Label: information for the patient

Hulio 40 mg injectable solution in pre-filled syringe

adalimumab

Read this label carefully before starting to use this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• Your doctor will give you a Patient Information Leaflet, which contains important safety information that you need to know before and during treatment with Hulio. Carry the Patient Information Leaflet with you at all times and for 4 months after you are injected with Hulio.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, 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 label. See section 4.

Humira contains adalimumab as its active substance, a medication that acts on the body's immune system (defenses).

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

• Rheumatoid arthritis;
• Polyarticular juvenile idiopathic arthritis;
• Arthritis associated with enthesitis;
• Ankylosing spondylitis;
• Undifferentiated spondyloarthritis without radiographic evidence of ankylosing spondylitis;
• Psoriatic arthritis;
• Poriasis;
• • Hidradenitis suppurativa;
  • Crohn's disease;
  • Ulcerative colitis;
  • Non-infectious uveitis in adults and children.

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

The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is present in elevated levels in the inflammatory diseases described above. By attacking TNFα, Humira reduces the inflammatory process in those diseases.153

Rheumatoid Arthritis

Rheumatoid arthritis is an inflammatory disease of the joints.

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

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

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

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

Polyarticular Juvenile Idiopathic Arthritis and Arthritis Associated with Enthesitis

Polyarticular juvenile idiopathic arthritis and arthritis associated with enthesitis are inflammatory joint diseases that usually first appear in childhood.

Humira is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years and arthritis associated with enthesitis in children and adolescents aged 6 to 17 years. You may have received other disease-modifying medications, such as methotrexate, first. If these medications do not respond well enough, you will receive Humira to treat your polyarticular juvenile idiopathic arthritis or arthritis associated with enthesitis.

Ankylosing Spondylitis and Undifferentiated Spondyloarthritis without Radiographic Evidence of Ankylosing Spondylitis

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

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

Psoriatic Arthritis

Psiatic arthritis is an inflammatory joint disease associated with psoriasis.

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

Poriasis in Adults and Children

Poriasis in plaques is an inflammatory skin disease that causes red, scaly, crusty areas covered with silver scales. Poriasis in plaques 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.154

Humira is used to treat moderate to severe psoriasis in adults. Humira is also used to treat severe psoriasis in children and adolescents aged 4 to 17 years who have not responded well or are not good candidates for topical therapy and UV 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 (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. It can also leave scars in the affected areas.

Humira is used to treat hidradenitis suppurativa in adults and adolescents aged 12 and older. Humira can reduce the number of nodules and abscesses you have, and the pain that usually comes with this disease. You may have received other medications previously. If these medications do not respond well enough, you will receive Humira.

Crohn's Disease in Adults and Children

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

Humira is used to treat Crohn's disease in adults and children aged 6 to 17 years. If you have Crohn's disease, you will be treated first with other medications. If you do not respond well enough to these medications, you will receive Humira 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.

Humira is used to treat ulcerative colitis in adults. If you have ulcerative colitis, you will be given other medications first. If these medications do not respond well enough, you will receive Humira 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 spots in the eye (black dots or thin lines that move across the field of vision). Humira acts by reducing this inflammation.

Humira is used to treat:

No use Hulio

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 hives, interrupt Hulio injections and contact your doctor immediately, as in rare cases, these reactions can be life-threatening.

Infections

Tuberculosis (TB)

Recurring or travel-related infections

Hepatitis B virus

People over 65 years old

Surgical or dental intervention

Demyelinating disease

Vaccinations

Heart failure

Fever, hematomas, bleeding, or pale appearance

Cancer

• In rare cases, certain types of cancer have been reported in children and adults treated with adalimumab or other TNFα blockers. People with severe rheumatoid arthritis who have had the disease for a long time may have a higher risk than average of developing lymphoma and leukemia (cancers that affect the blood and bone marrow). If you are being treated with Hulio, the risk of developing lymphoma, leukemia, and other types of cancer may increase. A specific and severe type of lymphoma has been observed in some patients being treated with Hulio. Some of these patients were also taking azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hulio.
• • Additionally, cases of skin cancer (non-melanoma) have been reported in patients using adalimumab. Inform your doctor if you develop new skin lesions during or after treatment or if existing lesions change appearance.
  • 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 using a TNFα blocker in your case.

Children and adolescents

Other medications and Hulio

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

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

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

Pregnancy and breastfeeding

Driving and using machines

The influence of Hulio on the 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 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 indicated that you (or your child) 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 (or your child) before administering the medication (or administering it to the child).

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

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. If in doubt, ask your doctor or pharmacist. Your doctor may prescribe another 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 usual 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 use of

Hulio. If your doctor determines that methotrexate is not appropriate, Hulio may be administered alone.

If you have rheumatoid arthritis and do not receive methotrexate during 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 or less:

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 arthritis associated with enthesitis

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

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 usual dosage in adults with psoriasis consists of an initial dose of 80 mg (as two injections of 40 mg on the same 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 told you. 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 or less:

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 dosing regimen for hidradenitis suppurativa is an initial dose of 160 mg (as four injections of 40 mg on the same day or two injections of 40 mg per day for two consecutive days), followed by a dose of 80 mg (as two injections of 40 mg on the same 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 the same day), followed by 40 mg every other week starting one week later. If this dose does not have the desired result, your 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 dosing regimen for Crohn's disease is 80 mg (as two injections of 40 mg on the same 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 injections of 40 mg on the same day or two injections of 40 mg per day for two consecutive days), followed by 80 mg (as two injections of 40 mg on the same 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 an initial dose of 40 mg, followed by 20 mg two weeks later. If a faster response is required, your doctor may prescribe an initial dose of 80 mg (as two injections of 40 mg on the same 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 an initial dose of 80 mg (as two injections of 40 mg on the same day), 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 injections of 40 mg on the same day or two injections of 40 mg per day for two consecutive days), followed by 80 mg (as two injections of 40 mg on the same 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 less than 40 mg should use the 40 mg vial of Hulio.

Adults with ulcerative colitis

The usual dosage in adults with ulcerative colitis is 160 mg initially (as four injections of 40 mg on the same day or two injections of 40 mg per day for two consecutive days), followed by 80 mg (as two injections of 40 mg on the same 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 6 years of age with a weight of less than 40 kg:

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

Patients who are 18 years of age or older while receiving treatment with 40 mg every other week should continue their prescribed dose.

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

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

Patients who are 18 years of age or older while receiving treatment with 80 mg every other week should continue their prescribed dose.

Adults with non-infectious uveitis that affects 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 the same 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 told you.

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

Children and adolescents with chronic non-infectious uveitis

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

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

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

Children and adolescents from 2 to 17 years of age with a weight of 30 kg 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, which may be administered one week before starting the recommended regimen.

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

Form and route of administration

Hulio is injected under the skin (subcutaneous use).

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

If you use more Hulio than you should

If Hulio is accidentally injected with a frequency higher than usual, call your doctor or pharmacist and inform them that you received a higher dose than necessary. Always carry the medication 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, administer the next dose as usual, as if you had not forgotten a dose.

If you interrupt treatment with Hulio

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

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 severe and require urgent medical treatment.

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

Seek immediate medical attentionif you experience any of the following signs of

allergic reaction or heart failure:

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

The following side effects have been observed with adalimumab:

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

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

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

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

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

Reporting of side effects

If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet.

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

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

Do not use this medication after the expiration date that appears on the label, the blister pack, or the container after CAD. The expiration date is the last day of the month indicated.

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

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

Alternative Storage:

When necessary (for example, when traveling), you may store an individual pre-filled syringe of Hulio at room temperature (up to 25 °C) for a maximum period of 8 weeks (ensure it is protected from light). Once you have removed the syringe from the refrigerator to store it at room temperature,you must usethe syringewithin the following 8 weeks or discard it, even if you return it to the refrigerator.

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

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

Composition of Hulio

Appearance of the product and contents of the pack

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

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

Each pack 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

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet {MM/AAAA}

Other sources of information

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

7. Instructions for use

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

Do not attempt to administer the injection before you are sure you understand how to prepare and administer it. After a suitable period of training, you may self-administer the injection or someone else may administer it for you, for example a family member or caregiver.

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

Do not mix the solution of Hulio with any other medicine.

It may be helpful to make notes in a calendar or diary to remind you which days of the week you need to 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-soaked swab

•1 sharps container (not included in the Hulio pack)

•1 gauze or cotton ball (not included in the Hulio pack)

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).

• Do not use any heat source, such as a microwave oven 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.
• Observe the syringe to ensure that the medicine is at or near the fill indicator (you may need to gently shake it to see the liquid), and that the liquid is transparent, colorless, and free of particles in suspension.
• Do not use the syringe if the medicine is not at or near the fill indicator.
• Do not use the syringe if the liquid is cloudy, white, or contains particles in suspension.

Steps for injection

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