HULIO 40 mg INJECTABLE SOLUTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the Patient

Hulio 40 mg Solution for Injection in Pre-filled Syringe

adalimumab

Read all of this leaflet carefully before you start 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 Alert Card, which contains important safety information that you need to know before and during treatment with Hulio. Carry the Patient Alert Card with you at all times and for 4 months after you are injected with Hulio.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the Pack

1. What is Hulio and what is it used for
2. What you need to know before you use Hulio
3. How to use Hulio
4. Possible side effects
5. Storage of Hulio
6. Contents of the pack and further information
7. Instructions for use

1. What is Hulio and what is it used for

Hulio contains the active substance adalimumab, a medicine that works on the body's immune system (defences).

Hulio is indicated for the treatment of the following inflammatory diseases:

• rheumatoid arthritis;
• juvenile idiopathic polyarticular arthritis;
• enthesitis-related arthritis;
• ankylosing spondylitis;
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis;
• psoriatic arthritis;
• psoriasis;
• • hidradenitis suppurativa;
  • Crohn's disease;
  • ulcerative colitis;
  • non-infectious uveitis in adults and children.

The active substance in Hulio, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that target a specific target in the body.

The target of adalimumab is a protein called tumour necrosis factor (TNFα), which is found in high levels in the inflammatory diseases described above. By targeting TNFα, Hulio reduces the inflammation process in these diseases.

Rheumatoid Arthritis

Rheumatoid arthritis is an inflammatory disease of the joints.

Hulio is used to treat rheumatoid arthritis in adults. If you have moderate to severe active rheumatoid arthritis, you may have been given other medicines that modify the disease, such as methotrexate, before. If these medicines do not respond well enough, you will receive Hulio to treat your rheumatoid arthritis.

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

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

Hulio is usually used in combination with methotrexate. If your doctor decides that methotrexate is not suitable, Hulio can be administered alone.

Juvenile Idiopathic Polyarticular Arthritis and Enthesitis-Related Arthritis

Juvenile idiopathic polyarticular arthritis and enthesitis-related arthritis are inflammatory diseases of the joints that usually appear for the first time in childhood.

Hulio is used to treat juvenile idiopathic polyarticular arthritis in children and adolescents from 2 to 17 years of age and enthesitis-related arthritis in children and adolescents from 6 to 17 years of age. You may have received other disease-modifying medicines, such as methotrexate, before. If these medicines do not respond well enough, you will receive Hulio to treat your juvenile idiopathic polyarticular arthritis or enthesitis-related arthritis.

Ankylosing Spondylitis and Axial Spondyloarthritis without Radiographic Evidence of Ankylosing Spondylitis

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory diseases that affect the spine.

Hulio is used to treat ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. If you have ankylosing spondylitis or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will be treated first with other medicines. If these medicines do not respond well enough, you will receive Hulio to reduce the signs and symptoms of the disease.

Psoriatic Arthritis

Psoriatic arthritis is an inflammatory disease of the joints associated with psoriasis.

Hulio is used to treat psoriatic arthritis in adults. Hulio can reduce the damage to the cartilage and bones of the joints caused by the disease and improve physical function.

Plaque Psoriasis in Adults and Children

Plaque psoriasis is an inflammatory disease of the skin that causes red, scaly, crusty, and silvery-scaled areas. Plaque psoriasis can also affect the nails, causing them to deteriorate, thicken, and lift off 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 the production of skin cells.

Hulio is used to treat moderate to severe plaque psoriasis in adults. Hulio is also used to treat severe plaque psoriasis in children and adolescents from 4 to 17 years of age who have not responded well to, or are not suitable for, topical therapy and light therapy.

Hidradenitis Suppurativa in Adults and Adolescents

Hidradenitis suppurativa (also known as inverse acne) is a chronic inflammatory skin disease that is often painful. Symptoms can include painful nodules (lumps) and abscesses (boils) that can secrete pus. It usually affects specific areas of the skin, such as under the breast, armpits, inner thighs, groin, and buttocks. There may also be scarring in the affected areas.

Hulio is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age. Hulio can reduce the number of nodules and abscesses you have, and the pain that is usually associated with this disease. You may have received other medicines before. If these medicines do not respond well enough, you will receive Hulio.

Crohn's Disease in Adults and Children

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

Hulio is used to treat Crohn's disease in adults and children from 6 to 17 years of age. If you have Crohn's disease, you will be treated first with other medicines. If you do not respond well enough to these medicines, you will receive Hulio to reduce the signs and symptoms of Crohn's disease.

Ulcerative Colitis in Adults and Children

Ulcerative colitis is an inflammatory disease of the intestine.

Hulio is used to treat ulcerative colitis in adults. If you have ulcerative colitis, you will be treated first with other medicines. If these medicines do not respond well enough, you will receive Hulio 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. This inflammation leads to a decrease in vision and/or the presence of floaters in the eye (small black dots or thin lines that move along the field of vision). Hulio works by reducing this inflammation.

Hulio is used to treat:

• adults with non-infectious uveitis with inflammation that affects the back of the eye;
• children and adolescents from 2 to 17 years of age for the treatment of chronic non-infectious uveitis with inflammation that affects the front of the eye.

2. What you need to know before you start using Hulio

Do not use Hulio

• If you are allergic to adalimumab or to any of the other components of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis (see “Warnings and precautions”). If you have symptoms of any infection, such as fever, wounds, fatigue, dental problems, it is important that you inform your doctor.
• If you have moderate or severe heart failure. It is important that you tell your doctor if you have had or have any serious heart problems (see “Warnings and precautions”).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Hulio.

Allergic reactions

If you have an allergic reaction with symptoms such as chest tightness, difficulty breathing, dizziness, swelling, or rash, stop Hulio injections and contact your doctor immediately, as these reactions can be life-threatening in rare cases.

Infections

• If you have any infection, including chronic or localized infections (e.g., a leg ulcer), consult your doctor before starting treatment with Hulio. If you are unsure, contact your doctor.
• With Hulio treatment, you may be more likely to get infections. This risk may be higher if you have lung problems. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites, or bacteria, or other infectious microorganisms, and sepsis (septicemia), which are rare. In rare cases, these infections can be life-threatening. Therefore, it is essential that if you have symptoms such as fever, wounds, fatigue, or dental problems, you tell your doctor. Your doctor may recommend that you temporarily stop treatment with Hulio.

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 Hulio. This includes a thorough medical evaluation, including your medical history and diagnostic tests (e.g., chest X-ray and tuberculin test). The performance and results of these tests must be recorded on your Patient Information Card. It is crucial that you inform your doctor if you have had tuberculosis or have been in contact with a tuberculosis patient. Tuberculosis can develop during treatment, even if you have received preventive treatment for tuberculosis. If symptoms of tuberculosis (persistent cough, weight loss, general malaise, low-grade fever) or any other infection appear during or after treatment, contact your doctor immediately.

Recurrent/contracted infection during travel

• Tell your doctor if you live or travel to areas where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common.
• Tell your doctor if you have a history of recurrent infections or other conditions or factors that increase the risk of infections.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have had active HBV infections, or if you think you may be at risk of contracting HBV. Your doctor will perform an HBV test. Hulio may cause the reactivation of HBV infection in people carrying this virus. In rare cases, especially if you are taking other medications that suppress the immune system, the reactivation of HBV infection can be life-threatening.

People over 65 years

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

Surgical or dental intervention

• If you are going to have surgery or dental treatment, inform your doctor that you are using Hulio. Your doctor may recommend that you temporarily stop treatment with Hulio.

Demyelinating disease

• 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 Hulio. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccines

• Certain vaccines contain live, attenuated forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hulio if they cause infection. Consult your doctor before administering any type of vaccine. It is recommended that, whenever possible, children receive all scheduled vaccinations for their age before starting treatment with Hulio. If you received Hulio while pregnant, your baby may have a higher risk of infection during the approximately 5 months following the last dose you received during pregnancy. It is essential that you inform your child's doctor and other healthcare professionals about your use of Hulio during pregnancy, so they can decide whether your child should receive any vaccine.

Heart failure

• It is essential that you inform your doctor if you have had or have serious heart problems. If you have mild heart failure and are being treated with Hulio, your doctor should continuously monitor your heart failure. If new symptoms of heart failure appear or existing ones worsen (e.g., difficulty breathing or swelling of the feet), you should contact your doctor immediately.

Fever, bruising, bleeding, or pale appearance

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

Cancer

• In very rare cases, certain types of cancer have been reported in children and adults treated with adalimumab or other TNFα blockers. People with more severe rheumatoid arthritis who have had the disease for a long time may have a higher-than-average risk of developing lymphoma and leukemia (cancers that affect the blood and bone marrow). If you are being treated with Hulio, the risk of lymphoma, leukemia, and other types of cancer may increase. A specific and severe type of lymphoma has been observed in some patients treated with Hulio. Some of these patients were also receiving treatment with azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hulio.
• • Additionally, cases of non-melanoma skin cancer have been observed in patients using adalimumab. Inform your doctor if new skin lesions appear during or after treatment, or if existing marks or lesions change in appearance.
  • Cancers other than lymphoma have been reported in patients with a specific lung disease, called chronic obstructive pulmonary disease (COPD), treated with another TNFα blocker. If you have COPD or are a heavy smoker, you should consult your doctor to determine if treatment with a TNFα blocker is suitable for you.

Children and adolescents

• Do not administer Hulio to children under 2 years old with polyarticular juvenile idiopathic arthritis and chronic non-infectious uveitis.
• Do not administer Hulio to children under 6 years old with enthesitis-related arthritis and Crohn's disease.
• Do not administer Hulio to children under 4 years old with plaque psoriasis.
• Do not administer Hulio to children under 12 years old with hidradenitis suppurativa.
• Do not use the 40 mg pre-filled syringe if doses other than 40 mg are recommended.

Other medicines and Hulio

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicine.

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

Do not use Hulio with medicines whose active substances are anakinra or abatacept. Based on the possible increased risk of infections, including severe infections, and other potential pharmacological interactions, the combination of Hulio with anakinra or abatacept is not recommended. If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

• Your daughter should consider using adequate contraceptive methods to avoid becoming pregnant and continue using them for at least 5 months after the last treatment with Hulio.
• If your daughter is pregnant, thinks she may be pregnant, or plans to have a baby, she should ask her doctor for advice on using this medicine.
• Hulio should be used during pregnancy only if necessary.

• According to a pregnancy study, there was no increased risk of congenital defects when the mother had received treatment with Hulio during pregnancy compared to mothers with the same disease who did not receive treatment with Hulio.
• Hulio can be used during breastfeeding.
• If your daughter uses Hulio during pregnancy, her baby may have a higher risk of infection.
• It is essential that you tell your child's doctor and other healthcare professionals about your use of Hulio during pregnancy before the baby receives any vaccine. For more information on vaccines, see the “Warnings and precautions” section.

Driving and using machines

The influence of Hulio on the ability to drive, ride a bicycle, or use machines is small. You may experience dizziness (vertigo) and vision disturbances after using Hulio.

Hulio contains sodium and sorbitol

Each Hulio pre-filled syringe contains 38.2 mg of sorbitol. Sorbitol is a source of fructose. If your doctor has told you (or your child) that you have an intolerance to certain sugars or have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient cannot break down fructose, consult your doctor before administering the medicine (or administering it to the child).

Additionally, this medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe, which is essentially “sodium-free”.

3. How to use Hulio

Follow the administration instructions of this medication exactly as indicated by your doctor or pharmacist. In case of doubt, ask your doctor or pharmacist. Your doctor may prescribe a different dose of Hulio if your child needs a different dose.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis.

The normal dose in adults with these diseases is 40 mg of adalimumab administered every other week as a single dose.

In the case of rheumatoid arthritis, treatment with methotrexate is maintained during the use of Hulio. If your doctor determines that methotrexate is not appropriate, Hulio can be administered alone.

If you have rheumatoid arthritis and do not receive methotrexate during your treatment with Hulio, your doctor may decide to give you 40 mg of adalimumab every week or 80 mg every two weeks.

Children and adolescents with polyarticular juvenile idiopathic arthritis

Children and adolescents from 2 to 17 years of age with a weight of 10 kg to less than 30 kg:

The recommended dose of Hulio is 20 mg every other week.

Children and adolescents from 2 to 17 years of age with a weight of 30 kg or more:

The recommended dose of Hulio is 40 mg every other week.

Children and adolescents with enthesitis-related arthritis

Children and adolescents from 6 to 17 years of age with a weight of 15 kg to less than 30 kg:

The recommended dose of Hulio is 20 mg every other week.

Children and adolescents from 6 to 17 years of age with a weight of 30 kg or more:

The recommended dose of Hulio is 40 mg every other week.

Adults with psoriasis

The normal dosage in adults with psoriasis consists of an initial dose of 80 mg (as two 40 mg injections on one day), followed by 40 mg every other week starting one week after the initial dose. You should continue injecting Hulio for as long as your doctor has indicated. If this dose does not have the desired result, your doctor may increase the frequency of the doses to 40 mg every week or 80 mg every other week.

Children or adolescents with plaque psoriasis

Children and adolescents from 4 to 17 years of age with a weight of 15 kg to less than 30 kg:

The recommended dose of Hulio is an initial dose of 20 mg, followed by 20 mg one week later. From then on, the usual dose is 20 mg every other week.

Children and adolescents from 4 to 17 years of age with a weight of 30 kg or more:

The recommended dose of Hulio is an initial dose of 40 mg, followed by 40 mg one week later. From then on, the usual dose is 40 mg every other week.

Adults with hidradenitis suppurativa

The usual dosage regimen for hidradenitis suppurativa is an initial dose of 160 mg (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by a dose of 80 mg (as two 40 mg injections on one day) two weeks later. After two more weeks, continue with a dose of 40 mg weekly or 80 mg every two weeks, as prescribed by your doctor.

It is recommended that you use an antiseptic liquid daily on the affected areas.

Adolescents with hidradenitis suppurativa in adolescents from 12 to 17 years of age, with a weight of at least 30 kg

The recommended dose of Hulio is an initial dose of 80 mg (2 injections of 40 mg on one day), followed by 40 mg every other week starting one week later. If this dose does not have the desired result, the pediatrician may increase it to 40 mg every week or 80 mg every other week.

It is recommended that your child use an antiseptic liquid daily on the affected areas.

Adults with Crohn's disease

The usual dosage regimen for Crohn's disease is 80 mg (as two 40 mg injections on one day) initially, followed by 40 mg every other week starting two weeks later. If a faster effect is required, your doctor may prescribe an initial dose of 160 mg (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (as two 40 mg injections on one day) two weeks later and then 40 mg every other week. If this dose does not have the desired result, your doctor may increase the frequency of the doses to 40 mg every week or 80 mg every other week.

Children or adolescents with Crohn's disease

Children or adolescents from 6 to 17 years of age with a weight of less than 40 kg:

The usual dosage is 40 mg initially followed by 20 mg two weeks later. If a faster response is required, your doctor may prescribe an initial dose of 80 mg (as 2 injections of 40 mg on one day) followed by 40 mg two weeks later.

From then on, the usual dose is 20 mg every other week. If this dose does not have the desired result, your doctor may increase the frequency of the doses to 20 mg every week.

Children or adolescents from 6 to 17 years of age with a weight of 40 kg or more:

The usual dosage is 80 mg (as two 40 mg injections on one day) initially followed by 40 mg two weeks later. If a faster response is required, your doctor may prescribe an initial dose of 160 mg (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days) followed by 80 mg (as two 40 mg injections on one day) two weeks later.

From then on, the usual dose is 40 mg every other week. If this dose does not have the desired result, your doctor may increase the dose to 40 mg every week or 80 mg every other week.

Patients who need a dose lower than 40 mg must use the 40 mg vial presentation of Hulio.

Adults with ulcerative colitis

The normal dosage in adults with ulcerative colitis is 160 mg initially (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days) followed by 80 mg (as two 40 mg injections on one day) two weeks later and then 40 mg every other week. If this dose does not have the desired result, your doctor may increase the frequency of the doses to 40 mg every week or 80 mg every other week.

Children and adolescents with ulcerative colitis

Children and adolescents from 6years with a weight of less than 40kg

The usual dose of Hulio is 80 mg (as two 40 mg injections on one day) initially, followed by a dose of 40 mg (as one 40 mg injection) two weeks later. From then on, the usual dose is 40 mg every other week.

Patients who turn 18 years old while receiving treatment with 40 mg every other week must continue with their prescribed dose.

Children and adolescents from 6years with a weight of 40kg or more

The usual dose of Hulio is 160 mg (as four 40 mg injections on one day or two 40 mg injections per day for two consecutive days) initially, followed by a dose of 80 mg (as two 40 mg injections on one day) two weeks later. From then on, the usual dose is 80 mg every other week.

Patients who turn 18 years old while receiving treatment with 80 mg every other week must continue with their prescribed dose.

Adults with non-infectious uveitis affecting the back of the eye

The usual dose in adults with non-infectious uveitis is an initial dose of 80 mg (as two injections on one day), followed by 40 mg every other week starting one week after the initial dose. You should continue injecting Hulio for as long as your doctor has indicated.

In non-infectious uveitis, treatment with corticosteroids or other medications that affect the immune system may be continued. Hulio can also be administered alone.

Children and adolescents with chronic non-infectious uveitis

Children and adolescents from 2 to 17years of age with a weight of less than 30kg:

The usual dose of Hulio is 20 mg every other week along with methotrexate.

Your pediatrician may prescribe an initial dose of 40 mg that can be administered one week before starting the recommended usual regimen.

Children and adolescents from 2 to 17years of age with a weight of 30kg or more:

The usual dose of Hulio is 40 mg every other week along with methotrexate.

Your pediatrician may prescribe an initial dose of 80 mg that can be administered one week before starting the recommended usual regimen.

For patients who have been prescribed a dose lower than 40 mg, Hulio 20 mg solution for injection in a pre-filled syringe or Hulio 40 mg/0.8 ml solution for injection in a vial (available at the pharmacy) must be used.

Form and route of administration

Hulio is injected under the skin (subcutaneous use).

The instructions for use provide detailed instructions on how to inject Hulio.

If you use more Hulio than you should

If you accidentally inject Hulio with a higher frequency than normal, call your doctor or pharmacist and inform them that you received a higher dose than necessary. Always carry the medicine box with you, even if it is empty.

If you forget to use Hulio

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

If you stop treatment with Hulio

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

If you have any other questions about the use of this medication, ask 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. However, some can be serious and require urgent medical treatment.

Side effects can appear up to 4 months, or more, after the last injection of Hulio.

Seek medical attention immediatelyif you present any of the following signs of an allergic reaction or heart failure:

• severe rash, hives;
• swelling of the face, hands, or feet;
• difficulty breathing or swallowing;
• pale appearance, dizziness, persistent fever, bruising, or bleeding easily.

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 when urinating, weakness, fatigue, or cough;
• symptoms of nervous system problems such as tingling, numbness, double vision, or weakness in arms or legs;
• signs of skin cancer, such as a lump or an open sore that does not heal;
• signs and symptoms of blood disorders such as persistent fever, bruising, and bleeding.

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, runny nose, sinusitis, sore throat, pneumonia);
• abnormal blood values;
• headache;
• abdominal pain;
• nausea and vomiting;
• pain in bones and muscles.

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

• any infection (including tuberculosis, blood toxicity, flu, cellulitis, herpes, ear infections, dental infections, cold sores, infections of the reproductive system, urinary tract infections, fungal infections, joint infections);
• benign tumors;
• skin cancer;
• moderate allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• difficulty sleeping;
• sensory disturbances such as tingling, itching, or numbness;
• migraine;
• back or neck pain;
• visual disturbances;
• inflammation or swelling of the eyes/lids;
• vertigo (feeling that the room is spinning);
• cough;
• feeling of rapid heartbeat;
• high blood pressure;
• flushing;
• blood clots;
• asthma;
• stomach bleeding;
• indigestion, bloating, and heartburn;
• acid reflux;
• dryness in eyes and mouth;
• itching, skin inflammation (including eczema);
• increased sweating;
• hair loss;
• new or worsening psoriasis (red and scaly skin);
• muscle spasms;
• blood in urine;
• kidney problems;
• slow wound healing.

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

• cancer affecting the lymphatic system (lymphoma);
• immune system disorders that can affect the lungs, skin, and lymph nodes (the most common presentation is sarcoidosis);
• inflammation of blood vessels;
• tremors;
• nerve damage;
• stroke;
• double vision;
• hearing loss, ringing in the ears;
• irregular heartbeat;

• pulmonary diseases that can cause difficulty breathing (including inflammation);
• blockage of a pulmonary artery;
• excessive fluid around the lung;
• pancreatitis;
• difficulty swallowing;
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scars;
• abnormal muscle crisis;
• systemic lupus erythematosus (including skin inflammation, heart, lungs, joints, and other organs);
• excessive nocturnal urination;
• impotence.

Rare(may affect up to 1 in 1000 people):

• leukemia (cancer affecting the blood and bone marrow);
• multiple sclerosis;
• nervous system disorders (such as optic neuritis and Guillain-Barré syndrome, which can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• heart attack;
• pulmonary fibrosis (scarring in the lung);
• intestinal perforation/tear;
• hepatitis;
• inflammation of blood vessels in the skin;
• Stevens-Johnson syndrome;
• inflammatory rash on the skin;
• lupus-like syndrome;
• lichenoid skin reaction (red-purple rash with itching).

Frequency not known(cannot be estimated from the available data):

• hepatosplenic T-cell lymphoma (a rare blood cancer);
• Merkel cell carcinoma (a type of skin cancer);
• liver failure;
• worsening of a skin rash with muscle weakness.

Reporting of side effects

If you experience side effects, consult your doctor or pharmacist, even if it is a side effect not listed in this leaflet.

You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Hulio

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

Do not use this medicine after the expiration date that appears on the label, blister, or packaging after EXP. The expiration date is the last day of the month indicated.

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

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

Alternative storage:

When necessary (e.g., when traveling), you can store a single Hulio pre-filled syringe at room temperature (up to 25 °C) for a maximum period of 8 weeks (make sure to protect it from light). Once you have removed it from the refrigerator to store it at room temperature, you must usethe syringe within the next 8 weeks or discard it, even if you put it back in the refrigerator.

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

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

6. Container Contents and Additional Information

Hulio Composition

• The active ingredient is adalimumab.
• The other components are: monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid, and water for injectable preparations.

Product Appearance and Container Contents

Hulio 40 mg injectable solution (injection) in a pre-filled syringe is supplied as a sterile solution of 40 mg of adalimumab dissolved in 0.8 ml of a clear or slightly opalescent, yellowish-brown solution, ranging from colorless to pale.

The Hulio pre-filled syringe consists of a plastic syringe with a plug and a needle with a cap. Each container contains 1, 2, 4, or 6 pre-filled syringes and 2, 2, 4, or 6 alcohol swabs.

Each container contains 1, 2, 4, or 6 pre-filled syringes.

Only some pack sizes may be marketed.

Hulio is also available in a vial for pediatric use or in a pre-filled pen.

Marketing Authorization Holder

Biosimilar Collaborations Ireland Limited

Unit 35/36

Grange Parade,

Baldoyle Industrial Estate,

Dublin 13

DUBLIN

Ireland

D13 R20R

Manufacturer

Biosimilar Collaborations Ireland Limited

Block B, The Crescent Building, Santry Demesne

Dublin

D09 C6X8

Ireland

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet {MM/YYYY}

Other Sources of Information

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

1. Instructions for Use

Read the instructions carefully and follow them step by step. Your doctor, a nurse, or another healthcare professional will show you how to administer the injection with the Hulio pre-filled syringe. Consult your doctor or nurse if there is anything you do not understand.

Do not attempt to administer the injection until you are sure you understand how to prepare and administer it. After a suitable training period, you may self-inject or have another person, such as a family member or caregiver, administer the injection for you.

Each pre-filled syringe is for single use only and contains a dose of 40 mg of adalimumab.

Do not mix the Hulio solution with any other medicinal product.

It may be helpful to make notes on a calendar or diary to remind you which days of the week you should inject Hulio.

Before Starting

Find a quiet place with a well-lit, clean, and flat work surface and gather all the supplies you will need to administer the injection.

Supplies you will need:

• 1 pre-filled syringe
• 1 alcohol swab
• 1 container for disposal of sharp objects (not included in the Hulio box)
• 1 gauze or cotton ball (not included in the Hulio box)

If you do not have all the necessary supplies, ask your nurse or pharmacist for them.

Preparing the Pre-filled Syringe

Pre-filled syringes should be stored in the refrigerator (between 2 °C and 8 °C).

• Remove the pre-filled syringe from the refrigerator at least 30 minutes before using it, to allow the contents to reach room temperature.

• DO NOT use any heat source, such as a microwave or hot water, to warm the syringe.
• DO NOT put the syringe back in the refrigerator once it has reached room temperature.
• • Check the expiration date printed on the syringe.

• DO NOT use the syringe after the expiration date.
• Inspect the syringe to ensure the medication is at or near the fill indicator (you may need to gently shake to see the liquid), and that the liquid is clear, colorless, and free of particles.
• DO NOT use the syringe if the medication is not near the fill indicator.
• DO NOT use the syringe if the liquid is cloudy, whitish, or contains particles.

Injection Steps

Follow the steps below carefully each time you inject Hulio with the pre-filled syringe: