Hulio 40 mg solution for injection in pre-filled pen

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Hulio 40 mg solution for injection in a pre-filled pen

adalimumab

Read all of 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 a Patient Information Card, which contains important safety information you need to know before and during treatment with Hulio. Carry the Patient Information Card with you at all times and for 4 months after you are injected with Hulio.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Hulio is and what it is used for

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

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

• rheumatoid arthritis;
• polyarticular juvenile idiopathic 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 site in the body.

Adalimumab targets a protein called tumor necrosis factor (TNFα), which is present at elevated levels in the inflammatory diseases described above. By targeting TNFα, Hulio reduces the inflammatory process in these diseases.

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease affecting the joints.

Hulio is used to treat rheumatoid arthritis in adults. If you have moderate to severe active rheumatoid arthritis, you may have previously been treated with disease-modifying drugs such as methotrexate. If these medicines do not provide an adequate response, you will receive Hulio to treat rheumatoid arthritis.

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

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

Hulio is usually used in combination with methotrexate. If your doctor considers methotrexate inappropriate, Hulio may be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory joint diseases that typically first appear in childhood.

Hulio is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged 2 to 17 years and enthesitis-related arthritis in children and adolescents aged 6 to 17 years. You may have first received other disease-modifying drugs, such as methotrexate. If these medicines do not provide an adequate response, you will receive Hulio to treat your polyarticular juvenile idiopathic 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 affecting 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 first be treated with other medicines. If these medicines do not provide an adequate response, you will receive Hulio to reduce the signs and symptoms of the disease.

Psoriatic arthritis

Psoriatic arthritis is an inflammatory joint disease associated with psoriasis.

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

Plaque psoriasis in adults and children

Plaque psoriasis is an inflammatory skin disease that causes red, scaly, crusted 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. Psoriasis is thought to be caused by a defect in the body's immune system that leads to increased production of skin cells. 154

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 aged 4 to 17 years who have not responded well to, or are not good candidates for, topical therapy and UV light treatment.

Hidradenitis suppurativa in adults and adolescents

Hidradenitis suppurativa (sometimes called inverse acne) is a chronic inflammatory and often painful skin disease. Symptoms may include painful nodules (lumps) and abscesses (boils) that may discharge pus. It usually affects specific skin areas such as under the breasts, under the arms, inner thighs, groin, and buttocks. Scarring may also occur in affected areas.

Hulio is used to treat hidradenitis suppurativa in adults and adolescents aged 12 years and older. Hulio can reduce the number of nodules and abscesses you have, as well as the pain typically associated with this disease. You may have previously received other medicines. If these medicines do not provide an adequate response, 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 aged 6 to 17 years. If you have Crohn's disease, you will first be treated with other medicines. If you do not respond adequately 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, other medicines will first be prescribed. If these medicines do not provide an adequate response, you will receive Hulio to reduce the signs and symptoms of the disease.

Non-infectious uveitis affecting the back of the eye

Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. This inflammation leads to decreased vision and/or the presence of floaters (black spots or thin lines moving across the field of vision). Hulio works by reducing this inflammation.

Hulio is used to treat:

• adults with non-infectious uveitis with inflammation affecting 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 affecting the front of the eye.

2. What you need to know before using Hulio

Do not use Hulio

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

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Hulio.

Allergic reactions

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

Infections

• If you have any infection, including chronic or localized infections (for example: a leg ulcer), consult your doctor before starting treatment with Hulio. If you are unsure, contact your doctor.
• You may be more likely to get infections while being treated with Hulio. 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, other infectious microorganisms, and sepsis (septicemia), which are uncommon. In rare cases, these infections may be life-threatening. Therefore, it is important to inform your doctor if you develop symptoms such as fever, wounds, fatigue, or dental problems. Your doctor may recommend temporarily stopping 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 treatment with Hulio. This will include a thorough medical evaluation, including your medical history and diagnostic tests (for example, chest X-ray and tuberculin test). The performance and results of these tests must be recorded in your Patient Information Card. It is very important to inform your doctor if you have had tuberculosis or have been in contact with a person with tuberculosis. Tuberculosis may 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 occur during or after treatment, contact your doctor immediately.

Recurrent or travel-related infections

• Inform your doctor if you live in or travel 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 risk factors that increase the likelihood of infections.

Hepatitis B virus (HBV)

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

People aged 65 years and older

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

Surgery or dental procedures

• If you are scheduled for surgery or a dental procedure, inform your doctor that you are using Hulio. Your doctor may recommend temporarily stopping treatment with Hulio.

Demyelinating disease

• If you have or develop a demyelinating disease (a disease affecting the protective covering of nerves), such as multiple sclerosis, your doctor will decide whether you should start 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 anywhere in the body.

Vaccines

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause disease and should not be given during treatment with Hulio if they could cause infection. Consult your doctor before receiving any type of vaccine. It is recommended that, whenever possible, children receive all age-appropriate vaccines before starting treatment with Hulio. If you received Hulio during pregnancy, your baby may have an increased risk of infections for approximately the 5 months following your last dose during pregnancy. It is important to 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 vaccines.

Heart failure

• It is important to inform your doctor if you have had or currently have serious heart problems. If you have mild heart failure and are being treated with Hulio, your doctor should closely monitor your condition. If new symptoms of heart failure appear or existing symptoms worsen (for example: difficulty breathing or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding, or paleness

• In some patients, the body may be unable to produce enough of certain types of blood cells that fight infections (white blood cells) or help stop bleeding (platelets). If you have persistent fever, bruising, easy bleeding, or look very pale, contact your doctor immediately. Your doctor may decide to stop treatment.

Cancer

• Very rarely, certain types of cancer have been reported in children and adults treated with adalimumab or other agents that block TNFα. 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 affecting blood and bone marrow). If you are being treated with Hulio, your risk of developing lymphoma, leukemia, and other types of cancer may increase. A specific and serious type of lymphoma has been observed, rarely, in some patients treated with Hulio. Some of these patients were also receiving azathioprine or mercaptopurine. Inform your doctor if you are taking azathioprine or mercaptopurine with Hulio.
  • In addition, cases of skin cancer (non-melanoma type) 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) who were treated with another TNFα blocker. If you have COPD or are a heavy smoker, you should consult your doctor about whether treatment with a TNFα blocker is appropriate for you.

Children and adolescents

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

Other medicines and Hulio

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

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

You must not use Hulio together with medicines containing anakinra or abatacept as active ingredients. Based on the potential increased risk of infections, including serious infections, and other possible 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 appropriate contraceptive methods to avoid becoming pregnant and continue using them for at least 5 months after the last dose of Hulio.

• If your daughter is pregnant, thinks she might be pregnant, or plans to have a baby, she should seek advice from her doctor about using this medicine.

• Hulio should only be used during pregnancy if necessary.

• According to a pregnancy study, there was no increased risk of congenital malformations when the mother received Hulio during pregnancy compared to mothers with the same condition who did not receive Hulio treatment.

• Hulio may be used during breastfeeding.

• If your daughter used Hulio during her pregnancy, her baby may have a higher risk of infection.

• It is important to inform the pediatrician or other healthcare professionals that your daughter used Hulio during pregnancy before the baby receives any vaccines. For more information on vaccines, see the section “Warnings and precautions”.

Driving and using machines

The effect of Hulio on the ability to drive, ride a bicycle, or operate machinery is minor. Dizziness and vision disturbances may occur after using Hulio.

Hulio contains sodium and sorbitol

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

In addition, 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 exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, ask your doctor or pharmacist. Your doctor may prescribe a different dose of Hulio if your child requires it.

Adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis

The usual adult dose for these conditions is 40 mg of adalimumab administered every other week as a single dose.

In the case of rheumatoid arthritis, treatment with methotrexate should be continued during use of Hulio. If your doctor determines that methotrexate is not appropriate, Hulio may be given alone.

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

Children and adolescents with polyarticular juvenile idiopathic arthritis

Children and adolescents aged 2 to 17 years weighing 10 kg up to less than 30 kg:

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

Children and adolescents aged 2 to 17 years weighing 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 aged 6 to 17 years weighing 15 kg up to less than 30 kg:

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

Children and adolescents aged 6 to 17 years weighing 30 kg or more:

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

Adults with psoriasis

The usual dosage for adults with psoriasis is an initial dose of 80 mg (as two 40 mg 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 instructed. If this dose does not achieve the desired effect, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children or adolescents with plaque psoriasis

Children and adolescents aged 4 to 17 years weighing 15 kg up to less than 30 kg:

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

Children and adolescents aged 4 to 17 years weighing 30 kg or more:

The recommended dose of Hulio is an initial dose of 40 mg, followed by 40 mg one week later. Thereafter, 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 40 mg injections on the same 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 the same day) two weeks later. After an additional two weeks, continue with a dose of 40 mg weekly or 80 mg every other week, as prescribed by your doctor.

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

Adolescents with hidradenitis suppurativa, aged 12 years or older, weighing at least 30 kg

The recommended dose of Hulio is an initial dose of 80 mg (two 40 mg injections on the same day), followed by 40 mg every other week starting one week after the initial dose. If this dose does not achieve the desired effect, the pediatrician may increase it to 40 mg weekly or 80 mg every other week.

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

Adults with Crohn's disease

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

Children or adolescents with Crohn's disease

Children or adolescents aged 6 to 17 years weighing less than 40 kg:

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

Thereafter, the usual dose is 20 mg every other week. If this dose does not achieve the desired effect, your doctor may increase the frequency to 20 mg weekly.

Children or adolescents aged 6 to 17 years weighing 40 kg or more:

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

Thereafter, the usual dose is 40 mg every other week. If this dose does not achieve the desired effect, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Patients who require a dose lower than 40 mg should use the Hulio 40 mg vial presentation.

Adults with ulcerative colitis

The usual dosage for adults with ulcerative colitis is 160 mg initially (as four 40 mg injections on the same day or two 40 mg injections per day for two consecutive days), followed by 80 mg (as two 40 mg injections on the same day) in week 2, and then 40 mg every other week. If this dose does not achieve the desired effect, your doctor may increase the frequency to 40 mg weekly or 80 mg every other week.

Children and adolescents with ulcerative colitis

Children and adolescents aged 6 years and older weighing less than 40 kg:

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

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

Children and adolescents aged 6 years and older weighing 40 kg or more:

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

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

Adults with non-infectious uveitis affecting the posterior part of the eye

The usual dose for 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 instructed.

In non-infectious uveitis, treatment with corticosteroids or other immunosuppressive medications may be continued. Hulio may also be administered alone.

Children and adolescents with chronic non-infectious uveitis

Children and adolescents aged 2 to 17 years weighing less than 30 kg:

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

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

Children and adolescents aged 2 to 17 years weighing 30 kg or more:

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

Your pediatrician may prescribe an initial dose of 80 mg, which may be administered one week before starting the recommended maintenance regimen.

For patients who have been prescribed a dose lower 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 from the pharmacy) should be used.

Method and route of administration

Hulio is injected under the skin (subcutaneous use).

Detailed instructions on how to inject Hulio are provided in the instructions for use.

If you use more Hulio than you should

If you accidentally inject Hulio more frequently than usual, contact your doctor or pharmacist and inform them that you received a higher dose than required. Always carry the medicine carton with you, even if it is empty.

If you forget to use Hulio

If you forget to administer an injection, inject the next dose of Hulio as soon as you remember. Then administer the following dose as usual, as if you had not missed a dose.

If you stop using Hulio

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Most adverse effects are mild to moderate. However, some may be serious and require urgent medical treatment.

Adverse effects may occur up to 4 months, or longer, after the last injection of Hulio.

Seek immediate medical attention if you experience 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 possible if you notice any of the following:

• 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, bleeding and paleness.

The following adverse effects have been observed with adalimumab:

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

• injection site reactions (including pain, swelling, redness or itching);
• lower respiratory tract infections (including cold, runny nose, sinusitis, throat infection, pneumonia);
• abnormal blood test results;
• headache;
• abdominal pain;
• nausea and vomiting;
• bone and muscle pain.

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

• any infections (including tuberculosis, blood poisoning, flu, cellulitis, herpes, ear infections, dental infections, cold sores, reproductive system infections, 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, stinging or numbness;
• migraine;
• back or neck pain;
• visual disturbances;
• eye/palpebral inflammation or swelling;
• dizziness (sensation that the room is spinning);
• cough;
• sensation of rapid heartbeat;
• high blood pressure;
• flushing;
• blood clots;
• asthma;
• stomach bleeding;
• indigestion, bloating and burning;
• heartburn/acid reflux;
• dry eyes and mouth;
• itching, skin inflammation (including eczema);
• increased sweating;
• hair loss;
• new onset psoriasis or worsening of existing psoriasis (red, 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);
• immunological disorders that may affect the lungs, skin and lymph nodes (the most frequent presentation is sarcoidosis);
• inflammation of blood vessels;
• tremor;
• nerve injury;
• stroke;
• double vision;
• hearing loss, ringing in the ears;
• irregular heartbeat;
• lung diseases that may cause difficulty breathing (including inflammation);
• blockage of a lung artery;
• excessive fluid around the lung;
• inflammation of the pancreas;
• difficulty swallowing;
• gallbladder inflammation, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle spasms;
• systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints and other organs);
• excessive nighttime urination;
• impotence.

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

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

Frequency not known (cannot be estimated from 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 adverse effects

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

You may also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 expiry date stated on the label, blister pack, or carton following EXP. The expiry date refers to 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 its outer packaging to protect it from light.

Alternative storage:

When necessary (for example, when travelling), a single pre-filled pen of Hulio may be stored at room temperature (up to 25 °C) for a maximum period of 8 weeks (ensure it is protected from light). Once removed from the refrigerator for storage at room temperature, the pen must be used within the following 8 weeks or discarded, even if it is returned to the refrigerator.

You should record the date on which the pen was removed from the refrigerator, and the date after which the pen must be discarded.

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

6. Contents of the pack and other information

Composition of Hulio

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

Appearance of the product and contents of the pack

Hulio 40 mg solution for injection (injection) in a prefilled pen is supplied as a sterile solution containing 40 mg of adalimumab dissolved in 0.8 ml of a clear or slightly opalescent, colourless to pale brownish-yellow solution.

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

Hulio is also available in vials for paediatric use or in prefilled syringes.

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

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet {MM/YYYY}

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: 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 using the Hulio pre-filled pen. Consult your doctor or nurse if anything is unclear.

Do not attempt to give yourself the injection until you are confident that you understand how to prepare and administer it. After an appropriate training period, you may self-inject, or someone else may administer the injection for you, for example a family member or caregiver.

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

Do not mix the Hulio solution with any other medicine.

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

Before you begin

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

Supplies you will need:

• 1 pre-filled pen
• 1 alcohol-impregnated wipe
• 1 sharps disposal container (not included in the Hulio package)
• 1 gauze pad or cotton ball (not included in the Hulio package)

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

Preparing the pre-filled pen

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

• Remove only one pen from the refrigerator at least 30 minutes before use, to allow the contents to reach room temperature.

• DO NOT use any external heat source, such as a microwave or hot water, to warm the pen.

• DO NOT return the pen to the refrigerator once it has reached room temperature.

  • Check the expiry date printed on the pen.

• DO NOT use the pen after the expiry date.

• Look through the viewing window to ensure that the medicine is at or near the fill indicator (you may need to gently shake the pen to see this), and that the liquid is clear, colourless, and free from particles.

• DO NOT use the pen if the medicine level is not near the fill indicator.

• DO NOT use the pen if the liquid is cloudy, whitish, or contains particles in suspension.

Steps for injection

Carefully follow the steps below each time you inject Hulio using the pre-filled pen: