Patient Information Leaflet: Medicinal Product Information

Hyrimoz 80 mg pre-filled syringe solution for injection

adalimumab

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

• Keep this leaflet, as you may need to read it again.
• Your doctor will give you aPatient Information Leaflet, which contains important safety information that you need to know before and during treatment with Hyrimoz.

Keep thisPatient Information Leafletduring your treatment and for the 4 months following your last injection (or that of your child) of Hyrimoz.

• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Hyrimoz contains the active ingredient adalimumab, a medication that acts on the body's immune system.

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

• rheumatoid arthritis,
• plaque psoriasis,
• hidradenitis supurativa,
• Crohn's disease,
• ulcerative colitis,
• non-infectious uveitis.

The active ingredient of Hyrimoz, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that attack a specific target in the body.

The target of adalimumab is another protein called tumor necrosis factor (TNFα), which is present in high concentrations in the aforementioned inflammatory diseases. By binding to TNFα, Hyrimoz blocks its action and reduces inflammation in these diseases.

Rheumatoid Arthritis

Rheumatoid arthritis is an inflammatory disease of the joints.

Hyrimoz is used to treat rheumatoid arthritis in adults. If you have active moderate to severe rheumatoid arthritis, you may be given other disease-modifying medications such as methotrexate first. If these medications do not work well enough, you will be given Hyrimoz to treat your rheumatoid arthritis.

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

Hyrimoz can reduce the damage to the cartilage and bones of the joints caused by the disease and improve physical performance.

Hyrimoz is usually used in combination with methotrexate. If your doctor considers methotrexate not suitable, Hyrimoz can be administered alone.

Plaque Psoriasis

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

Hyrimoz is used to treat moderate to severe plaque psoriasis in adults.

Hidradenitis Supurativa in Adults and Adolescents

Hidradenitis supurativa (also known as inverse acne) is a long-lasting and often painful inflammatory skin disease. Symptoms can include sensitive nodules (bumps) and abscesses (boils) that can secrete pus.

It usually affects specific areas of the skin, such as under the chest, armpits, inner thighs, groin, and buttocks. There may also be scars in the affected areas.

Hyrimoz is used to treat

• moderate to severe hidradenitis supurativa in adults and
• moderate to severe hidradenitis supurativa in adolescents from 12 to 17 years old.

Hyrimoz can reduce the number of nodules and abscesses and the pain associated with this disease. You may have received other medications previously. If those medications do not work well enough, you will receive Hyrimoz.

Crohn's Disease in Adults and Children

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

Hyrimoz is used to treat

• moderate to severe Crohn's disease in adults and
• moderate to severe Crohn's disease in children and adolescents from 6 to 17 years old.

If you have Crohn's disease, you will be treated first with other medications. If you do not respond well enough to these medications, you will receive Hyrimoz to reduce the signs and symptoms of Crohn's disease.

Ulcerative Colitis in Adults and Children

Ulcerative colitis is an inflammatory disease of the large intestine.

Hyrimoz is used to treat

• moderate to severe ulcerative colitis in adults and
• moderate to severe ulcerative colitis in children and adolescents from 6 to 17 years old.

If you suffer from ulcerative colitis, you may be given other medications first. If those medications do not work well enough, you will be prescribed Hyrimoz to reduce the signs and symptoms of the disease.

Non-infectious Uveitis in Adults and Children

Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye. Inflammation causes a decrease in vision and/or the presence of flying spots in the eye (black dots or thin lines that move across the field of vision). Hyrimoz acts by reducing this inflammation.

Hyrimoz is used to treat

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

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

No use Hyrimoz

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

• If you have a severe infection, including tuberculosis, sepsis (blood poisoning), or other opportunistic infections (unusual infections associated with a weakened immune system). If you have symptoms of any infection, such as fever, wounds, fatigue, or dental problems, inform your doctor (see "Warnings and precautions").

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

Warnings and precautions

Consult your doctor or pharmacist before starting to use Hyrimoz.

Allergic reaction

• If you have an allergic reaction with symptoms such as chest tightness, difficulty breathing, dizziness, swelling, or hives, discontinue Hyrimoz administration and contact your doctor immediately, as these reactions can be life-threatening in rare cases.

Infections

• With Hyrimoz treatment, you may be more susceptible to infections. This risk may be higher if your lung function decreases. These infections can be severe and include tuberculosis, viral, fungal, parasitic, or bacterial infections, or other unusual infectious organisms, and sepsis (blood poisoning).

• In rare cases, these infections can be life-threatening. If you have symptoms such as fever, wounds, fatigue, or dental problems, inform your doctor. Your doctor may recommend temporarily stopping Hyrimoz treatment.

Tuberculosis (TB)

• Since cases of tuberculosis have been reported in patients treated with adalimumab, your doctor will examine you for signs or symptoms of tuberculosis before starting your treatment with Hyrimoz. This will include a thorough medical evaluation, including your medical history and diagnostic tests (e.g., chest X-ray and tuberculin test). The results of these tests should be noted in yourpatient information card. It is essential to inform your doctor if you have had tuberculosis or have been in contact with a tuberculosis patient. You can develop tuberculosis during treatment, even if you have received preventive treatment for tuberculosis. If you experience symptoms of tuberculosis (persistent cough, weight loss, fatigue, or low-grade fever) or any other infection during or after treatment, contact your doctor immediately.

Travel/infection recurrence

• Inform your doctor if you have lived or traveled to areas where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.

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

Hepatitis B virus

• Inform your doctor if you are a hepatitis B virus (HBV) carrier, have active HBV infection, or think you may be at risk of contracting HBV. Your doctor should perform an HBV test. Adalimumab can reactivate HBV in individuals who are carriers of this virus. In rare cases, especially if you are taking other medications that suppress the immune system, reactivation of HBV infection can be life-threatening.

Age 65 or older

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

Dental procedures or surgery

• If you are to undergo a surgical or dental procedure, inform your doctor that you are using Hyrimoz. Your doctor may recommend temporarily stopping Hyrimoz treatment.

Demyelinating diseases

• If you have or develop a demyelinating disease (a disease that affects the insulating layer surrounding nerves, such as multiple sclerosis), your doctor will decide whether you should be treated or continue treatment with Hyrimoz. Inform your doctor immediately if you experience symptoms such as vision changes, weakness in arms or legs, or numbness or tingling in any part of your body.

Vaccinations

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be administered during Hyrimoz treatment, as they may cause infections. Consult your doctor before receiving any type of vaccine. It is recommended that children receive all scheduled vaccinations before starting Hyrimoz treatment. If you receive Hyrimoz while pregnant, your child may be at a higher risk of developing infections for approximately 5 months after the last dose you received during pregnancy. It is essential to inform your child's doctor and other healthcare professionals about your use of Hyrimoz during pregnancy, so they can decide whether your child should receive any vaccine.

Heart failure

• It is essential to inform your doctor if you have had or have any serious heart problems. If you have mild heart failure and are being treated with Hyrimoz, your doctor should closely monitor your heart failure. If you experience new symptoms of heart failure or worsening existing symptoms (e.g., difficulty breathing or swelling in your feet), contact your doctor immediately.

Fever, rashes, bleeding, or pale appearance

• In some patients, the body may be unable to produce enough of the type of white blood cells that fight infections (white blood cells) or the platelets that contribute to stopping bleeding. If you have persistent fever, rashes, or bleed easily or appear pale, consult your doctor immediately. Your doctor may decide to interrupt treatment.

Cancer

• In rare cases, certain types of cancer have been reported in children and adults treated with adalimumab or other TNFα blockers. Individuals with severe rheumatoid arthritis and those who have had the disease for a long time may be at a higher risk of developing lymphoma and leukemia (cancer affecting blood cells and bone marrow). If you are being treated with Hyrimoz, the risk of developing lymphoma, leukemia, and other types of cancer may increase. A rare and severe type of lymphoma has been observed in patients treated with adalimumab.

Some of these patients were also taking azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hyrimoz.

• Additionally, cases of skin cancer (non-melanoma) have been reported in patients using adalimumab. Inform your doctor if you experience new skin damage or if existing marks or damaged areas change appearance during or after treatment.

• Cases of cancers other than lymphoma have been reported in patients with a specific lung disease, known as chronic obstructive pulmonary disease (COPD), treated with another TNFα blocker. If you have COPD or smoke heavily, consult your doctor about whether treatment with a TNFα blocker is suitable for you.

Autoimmune diseases

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

Children and adolescents

• Do not administer Hyrimoz to children under 2 years old with juvenile idiopathic polyarticular arthritis.
• Do not administer Hyrimoz to children under 4 years old with pediatric psoriasis or pediatric ulcerative colitis.
• Do not administer Hyrimoz to children under 6 years old with pediatric Crohn's disease.
• Do not use the 80 mg pre-filled pen if recommended doses are different from 80 mg.

Other medications and Hyrimoz

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

Hyrimoz can be taken with methotrexate or certain disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide, and gold injectable preparations), corticosteroids, or pain medications, including nonsteroidal anti-inflammatory drugs (NSAIDs).

Do not use Hyrimoz with medications whose active ingredients are anakinra or abatacept due to an increased risk of severe infection. Do not recommend combining adalimumab and other TNF antagonists with anakinra or abatacept, as this may increase the risk of infections, including severe infections, and other possible pharmacological interactions. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

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

Driving and using machines

The influence of Hyrimoz on your ability to drive, ride a bike, or use machines is small. You may experience a sensation of the room spinning (vertigo) and visual disturbances after using Hyrimoz.

Hyrimoz contains sodium

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

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

Form and route of administration

Hyrimoz is injected under the skin (subcutaneously).

The detailed instructions on how to inject Hyrimoz are found in section 7, “Instructions for use”.

If you use more Hyrimoz than you should

If you accidentally inject Hyrimoz more frequently than you should, call your doctor or pharmacist and explain that you have taken more than necessary. Always carry the medication box with you, even if it is empty.

If you forget to use Hyrimoz

If you forget to administer an injection, you should inject the next dose of Hyrimoz as soon as you remember. Then, administer the next dose as usual, as if you had not forgotten a dose.

If you interrupt treatment with Hyrimoz

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

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

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

Seek urgent medical attentionif you notice any of the following signs of allergic reaction or heart failure:

• severe rash, urticaria;
• swelling of the face, hands, feet;
• difficulty breathing, swallowing;
• difficult breathing with physical activity or lying down, or swelling of the feet.

Contact your doctor as soon as possibleif you notice any of the following effects:

• signs and symptoms of infection such as fever, nausea, wounds, dental problems, burning sensation while urinating, feeling weak, fatigue, or cough;
• symptoms of nervous system problems, such as tingling, numbness, double vision, weakness in arms or legs;
• signs of skin cancer, such as a lump or an open wound that does not heal;
• signs and symptoms of blood disorders such as persistent fever, petechiae, bleeding, and pallor.

The following side effects have been observed with adalimumab:

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

• reactions at the injection site (including pain, swelling, redness, or itching);
• lower respiratory tract infections (including colds, coughing, sinusitis, pneumonia);
• headache;
• abdominal pain;
• nausea and vomiting;

• pruritus;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• gastrointestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes);
• ear infection;
• oral infections (including dental infection and cold sore);
• reproductive system infections;
• urinary tract infections;
• fungus infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• drowsiness and difficulty sleeping;
• sensorial alterations such as tingling, itching, or numbness;
• migraine;
• symptoms of nerve root compression (including lower back and leg pain);
• visual disturbances;
• conjunctivitis;
• conjunctival and eyelid edema;
• dizziness (feeling the room is spinning);
• feeling of rapid heartbeat;
• high blood pressure;
• flushing;
• hematomas (solid swelling with coagulated blood);
• cough;
• asthma;
• difficulty breathing;
• gastrointestinal bleeding;
• indigestion, bloating, and heartburn;
• acid reflux;
• dry eye syndrome (including dry eyes and mouth);
• itching;
• pruritic urticaria;
• bruises;
• skin inflammation (such as eczema);
• hand and foot nail breakage;
• excessive sweating;
• hair loss;
• new-onset or worsening psoriasis;
• muscle spasms;
• blood in urine;
• renal problems;
• chest pain;
• edema (accumulation of fluid in the body that can cause swelling of the affected tissue);
• fever;
• decreased platelet count in blood, increasing the risk of bleeding or bruising;
• wound healing problems.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis) and other infections that occur when resistance to disease decreases;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• cancer, including cancer affecting the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immunological disorders that can affect the lungs, skin, and lymph nodes (the most common presentation is in the form of a disease called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (feeling shaky);
• neuropathy (nerve damage);
• cerebral hemorrhage;
• hearing loss, tinnitus;
• feeling of irregular heartbeat like skipping;
• heart problems that can cause difficulty breathing or swelling of the ankles;
• heart attack;
• sac in the wall of a major artery, inflammation and coagulation in a vein, blockage of a blood vessel;
• pulmonary diseases that can cause difficulty breathing (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal fluid accumulation in the pleural space);
• pancreatitis (inflammation of the pancreas causing severe abdominal and back pain);
• difficulty swallowing;
• facial edema;
• inflammation of the gallbladder; gallstones;
• fat accumulation in the liver (accumulation of fat in liver cells);
• nocturnal sweating;
• scars;
• abnormal muscle crisis;
• systemic lupus erythematosus (a disorder of the immune system that includes inflammation of the skin, heart, lungs, joints, and other organs);
• sleep interruptions;
• impotence;
• inflammations.

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

• leukemia (cancer affecting the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic nerve inflammation in the eye and Guillain-Barré syndrome, a disease that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• lung fibrosis (scar tissue in the lung);
• intestinal perforation (hole in the intestinal wall);
• hepatitis (inflammation of the liver);

• reactivation of hepatitis B virus infection;
• autoimmune hepatitis (inflammation of the liver caused by the body's own immune system);
• cutaneous vasculitis (inflammation of blood vessels in the skin);
• Stevens-Johnson syndrome (a potentially life-threatening disease with flu-like symptoms and rash with blisters);
• facial edema associated with allergic reactions;
• erythema multiforme (inflammatory rash on the skin);
• syndrome similar to lupus;
• angioedema (localized swelling of the skin);
• lichenoid reaction in the skin (red-purple rash with itching).

Frequency not known(cannot be estimated from available data)

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

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

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

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

Common(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• high bilirubin levels (blood test of liver function).

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

• low counts in blood for white cells, red cells, and platelets.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet.

You can also report them directly through thenational reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label/blister/package after “CAD” or “EXP”. The expiration date is the last day of the month indicated.

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

Store the preloaded pen in the outer packaging to protect it from light.

Alternative Storage:

When necessary (for example, when traveling), you can store Hyrimoz at room temperature (up to 25 °C) for a maximum period of 42 days (ensure it is protected from light). Once removed from the refrigerator for storage at room temperature, the preloaded penmust be used within the next 42 days or discarded, even if it is returned to the refrigerator later. You must note the date when you removed the preloaded pen from the refrigerator and the date after which it must be discarded.

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

Composition of Hyrimoz

• The active ingredient is adalimumab. Each pre-filled syringe contains 80 mg of adalimumab in 0.8 ml of solution.
• The other components are: adipic acid, mannitol (E 421), polisorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524), and water for injection.

Appearance of the product and contents of the pack

Hyrimoz 80 mg solution for injection (injection) in pre-filled syringe is supplied as 0.8 ml of transparent to slightly opalescent, colourless or slightly yellowish solution.

Hyrimoz is supplied in a single-use pre-filled syringe attached to a triangular needle with a transparent viewer and label. The syringe inside the needle is made of type I glass with a stainless steel 29 gauge needle and the internal needle cap is made of rubber (thermoplastic elastomer), with 0.8 ml of solution.

Cases with 1, 2, and 3 pre-filled syringes of Hyrimoz.

Only some pack sizes may be marketed.

Hyrimoz is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Responsible for manufacturing

Sandoz GmbH Schaftenau

Biochemiestr. 10

6336 Langkampfen

Austria

Novartis Pharmaceutical Manufacturing GmbH

Biochemiestrasse 10

6336 Langkampfen

Austria

For more information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of the leaflet

Other sources of information

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

7. Instructions for use

To help prevent possible infections and ensure correct use of Hyrimoz, it is essential to follow these instructions.

Make sure to read, understand, and follow these instructions for use before injecting Hyrimoz. Your healthcare professional should teach you how to prepare and inject Hyrimoz correctly with the single-use pre-filled syringe of Hyrimoz before using it for the first time. If you have any questions, consult your healthcare professional.

Your single-use pre-filled syringe of Hyrimoz

Figure A:parts of the Hyrimoz syringe

In theFigure Ayou can see the syringe once the cap has been removed. Do not remove the cap until you are ready to administer the injection.

If you have any questions, consult a doctor, pharmacist, or nurse who is familiar with Hyrimoz.