HULIO 40 mg INJECTABLE SOLUTION IN PRE-FILLED PEN

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, viral, fungal, parasitic, or bacterial infections, 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 will include 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 while traveling

• Tell your doctor if you live or travel to regions 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 hepatitis B virus (HBV) carrier, 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 old

• 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 infection signs 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 work, 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 have 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 vaccines 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 pen 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 that your daughter used 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 pen 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 disease 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 pen, which is essentially “sodium-free”.

3. How to use Hulio

Follow your doctor's or pharmacist's administration instructions for this medication exactly. If in 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 12 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 as 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 frequency of the doses to 40 mg every week or 80 mg every other week.

Patients who need a dose less 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) in week 2 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.

Patient who reach 18 years while receiving treatment with 40 mg every other week should 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 reach 18 years while receiving treatment with 80 mg every other week should 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 less 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) should 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 more frequently 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. Then, the next dose will be administered 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 may 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 nerve 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 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, runny nose, sinusitis, throat infection, 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, tinnitus;
• 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, heart, lung, joint, and other organ inflammation);
• excessive nocturnal urination;
• impotence.

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

• leukemia (cancer affecting the blood and bone marrow);
• multiple sclerosis;
• nerve 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;
• liver inflammation;
• 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 pen 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 pen 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 pen within the next 8 weeks or discard it, even if you put it back in the refrigerator.

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

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

Composition of Hulio

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

Appearance of the Product and Container Contents

Hulio 40 mg injectable solution (injection) in a pre-filled pen 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.

The Hulio pre-filled pen is made of plastic with a plug and a needle with a cap. Each pack contains 1, 2, 4, or 6 pre-filled pens and 2, 2, 4, or 6 alcohol swabs.

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

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 medication 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 pen. Consult your doctor or nurse if there is anything you do not understand.

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

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

Do not mix the Hulio solution with any other medication.

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

Before You Start

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 pen
• 1 alcohol swab
• 1 container for disposing 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 Pen

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

• Remove one pen 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 up the pen.
• DO NOT put the pen back in the refrigerator once it has reached room temperature.
• • Check the expiration date printed on the pen.

• DO NOT use the pen after the expiration date.
• Look at the viewing window to make sure the medication is at or near the fill indicator (you may need to gently shake to see it), and that the liquid is clear, colorless, and free of particles.
• DO NOT use the pen if the medication is not near the fill indicator.
• DO NOT use the pen if the liquid is cloudy, white, or contains particles.

Steps for Injection

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