15–30 minutes.

• Do not remove the needle cap while waiting for Humira to warm to room temperature
• Do not heat Humira by any other method. For example, do not heat it in a microwave or in hot water.

STEP 2 Check the expiration date (Exp.). Do not use the pre-filled
syringe if the expiration date (Exp.) has passed.
Syringe
Gather the following items on a clean, flat surface:

• 1 single-use pre-filled syringe
• 1 alcohol swab

Wash and dry your hands.
Swab
STEP 3 Choose an injection site:
Injection Sites • On the front of the thigh or

• On the abdomen (belly), at least 5 cm away from the navel
• At least 3 cm away from the previous injection site

Clean the injection site using circular motions
with the alcohol swab.
I

• Do not inject through clothing
• Do not inject into areas where the skin appears red, hardened, bruised, ulcerated, scarred, or has stretch marks, or areas affected by plaque psoriasis

Injection Sites
STEP 4 Hold the pre-filled syringe in one hand.
Inspect the liquid in the pre-filled syringe.

• Ensure the liquid is clear and colorless
• Do not use the pre-filled syringe if the liquid is cloudy or contains particles
• Do not use the pre-filled syringe if it has been dropped or damaged

Gently remove the needle cap with the other hand. Discard the cap. Do not reuse the cap.

• Do not touch the needle with your fingers, and ensure the needle does not come into contact with anything

STEP 5 Hold the pre-filled syringe with the needle pointing
upwards.

• Hold the pre-filled syringe at eye level with one hand so you can see any air bubbles in the syringe

Slowly push the plunger to expel air through
the needle.

• It is normal to see a drop of liquid at the tip of the needle

STEP 6 Hold the pre-filled syringe between your thumb and
index finger with one hand, like a pencil.

With the other hand, pinch the skin at the injection site to lift and firmly hold it.
STEP 7 Insert the needle completely into the skin at an angle of approximately 45° with a quick, firm motion.

• Once the needle is inserted, release the skin.

Push the plunger completely until all the
liquid has been injected and the pre-filled syringe is empty.
a
STEP 8 When the syringe is empty, slowly remove the needle from the skin, maintaining the same angle used during insertion.
After the injection, apply a cotton ball or gauze pad to the injection site and press gently.

• Do not rub the area
• Mild bleeding at the injection site is normal

Cotton Ball
STEP 9
Dispose of the used pre-filled syringe in a special sharps container, according to instructions from your doctor, nurse, or pharmacist. Never recap the needle.

• Do not recycle or dispose of the pre-filled syringe in household waste
• Always keep the pre-filled syringe and the sharps container out of the sight and reach of children

The needle cap, alcohol swab, cotton ball or gauze, blister pack, and outer packaging may be disposed of in household waste.

Patient information leaflet

Humira 80 mg solution for injection in pre-filled pen

adalimumab
Please read this leaflet carefully before using this medicine as it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before starting Humira and during treatment with Humira. Keep this Patient Reminder Card.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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. Injection of Humira

1. What is Humira and what is it used for

Humira contains the active substance adalimumab.
Humira is used to treat:

• Rheumatoid 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 bind to a specific target.
Adalimumab targets a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to 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.
Initially, other disease-modifying drugs such as methotrexate may be used. If the response to these drugs is not satisfactory, 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 slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Humira should be taken with methotrexate or alone.
Plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly, hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken or lift from the nail bed, which can be painful.
Humira is used to treat chronic moderate to severe plaque psoriasis in adults.
Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called acne inversa) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful lumps and abscesses (cysts) that may drain pus. It most commonly affects specific areas of the skin, such as the area under the breasts, armpits, inner thighs, groin and buttocks. Scarring may also develop in the 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 lumps and abscesses caused by the disease, as well as the pain often associated with it. Other medicines may be used first. If the response to these medicines is not adequate, you will be given Humira.
Crohn’s disease
Crohn’s disease is an inflammation 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 aged 6 to 17 years.

Other medicines may be used first. If the response to these medicines is not adequate, you will be given Humira to treat Crohn’s disease.
Ulcerative colitis
Ulcerative colitis is an inflammation of the large intestine (colon).
Humira is used to treat:

• Moderate to severe ulcerative colitis in adults, and
• Moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

Other medicines may be used first. If the response to these medicines is not adequate, you will be given 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.
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front part of the eye.

This inflammation may lead to reduced vision and/or the presence of floating bodies in the eye (black spots or thin lines moving across the visual field). Humira works by reducing this inflammation. You will first be given other medicines. If you do not respond adequately to these medicines, Humira will be administered.

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 ingredients of this medicine (listed in section 6).
• If you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
• If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Humira.

Allergic reactions

• If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or skin rash, do not take Humira again and contact your doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

• If you have an infection, including long-term infections or an infection in a specific part of the body (e.g., leg ulcers), consult your doctor before starting treatment with Humira. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Humira. This risk may be higher if you have lung problems. These infections can be serious and may include:
• tuberculosis,
• infections caused by viruses, fungi, parasites, or bacteria,
• serious blood infections (sepsis).

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you develop symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may instruct you to temporarily stop taking Humira.

• Inform your doctor if you live in or travel to regions where fungal infections are common (e.g., histoplasmosis, coccidioidomycosis, or blastomycosis).
• Inform your doctor if you have had recurring infections or if you have other medical conditions that increase your risk of infection.
• If you are over 65 years old, you may be more prone to infections while taking Humira. You and your doctor should pay particular attention to signs of infection during treatment. It is important to inform your doctor if you develop symptoms of infection such as fever, wounds, feeling tired, or dental problems.

Tuberculosis

• It is very important to inform your doctor if you have ever had tuberculosis or have been in close contact with someone who had tuberculosis. You must not take Humira if you have active tuberculosis.
• Since cases of tuberculosis have occurred in patients treated with Humira, your doctor will check for signs and symptoms of tuberculosis before starting Humira therapy. This will involve a thorough medical evaluation of your medical history and appropriate clinical tests (e.g., a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
• Tuberculosis may occur during treatment even if you have received treatment to prevent tuberculosis.
• Contact your doctor immediately if you develop symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

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

Surgery or dental procedures

• Before undergoing surgery or dental procedures, inform your doctor that you are taking Humira. Your doctor may advise you to temporarily stop taking Humira.

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease affecting the protective covering of nerves, such as multiple sclerosis), your doctor will decide whether to start or continue Humira treatment. 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.

Vaccinations

• Certain vaccines may cause infections and must not be given during treatment with Humira.
• Consult your doctor before receiving any vaccinations.
• It is recommended, if possible, that children receive all age-appropriate vaccinations before starting Humira treatment.
• If you have taken Humira during pregnancy, the baby may have an increased risk of infection for up to approximately 5 months after your last dose of Humira. It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy, so they can determine when the baby should receive any vaccinations.

Heart failure

• If you have mild heart failure and are being treated with Humira, your heart failure condition must be closely monitored by your doctor. It is important to inform your doctor if you have had or currently have a serious heart condition. If you develop new symptoms of heart failure or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether you can continue taking Humira.

Fever, bruising, bleeding, or paleness

• In some patients, the body may not produce enough blood cells to fight infections or stop bleeding. Your doctor may decide to stop treatment. If you develop persistent fever, bruising, easy bleeding, or paleness, contact your doctor immediately.

Tumors

• Very rarely, certain types of tumors have occurred in patients, both children and adults, treated with Humira or other anti-TNF medicines.
• Patients with long-standing, severe rheumatoid arthritis may have a higher-than-average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
• If you are taking Humira, your risk of developing lymphomas, leukemia, or other tumors 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 taking Humira.
• If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform your doctor.
• Cases of malignancies other than lymphoma have been reported in patients with a specific lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine.

If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

• Rarely, treatment with Humira may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue.

Children and adolescents

• Vaccinations: if possible, children should have completed all recommended vaccinations before starting Humira.

Other medicines and Humira
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use Humira with medicines containing the following active substances due to an increased risk of serious infections:

• anakinra
• abatacept

Humira may be taken with:

• methotrexate
• other disease-modifying antirheumatic drugs (DMARDs) (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
• corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs). If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• You should use an effective method of contraception to prevent pregnancy and continue using it for at least 5 months after your last dose of Humira.
• If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor for advice about taking this medicine.
• Humira should be used during pregnancy only if clearly needed.
• According to a pregnancy study, no increased risk of birth defects was observed in babies whose mothers received Humira during pregnancy compared to mothers with the same condition who did not receive Humira.
• Humira may be used during breastfeeding.
• If you take Humira during pregnancy, the baby may have an increased risk of infection.
• It is important that you inform the pediatrician or other healthcare provider about your use of Humira during pregnancy before the baby receives any vaccinations. For more information on vaccinations, see the section "Warnings and precautions".

Driving and using machines
Humira may affect your ability to drive, ride a bicycle, or operate machinery, although only to a minor extent. After taking Humira, you may experience vision disturbances or a sensation that your surroundings are spinning.

3. How to use Humira

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Humira for each of the approved uses are shown in the table
below. Your doctor may prescribe a different dosage of Humira if needed.

Method and route of administration
Humira is administered by subcutaneous injection (by injection under the skin).
Detailed instructions for injecting Humira are provided in section 7, “Injecting Humira”.
If you use more Humira than you should
If you accidentally inject Humira more frequently than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that you have taken more medication than directed. Always keep the medicine packaging, even if it is empty.
If you forget to use Humira
If you forget to give an injection, you should inject the next dose of Humira as soon as you remember. Then continue with your regular dosing schedule.
If you stop using Humira
The decision to stop using Humira should be discussed with your doctor. Symptoms may return if you stop taking Humira.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months after the last Humira injection.

Immediately inform your doctor if you notice any of the following reactions

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

Inform your doctor as soon as possible if you notice any of the following reactions

• signs of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating
• fatigue or weakness
• cough
• tingling
• numbness
• double vision
• weakness in arms or legs
• swelling or open sore that does not heal
• signs and symptoms suggesting the onset of disorders affecting the blood-forming system, such as persistent fever, bruising, bleeding, paleness

The symptoms described above may be signs of the following side effects, 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)
• respiratory tract infections (including cold, runny nose, sinusitis, and pneumonia)
• headache
• abdominal pain
• nausea and vomiting
• skin rash
• musculoskeletal pain

Common (may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza)
• intestinal infections (including gastroenteritis)
• skin infections (including cellulitis and herpes zoster infection)
• ear infections
• oral infections (including dental infections and herpes simplex)
• reproductive system infections
• urinary tract infections
• fungal infections
• joint infections
• benign tumors
• skin cancer
• allergic reactions (including seasonal allergies)
• dehydration
• mood changes (including depression)
• anxiety
• sleep disorders
• sensory disturbances such as tingling, stabbing sensations, or numbness
• migraine
• nerve root compression (including lower back pain and leg pain)
• visual disturbances
• eye inflammation
• eyelid inflammation and eye swelling
• dizziness (feeling of dizziness or spinning)
• sensation of rapid heartbeat
• high blood pressure
• hot flushes
• bruising (accumulation of blood outside blood vessels)
• cough
• asthma
• shortness of breath
• gastrointestinal bleeding
• dyspepsia (indigestion, bloating, heartburn)
• acid reflux disorder
• dry syndrome (including dry eyes and dry mouth)
• itching
• itchy skin rash
• contusion
• skin inflammation (such as eczema)
• cracking of fingernails and toenails
• increased sweating
• hair loss
• onset or worsening of psoriasis
• muscle spasms
• blood in urine
• kidney problems
• chest pain
• edema (swelling)
• fever
• reduced platelet count in blood, increasing the risk of bleeding or bruising
• difficulty healing

Uncommon (may affect up to 1 in 100 people)

• opportunistic infections (including tuberculosis and other infections occurring when immune defenses are reduced)
• neurological infections (including viral meningitis)
• eye infections
• bacterial infections
• diverticulitis (inflammation and infection of the large intestine)
• tumors
• lymphatic system tumors
• melanoma
• immune system disorders that may affect lungs, skin, and lymph nodes (most commonly presenting as sarcoidosis)
• vasculitis (inflammation of blood vessels)
• tremor
• neuropathy (nerve disorder)
• stroke
• hearing loss, ringing in the ears
• sensation of irregular heartbeat such as palpitations
• heart problems that may cause shortness of breath or swelling of the ankles
• acute myocardial infarction
• formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel
• lung disease causing shortness of breath (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)
• gallbladder inflammation, gallstones
• fatty liver
• night sweats
• scarring
• abnormal muscle breakdown
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints, and other organs)
• interrupted sleep
• impotence
• inflammations

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

• leukemia (a cancer affecting blood and bone marrow)
• severe allergic reaction with shock
• multiple sclerosis
• neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
• cardiac arrest
• pulmonary fibrosis (scarring of the lungs)
• intestinal perforation (hole in the intestine)
• hepatitis
• reactivation of hepatitis B
• 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 (itchy red-purple rash)

Not known (frequency cannot be estimated from the available data)

• hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal)
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi’s sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly presents with purple lesions on the skin
• liver failure
• worsening of a condition called dermatomyositis (which manifests as skin rash accompanied by muscle weakness)
• weight gain (in most patients, weight gain has been low)

Some of the side effects observed with Humira may be asymptomatic and may only be detected 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
• increased blood lipids
• increased liver enzymes

Common (may affect up to 1 in 10 people)

• increased white blood cell count
• reduced platelet count
• increased uric acid in blood
• altered sodium levels in blood
• reduced calcium levels in blood
• reduced phosphorus levels in blood
• increased blood sugar
• increased lactate dehydrogenase in blood
• presence of autoantibodies in blood
• reduced potassium levels in blood

Uncommon (may affect up to 1 in 100 people)

• elevated bilirubin levels in blood (liver blood test)

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

• low white blood cell, red blood cell, and platelet counts

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Humira

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister pack/box following the word "Exp".
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.

Alternative storage conditions:
When necessary (for example, when travelling), a single pre-filled pen may be stored at room temperature (up to 25°C) for a maximum of 14 days – ensure the medicine is protected from light. Once removed from the refrigerator for storage at room temperature, the pen must be used within 14 days or discarded, even if it is returned to the refrigerator.
You must record the date when the pen is first removed from the refrigerator and the date after which the pen must be discarded.

Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Humira contains
The active substance is adalimumab.
The excipients are mannitol, polysorbate 80 and water for injections.

Description of the appearance of Humira pre-filled pen and contents of the pack
Humira 80 mg solution for injection in pre-filled pen is supplied as a sterile solution containing 80 mg of adalimumab dissolved in 0.8 ml of solution.
The Humira pre-filled pen is a single-use grey and purple pen containing a glass syringe filled with Humira. The pen has two caps – one grey marked with the number '1' and the other purple marked with the number '2'. On each side of the pen there is a viewing window through which the Humira solution inside the syringe can be seen.

The Humira pre-filled pen is available in packs containing:

• 1 pre-filled pen for patient use with 2 alcohol swabs (1 extra)
• 3 pre-filled pens for patient use with 4 alcohol swabs (1 extra)

Not all pack sizes may be marketed.
Humira may be available in vial, pre-filled syringe and/or pre-filled pen.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie Biotechnology GmbH
Knollstrasse
67061 Ludwigshafen
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.:+359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.:+36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (free of charge) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0) 1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel + 385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ.: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

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

To listen to or request a copy of this package leaflet in , or , please contact the local representative of the Marketing Authorisation Holder.

7. Humira Injection

• The following instructions explain how to perform a subcutaneous self-injection of Humira using the pre-filled pen. First, read these instructions carefully and follow them step by step.
• Your doctor, nurse, or pharmacist will provide you with training on the technique of self-administration.
• Do not administer the injection by yourself until you are certain you understand how to prepare and perform the injection correctly.
• After proper training, the injection may be given by you or by someone else, such as a family member or friend.
• Use each pre-filled pen only once for a single injection.

Humira Pre-filled Pen
Gray cap 1 White sheath
covering the needle White arrow Purple cap 2

Needle Inspection window Purple activation button

Do not use the pre-filled pen and contact your doctor or pharmacist if:

• the solution appears cloudy, has changed color, or contains flakes or particles
• the expiration date (Exp.) has passed
• the solution has been frozen or exposed to direct sunlight
• the pre-filled pen has been dropped or damaged

Remove the cap only immediately before injection. Keep Humira out of the sight and
reach of children.
STEP 1
Take Humira out of the refrigerator.
Before injection, allow Humira to reach room temperature for 15–30 minutes.

• Do not remove the gray cap and purple cap while Humira is reaching room temperature
• Do not heat Humira in any other way. For example, do not heat Humira in a microwave or in hot water
  STEP 2 Check the expiration date (Exp.). Do not use the pre-filled pen if the expiration date has passed.

Place the following items on a clean, flat surface:

• 1 single-use pre-filled pen
• 1 alcohol swab

Wash and dry your hands.
Alcohol swab
STEP 3
Choose an injection site:
Injection sites

On the front of the thigh or

• On the abdomen (belly), at least 5 cm away from the navel
• At least 3 cm away from the previous injection site

Clean the injection site thoroughly using circular motions with the alcohol swab.

• Do not inject through clothing
• Do not inject into damaged, bruised, red, hardened skin, or areas with scars, stretch marks, or plaque psoriasis

Injection sites
STEP 4
Hold the pre-filled pen with the gray cap (1) pointing

upward.
Look through the inspection window.

• It is normal to see one or more small bubbles in the window
• Make sure the solution is clear and colorless
• Do not use the pre-filled pen if the solution appears cloudy or contains particles
• Do not use if the pre-filled pen has been dropped or damaged

STEP 5
Remove the gray cap (1). Discard the cap. Do not replace the
Cap 1 cap.

• Check that the black protective cover over the needle

has been removed together with the cap

• It is normal for a few small drops of liquid to appear at the needle tip

Remove the purple cap (2). Discard the cap. Do not replace the
cap.
The pre-filled pen is now ready to use.
Rotate the pre-filled pen so that the white arrow points toward the injection site.
Cap 2
STEP 6
With your other hand, pinch the skin at the injection site to create a raised area and hold it firmly until the injection is complete.
Position the white arrow toward the injection site (thigh or abdomen).
Place the white sheath covering the needle at a right angle (90° angle) to the injection site.

Hold the pre-filled pen so that you can see the inspection window.
Do not press the purple activation button until you are ready to administer the injection.
STEP 7
Firmly press the pre-filled pen against the injection site before starting the injection.

Continue to press firmly to prevent the pre-filled pen from moving away from the skin during injection.
Press the purple activation button and slowly count to
15 seconds.
a

• A distinct “click” will signal the start of the injection
• Continue to hold the pre-filled pen firmly against the injection site until the injection is complete.

The injection is complete when the yellow indicator has stopped moving.
STEP 8
Once the injection is complete, slowly remove the

pre-filled pen from the skin. The white sheath covering the needle will automatically cover the needle tip.

• It is normal to see a small amount of liquid at the injection site. If more than a few drops are present at the injection site, contact your doctor, nurse, or pharmacist.

After completing the injection, apply a cotton ball or gauze pad to the injection site.

• Do not rub the area
• Mild bleeding at the injection site is normal
  STEP 9

Dispose of the used pre-filled pen in a special sharps container, following the instructions provided by your doctor,
nurse, or pharmacist.

• Do not reuse or throw the pre-filled pen into household waste
• Always keep the pre-filled pen and the special container out of the sight and reach of children

The caps, used alcohol swabs, cotton ball or gauze, blister pack, and packaging may be disposed of in household waste.