Patient leaflet - Hulio

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Hulio 20 mg solution for injection in pre-filled syringe adalimumab

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before giving your child this medicine because it contains important information for him/her.

– Keep this leaflet. You may need to read it again.
– Your doctor will also give you a patient reminder card, which contains important safety information that you need to be aware of before your child is given Hulio and during treatment with Hulio. Keep this patient reminder card with you or your child at all times and for 4 months after your child’s last injection of Hulio.
– If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as your child’s.
– If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Hulio is and what it is used for
2. What you need to know before giving your child 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 your body’s immune (defence) system.

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

– Polyarticular juvenile idiopathic arthritis
– Enthesitis-related arthritis
– Paediatric plaque psoriasis
– Paediatric Crohn’s disease
– Paediatric uveitis

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

The target of adalimumab is another protein called tumour necrosis factor (TNFa), which is involved in the immune (defence) system and is present at increased levels in the inflammatory diseases listed above. By attaching to TNFa, Hulio decreases the process of inflammation in these diseases.

Polyarticular juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually first appears in childhood.

Hulio is used to treat polyarticular juvenile idiopathic arthritis in patients from 2 years of age. Your child may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, your child will be given Hulio to treat his/her polyarticular juvenile idiopathic arthritis.

Your doctor will decide if Hulio should be used with methotrexate or alone.

Enthesitis-related arthritis

Enthesitis-related arthritis is an inflammatory disease of the joints and the places where tendons join the bone.

Hulio is used to treat enthesitis-related arthritis in patients from 6 years of age. Your child may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, your child will be given Hulio to treat his/her enthesitis-related arthritis.

Paediatric plaque psoriasis

Plaque psoriasis is an inflammatory skin condition that causes red, flaky, crusty patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to crumble, become thickened and lift away from the nail bed which can be painful. Psoriasis is believed to be caused by a problem with the body’s immune system that leads to an increased production of skin cells.

Hulio is used to treat severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years for whom medicines applied to the skin and treatment with UV light have either not worked very well or are not suitable.

Paediatric Crohn’s disease

Crohn’s disease is an inflammatory disease of the gut.

Hulio is used to treat moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.

Your child may first be given other medicines. If these medicines do not work well enough, your child will be given Hulio to reduce the signs and symptoms of his/her disease.

Paediatric uveitis

Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.

Hulio is used to treat children with chronic non-infectious uveitis from 2 years of age with inflammation affecting the front of the eye

This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or wispy lines that move across the field of vision). Hulio works by reducing this inflammation.

Your child may first be given other medicines. If these medicines do not work well enough, your child will be given Hulio to reduce the signs and symptoms of his/her disease.

Hulio is used to treat:

– children and adolescents aged 2 to 17 years with chronic non-infectious uveitis who have inflammation affecting the front of the eye.

2. What you need to know before giving your child Hulio

Do not give Hulio

– If your child is allergic to adalimumab or any of the other ingredients of this medicine (listed in section 6).
– If your child has a severe infection, including tuberculosis (see “Warnings and precautions”). It is important that you tell your doctor if your child has symptoms of infections, e.g. fever, wounds, feeling tired, dental problems.
– If your child has moderate or severe heart failure. It is important to tell your doctor if your child has had or has a serious heart condition (see “Warnings and precautions”).

Warnings and precautions

Talk to your doctor or pharmacist before using Hulio.

Allergic Reaction

If your child has allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or a rash, do not inject more Hulio and contact your child’s doctor immediately since, in rare cases, these reactions can be life-threatening.

Infections

If your child has an infection, including long-term infection or an infection in one part of the body (e.g. leg ulcer), consult your child’s doctor before starting Hulio. If you are unsure, contact your child’s doctor.
Your child might get infections more easily while he/she is receiving Hulio treatment. This risk may increase if your child has problems with his/her lungs. These infections may be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
In rare cases, these infections may be life-threatening. It is important to tell your child’s doctor if your child gets symptoms such as fever, wounds, feeling tired or dental problems. Your child’s doctor may recommend temporarily stopping Hulio.
Tell your doctor if your child lives or travels in regions where fungal infections (for example, histoplasmosis, coccidioidomycosis or blastomycosis) are very common.
Tell your doctor if your child has had infections which keep coming back or other conditions that increase the risk of infections.
Your child and his/her doctor should pay special attention to signs of infection while your child is being treated with Hulio. It is important to tell your doctor if your child gets symptoms of infections, such as fever, wounds, feeling tired or dental problems.

Tuberculosis (TB)

As cases of tuberculosis have been reported in patients treated with adalimumab, your child’s doctor will check your child for signs and symptoms of tuberculosis before starting Hulio. This will include a thorough medical evaluation including your child’ s medical history and screening tests (for example chest X-ray and a tuberculin test). The conduct and results of these tests should be recorded on your child’s patient reminder card.
It is very important that you tell your doctor if your child has ever had tuberculosis, or if your child has been in close contact with someone who has had tuberculosis. If your child has active tuberculosis, do not use Hulio.
Tuberculosis can develop during therapy even if your child has received treatment for the prevention of tuberculosis.
If symptoms of tuberculosis (for example, cough that does not go away, weight loss, lack of energy, mild fever), or any other infection appear during or after therapy tell your doctor

immediately.

Hepatitis B virus

Tell your child’s doctor if your child is a carrier of the hepatitis B virus (HBV), if he/she has active HBV infection or if you think he/she might be at risk of contracting HBV. Your child’s doctor will test your child for HBV. Adalimumab can reactivate HBV infection in people who carry this virus. In some rare cases, especially if your child is taking other medicines that suppress the immune system, reactivation of HBV infection can be life-threatening.

Surgery or dental procedure

If your child is about to have surgery or dental procedures, tell your child’s doctor that your child is taking Hulio. The doctor may recommend temporarily stopping Hulio.

Demyelinating disease

If your child has or develops demyelinating disease (a disease that affects the insulating layer around the nerves), such as multiple sclerosis, your child’s doctor will decide if he/she should receive or continue to receive Hulio. Tell your child’s doctor immediately if your child gets symptoms like changes in vision, weakness in arms or legs or numbness or tingling in any part of the body.

Vaccination

Certain vaccines contain living but weakened forms of bacteria or viruses that may cause infections and should not be given during treatment with Hulio.
Check with your child’s doctor before he/she receives any vaccines.
It is recommended that, if possible, children be given all the scheduled vaccinations for their age before they start treatment with Hulio.
If your child received Hulio while she was pregnant, her baby may be at higher risk for getting such an infection for up to about five months after the last dose she received during her pregnancy. It is important that you tell the baby's doctors and other health care professionals about your child’s Hulio use during her pregnancy so they can decide when her baby should receive any vaccine.

Heart failure

It is important to tell your child’s doctor if your child has had or has a serious heart condition. If your child has mild heart failure and is being treated with Hulio his/her heart failure status must be closely monitored by the doctor. If your child develops new or worsening symptoms of heart failure (e. g. shortness of breath, or swelling of the feet), you must contact your child’s doctor immediately.

Fever, bruising, bleeding or looking pale

In some patients the body may fail to produce enough of the blood cells that fight infections or help your child to stop bleeding. If your child develops a fever that does not go away, or bruises or bleeds very easily or looks very pale, call your child’s doctor right away. Your child’s doctor may decide to stop treatment.

Cancer

There have been very rare cases of certain kinds of cancer in children and adults taking adalimumab or other TNFa blockers. People with more serious rheumatoid arthritis who have had the disease for a long time may have a higher than average risk of getting lymphoma (a cancer that affects the lymph system) and leukaemia (cancers that affect blood cells and bone marrow). If your child takes Hulio the risk of getting lymphoma, leukaemia, or other cancers may increase. On rare occasions, a specific and severe type of lymphoma has been seen in some patients taking adalimumab. Some of those patients were also treated with the medicines azathioprine or mercaptopurine. Tell your child’s doctor if your child is taking azathioprine or mercaptopurine with Hulio.
In addition cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks or areas of damage change appearance, tell your child’s doctor.
There have been cases of cancers, other than lymphoma, reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another TNFa blocker. If your child has COPD, or is a heavy smoker, you should discuss with your child’s doctor whether treatment with a TNF a blocker is appropriate for your child.

Autoimmune disease

On rare occasions, treatment with adalimumab could result in lupus-like syndrome. Contact your doctor if symptoms such as persistent unexplained rash, fever, joint pain or tiredness occur.

Other medicines and Hulio

Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any other medicines.

Your child should not take Hulio with medicines containing the active substances anakinra or abatacept. The combination of Hulio and anakinra or abatacept is not recommended based upon the possible increased risk for infections, including serious infections and other potential pharmacological interactions. If you have questions, please ask your child’s doctor.

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

Pregnancy and breast-feeding

Your child should consider the use of adequate contraception to prevent pregnancy and continue its use for at least 5 months after her last Hulio injection.
If your child is pregnant, thinks she may be pregnant or is planning to have a baby, ask her doctor for advice about taking this medicine.
Hulio should only be used during a pregnancy if needed.
According to a pregnancy study, there was no higher risk of birth defects when the mother had received adalimumab during pregnancy compared with mothers with the same disease who did not receive adalimumab.
Hulio can be used during breast-feeding.
If your child receives Hulio during her pregnancy, her baby may have a higher risk for getting an infection.
It is important that you tell her baby’s doctors and other health care professionals about her Hulio use during her pregnancy before the baby receives any vaccine. For more information on vaccines, see “Warnings and precautions”.

Driving and using machines

Hulio may have a minor influence on your child’s ability to drive, cycle or use machines. Room spinning sensation (vertigo) and vision disturbances may occur after taking Hulio.

Hulio contains sodium and sorbitol

Each Hulio pre-filled syringe contains 19.1 mg of sorbitol. Sorbitol is a source of fructose. If your child’s doctor has told you that your child has an intolerance to some sugars or if your child has been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your child’s doctor before you give your child this medicine.

Also this medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe, that is to say essentially ‘sodium-free’.

3. How to use Hulio

Always use this medicine exactly as your child’s doctor or pharmacist has instructed. Check with your child’s doctor or pharmacist if you are not sure about any of the instructions or if you have any questions. Your doctor may prescribe another strength of Hulio if your child needs a different dose.

Children with juvenile idiopathic arthritis

Children and adolescents from 2 to 17 years of age weighing 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 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 from 6 to 17 years of age weighing 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 weighing 30 kg or more:

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

Children or adolescents with paediatric plaque psoriasis

Children and adolescents from 4 to 17 years of age weighing 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, Thereafter the usual dose is 20 mg every other week.

Children and adolescents from 4 to 17 years of age 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.

Children and adolescents with paediatric Crohn's disease

Children and adolescents from 6 to 17 years of age weighing less than 40 kg:

The usual dose regimen is 40 mg initially (as two 20 mg injections in one day), followed by 20 mg two weeks later. If a faster response is required, your child’s doctor may prescribe an initial dose of 80 mg (as four 20 mg injections in one day) followed by 40 mg two weeks later.

Thereafter, the usual dose is 20 mg every other week. If this dose does not work well enough, your child’s doctor may increase the dose frequency to 20 mg every week.

Children and adolescents from 6 to 17 years of age weighing 40 kg or more:

The usual dose regimen is 80 mg initially (as four 20 mg injections in one day), followed by 40 mg two weeks later. If a faster response is required, your child’s doctor may prescribe an initial dose of 160 mg (as eight 20 mg injections in one day or four 20 mg injections per day for two consecutive days) followed by 80 mg (as four 20 mg injections in one day) two weeks later.

Thereafter, the usual dose is 40 mg every other week. If this dose does not work well enough, your child’s doctor may increase the dosage to 40 mg every week or 80 mg every other week.

Children and adolescents with paediatric uveitis

Children and adolescents from 2 to 17 years of age weighing less than 30 kg:

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

Your child’s doctor may also prescribe an initial dose of 40 mg (as two 20 mg injections in one day) which may be administered one week prior to the start of the usual recommended dose. Hulio is recommended for use in combination with methotrexate.

Children and adolescents from 2 to 17 years of age weighing 30 kg or more:

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

Your child’s doctor may also prescribe an initial dose of 80 mg which may be administered one week prior to the start of the usual dose of 40 mg every other week. Hulio is recommended for use in combination with methotrexate.

Method and route of administration

Hulio is administered by injection under the skin (subcutaneous use).

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

If you use more Hulio than you should

If you accidentally inject your child with Hulio more frequently than you should, call your child’s doctor or pharmacist and explain that your child has been given more than required. Always take the outer carton or the medicine with you, even if it is empty.

If you forget to use Hulio

If you forget to give your child an injection, you should inject the next dose of Hulio as soon as you remember. Then give your child’s next dose as you would have on the originally scheduled day, had you not forgotten a dose.

If your child stops using Hulio

The decision to stop using Hulio should be discussed with your child’s doctor. Your child’s symptoms may return upon stopping treatment.

If you have any further questions on the use of this medicine, ask your child’s 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 may be serious and require urgent medical treatment.

Side effects may occur up to 4 months or more after the last Hulio injection.

Seek medical attention urgently if your child develops any of the following signs of allergic reaction or heart failure:

severe rash, hives;
swollen face, hands or feet;
trouble breathing or swallowing;
shortness of breath with physical activity or upon lying down or swelling of the feet.

Tell your doctor as soon as possible , if you notice any of the following:

signs and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning on urination, feeling weak or tired or coughing;
symptoms of nerve problems such as tingling, numbness, double vision or arm or leg weakness;
signs of skin cancer such as a bump or open sore that doesn't heal;
signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, paleness.

The signs and symptoms described above can represent the side effects listed below, which have been observed with adalimumab.

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

injection site reactions (including pain, swelling, redness or itching);
respiratory tract infections (including cold, runny nose, sinus infection, throat infection, pneumonia);
headache;
abdominal (belly) pain;
nausea and vomiting;
rash;
pain in bone and muscles.

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

serious infections (including blood poisoning and influenza);
intestinal infections (including gastroenteritis);
skin infections (including cellulitis and shingles);
ear infections;
oral infections (including tooth infections and cold sores);
reproductive tract infections;
urinary tract infection;
fungal infections;
joint infections;
benign tumours;
skin cancer;
mild allergic reactions (including seasonal allergy);
dehydration;
mood swings (including depression);
anxiety;
difficulty sleeping;
sensation disorders such as tingling, prickling or numbness;
migraine;
nerve root compression (including low back pain and leg pain)
vision disturbances;
eye/eyelid inflammation or swelling;
vertigo (sensation of the room spinning);
sensation of heart beating rapidly;
high blood pressure;
skin flushing;
haematoma (collection of blood outside of blood vessels);
cough;
asthma;
shortness of breath;
gastrointestinal bleeding;
indigestion, bloating, heart burn;
acidity/acid reflux;
sicca syndrome (including dry eyes and dry mouth);
bruising;
itchy rash;
itching, inflammation of the skin (including eczema);
breaking of finger nails and toe nails;
increased sweating;
hair loss;
new or worsening psoriasis (red, flaky skin);
muscle spasms;
blood in urine;
kidney problems;
chest pain;
oedema (swelling);
fever;
reduction in blood platelets which increases risk of bleeding or bruising;
slow healing of wounds.

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

opportunistic infections (which include tuberculosis and other infections that occur when

resistance to disease is lowered);

neurological infections (including viral meningitis);
eye infections;
bacterial infections;
diverticulitis (inflammation and infection of the large intestine);
cancer;
lymphoma (cancer of the lymph system );
melanoma;
immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a condition called sarcoidosis);
vasculitis (inflammation of blood vessels);
tremor (shaking);
neuropathy (nerve damage);
stroke;
hearing loss, buzzing;
irregular heart beat;
heart problems that can cause shortness of breath or ankle swelling;
heart attack;
a sac in the wall of a major artery, inflammation and clot of a vein, blockage of a blood vessel;
lung diseases causing shortness of breath (including inflammation);
pulmonary embolism (blockage in an artery of the lung);
excessive fluid around the lung;
inflammation of the pancreas;
difficulty in swallowing;
swelling of the face (facial oedema );
gallbladder inflammation, gallbladder stones;
fatty liver (build up of fat in liver cells);
night sweats;
scarring;

abnormal muscle breakdown;

systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ systems);

sleep interruptions;

impotence;

inflammations.

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

leukaemia (cancer affecting the blood and bone marrow);
severe allergic reaction with shock;
multiple sclerosis;
nerve disorders (such as inflammation of the optic nerve to the eye, and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
heart stops pumping;
pulmonary fibrosis (scarring of the lung);
intestinal perforation (hole/tear in the intestine);
hepatitis (inflammation of the liver;
reactivation of hepatitis B;
autoimmune hepatitis (inflammation of the liver caused by the body’s own immune disease);
cutaneous vasculitis (inflammation of blood vessels in the skin);
Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash);
facial oedema (swelling of the face) associated with allergic reactions;
inflammatory skin rash;
lupus-like syndrome;
angioedema (localized swelling of the skin);
lichenoid skin reaction (itchy reddish-purple skin rash).

Not known (frequency cannot be estimated from the available data):

hepatosplenic T-cell lymphoma (a rare blood cancer);
Merkel cell carcinoma (a type of skin cancer);
Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appears as purple lesions on the skin;
liver failure;
worsening skin rash with muscle weakness;
Weight gain (for most patients, the weight gain was small).

Reporting of side effects

If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Hulio

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

Do not use this medicine after the expiry date which is stated on the label/blister/carton after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled syringe in the outer carton in order to protect from light.

Alternative storage:

When needed (for example, when you are travelling), a single Hulio pre-filled syringe may be stored at room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or discarded , even if it is returned to the refrigerator.

You should record the date when the syringe is first removed from refrigerator and the date after which it should be discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Hulio contains

– The active substance is adalimumab.
– The other ingredients are monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid and water for injections (see section 2 – Hulio contains sodium and sorbitol).

What Hulio looks like and contents of the pack

Hulio 20 mg solution for injection (injection) in pre-filled syringe is supplied as a sterile solution of 20 mg adalimumab dissolved in 0.4 ml clear or slightly opalescent, colourless to pale brownish-yellow solution.

The Hulio pre-filled syringe is made of plastic syringe with a stopper and a needle with a needle cap. Each pack contains 1 or 2 pre-filled syringes. Not all pack sizes may be marketed.

Hulio is also available as a vial for paediatric use or a pre-filled pen.

Marketing Authorisation Holder

Viatris Limited

Damastown Industrial Park

Mulhuddart

Dublin 15

DUBLIN

Ireland

Manufacturer

McDermott laboratories T/A Mylan Dublin Biologics

Newenham Court, Northern Cross, Malahide Road

Dublin 17

Ireland

Mylan Germany GmbH

Benzstraße 1

61352 Bad Homburg v. d. Höhe

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgique/Belgien

Mylan EPD bvba/sprl

Tél/Tel: + 32 (0)2 658 61 00

Lietuva

Mylan Healthcare UAB

Tel: +370 5 205 1288

Etnrapwa

Vlaíí.ian EOO^

Ten: +359 2 44 55 400

Luxembourg/Luxemburg

Mylan EPD bvba/sprl

Tel: + 32 (0)2 658 61 00

(Belgique/Belgien)

Česká republika

Mylan Healthcare CZ s.r.o.

Tel: + 420 222 004 400

Magyarország

Mylan EPD Kft

Tel: + 36 1 465 2100

Danmark

Viatris ApS

Tlf: +45 28116932

Malta

V.J. Salomone Pharma Ltd

Tel: + 356 21 22 01 74

Deutschland

Mylan Healthcare GmbH

Tel: +49 (0) 800 0700 800

Nederland

Mylan Healthcare B.V.

Tel: +31 (0)20 426 3300

Eesti

BGP Products Switzerland GmbH Eesti filiaal

Tel: + 372 6363 052

Norge

Viatris AS

Tel: + 47 66 75 33 00

EZZáňa

BGP nPOIONTA M.E.n.E.

TqX.: +30 210 9891 777

Österreich

Mylan Österreich GmbH

Tel: +43 1 86390

España

Mylan Pharmaceuticals, S.L.

Tel: + 34 900 102 712

Polska

Mylan Healthcare Sp. z o.o

Tel: + 48 22 546 64 00

France

Mylan Medical SAS

Tel: +33 1 56 64 10 70

Portugal

Mylan, Lda.

Tel: + 351 21 412 72 56

Hrvatska

Mylan Hrvatska d.o.o.

Tel: +385 1 23 50 599

Romania

BGP Products SRL

Tel: + 40 372 579 000

Ireland

Mylan Ireland Limited

Tel: +353 1 8711600

Slovenija

Mylan Healthcare d.o.o.

Tel: + 386 1 23 63 180

Ísland

Icepharma hf.

Símí: +354 540 8000

Slovenská republika

Mylan s.r.o.

Tel: +421 2 32 199 100

Italia

Mylan Italia S.r.l

Tel: + 39 02 612 46921

Suomi/Finland

Viatris Oy

Puh/Tel: +358 20 720 9555

Kúnpog

Sverige

Varnavas Hadjipanayis Ltd

Mylan AB

Tel: + 46 855 522 750

Tnk + 357 22207700

Latvija

Mylan Healthcare SIA

Tel: +371 676 055 80

United Kingdom (Northern Ireland)

Mylan IRE Healthcare Limited

Tel: +353 18711600

This leaflet was last revised in {MM/YYYY }

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www. ema europa.eu.

Instructions for use

Read the instructions carefully and follow them step by step. Your child’s doctor, nurse or other healthcare professional will show you how to inject Hulio pre-filled syringe. Ask your child’s doctor or nurse if there is anything you do not understand.

Do not allow your child to self-inject until you are sure that he/she understands how to prepare and administer the injection. After proper training, the injection can be self-administered or given by another person, for example a family member or carer.

Each pre-filled syringe is for single-use only and contains one 20 mg dose of adalimumab.

Do not mix the Hulio solution with any other medicine.

To help you remember which day(s) Hulio should be injected, it may be helpful to make a note on a calendar or in a diary.

Before you start

Find a quiet area with a well-lit, clean and flat work surface and gather all the supplies you will need to give yourself or receive the injection.

Supplies you will need:

1 pre-filled syringe
1 alcohol swab (not included in Hulio pack)
1 sharps disposal container (not included in Hulio pack)
1 gauze pad or cotton ball (not included in Hulio pack)

If you do not have all the supplies you need, ask your nurse or pharmacist.

Preparing the pre-filled syringe

The pre-filled syringes should be stored in the fridge (between 2°C to 8°C).

Take a single pre-filled syringe out of the fridge at least 30 minutes before you intend to use it to allow the contents to reach room temperature.

o DO NOT use other heat sources such as a microwave oven or hot water to warm the syringe. o DO NOT put the syringe back in the fridge after it has reached room temperature.

Check the expiry date printed on the syringe.

o DO NOT use the syringe if past the expiry date.

Check syringe to make sure the medication is at or near the Fill Marker (you may need to shake gently to see the liquid), and the liquid is clear, colourless and has no particles.

o DO NOT use the syringe if the medication is not near the Fill Marker.

o DO NOT use the syringe if the liquid is cloudy, discoloured, or has particles in it.

Injection steps

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

Step 1 – Choose and prepare injection site

Abdomen or Thighs

Hulio pre-filled syringe is for subcutaneous injection. It should be injected into the thigh or abdomen.

You should rotate and change the injection site each time, staying at least 3 cm from the previous site used.

If you are injecting into the abdomen, choose a site that is at least 5 cm away from the belly button.

DO NOT inject into skin that is red, hard, bruised, or tender.
DO NOT inject into scars or stretch marks.
If your child have psoriasis, DO NOT inject into any raised, thick, red, or scaly skin patches, or lesions.
DO NOT inject through clothes. Roll back any clothing

______________________________________________that may interfere with the inj ection site.

Step 2 – Wash hands

________Wash your hands with soap and water. _________________________________

Step 3 – Prepare injection site

Wipe the skin at the chosen injection site with an alcohol swab.

Wait for it to dry on its own, do not blow dry it.
DO NOT touch this area again before giving the inj ection

Step 4 – Uncap needle

Pull the needle cover straight off the syringe. A few drops of liquid may come out of the needle, this is normal. It is also normal to see air bubble(s).

DO NOT remove the needle cover until you are ready to inject.

Step 5 – Squeeze and hold injection site

Step 6 – Insert needle into site

Step 7 – Inject Hulio

DO NOT twist or bend the needle cover while removing it, this may damage the needle.
DO NOT touch or pull back on the plunger at any time.
DO NOT re-cap or touch the needle with your fingers, or let the needle touch anything.
DO NOT expel any air bubble(s).
DO NOT use the pre-filled syringe if dropped after uncapping.

Gently squeeze the injection site to create a raised area, and hold that area firmly.

At a 45° angle to the injection site, use a quick dart-like motion to insert the needle into the site.

Be careful to insert the needle so that it will not inject into your fingers holding the injection site.

After the needle is completely inserted, let go of the site you are squeezing.

Slowly push the plunger completely down until all the medicine is injected and the syringe is empty.

If the plunger is not pressed all the way the safety feature will not activate afterwards to cover the needle.
DO NOT move, twist, or rotate the syringe during

Pull the syringe away from the injection site at the same angle as inserted and release your thumb from the plunger.

Each pre-filled syringe has a safety feature, this will retract and cover the needle after the plunger is released. If the needle did not retract, carefully place the used syringe into a sharps container to avoid injury.

Step 9 – Dispose syringe and cap

Dispose of the used syringe and cap in an approved sharps disposal container.

Check with your healthcare provider for instructions on how to properly dispose of a

filled sharps container.

DO NOT re-use the syringe.

Package leaflet: Information for the patient

Hulio 40 mg/0.8 ml solution for injection

adalimumab

Read all of this leaflet carefully before giving your child this medicine because it contains important information for him/her.

– Keep this leaflet. You may need to read it again.
– Your doctor will also give you a patient reminder card, which contains important safety information that you need to be aware of before your child is given Hulio and during treatment with Hulio. Keep this patient reminder card with you or your child at all times and for 4 months after your child’s last injection of Hulio.
– If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as your child's.
– If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Hulio is and what it is used for
2. What you need to know before giving your child 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 your body’s immune (defence) system.

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

– polyarticular juvenile idiopathic arthritis in children aged 2–17 years;
– enthesitis-related arthritis in children aged 6–17 years;
– Crohn’s disease in children aged 6–17 years
– plaque psoriasis in children aged 4–17 years;
– hidradenitis suppurativa in adolescents aged 12–17 years;
– Ulcerative colitis in children aged 6–17 years;
– chronic non-infectious uveitis in children aged 2–17 years affecting the front of the eye.

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

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases of the joints that usually 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. Your child may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, your child will be given Hulio to treat his/her polyarticular juvenile idiopathic arthritis or enthesitis-related arthritis.

Paediatric Crohn's disease

Crohn’s disease is an inflammatory disease of the gut.

Hulio is used to treat Crohn’s disease in children aged 6 to 17 years. Your child may first be given other medicines. If these medicines do not work well enough your child will be given Hulio to reduce the signs and symptoms of his/her Crohn’ s disease.

Paediatric plaque psoriasis

Hulio is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years for whom medicines applied to the skin and treatment with UV light have either not worked very well or are not suitable.

Adolescent hidradenitis suppurativa

Hidradenitis suppurativa (sometimes called ‘acne inversa’) is a long-term and often painful inflammator Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most commonly affects specific areas of the skin, such asthe armpits, inner thighs, groin and buttocks. Scarring may also occur in affected areas.

Hulio is used to treat hidradenitis suppurativa in adolescents from 12 years of age. Hulio can reduce the number of nodules and abscesses you have, and the pain that is often associated with the disease. Patients may first be given other medicines. If these medicines do not work well enough, patients will be given Hulio.

Paediatric ulcerative colitis

Ulcerative colitis is an inflammatory disease of the large intestine. Hulio is used to treat moderate to severe ulcerative colitis in children aged 6 to 17 years. Your child may first be given other medicines. If these medicines do not work well enough, your child will be given Hulio to reduce the signs and symptoms of his/her disease.

Chronic non-infectious uveitis affecting the front of the eye

Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. This inflammation may lead to a decrease of vision and/or the presence of floaters in the eye (black dots or wispy lines that move across the field of vision). Hulio works by reducing this inflammation.

Hulio is used to treat children and adolescents aged 2 to 17 years with chronic non-infectious uveitis who have inflammation affecting the front of the eye.

2. What you need to know before giving your child Hulio

Do not give Hulio

– If your child is allergic to adalimumab or any of the other ingredients of this medicine (listed in

section 6).

– If your child has a severe infection, including tuberculosis (see “Warnings and precautions”). It

is important that you tell your doctor if your child has symptoms of infections, e.g. fever, wounds, feeling tired, dental problems.

If your child has moderate or severe heart failure. It is important to tell your doctor if your child has had or has a serious heart condition (see “Warnings and precautions”).

Warnings and precautions

Talk to your doctor or pharmacist before using Hulio.

Allergic Reaction

If your child has allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or a rash, do not inject more Hulio and contact your child’s doctor immediately since, in rare cases, these reactions can be life-threatening.

Infections

If your child has an infection, including long-term infection or an infection in one part of the body (e.g. leg ulcer), consult your child’s doctor before starting Hulio. If you are unsure, contact your child’s doctor.
Your child might get infections more easily while he/she is receiving Hulio treatment. This risk may increase if your child has problems with his/her lungs. These infections may be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning). In rare cases, these infections may be lifethreatening. It is important to tell your child’s doctor if your child gets symptoms such as fever, wounds, feeling tired or dental problems. Your child’s doctor may recommend temporarily stopping Hulio.

Tuberculosis (TB)

As cases of tuberculosis have been reported in patients treated with adalimumab, your child’s doctor will check your child for signs and symptoms of tuberculosis before starting Hulio. This will include a thorough medical evaluation including your child’ s medical history and screening tests (for example chest X-ray and a tuberculin test). The conduct and results of these tests should be recorded on your child’s patient reminder card. It is very important that you tell your child’s doctor if he/she have ever had tuberculosis, or if he/she have been in close contact with someone who has had tuberculosis. Tuberculosis can develop during therapy even if your child has had preventative treatment for tuberculosis. If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy tell your child’s doctor immediately.

Travel/recurrent infection

Tell your child’s doctor if you reside or travel in regions where fungal infections such as histoplasmosis, coccidioidomycosis or blastomycosis are common.
Tell your child’s doctor if you have a history of recurrent infections or other conditions that increase the risk of infections.

Hepatitis B virus

Tell your child’s doctor if your child is a carrier of the hepatitis B virus (HBV), if he/she has active HBV infection or if you think he/she might be at risk of contracting HBV. Your child’s doctor will test your child for HBV. Adalimumab can reactivate HBV infection in people who carry this virus. In some rare cases, especially if your child is taking other medicines that suppress the immune system, reactivation of HBV infection can be life-threatening.

Surgery or dental procedure

If your child is about to have surgery or dental procedures, tell your child’s doctor that your child is taking Hulio. The doctor may recommend temporarily stopping Hulio.

Demyelinating disease

If your child has or develops demyelinating disease (a disease that affects the insulating layer around the nerves), such as multiple sclerosis, your child’s doctor will decide if he/she should receive or continue to receive Hulio. Tell your child’s doctor immediately if your child gets symptoms like changes in vision, weakness in arms or legs or numbness or tingling in any part of the body.

Vaccination

Certain vaccines contain living but weakened forms of bacteria or viruses that may cause infections and should not be given during treatment with Hulio.
Check with your child’s doctor before he/she receives any vaccines.
It is recommended that, if possible, children be given all the scheduled vaccinations for their age before they start treatment with Hulio.
If you received Hulio while you were pregnant, your baby may be at higher risk for getting such

an infection for up to about five months after the last dose you received during pregnancy. It is important that you tell your baby's doctors and other health care professionals about your Hulio use during your pregnancy so they can decide when your baby should receive any vaccine.

Heart failure

It is important to tell your child’s doctor if your child has had or has a serious heart condition. If your child has mild heart failure and is being treated with Hulio, his/her heart failure status must be closely monitored by the doctor. If your child develops new or worsening symptoms of heart failure (e.g. shortness of breath, or swelling of the feet), you must contact your child’s doctor immediately.

Fever, bruising, bleeding or looking pale

In some patients the body may fail to produce enough of the blood cells that fight infections or help your child to stop bleeding. If your child develops a fever that does not go away, or bruises or bleeds very easily or looks very pale, call your child’s doctor right away. Your child’s doctor may decide to stop treatment.

Cancer

There have been very rare cases of certain kinds of cancer in children and adults taking adalimumab or other TNFa blockers. People with more serious rheumatoid arthritis who have had the disease for a long time may have a higher than average risk of getting lymphoma (a cancer that affects the lymph system) and leukaemia (cancers that affect blood cells and bone marrow). If your child takes Hulio the risk of getting lymphoma, leukaemia, or other cancers may increase. On rare occasions, a specific and severe type of lymphoma has been seen in some patients taking adalimumab. Some of those patients were also treated with the medicines azathioprine or mercaptopurine. Tell your child’s doctor if your child is taking azathioprine or mercaptopurine with Hulio.
In addition cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks or areas of damage change appearance, tell your child’s doctor.
There have been cases of cancers, other than lymphoma, reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another TNFa blocker. If your child has COPD, or is a heavy smoker, you should discuss with your child’s doctor whether treatment with a TNF a blocker is appropriate for your child.

Other medicines and Hulio

Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any other medicines.

Pregnancy and breast-feeding

Your child should consider the use of adequate contraception to prevent pregnancy and continue its use for at least 5 months after her last Hulio injection.
If your child is pregnant, thinks she may be pregnant or is planning to have a baby, ask her doctor for advice about taking this medicine.
Hulio should only be used during a pregnancy if needed.
According to a pregnancy study, there was no higher risk of birth defects when the mother had received adalimumab during pregnancy compared with mothers with the same disease who did not receive adalimumab.
Hulio can be used during breast-feeding.
If your child receives Hulio during her pregnancy, her baby may have a higher risk for getting an infection.
It is important that you tell her baby’s doctors and other health care professionals about her Hulio use during her pregnancy before the baby receives any vaccine. For more information on vaccines, see “Warnings and precautions”.

Driving and using machines

Hulio may have a minor influence on your child’s ability to drive, cycle or use machines. Room spinning sensation (vertigo) and vision disturbances may occur after taking Hulio.

Hulio contains sodium and sorbitol

Each Hulio vial contains 38.2 mg of sorbitol. Sorbitol is a source of fructose. If your child’s doctor has told you that your child has an intolerance to some sugars or if your child has been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your child’s doctor before you give your child this medicine.

Also this medicine contains less than 1 mmol of sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

3. How to use Hulio

Children and adolescents with polyarticular juvenile idiopathic arthritis

Children and adolescents from 2 to 17 years of age weighing 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 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 from 6 to 17 years of age weighing 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 weighing 30 kg or more:

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

Children and adolescents with Crohn's disease

Children and adolescents from 6 to 17 years of age weighing less than 40 kg:

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

Thereafter, the usual dose is 20 mg every other week. If this dose does not work well enough, your child’s doctor may increase the dose frequency to 20 mg every week.

Children and adolescents from 6 to 17 years of age weighing 40 kg or more:

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

Thereafter, the usual dose is 40 mg every other week. If this dose does not work well enough, your child’s doctor may increase the dosage 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 weighing 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, Thereafter the usual dose is 20 mg every other week.

Children and adolescents from 4 to 17 years of age 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.

Adolescents with hidradenitis suppurativa (from 12 to 17 years of age, weighing at least 30 kg)

The recommended dose of Hulio is an initial dose of 80 mg (as two 40 mg injections in one day), followed by 40 mg every other week starting one week later. If this dose does not work well enough, then your child’s doctor may increase this to 40 mg every week or 80 mg every other week.

It is recommended that your child uses an antiseptic wash daily on the affected areas during treatment with Hulio.

Children and adolescents with ulcerative colitis

Children and adolescents from 6 years of age weighing less than 40 kg

The usual dose of Hulio is 80 mg (as two 40 mg injections in one 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 of age while on 40 mg every other week, should continue their prescribed dose.

Children and adolescents from 6 years of age weighing 40 kg or more

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

Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose.

Children and adolescents with chronic non-infectious uveitis

Children and adolescents from 2 to 17 years of age weighing less than 30 kg:

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

Your child’s doctor may also prescribe an initial dose of 40 mg which may be administered one week prior to the start of the usual recommended dose.

Children and adolescents from 2 to 17 years of age weighing 30 kg or more:

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

Your child’s doctor may also prescribe an initial dose of 80 mg which may be administered one week prior to the start of the usual dose.

For patients who are prescribed a full 40 mg dose of Hulio, a 40 mg pre-filled pen and a 40 mg prefilled syringe are also available from your pharmacist.

Method and route of administration

Hulio is administered by injection under the skin (subcutaneous use).

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

If you use more Hulio than you should

If you forget to use Hulio

If your child stops using Hulio

The decision to stop using Hulio should be discussed with your child’s doctor. Your child’s symptoms may return upon stopping treatment.

If you have any further questions on the use of this medicine, ask your child’s 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 may be serious and require urgent medical treatment.

Side effects may occur up to 4 months or more after the last Hulio injection.

Seek medical attention urgently if your child develops any of the following signs of allergic reaction or heart failure:

severe rash, hives;
swollen face, hands or feet;
trouble breathing or swallowing;
shortness of breath with physical activity or upon lying down or swelling of the feet
pale complexion, dizziness, persistent fever, bruising or bleeding very easily.

Tell your doctor as soon as possible , if you notice any of the following:

signs and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning on urination, feeling weak or tired or coughing;
symptoms of nerve problems such as tingling, numbness, double vision or arm or leg weakness;
signs of skin cancer such as a bump or open sore that doesn't heal;
signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, paleness.

The signs and symptoms described above can represent the side effects listed below, which have been observed with adalimumab:

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

injection site reactions (including pain, swelling, redness or itching);
respiratory tract infections (including cold, runny nose, sinus infection, throat infection, pneumonia);
abnormal blood results;
headache;
abdominal (belly) pain;
nausea and vomiting;
rash;
pain in bone and muscles.

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

serious infections (including blood poisoning and influenza);
intestinal infections (including gastroenteritis);
skin infections (including cellulitis and shingles);
ear infections;
oral infections (including tooth infections and cold sores);
reproductive tract infections;
urinary tract infection;
fungal infections;
joint infections;
benign tumours;
skin cancer;
mild allergic reactions (including seasonal allergy);
dehydration;
mood swings (including depression);
anxiety;
difficulty sleeping;
sensation disorders such as tingling, prickling or numbness;
migraine;
nerve root compression (including low back pain and lag pain);
vision disturbances;
eye/eyelid inflammation or swelling;
vertigo (sensation of the room spinning);
sensation of heart beating rapidly;
high blood pressure;
skin flushing;
haematoma (collection of blood outside of blood vessels);
cough;
asthma;
shortness of breath;
gastrointestinal bleeding;
indigestion, bloating, heart burn;
acidity/acid reflux;
sicca syndrome (including dry eyes and dry mouth;
bruising;
itchy rash;
itching, inflammation of the skin (including eczema);
breaking of finger nails and toe nails;
increased sweating;
hair loss;
new or worsening psoriasis (red, flaky skin);
muscle spasms;
blood in urine;
kidney problems;
chest pain;
oedema (swelling);
fever;
reduction in blood platelets which increases risk of bleeding or bruising;
slow healing of wounds.

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

opportunistic infections (which include tuberculosis and other infections that occur when resistance to disease is lowered);
neurological infections (including viral meningitis);
eye infections;
bacterial infections;
diverticulitis (inflammation and infection of the large intestine);

melanoma;

lymphoma (cancer of the lymph system );

immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a condition called sarcoidosis);

vasculitis (inflammation of blood vessels);

tremor (shaking);

neuropathy (nerve damage);

stroke;

hearing loss, buzzing;

irregular heart beat;

lung diseases causing shortness of breath (including inflammation);

pulmonary embolism (blockage in an artery of the lung);

excessive fluid around the lung;

inflammation of the pancreas;

difficulty in swallowing;

gallbladder inflammation, gallbladder stones;

fatty liver (build-up of fat in liver cells);

night sweats;

scarring;

abnormal muscle breakdown;

systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ systems);

sleep interruptions,

impotence;

inflammations.

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

leukaemia (cancer affecting the blood and bone marrow);
severe allergic reaction with shock;
multiple sclerosis;
nerve disorders (such as inflammation of the optic nerve to the eye, and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
heart attack (heart stop pumping);
pulmonary fibrosis (scarring of the lung);
intestinal perforation (hole/tear in the intestine);
hepatitis (inflammation of the liver);
reactivation of hepatitis B;
autoimmune hepatitis (inflammation of the liver caused by the body’s own immune disease);
cutaneous vasculitis (inflammation of blood vessels in the skin);
Stevens-Johnson syndrome;
facial oedema (swelling of the face) associated with allergic reactions
inflammatory skin rash;
lupus-like syndrome;
angioedema (localized swelling of the skin);
lichenoid skin reaction (itchy reddish-purple skin rash).

Not known (frequency cannot be estimated from the available data):

hepatosplenic T-cell lymphoma (a rare blood cancer);
Merkel cell carcinoma (a type of skin cancer);
Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appears as purple lesions on the skin;
liver failure;
worsening skin rash with muscle weakness;
weight gain (for most patients, the weight gain was small).

Reporting of side effects

If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the national reporting system listed i. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Hulio

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

Do not use this medicine after the expiry date which is stated on the label/ carton after EXP. The expiry date refers to the last day of that month.

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

Keep the vial in the outer carton in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Hulio contains

– The active substance is adalimumab
– The other ingredients are monosodium glutamate, sorbitol, methionine, polysorbate 80, hydrochloric acid and water for injections (see section 2 – Hulio contains sodium and sorbitol).

What Hulio looks like and contents of the pack

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

The Hulio vial is a glass vial with a rubber stopper. Hulio is supplied as packs containing 1 or 2 boxes. Each box contains 1 vial, 1 sterile injection syringe, 1 sterile needle, 1 sterile vial adapter and 2 alcohol pads.

Hulio is also available as a pre-filled syringe or a pre-filled pen.

Marketing Authorisation Holder

Viatris Limited

Damastown Industrial Park

Mulhuddart

Dublin 15

DUBLIN

Ireland

Manufacturer

McDermott laboratories T/A Mylan Dublin Biologics

Newenham Court, Northern Cross, Malahide Road

Dublin 17

Ireland

Mylan Germany GmbH

Benzstraße 1

61352 Bad Homburg v. d. Höhe

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgique/Belgien

Mylan EPD bvba/sprl

Tél/Tel: + 32 (0)2 658 61 00

Lietuva

Mylan Healthcare UAB

Tel: +370 5 205 1288

Etnrapaa

MannaH EOO^

Ten: +359 2 44 55 400

Luxembourg/Luxemburg

Mylan EPD bvba/sprl

Tel: + 32 (0)2 658 61 00

(Belgique/Belgien)

Česká republika

Mylan Healthcare CZ s.r.o.

Tel: + 420 222 004 400

Magyarorszag

Mylan EPD Kft

Tel: + 36 1 465 2100

Danmark

Viatris ApS

Tlf: +45 28116932

Malta

V.J. Salomone Pharma Ltd

Tel: + 356 21 22 01 74

Deutschland

Mylan Healthcare GmbH

Tel: +49 (0) 800 0700 800

Nederland

Mylan Healthcare B.V.

Tel: +31 (0)20 426 3300

Eesti

BGP Products Switzerland GmbH Eesti filiaal

Tel: + 372 6363 052

Norge

Viatris AS

Tel: + 47 66 75 33 00

EXXáSa

BGP nPOIONTA M.E.n.E.

T|X.: +30 210 9891 777

Österreich

Mylan Österreich GmbH

Tel: +43 1 86390

España

Mylan Pharmaceuticals, S.L.

Tel: + 34 900 102 712

Polska

Mylan Healthcare Sp. z o.o

Tel: + 48 22 546 64 00

France

Mylan Medical SAS

Tel: +33 1 56 64 10 70

Portugal

Mylan, Lda.

Tel: + 351 21 412 72 56

Hrvatska

Mylan Hrvatska d.o.o.

Tel: +385 1 23 50 599

Romania

BGP Products SRL

Tel: + 40 372 579 000

Ireland

Mylan Ireland Limited

Tel: +353 1 8711600

Slovenija

Mylan Healthcare d.o.o.

Tel: + 386 1 23 63 180

Ísland

Icepharma hf.

Símí: +354 540 8000

Slovenská republika

Mylan s.r.o.

Tel: +421 2 32 199 100

Italia

Mylan Italia S.r.l

Tel: + 39 02 612 46921

Suomi/Finland

Viatris Oy

Puh/Tel: +358 20 720 9555

Kúnpog

Varnavas Hadjipanayis Ltd

Tnk + 357 22207700

Sverige

Mylan AB

Tel: + 46 855 522 750

Latvija

Mylan Healthcare SIA

Tel: +371 676 055 80

United Kingdom (Northern Ireland)

Mylan IRE Healthcare Limited

Tel: +353 18711600

This leaflet was last revised in {MM/YYYY }

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www. ema europa.eu.

Instructions for use

Read the instructions carefully and follow them step by step. Your child’s doctor, nurse or other healthcare professional will show you how to prepare the injection and give it to your child. They will also tell you the prescribed amount (volume).

Do not attempt to give your child an injection until you are sure that you understand how to do this. After proper training, the injection can be self-administered or given by another person, for example a family member or carer.

Each vial contains one 40 mg dose of adalimumab.

Do not mix any other medicine into the same syringe or vial with the Hulio solution.

To help you remember which day(s) Hulio should be injected, it may be helpful to make a note on a calendar or in a diary.

Before you start

Make sure you know the prescribed amount. If you don’t know this, STOP HERE and ask your child’s doctor.

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

Supplies you will need:

1 box of Hulio vial for paediatric use
1 sharps disposal container (not included in Hulio pack)
1 gauze pad or cotton ball (not included in Hulio pack)

If you do not have all the supplies you need, ask your nurse or pharmacist.

Preparing the Hulio injection

Each Hulio single vial box will contain:

1 syringe (1)
1 vial adapter (2)
1 vial of Hulio solution (3)
2 alcohol pads (4)
1 needle (5)

Hulio packs should be stored in the fridge (between 2 to 8°C) until needed for use.

Take a single vial box out of the fridge at least 30 minutes before you intend to use it to allow the contents to reach room temperature. If there is a second box in the Hulio pack for a future injection, place it back in the refrigerator immediately.

o DO NOT use other heat sources such as a microwave oven or hot water to warm the vial.

o DO NOT put the vial back in the fridge after it has reached room temperature.

Check the expiry date printed on the vial.

o DO NOT use the vial if past the expiry date.

Check the solution in the vial is clear, colourless and has no particles.

o DO NOT use the vial if the solution is cloudy, discoloured, or has particles in it.

Injection steps

Follow the steps below carefully each time you inject Hulio:

Step 1 – Choose and prepare injection site

Hulio is for subcutaneous injection. It should be injected into the thigh or abdomen.

Abdomen or Thighs

You should rotate and change the injection site each time, staying at least 3 cm from the previous site used.

If you are injecting into the abdomen, choose a site that is at least 5 cm away from the belly button.

DO NOT inject into skin that is red, hard, bruised, or tender.
DO NOT inject into scars or stretch marks.
If your child has psoriasis, DO NOT inject into any raised, thick, red, or scaly skin patches, or lesions.
DO NOT inject through clothes. Roll back any clothing that
DO NOT touch the vial stopper after wiping with the alcohol pad.__________________________________________________________
If the white plunger rod is pulled out of the syringe, discard the syringe and

Step 7 – Attach syringe to vial adapter and push plunger rod

Hold the syringe on the graduated area and remove it from the packaging.

DO NOT hold the syringe by the white plunger rod.

Insert the syringe tip into the vial adapter and twist it clockwise until firmly attached.

DO NOT over-tighten.

| Push the plunger rod all the way down. This step is important to get the proper

dose.

Step 8 – Pull plunger to draw dose + 0.1 ml

Keep the plunger rod pressed down and turn the connected syringe and vial M upside down.

SLOWLY pull the plunger rod to draw the Hulio solution into the syringe. Pull the plunger to 0.1 ml beyond the prescribed dose (for example, if the prescribed dose is 0.5 ml, pull the white plunger rod to 0.6 ml).

You will set the volume to the prescribed dose in a later step.

If there are air bubbles in the syringe, push the plunger rod all the way back in to push the solution back into the vial.

Repeat this step to draw the solution back into the syringe again, pulling the plunger rod SLOWLY.

If you see air bubbles in the solution again, you may repeat this step up to

3 times.

DO NOT hold the syringe by the plunger rod.
DO NOT shake the syringe.
If the white plunger rod is pulled out of the syringe, discard the syringe and contact your Hulio provider for a replacement. DO NOT try to reinsert the white plunger rod.

Step 9 – Detach syringe from vial adapter and attach needle

Remove the vial adapter by twisting it off the syringe.

DO NOT touch the top of the syringe.
DO NOT hold the syringe by the white plunger rod.

Attach the needle to the syringe by inserting the syringe tip into the yellow syringe connector on the needle. Twist the syringe until the needle is firmly attached.

Once syringe is firmly attached to the needle, remove the clear needle packaging.

Dose Preparation

Step 10 – Flip down pink needle cover and remove needle cap

Hold the syringe with the needle pointing up.

Flip down the pink needle cover and remove the needle cap by pulling it straight up. DO NOT twist the needle cap.

DO NOT touch the needle.
DO NOT put the needle cap back on the needle after it has been removed.

Step 11 – Check and set prescribed dose

Hold the syringe at eye-level with the needle pointing up to see the amount of solution clearly. Recheck the doctor’s prescription for the correct prescribed amount.

Push the plunger rod gently in until the syringe contains the prescribed amount. Excess solution may come out of the needle while pushing the plunger rod in. Be careful not to squirt the solution into your eye.

Gently place the syringe on a clean, flat surface.

DO NOT wipe the needle or syringe.

Injecting Hulio

Step 12 – Prepare injection site

Wipe the skin at the chosen injection site with a new alcohol swab.

Wait for the skin to dry on its own, do not blow it dry.
DO NOT touch this area again before giving the inj ection.
DO NOT rub the injection site.

Gently flip the pink needle cover over the needle and snap into place. Set the syringe with covered needle on the work surface.

DO NOT put the clear needle cap back on the needle.

Throwing away supplies

Each vial, syringe, vial adapter and needle are for single-use only. These must NEVER be re-used.

Put the used syringe, needle, vial and vial adapter in a sharps disposal container after use.

DO NOT throw the sharps container in your household bin.
DO NOT recycle your used sharps disposal container.
Always keep your sharps container out of the sight and reach of children.
Throw away all other used items and empty packaging into your regular household waste.

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 also give you a patient reminder card, which contains important safety information that you need to be aware of before you are given Hulio and during treatment with Hulio. Keep this patient reminder card with you at all times and for 4 months after your last injection of 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. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Hulio is and what it is used for
2. What you need to know before you use 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 your body’s immune (defence) system.

Hulio is intended 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 ingredient in Hulio, adalimumab, is a monoclonal antibody. Monoclonal antibodies are proteins that attach to a specific target in the body.

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 first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, you will be given Hulio to treat your rheumatoid arthritis.

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

Hulio can slow down the damage to the cartilage and bone of the joints caused by the disease and improve physical function.

Usually, Hulio is used with methotrexate. If your doctor considers that methotrexate is inappropriate, Hulio can be given alone.

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis

Polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis are inflammatory diseases of the joints that usually 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 first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, you will be given 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 of 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 given other medicines. If these medicines do not work well enough, you will be given Hulio to reduce the signs and symptoms of your 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 slow down the damage to the cartilage and bone of the joints caused by the disease and improve physical function.

Plaque psoriasis in adults and children

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 for whom medicines applied to the skin and treatment with UV light have either not worked very well or are not suitable.

Hidradenitis suppurativa in adults and adolescents

Hidradenitis suppurativa (sometimes called ‘acne inversa’) is a long-term and often painful inflammatory skin disease. Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus. It most commonly affects specific areas of the skin, such as under the breasts, the armpits, inner thighs, groin and buttocks. Scarring may also occur in 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 often associated with the disease. You may first be given other medicines. If these medicines do not work well enough, you will be given Hulio.

Crohn’s disease in adults and children

Crohn’s disease is an inflammatory disease of the gut.

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 given other medicines. If you do not respond well enough to these medicines, you will be given Hulio to reduce the signs and symptoms of your Crohn’s disease.

Ulcerative colitis in adults and children

Ulcerative colitis is an inflammatory disease of the bowel.

Hulio is used to treat ulcerative colitis in adults and children aged 6 to 17 years. If you have ulcerative colitis you will first be given other medicines. If these medicines do not work well enough, you will be given Hulio to reduce the signs and symptoms of your disease.

Non-infectious uveitis in adults and children

Hulio is used to treat:

– adults with non-infectious uveitis with inflammation affecting the back of the eye.
– children and adolescents aged 2 to 17 years with chronic non-infectious uveitis who have inflammation affecting the front of the eye.

2. What you need to know before you use 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 severe infection, including tuberculosis (see “Warnings and precautions”). It is important that you tell your doctor if you have symptoms of infections, e.g. fever, wounds, feeling tired, dental problems.
– If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions

Talk to your doctor or pharmacist before using Hulio.

Allergic Reaction

If you have allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or a rash, do not inject more Hulio and contact your doctor immediately since, in rare cases, these reactions can be life-threatening.

Infections

If you have an infection, including long-term infection or an infection in one part of the body (e.g. leg ulcer), consult your doctor before starting Hulio. If you are unsure, contact your doctor.
You might get infections more easily while you are receiving Hulio treatment. This risk may increase if your lung function is reduced. These infections may be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning). In rare cases, these infections may be lifethreatening. It is important to tell your doctor if you get symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may recommend temporarily stopping Hulio.

Tuberculosis (TB)

As cases of tuberculosis have been reported in patients treated with adalimumab, your doctor will check you for signs and symptoms of tuberculosis before starting Hulio. This will include a thorough medical evaluation including your medical history and screening tests (for example chest X-ray and a tuberculin test). The conduct and results of these tests should be recorded on your patient reminder card. It is very important that you tell your doctor if you have ever had tuberculosis, or if you have been in close contact with someone who has had tuberculosis. Tuberculosis can develop during therapy even if you have had preventative treatment for tuberculosis. If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy tell your doctor immediately.

Travel/recurrent infection

Tell your doctor if you reside or travel in 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 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 active HBV infection or if you think you might be at risk of contracting HBV. Your doctor will test you for HBV. Adalimumab can reactivate HBV infection in people who carry this virus. In some rare cases, especially if you are taking other medicines that suppress the immune system, reactivation of HBV infection can be life-threatening.

Age over 65 years

If you are over 65 years you may be more susceptible to infections while taking Hulio. You and your doctor should pay special attention to signs of infection while you are being treated with Hulio. It is important to tell your doctor if you get symptoms of infections, such as fever, wounds, feeling tired or dental problems.

Surgery or dental procedure

If you are about to have surgery or dental procedures, tell your doctor that you are taking Hulio. Your doctor may recommend temporarily stopping Hulio.

Demyelinating disease

If you have or develop demyelinating disease (a disease that affects the insulating layer around the nerves), such as multiple sclerosis, your doctor will decide if you should receive or continue to receive Hulio. Tell your doctor immediately if you get symptoms like changes in your vision, weakness in your arms or legs or numbness or tingling in any part of the body.

Vaccination

Certain vaccines contain living but weakened forms of bacteria or viruses that may cause infections and should not be given during treatment with Hulio.
Check with your doctor before you receive any vaccines.
It is recommended that, if possible, children be given all the scheduled vaccinations for their age

before they start treatment with Hulio.

If you received Hulio while you were pregnant, your baby may be at higher risk for getting such

Heart failure

It is important to tell your doctor if you have had or have a serious heart condition. If you have mild heart failure and you are being treated with Hulio your heart failure status must be closely monitored by your doctor. If you develop new or worsening symptoms of heart failure (e. g. shortness of breath, or swelling of your feet), you must contact your doctor immediately.

Fever, bruising, bleeding or looking pale

In some patients the body may fail to produce enough of the blood cells that fight infections or help you to stop bleeding. If you develop a fever that does not go away, or you bruise or bleed very easily or look very pale, call your doctor right away. Your doctor may decide to stop treatment.

Cancer

There have been very rare cases of certain kinds of cancer in children and adults taking adalimumab or other TNFa blockers. People with more serious rheumatoid arthritis who have had the disease for a long time may have a higher than average risk of getting lymphoma (a cancer that affects the lymph system) and leukaemia (cancers that affect blood cells and bone marrow). If you take Hulio the risk of getting lymphoma, leukaemia, or other cancers may increase. On rare occasions, a specific and severe type of lymphoma has been seen in some patients taking adalimumab. Some of those patients were also treated with the medicines azathioprine or mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hulio.
In addition cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If new areas of damaged skin appear during or after treatment or if existing marks or areas of damage change appearance, tell your doctor.
There have been cases of cancers, other than lymphoma, reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another TNFa blocker. If you have COPD, or you are a heavy smoker, you should discuss with your doctor whether treatment with a TNFa blocker is appropriate for you.

Children and adolescents

Do not give Hulio to children with polyarticular juvenile idiopathic arthritis and chronic non-infectious uveitis below the age of 2 years.
Do not give Hulio to children with enthesitis-related arthritis and Crohn's disease below the age of 6 years.
Do not give Hulio to children with plaque psoriasis below the age of 4 years.
Do not give Hulio to children with hidradenitis suppurativa below the age of 12 years.
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 taking, have recently taken or might take any other medicines.

You should not take Hulio with medicines containing the active substances anakinra or abatacept. The combination of Hulio and anakinra or abatacept is not recommended based upon the possible increased risk for infections, including serious infections and other potential pharmacological interactions. If you have questions, please ask your doctor.

Pregnancy and breast-feeding

You should consider the use of adequate contraception to prevent pregnancy and continue its use for at least 5 months after the last Hulio injection.
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice about taking this medicine.
Hulio should only be used during a pregnancy if needed.
According to a pregnancy study, there was no higher risk of birth defects when the mother had received adalimumab during pregnancy compared with mothers with the same disease who did not receive adalimumab.
Hulio can be used during breast-feeding.
If you received Hulio during your pregnancy, your baby may have a higher risk for getting an

infection.

It is important that you tell your baby’s doctors and other health care professionals about your Hulio use during your pregnancy before the baby receives any vaccine. For more information on vaccines see the “Warnings and precautions”.

Driving and using machines

Hulio may have a minor influence on your ability to drive, cycle or use machines. Room spinning sensation (vertigo) and vision disturbances may occur after taking 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 that you (or your child) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you (or your child) take or receive this medicine.

Also this medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe, that is to say essentially ‘sodium-free’.

3. How to use Hulio

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Your doctor may prescribe another strength of Hulio if you need a different dose.

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

The usual dose for adults with these conditions is 40 mg adalimumab given every two weeks as a single dose.

In rheumatoid arthritis, methotrexate is continued while using Hulio. If your doctor determines that methotrexate is inappropriate, Hulio can be given alone.

If you have rheumatoid arthritis and you do not receive methotrexate with your Hulio therapy, your doctor may decide to give you 40 mg adalimumab every week or 80 mg every other week.

Children and adolescents with polyarticular juvenile idiopathic arthritis

Children and adolescents from 2 to 17 years of age weighing 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 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 from 6 to 17 years of age weighing 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 weighing 30 kg or more:

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

Adults with psoriasis

The usual dose for adults with psoriasis is an initial dose of 80 mg (as two 40 mg injections in one day), followed by 40 mg given every other week starting one week after the initial dose. You should continue to inject Hulio for as long as your doctor has told you. If this dose does not work well enough, your doctor may increase the dose frequency 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 weighing 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, Thereafter the usual dose is 20 mg every other week.

Children and adolescents from 4 to 17 years of age 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 dose regimen for hidradenitis suppurativa is an initial dose of 160 mg (as four 40 mg injections in one day or two 40 mg injections per day for two consecutive days), followed by an 80 mg dose (as two 40 mg injections on the same day) two weeks later. After two further weeks, continue with a dose of 40 mg every week or 80 mg every other week, as prescribed by your doctor.

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

Adolescents with hidradenitis suppurativa from 12 to 17 years of age weighing at least 30 kg

The recommended dose of Hulio is an initial dose of 80 mg (two 40 mg injections in one day), followed by 40 mg every other week starting one week later. If this dose does not work well enough then your child’s doctor may increase this to 40 mg every week or 80 mg every other week.

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

Adults with Crohn’s disease

The usual dose regimen for Crohn’s disease is 80 mg (as two 40 mg injections in 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 in one day or two 40 mg injections per day for two consecutive days), followed by 80 mg (as two 40 mg injections in one day) two weeks later, and thereafter as 40 mg every other week. If this dose does not work well enough, your doctor may increase the dose frequency 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 weighing less than 40 kg:

The usual dose regimen 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 two 40 mg injections in one day) followed by 40 mg two weeks later.

Thereafter, the usual dose is 20 mg every other week. If this dose does not work well enough, your doctor may increase the dose frequency to 20 mg every week.

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

The usual dose regimen is 80 mg (as two 40 mg injections in 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 in one day or as two 40 mg injections per day for two consecutive days) followed by 80 mg (as two 40 mg injections in one day) two weeks later.

Thereafter, the usual dose is 40 mg every other week. If this dose does not work well enough, your doctor may increase the dosage frequency to 40 mg every week or 80 mg every other week.

Patients requiring a dose less than 40 mg should use the 40 mg vial presentation of Hulio.

Adults with ulcerative colitis

The usual Hulio dose for adults with ulcerative colitis is 160 mg initially (given as four 40 mg injections in one day, or as two 40 mg injections per day for two consecutive days) followed by 80 mg (as two 40 mg injections in one day) two weeks later, and then 40 mg every other week. If this dose does not work well enough, your doctor may increase the dose frequency to 40 mg every week or 80 mg every other week.

Children or adolescent with ulcerative colitis

Children and adolescents from 6 years of age weighing less than 40 kg

The usual dose of Hulio is 80 mg (as two 40 mg injections in one 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 of age while on 40 mg every other week, should continue their prescribed dose.

Children and adolescents from 6 years of age weighing 40 kg or more

Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose.

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

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

In non-infectious uveitis, corticosteroids or other medicines that influence the immune system may be continued while using Hulio. Hulio can also be given alone.

Children and adolescents with chronic non-infectious uveitis

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

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

Your child’s doctor may also prescribe an initial dose of 40 mg which may be administered one week prior to the start of the usual recommended dose.

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

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

Your child’s doctor may also prescribe an initial dose of 80 mg which may be administered one week prior to the start of the usual recommended dose.

For patients who are prescribed a dose less than 40 mg, Hulio 40 mg/0.8 ml solution for injection in a vial (available from your pharmacist) should be used.

Method and route of administration

Hulio is administered by injection under the skin (subcutaneous use).

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

If you use more Hulio than you should

If you accidentally inject Hulio more frequently than you should, call your doctor or pharmacist and explain that you have taken more than required. Always take the outer carton of the medicine with you, even if it is empty.

If you forget to use Hulio

If you forget to give yourself an injection, you should inject the next dose of Hulio as soon as you remember. Then take your next dose as you would have on your originally scheduled day, had you not forgotten a dose.

If you stop using Hulio

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

If you have any further questions on the use of this medicine, 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 may be serious and require urgent medical treatment.

Side effects may occur up to 4 months or more after the last Hulio injection.

Seek medical attention urgently if you develop any of the following signs of allergic reaction or heart failure:

severe rash, hives;
swollen face, hands or feet;
trouble breathing or swallowing;
shortness of breath with physical activity or upon lying down or swelling of the feet;
pale complexion, dizziness, persistent fever, bruising or bleeding very easily.

Tell your doctor as soon as possible , if you notice any of the following:

signs and symptoms of infection such as fever, feeling sick, wounds, dental problems, burning on urination, feeling weak or tired or coughing;
symptoms of nerve problems such as tingling, numbness, double vision or arm or leg weakness;
signs of skin cancer such as a bump or open sore that doesn't heal;
signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, paleness.

The signs and symptoms described above can represent the side effects listed below, which have been observed with adalimumab:

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

injection site reactions (including pain, swelling, redness or itching);
respiratory tract infections (including cold, runny nose, sinus infection, throat infection, pneumonia);
abnormal blood results;
headache;
abdominal (belly) pain;
nausea and vomiting;
rash;
pain in bone and muscles.

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

serious infections (including blood poisoning and influenza);
intestinal infections (including gastroenteritis);
skin infections (including cellulitis and shingles);
ear infections;
oral infections (including tooth infections and cold sores);
reproductive tract infections;
urinary tract infection;
fungal infections;
joint infections;
benign tumours;
skin cancer;
mild allergic reactions (including seasonal allergy);
dehydration;
mood swings (including depression);
anxiety;
difficulty sleeping;
sensation disorders such as tingling, prickling or numbness;
migraine;
nerve root compression (including low back pain and leg pain);
vision disturbances;
eye/eyelid inflammation or swelling;
vertigo (sensation of the room spinning);
sensation of heart beating rapidly;
high blood pressure;
skin flushing;
haematoma (collection of blood outside of blood vessels);
cough;
asthma;
shortness of breath;
gastrointestinal bleeding;
indigestion, bloating, heart burn;
acidity/acid reflux;
sicca syndrome (including dry eyes and dry mouth;
bruising;
itchy rash;
itching, inflammation of the skin (including eczema);
breaking of finger nails and toe nails;
increased sweating;
hair loss;
new or worsening psoriasis (red, flaky skin);
muscle spasms;
blood in urine;
kidney problems;
chest pain;
oedema (swelling);
fever;
reduction in blood platelets which increases risk of bleeding or bruising
slow healing of wounds.

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

opportunistic infections (which include tuberculosis and other infections that occur when resistance to disease is lowered);
neurological infections (including viral meningitis);
eye infections;
bacterial infections;
diverticulitis (inflammation and infection of the large intestine);

melanoma;

lymphoma (cancer of the lymph system);

immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a condition called sarcoidosis);

vasculitis (inflammation of blood vessels);

tremor (shaking);

neuropathy (nerve damage);

stroke;

hearing loss, buzzing;

irregular heart beat;

lung diseases causing shortness of breath (including inflammation);

pulmonary embolism (blockage in an artery of the lung);

excessive fluid around the lung;

inflammation of the pancreas;

difficulty in swallowing;

gallbladder inflammation, gallbladder stones;

fatty liver (build up of fat in liver cells);

night sweats;

scarring;

abnormal muscle breakdown;

systemic lupus erythematosus (including inflammation of skin, heart, lung, joints and other organ systems);

sleep interruptions;

impotence;

inflammations.

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

leukaemia (cancer affecting the blood and bone marrow);
severe allergic reaction with shock;
multiple sclerosis;
nerve disorders (such as inflammation of the optic nerve to the eye, and Guillain-Barré syndrome, a condition that may cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
heart attack heart stop pumping);
pulmonary fibrosis (scarring of the lung);
intestinal perforation( (hole/tear in the intestine);
hepatitis (inflammation of the liver);
reactivation of hepatitis B;
autoimmune hepatitis (inflammation of the liver caused by the body’s own immune disease);
cutaneous vasculitis (inflammation of blood vessels in the skin);
Stevens-Johnson syndrome;
Facial oedema (swelling of the face) associated with allergic reactions
inflammatory skin rash;
lupus-like syndrome;
angioedema (localized swelling of the skin);
lichenoid skin reaction (itchy reddish-purple skin rash).

Not known (frequency cannot be estimated from the available data):

hepatosplenic T-cell lymphoma (a rare blood cancer);
Merkel cell carcinoma (a type of skin cancer);
Kaposi’ s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s

sarcoma most commonly appears as purple lesions on the skin;

liver failure;
worsening skin rash with muscle weakness;

weight gain (for most patients, the weight gain was small).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the national reporting system listed i. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Hulio

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

Do not use this medicine after the expiry date which is stated on the label/blister/carton after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled syringe in the outer carton in order to protect from light.

Alternative Storage :

When needed (for example when you are travelling), a single Hulio pre-filled syringe may be stored at room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once removed from the refrigerator for room temperature storage, the syringe must be used within 14 days or discarded , even if it is returned to the refrigerator.

You should record the date when the syringe is first removed from refrigerator, and the date after which it should be discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Hulio contains

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

What Hulio looks like and contents of the pack

Hulio 40 mg solution for injection (injection) in pre-filled syringe is supplied as a sterile solution of 40 mg adalimumab dissolved in 0.8 ml clear or slightly opalescent, colourless to pale brownish-yellow solution (see section 2 – Hulio contains sodium and sorbitol).

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

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

Not all pack sizes may be marketed.

Hulio is also available as a vial for paediatric use or a pre-filled pen.

Marketing Authorisation Holder

Viatris Limited

Damastown Industrial Park

Mulhuddart

Dublin 15

DUBLIN

Ireland

Manufacturer

McDermott laboratories T/A Mylan Dublin Biologics

Newenham Court, Northern Cross, Malahide Road

Dublin 17

Ireland

Mylan Germany GmbH

Benzstraße 1

61352 Bad Homburg v. d. Höhe

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Mylan EPD bvba/sprl

Tél/Tel: + 32 (0)2 658 61 00

Lietuva

Mylan Healthcare UAB

Tel: +370 5 205 1288

E’b.arapufl

MannaH EOO^

Ten: +359 2 44 55 400

Luxembourg/Luxemburg

Mylan EPD bvba/sprl

Tel: + 32 (0)2 658 61 00

(Belgique/Belgien)

Česká republika

Mylan Healthcare CZ s.r.o.

Tel: + 420 222 004 400

Magyarorszag

Mylan EPD Kft

Tel: + 36 1 465 2100

Danmark

Viatris ApS

Tlf: +45 28116932

Malta

V.J. Salomone Pharma Ltd

Tel: + 356 21 22 01 74

Deutschland

Mylan Healthcare GmbH

Tel: +49 (0) 800 0700 800

Nederland

Mylan Healthcare B.V.

Tel: +31 (0)20 426 3300

Eesti

BGP Products Switzerland GmbH Eesti filiaal

Tel: + 372 6363 052

Norge

Viatris AS

Tel: + 47 66 75 33 00

EXXáóa

BGP nPOÏONTA M.E.n.E.

T|X.: +30 210 9891 777

Österreich

Mylan Österreich GmbH

Tel: +43 1 86390

España

Mylan Pharmaceuticals, S.L.

Tel: + 34 900 102 712

Polska

Mylan Healthcare Sp. z o.o

Tel: + 48 22 546 64 00

France

Mylan Medical SAS

Tel: +33 1 56 64 10 70

Portugal

Mylan, Lda.

Tel: + 351 21 412 72 56

Hrvatska

Mylan Hrvatska d.o.o.

Tel: +385 1 23 50 599

Romania

BGP Products SRL

Tel: + 40 372 579 000

Ireland

Mylan Ireland Limited

Tel: +353 1 8711600

Slovenija

Mylan Healthcare d.o.o.

Tel: + 386 1 23 63 180

Ísland

Icepharma hf.

Símí: +354 540 8000

Slovenská republika

Mylan s.r.o.

Tel: +421 2 32 199 100

Italia

Mylan Italia S.r.l

Tel: + 39 02 612 46921

Suomi/Finland

Viatris Oy

Puh/Tel: +358 20 720 9555

Kúnpog

Varnavas Hadjipanayis Ltd

Tnk + 357 22207700

Sverige

Mylan AB

Tel: + 46 855 522 750

Latvija

Mylan Healthcare SIA

Tel: +371 676 055 80

United Kingdom (Northern Ireland)

Mylan IRE Healthcare Limited

Tel: +353 18711600

This leaflet was last revised in {MM/YYYY }

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www. ema europa.eu.

Instructions for use

Read the instructions carefully and follow them step by step. Your doctor, nurse or other healthcare professional will first show you how to inject Hulio pre-filled syringe. Ask your doctor or nurse if there is anything you do not understand.

Do not attempt to self-inject until you are sure that you understand how to prepare and administer the injection. After proper training, the injection can be self-administered or given by another person, for example a family member or carer.

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

Do not mix the Hulio solution with any other medicine.

To help you remember which day(s) of the week Hulio should be injected, it may be helpful to make a note on a calendar or in a diary.

Before you start

Find a quiet area with a well-lit, clean and flat work surface and gather all the supplies you will need to give yourself or receive the injection.

Supplies you will need:

1 pre-filled syringe
1 alcohol swab (not included in Hulio pack)
1 sharps disposal container (not included in Hulio pack)
1 gauze pad or cotton ball (not included in Hulio pack)

If you do not have all the supplies you need, ask your nurse or pharmacist.

Preparing the pre-filled syringe

The pre-filled syringes should be stored in the fridge (between 2°C to 8°C).

Take a single pre-filled syringe out of the fridge at least 30 minutes before you intend to use it to allow the contents to reach room temperature.

o DO NOT use other heat sources such as a microwave oven or hot water to warm the syringe.

o DO NOT put the syringe back in the fridge after it has reached room temperature.

Check the expiry date printed on the syringe.

o DO NOT use the syringe if past the expiry date.

Check syringe to make sure the medication is at or near the Fill Marker (you may need to shake gently to see the liquid), and the liquid is clear, colourless and has no particles.

o DO NOT use the syringe if the medication is not near the Fill Marker.

o DO NOT use the syringe if the liquid is cloudy, discoloured, or has particles in it.

Injection steps

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

Step 1 – Choose and prepare injection site

Abdomen or Thighs

Hulio pre-filled syringe is for subcutaneous injection. It should be injected into the thigh or abdomen.

You should rotate and change your injection site each time, staying at least 3 cm from the previous site used.

If you are injecting into the abdomen, choose a site that is at least 5 cm away from the belly button.

DO NOT inject into skin that is red, hard, bruised, or tender.
DO NOT inject into scars or stretch marks.
If you have psoriasis, DO NOT inject into any raised, thick, red, or scaly skin patches, or lesions.
DO NOT inject through clothes. Roll back any clothing
Wait for it to dry on its own, do not blow dry it.
DO NOT touch this area again before giving the inj ection.

Step 4 – Uncap needle

Pull the needle cover straight off the syringe. A few drops of liquid may come out of the needle, this is normal. It is also normal to see air bubble(s).

DO NOT remove the needle cover until you are ready to inject.
DO NOT twist or bend the needle cover while removing it, this may damage the needle.
DO NOT touch or pull back on the plunger at any time.

DO NOT re-cap or touch the needle with your fingers, or let the needle touch anything. DO NOT expel any air bubble(s). DO NOT use the pre-filled syringe if dropped after

Step 5 – Squeeze and hold injection site

Step 6 – Insert needle into site

uncapping.

Gently squeeze the injection site to create a raised area, and hold that area firmly.

At a 45° angle to the injection site, use a quick dart-like motion to insert the needle into the site.

Be careful to insert the needle so that it will not inject into your fingers holding the injection site.

Step 7 – Inject Hulio

After the needle is completely inserted, let go of the site you are squeezing.

Slowly push the plunger completely down until all the medicine is injected and the syringe is empty.

If the plunger is not pressed all the way the safety feature will not activate afterwards to cover the

needle.

DO NOT move, twist, or rotate the syringe during ___________________________________________________injection._______________________________________________

Step 8 – End of injection, remove syringe

Pull the syringe away from the injection site at the same angle as inserted and release your thumb from the plunger.

After injection, if slight bleeding occurs from the injection site, press a gauze pad or cotton ball lightly against the skin for a few seconds – DO NOT rub the injection site. If needed, cover the injection site with a __________________________________________________plaster. ______________________________________________________ Step 9 – Dispose syringe and cap

Dispose of the used syringe and cap in an approved sharps disposal container.

Check with your healthcare provider for instructions on how to properly dispose of a filled sharps container.

DO NOT re-use the syringe.
DO NOT re-cap the needle.
DO NOT throw the sharps container in your household bin.
DO NOT recycle your used sharps disposal container.
Always keep your sharps container out of the sight and reach of children

Package leaflet: Information for the patient

Hulio 40 mg solution for injection in 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. You may need to read it again.
– Your doctor will also give you a patient reminder card, which contains important safety information that you need to be aware of before you are given Hulio and during treatment with Hulio. Keep this patient reminder card with you at all times and for 4 months after your last injection of 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. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Hulio is and what it is used for
2. What you need to know before you use 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 your body’s immune (defence) system.

Hulio is intended 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.