Patient leaflet - Hefiya

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Hefiya 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 your child starts using this medicine because it contains important information.

– 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 begins using Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you or your child during your treatment and for 4 months after your child’s last injection of Hefiya.
– If you have any further questions, please 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 doctor or pharmacist. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on your body’s immune (defence) system.

Hefiya 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 non-infectious uveitis.

The active ingredient in Hefiya, 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 present at increased levels in the inflammatory diseases listed above. By attaching to TNFa, Hefiya blocks its action and reduces the inflammation in these diseases.

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.

Hefiya 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. Patients may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, patients will be given Hefiya to treat their polyarticular juvenile idiopathic arthritis or 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.

Hefiya 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.

Paediatric Crohn’s disease

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

Hefiya 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 Hefiya to reduce the signs and symptoms of his / her disease.

Paediatric non-infectious uveitis

Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye. The inflammation leads 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). Hefiya works by reducing this inflammation.

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

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

2. What you need to know before your child uses Hefiya

Do not use Hefiya

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, sepsis (blood poisoning) or other

opportunistic infections (unusual infections associated with a weakened immune system). It is important that you tell your doctor if your child shows symptoms of infections, e.g. fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).

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 Hefiya.

Allergic reaction

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

Infection

If your child has an infection, including long-term or localised infection (for example leg ulcer),

consult your doctor before starting Hefiya. If you are unsure, contact your doctor.

Your child might get infections more easily while he / she is receiving Hefiya treatment. This

risk may increase if your child’s lung function is reduced. These infections may be more 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 doctor if your child shows symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may recommend temporarily stopping Hefiya.

Tuberculosis (TB)

As cases of tuberculosis have been reported in patients treated with adalimumab, your doctor will check your child for signs and symptoms of tuberculosis before starting Hefiya. 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 he / she has 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 doctor immediately.

Travel / recurrent infection

Tell your doctor if your child has lived or travelled in regions where fungal infections such as histoplasmosis, coccidioidomycosis or blastomycosis are common.
Tell your doctor if your child has a history of recurrent infections or other conditions that

increase the risk of infections.

Hepatitis B virus

Tell your 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 doctor should 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 procedures

If your child is about to have surgery or dental procedures tell your doctor that your child is

taking Hefiya. Your doctor may recommend temporarily stopping Hefiya.

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 doctor will decide if he / she should receive or continue to receive Hefiya. Tell your doctor immediately if he / she experiences symptoms like changes in vision, weakness in arms or legs or numbness or tingling in any part of the body.

Vaccine

Certain vaccines contain living but weakened forms of disease-causing bacteria or viruses and should not be given during treatment with Hefiya in case they cause infections. Check with your doctor before your child receives any vaccines. It is recommended that, if possible, children be given all the scheduled vaccinations for their age before they start treatment with Hefiya.

If your child receives Hefiya while she is pregnant, her baby may be at higher risk for getting an infection for up to about five months after the last dose she received during pregnancy. It is important that you tell her baby's doctors and other health care professionals about your child’s Hefiya use during herpregnancy so they can decide when her baby should receive any vaccine.

Heart failure

It is important to tell your doctor if your child has had or has a serious heart condition. If your child has mild heart failure and is being treated with Hefiya, the heart failure status must be closely monitored by your doctor. If your child develops 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 off infections or help stop bleeding. If your child develops a fever that does not go away, or he / she bruises or bleeds very easily or looks 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 and leukaemia (cancers that affect blood cells and bone marrow). If your child takes Hefiya, the risk of getting lymphoma, leukaemia, or other cancers may increase. On rare occasions, a specific and severe type of lymphoma has been observed in patients taking adalimumab. Some of those patients were also treated with the medicines azathioprine or mercaptopurine. Tell your doctor if your child is taking azathioprine or mercaptopurine with Hefiya.
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, 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 doctor whether treatment with a TNFa blocker is appropriate.

Autoimmune diseases

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

Children and adolescents

Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis below the age of
2 years.

Do not give Hefiya to children with paediatric plaque psoriasis or paediatric ulcerative colitis below the age of 4 years.
Do not give Hefiya to children with paediatric Crohn’s disease below the age of 6 years.
Do not use the 40 mg pre-filled syringe if doses other than 40 mg are recommended.

Other medicines and Hefiya

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

Hefiya 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).

Your child should not take Hefiya with medicines containing the active substances anakinra or abatacept due to increased risk of serious infection. The combination of adalimumab as well as other TNF-antagonists 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

Your child should consider the use of adequate contraception to prevent pregnancy and continue

its use for at least 5 months after the last Hefiya treatment.

If your child is pregnant, thinks she may be pregnant or is planning to have a baby, ask her

doctor for advice before taking this medicine.

Hefiya 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.
Hefiya can be used during breast-feeding.
If your child receives Hefiya during her pregnancy, the 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 Hefiya use during her pregnancy before the baby receives any vaccine (for more information on vaccines see the “Warnings and precautions” section).

Driving and using machines

Hefiya may have a minor influence on the ability to drive, cycle or use machines. Room spinning sensation (vertigo) and vision disturbances may occur after taking Hefiya.

Hefiya contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 ml dose, that is to say essentially ‘sodium-free’.

3. How to use Hefiya

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Hefiya is available as a 40 mg pen as well as 20 mg and 40 mg pre-filled syringes for patients to administer a full 20 mg or 40 mg dose.

Polyarticular juvenile idiopathic arthritis
Age and body weight	How much and how often to take?	Notes
Children, adolescents and adults from 2 years of age weighing 30 kg or more	40 mg every other week	Not applicable
Children, adolescents from 2 years of age weighing 10 kg to less than 30 kg	20 mg every other week	Not applicable

Enthesitis-related arthritis
Age and body weight	How much and how often to take?	Notes
Children, adolescents and adults from 6 years of age weighing 30 kg or more	40 mg every other week	Not applicable
Children, adolescents from 6 years of age weighing 15 kg to less than 30 kg	20 mg every other week	Not applicable

Paediatric plaque psoriasis
Age and body weight	How much and how often to take?	Notes
Children and adolescents from 4 to 17 years of age weighing 30 kg or more	First dose of 40 mg, followed by 40 mg one week later. Thereafter, the usual dose is 40 mg every other week.	Not applicable
Children and adolescents from 4 to 17 years of age weighing 15 kg to less than 30 kg	First dose of 20 mg, followed by 20 mg one week later. Thereafter, the usual dose is 20 mg every other week.	Not applicable

Paediatric Crohn’s disease
Age and body weight	How much and how often to take?	Notes
Children and adolescent from 6 to	First dose of 80 mg (as two 40 mg injections in one day), followed by 40 mg every other	If this dose does not work well enough, your child’s doctor may increase the dosage to

17 years of age weighing 40 kg or

week starting two weeks later.

If a faster response is required your doctor may prescribe a first 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.

40 mg every week or 80 mg every other week.

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

First dose of 40 mg, followed by 20 mg every other week starting two weeks later.

If a faster response is required, your doctor may prescribe a first 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.

Paediatric non-infectious uveitis
Age and body weight	How much and how often to take?	Notes
Children and adolescents from 2 years of age weighing 30 kg or more	40 mg every other week with methotrexate	Your doctor may also prescribe a first dose of 80 mg which may be administered one week prior to the start of the usual dose.
Children and adolescents from 2 years of age weighing less than 30 kg	20 mg every other week with methotrexate	Your doctor may also prescribe a first dose of 40 mg which may be administered one week prior to the start of the usual dose.

Method and route of administration

Hefiya is administered by injection under the skin (by subcutaneous injection).

Detailed instructions on how to inject Hefiya are provided in section 7,

“Instructions for use”

If you use more Hefiya than you should

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

If you forget to use Hefiya

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

If you stop using Hefiya

The decision to stop using Hefiya should be discussed with your child’s doctor. The 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 treatment. Side effects may occur up to 4 months or more after the last Hefiya injection.

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

severe rash, hives;
swollen face, hands, feet;
trouble breathing, swallowing;
shortness of breath with exertion 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 following side effects have been observed with adalimumab:

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

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

mouth infections (including tooth infections and cold sores);

reproductive tract infections;
urinary tract infection;
fungal infections;
joint infections;
benign tumours;
skin cancer;
allergic reactions (including seasonal allergy);
dehydration;
mood swings (including depression);
anxiety;
difficulty sleeping;
sensation disorders such as tingling, prickling or numbness;
migraine;
symptoms of nerve root compression (including low back pain and leg pain);
vision disturbances;
eye inflammation;
inflammation of the eye lid and eye swelling;
vertigo (sensation of room spinning);
sensation of heart beating rapidly;
high blood pressure;
flushing;
haematoma (a solid swelling with clotted blood);
cough;
asthma;
shortness of breath;
gastrointestinal bleeding;
dyspepsia (indigestion, bloating, heart burn);
acid reflux disease;
sicca syndrome (including dry eyes and dry mouth);
itching;
itchy rash;
bruising;
inflammation of the skin (such as eczema);
breaking of finger nails and toe nails;
increased sweating;
hair loss;
new onset or worsening of psoriasis;
muscle spasms;
blood in urine;
kidney problems;
chest pain;
oedema (a build-up of fluid in the body which causes the affected tissue to swell);
fever;
reduction in blood platelets which increases risk of bleeding or bruising;
impaired healing.

Uncommon (may affect up to 1 in 100 people)

unusual 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, including cancer that affects the lymph system (lymphoma) and melanoma (a type of skin cancer);
immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a condition called sarcoidosis);
vasculitis (inflammation of blood vessels);
tremor;
neuropathy (nerve damage);
stroke;
double vision;
hearing loss, buzzing;
sensation of heart beating irregularly such as skipped beats;
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);
pleural effusion (abnormal collection of fluid in the pleural space);
inflammation of the pancreas which causes severe pain in the abdomen and back;
difficulty in swallowing;
facial oedema (swelling);
gallbladder inflammation, gallbladder stones;
fatty liver (build-up of fat in liver cells);
night sweats;
scar;
abnormal muscle breakdown;
systemic lupus erythematosus (an immune disorder 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-Barre 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 in the wall of the gut);
hepatitis (liver inflammation);
reactivation of hepatitis B infection;
autoimmune hepatitis (inflammation of the liver caused by the body's own immune system);
cutaneous vasculitis (inflammation of blood vessels in the skin);
Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and blistering

rash);

facial oedema (swelling) associated with allergic reactions;
erythema multiforme (inflammatory skin rash);
lupus-like syndrome;
angioedema (localised swelling of the skin);
lichenoid skin reaction (itchy reddish-purple skin rash).

Not known (frequency cannot be estimated from available data)

hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal);
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 of a condition called dermatomyositis (seen as a skin rash accompanying muscle weakness).
weight gain (for most patients, the weight gain was small)

Some side effects observed with adalimumab may not have symptoms and may only be discovered through blood tests. These include:

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

low blood measurements for white blood cells;
low blood measurements for red blood cells;
increased lipids in the blood;
raised liver enzymes.

Common (may affect up to 1 in 10 people)

high blood measurements for white blood cells;
low blood measurements for platelets;
increased uric acid in the blood;
abnormal blood measurements for sodium;
low blood measurements for calcium;
low blood measurements for phosphate;
high blood sugar;
high blood measurements for lactate dehydrogenase;
autoantibodies present in the blood;
low blood potassium.

Uncommon (may affect up to 1 in 100 people)

raised bilirubin measurement (liver blood test).

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

low blood measurements for white blood cells, red blood cells and platelet count.

Reporting of side effects

If your child gets 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 in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

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), Hefiya may be stored at room temperature (up to 25°C) for a maximum period of 21 days – be sure to protect it from light. Once removed from the refrigerator for room temperature storage, your pre-filled syringe must be used within 21 days or discarded , even if it is later returned to the refrigerator. You should record the date when your prefilled syringe is first removed from the 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 Hefiya contains

The active substance is adalimumab. Each pre-filled syringe contains 20 mg of adalimumab in 0.4 ml of solution.
The other ingredients are adipic acid, citric acid monohydrate, sodium chloride, mannitol (E 421), polysorbate 80 ( E 433), hydrochloric acid ( E 507), sodium hydroxide (E 524) and water for injections.

What Hefiya looks like and contents of the pack

Hefiya 20 mg solution for injection (injection) in pre-filled syringe for paediatric use is supplied as a 0.4 ml clear to slightly opalescent, colourless to slightly yellowish solution.

Hefiya is supplied in a single-use clear type I glass syringe with a stainless steel needle with a needle guard with finger flange, rubber needle cap and plastic plunger rod, containing 0.4 ml of solution.

Carton contains 2 pre-filled syringes of Hefiya.

Not all pack sizes may be marketed.

Hefiya is available as a pre-filled syringe and a pre-filled pen (SensoReady).

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestr. 10 6250 Kundl Austria

Manufacturer

Sandoz GmbH Schaftenau

Biochemiestr. 10

6336 Langkampfen

Austria

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

Authorisation Holder:

Belgie/Belgique/Belgien

Sandoz nv/sa

Tél/Tel: +32 2 722 97 97

Lietuva

Sandoz Pharmaceuticals d.d filialas

Tel: +370 5 2636 037

Etnrapna

CaHgo3 Etnrapua KHT

Luxembourg/Luxemburg

Sandoz nv/saTél/Tel.: +32 2 722 97 97

Ten.: +359 2 970 47 47

Česká republika

Sandoz s.r.o.

Tel: +420 225 775 111

Magyarország

Sandoz Hungária Kft.

Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige

Sandoz A/S

Tlf: +45 63 95 10 00

Malta

Sandoz Pharmaceuticals d.d.

Tel: +356 21222872

Deutschland

Hexal AG

Tel: +49 8024 908 0

Nederland

Sandoz B.V.

Tel: +31 36 52 41 600

Eesti

Sandoz d.d. Eesti filiaal

Tel: +372 665 2400

Österreich

Sandoz GmbH

Tel: +43 5338 2000

EZZaöa

Novartis (Hellas) A.E.B.E.

Tql: +30 210 281 17 12

Polska

Sandoz Polska Sp. z o.o.

Tel.: +48 22 209 70 00

España

Sandoz Farmacéutica, S.A.

Tel: +34 900 456 856

Portugal

Sandoz Farmacéutica Lda.

Tel: +351 21 196 40 00

France

Sandoz SAS

Tél: +33 1 49 64 48 00

Romania

Sandoz SRL

Tel: +40 21 407 51 60

Hrvatska

Slovenija

Sandoz d.o.o.

Lek farmacevtska družba d.d.

Tel: +386 1 580 21 11

Tel: +385 1 23 53 111

Ireland

Rowex Ltd.

Tel: + 353 27 50077

Slovenská republika

Sandoz d.d. – organizačná zložka

Tel: +421 2 48 200 600

Italia

Sandoz S.p.A.

Tel: +39 02 96541

Suomi/Finland

Sandoz A/S

Puh/Tel: +358 10 6133 400

Kvnpog

Sandoz Pharmaceuticals d.d.

Tql: +357 22 69 0690

United Kingdom (Northern Ireland)

Sandoz GmbH

Tel: +43 5338 2000

Latvija

Sandoz d.d. Pârstâvniecïba Latvija

Tel: +371 67 892 006

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: .

7. Instructions for use

throw away the used syringe right away after use. Do not re-use a syringe. See “4. Disposing of used syringes” at the end of these Instructions for Use.

How should you store Hefiya?

Store your outer carton of syringes in a refrigerator, between 2°C to 8°C.
When needed (for example when you are travelling), Hefiya may be stored at room temperature

(up to 25°C) for a maximum period of 21 days – be sure to protect it from light. Once removed from the refrigerator for room temperature storage, your pre-filled syringe must be used within 21 days or discarded , even if it is later returned to the refrigerator. You should record the date when your pre-filled syringe is first removed from the refrigerator, and the date after which it should be discarded.

Keep the syringes in the original carton until ready to use to protect from light.
Do not store the syringes in extreme heat or cold.
Do not freeze the syringes.

Keep Hefiya and all medicines out of the reach of children.

What do you need for your injection?

Place the following items on a clean, flat surface.

Included in your carton is:

Hefiya pre-filled syringe/s (see Figure A). Each syringe contains 20 mg / 0.4 ml of Hefiya.

Not included in your carton are (see Figure B ):

Alcohol wipe
Cotton ball or gauze
Sharps disposal container

See “4. Disposing of used syringes” at the end of these Instructions for Use.

Before your injection

Figure C: needle guard is not activated – the syringe is ready for use

Figure D: needle guard is activated – do not use

o In this configuration the needle guard is NOT ACTIVATED.

o The syringe is ready for use (see Figure C ).

o In this configuration the needle guard is ACTIVATED.

o DO NOT USE the syringe (see Figure D ).

Preparing the syringe

For a more comfortable injection, take the blister containing the syringe out of the refrigerator and leave it unopened on your work surface for about 15 to 30 minutes so that it reaches room temperature.
Take the syringe out of the blister.
Look through the viewing window. The solution should be colourless to slightly yellowish as well as clear to slightly opalescent. Do not use if any particulates and / or discolorations are observed. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.
Do not use the syringe if it is broken or the needle guard is activated. Return the syringe and the package it came in to the pharmacy.
Look at the expiration date (EXP) on your syringe. Do not use the syringe if the expiration date has passed.

Contact your pharmacist if the syringe fails any of the above mentioned checks.

1. Choosing your injection site:

The recommended injection site is the front of your thighs. You may also use the lower abdomen, but not the area 5 cm around your navel (belly button) (see Figure E ).

Choose a different site each time you give yourself an injection.

Do not inject into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks. If you have psoriasis, you should NOT inject directly into areas with psoriasis plaques.

2. Cleaning your injection site:

Wash your hands well with soap and water.

Using a circular motion, clean the injection site with an alcohol wipe. Leave it to dry before injecting (see Figure F ).

Do not touch the cleaned area before injecting.

Figure F: clean your injection site

3. Giving your injection:

Carefully pull the needle cap straight off to remove it from the syringe (see Figure G).

Discard the needle cap.

You may see a drop of liquid at the end of the needle. This is normal.

Gently pinch the skin at the injection site (see Figure H ).

Insert the needle into your skin as shown.

Push the needle all the way in to ensure that the medication can be fully administered.

Hold the syringe as shown (see Figure I ).

Slowly press down on the plunger as far as it will go, so that the plunger head is completely between the needle guard wings.

Keep the plunger pressed fully down while you hold the syringe in place for 5 seconds.

Keep the plunger fully pressed down while you carefully lift the needle straight out from the injection site and let go of your skin (see Figure J).

Figure G: pull the needle cap off

Figure H: insert the needle

Figure I: hold the syringe

Figure J: lift the needle straight out

Slowly release the plunger and allow the needle safety guard to automatically cover the exposed needle (see Figure K ).

There may be a small amount of blood at the injection site. You can press a cotton ball or gauze onto the injection site and hold it for 10 seconds. Do not rub the injection site. You may cover the injection site with a small adhesive bandage, if needed.

4. Disposing of used syringes:

Dispose of the used syringe in a sharps container (closable, puncture-resistant container). For the safety and health of you and others, needles and used syringes must never be re-used.

Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. Any unused product or waste material should be disposed of in accordance with local requirements.

Figure K: slowly release the plunger

If you have any questions, please talk to a doctor, pharmacist or nurse who is familiar with Hefiya.

Package leaflet: Information for the patient

Hefiya 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 Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you during your treatment and for 4 months after your (or your child’s) last injection of Hefiya.
– If you have any further questions, please 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 Hefiya is and what it is used for
2. What you need to know before you use Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on your body’s immune (defence) system.

Hefiya 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 and
non-infectious uveitis.

The active ingredient in Hefiya, 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.

Hefiya 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 Hefiya to treat your rheumatoid arthritis.

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

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

Usually, Hefiya is used with methotrexate. If your doctor considers that methotrexate is inappropriate, Hefiya 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.

Hefiya 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. Patients may first be given other disease-modifying medicines, such as methotrexate. If these medicines do not work well enough, patients will be given Hefiya to treat their 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.

Hefiya is used in adults to treat these conditions. 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 Hefiya to reduce the signs and symptoms of your disease.

Plaque psoriasis in adults and children

Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya 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.

Psoriatic arthritis

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

Hefiya is used to treat psoriatic arthritis in adults. Hefiya can slow down the damage to the cartilage and bone of the joints caused by the disease and improve physical function.

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.

Hefiya is used to treat hidradenitis suppurativa in adults and adolescents from 12 years of age. Hefiya 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 Hefiya.

Crohn’s disease in adults and children

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

Hefiya 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 Hefiya 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 large intestine.

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

Non-infectious uveitis in adults and children

Hefiya is used to treat

adults with non-infectious uveitis with inflammation affecting the back of the eye.
children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front of the eye.

2. What you need to know before you use Hefiya

Do not use Hefiya

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, sepsis (blood poisoning) or other

opportunistic infections (unusual infections associated with a weakened immune system). It is important that you tell your doctor if you have symptoms of infections, e.g. fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).

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 Hefiya.

Allergic reaction

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

Infection

If you have an infection, including long-term or localised infection (for example leg ulcer), consult your doctor before starting Hefiya. If you are unsure, contact your doctor.
You might get infections more easily while you are receiving Hefiya treatment. This risk may increase if your lung function is reduced. These infections may be more 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 doctor if you get symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may recommend temporarily stopping Hefiya.

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 Hefiya. 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 have lived or travelled 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 should 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 Hefiya. You and your doctor should pay special attention to signs of infection while you are being treated with Hefiya. 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 procedures

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

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 Hefiya. 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 your body.

Vaccine

Certain vaccines contain living but weakened forms of disease-causing bacteria or viruses and should not be given during treatment with Hefiya in case they cause infections. 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 Hefiya.

If you receive Hefiya while you are pregnant, your baby may be at higher risk for getting 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 Hefiya use during your pregnancy so they can decide when your baby should receive any vaccine.

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 Hefiya, 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 off 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 and leukaemia (cancers that affect blood cells and bone marrow). If you take Hefiya the risk of getting lymphoma, leukaemia, or other cancers may increase. On rare occasions, a specific and severe type of lymphoma has been observed in 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 Hefiya.
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, 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 are a heavy smoker, you should discuss with your doctor whether treatment with a TNFa blocker is appropriate for you.

Autoimmune diseases

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

Children and adolescents

Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis below the age of 2 years.
Do not give Hefiya to children with paediatric plaque psoriasis or paediatric ulcerative colitis below the age of 4 years.
Do not give Hefiya to children with paediatric Crohn’s disease below the age of 6 years.
Do not use the 40 mg pre-filled syringe if doses other than 40 mg are recommended.

Other medicines and Hefiya

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

You should not take Hefiya with medicines containing the active substances anakinra or abatacept due to increased risk of serious infection. The combination of adalimumab as well as other TNF-antagonists 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 Hefiya treatment.
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Hefiya 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.
Hefiya can be used during breast-feeding.
If you receive Hefiya 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 Hefiya use during your pregnancy before the baby receives any vaccine (for more information on vaccines see the “Warnings and precautions” section).

Driving and using machines

Hefiya 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 Hefiya.

Hefiya contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, that is to say essentially ‘sodium-free’.

3. How to use Hefiya

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Hefiya is available as a 40 mg pen as well as 20 mg and 40 mg pre-filled syringes for patients to administer a full 20 mg or 40 mg dose.

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis

Age and body weight

How much and how often to take?

Notes

Adults

40 mg every other week as a single dose

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

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

Polyarticular juvenile idiopathic arthritis
Age and body weight	How much and how often to take?	Notes
Children, adolescents and adults from 2 years of age weighing 30 kg or more	40 mg every other week	Not applicable
Children, adolescents from 2 years of age weighing 10 kg to less than 30 kg	20 mg every other week	Not applicable

Enthesitis-related arthritis
Age and body weight	How much and how often to take?	Notes
Children, adolescents and adults from 6 years of age weighing 30 kg or more	40 mg every other week	Not applicable
Children and adolescents from 6 years of age weighing 15 kg to less than 30 kg	20 mg every other week	Not applicable

Psoriasis
Age and body weight	How much and how often to take?	Notes
Adults	First 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 first dose.	You should continue to inject Hefiya for as long as your doctor has told you. If this dose does not work well enough, your doctor may increase the dosage to 40 mg every week or 80 mg every other week.

Paediatric plaque psoriasis
Age and body weight	How much and how often to take?	Notes
Children and adolescents from 4 to 17 years of age weighing 30 kg or more	First dose of 40 mg, followed by 40 mg one week later. Thereafter, the usual dose is 40 mg every other week.	Not applicable
Children and adolescents from 4 to 17 years of age weighing 15 kg to less than 30 kg	First dose of 20 mg, followed by 20 mg one week later. Thereafter, the usual dose is 20 mg every other week.	Not applicable

Hidradenitis suppurativa
Age and body weight	How much and how often to take?	Notes
Adults	First 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 dosage 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 from 12 to 17 years of age weighing 30 kg or more	First 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, your doctor may increase the dosage to 40 mg every week or 80 mg every other week. It is recommended that you use an antiseptic wash daily on the affected areas.

Crohn’s disease

Age and body weight

How much and how often to take?

Notes

Adults

First dose of 80 mg (as two 40 mg injections in one day), followed by 40 mg every other week starting 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 to 40 mg every week or 80 mg every other week.

Paediatric Crohn’s disease
Age and body weight	How much and how often to take?	Notes
Children and adolescent from 6 to 17 years of age weighing 40 kg or more	First dose of 80 mg (as two 40 mg injections in one day), followed by 40 mg every other week starting two weeks later. If a faster response is required your doctor may prescribe a first 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 and adolescents from 6 to 17 years of age weighing less than 40 kg	First dose of 40 mg, followed by 20 mg every other week starting two weeks later. If a faster response is required, your doctor may prescribe a first 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.

Ulcerative colitis

Age and body weight

How much and how often to take?

Notes

Adults

First dose is 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 to 40 mg every week or 80 mg every other week.

Paediatric ulcerative colitis
Age and body weight	How much and how often to take?	Notes
Children and adolescents from 6 years of age weighing 40 kg or	First dose 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	Patients who turn 18 years of age while on 80 mg every other week, should continue their prescribed dose

more	injections in one day) two weeks later. Thereafter the usual dose is 80 mg every other week. (as two 40 mg injections in one day)
Children and adolescents from 6 years of age weighing less than 40 kg	First dose 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.
Non-infectious uveitis
Age and body weight	How much and how often to take?	Notes
Adults	First dose of 80 mg (as two 40 mg injections), followed by 40 mg every other week starting one week after the first dose.	In non-infectious uveitis, corticosteroids or other medicines that influence the immune system may be continued while using Hefiya. Hefiya can also be given alone. You should continue to inject Hefiya for as long as your doctor has told you.
Children and adolescents from 2 years of age weighing 30 kg or more	40 mg every other week with methotrexate	Your doctor may also prescribe a first dose of 80 mg which may be administered one week prior to the start of the usual dose.
Children and adolescents from 2 years of age weighing less than 30 kg	20 mg every other week with methotrexate	Your doctor may also prescribe a first dose of 40 mg which may be administered one week prior to the start of the usual dose.

Method and route of administration

Hefiya is administered by injection under the skin (by subcutaneous injection).

Detailed instructions on how to inject Hefiya are provided in section 7,

“Instructions for use”

If you use more Hefiya than you should

If you accidentally inject Hefiya 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 medicine with you, even if it is empty.

If you forget to use Hefiya

If you forget to give yourself an injection, you should inject the next dose of Hefiya 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 Hefiya

The decision to stop using Hefiya 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

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

severe rash, hives;
swollen face, hands, feet;
trouble breathing, swallowing;
shortness of breath with exertion 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 following side effects have been observed with adalimumab:

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

injection site reactions (including pain, swelling, redness or itching);
respiratory tract infections (including cold, runny nose, sinus infection, pneumonia);
headache;
abdominal (belly) pain;
nausea and vomiting;
rash;
pain in the 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;
mouth infections (including tooth infections and cold sores);
reproductive tract infections;
urinary tract infection;
fungal infections;
joint infections;
benign tumours;
skin cancer;
allergic reactions (including seasonal allergy);
dehydration;
mood swings (including depression);
anxiety;
difficulty sleeping;
sensation disorders such as tingling, prickling or numbness;
migraine;
symptoms of nerve root compression (including low back pain and leg pain);
vision disturbances;
eye inflammation;
inflammation of the eye lid and eye swelling;
vertigo (sensation of room spinning);
sensation of heart beating rapidly;
high blood pressure;
flushing;
haematoma (a solid swelling with clotted blood);
cough;
asthma;
shortness of breath;
gastrointestinal bleeding;
dyspepsia (indigestion, bloating, heart burn);
acid reflux disease;
sicca syndrome (including dry eyes and dry mouth);
itching;
itchy rash;
bruising;
inflammation of the skin (such as eczema);
breaking of finger nails and toe nails;
increased sweating;
hair loss;
new onset or worsening of psoriasis;
muscle spasms;
blood in urine;
kidney problems;
chest pain;
oedema (a build-up of fluid in the body which causes the affected tissue to swell);
fever;
reduction in blood platelets which increases risk of bleeding or bruising;
impaired healing.

Uncommon (may affect up to 1 in 100 people)

unusual 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, including cancer that affects the lymph system (lymphoma) and melanoma (a type of

skin cancer);

immune disorders that could affect the lungs, skin and lymph nodes (most commonly as a condition called sarcoidosis);
vasculitis (inflammation of blood vessels);
tremor;
neuropathy (nerve damage);
stroke;
double vision;
hearing loss, buzzing;
sensation of heart beating irregularly such as skipped beats;
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);
pleural effusion (abnormal collection of fluid in the pleural space);
inflammation of the pancreas which causes severe pain in the abdomen and back;
difficulty in swallowing;
facial oedema (swelling);
gallbladder inflammation, gallbladder stones;
fatty liver (build-up of fat in liver cells);
night sweats;
scar;
abnormal muscle breakdown;
systemic lupus erythematosus (an immune disorder 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-Barre 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 in the wall of the gut);
hepatitis (liver inflammation);
reactivation of hepatitis B infection;
autoimmune hepatitis (inflammation of the liver caused by the body's own immune system);
cutaneous vasculitis (inflammation of blood vessels in the skin);
Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and blistering

rash);

facial oedema (swelling) associated with allergic reactions;
erythema multiforme (inflammatory skin rash);
lupus-like syndrome;
angioedema (localised swelling of the skin);
lichenoid skin reaction (itchy reddish-purple skin rash).

Not known (frequency cannot be estimated from available data)

hepatosplenic T-cell lymphoma (a rare blood cancer that is often fatal);
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 of a condition called dermatomyositis (seen as a skin rash accompanying muscle weakness).
weight gain (for most patients, the weight gain was small)

Some side effects observed with adalimumab may not have symptoms and may only be discovered through blood tests. These include:

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

low blood measurements for white blood cells;
low blood measurements for red blood cells;
increased lipids in the blood;
raised liver enzymes.

Common (may affect up to 1 in 10 people)

high blood measurements for white blood cells;
low blood measurements for platelets;
increased uric acid in the blood;
abnormal blood measurements for sodium;
low blood measurements for calcium;
low blood measurements for phosphate;
high blood sugar;
high blood measurements for lactate dehydrogenase;
autoantibodies present in the blood;
low blood potassium.

Uncommon (may affect up to 1 in 100 people)

raised bilirubin measurement (liver blood test).

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

low blood measurements for white blood cells, red blood cells and platelet count.

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 in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hefiya

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:

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 Hefiya contains

The active substance is adalimumab. Each pre-filled syringe contains 40 mg of adalimumab in 0.8 ml of solution.
The other ingredients are adipic acid, citric acid monohydrate, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections.

What Hefiya looks like and contents of the pack

Hefiya 40 mg solution for injection (injection) in pre-filled syringe is supplied as a 0.8 ml clear to slightly opalescent, colourless to slightly yellowish solution.

Cartons contain 1 and 2 pre-filled syringes of Hefiya.

Multipack cartons contain 6 (3 packs of 2) pre-filled syringes of Hefiya.

Not all pack sizes may be marketed.

Hefiya is available as a pre-filled syringe and a pre-filled pen (SensoReady).

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Manufacturer

Sandoz GmbH Schaftenau

Biochemiestr. 10

6336 Langkampfen

Austria

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

Belgie/Belgique/Belgien

Sandoz nv/sa

Tél/Tel: +32 2 722 97 97

Lietuva

Sandoz Pharmaceuticals d.d filialas

Tel: +370 5 2636 037

Etnrapna

CaHgo3 Etnrapua KHT

Luxembourg/Luxemburg

Sandoz nv/saTél/Tel.: +32 2 722 97 97

Ten.: +359 2 970 47 47

Česká republika

Sandoz s.r.o.

Tel: +420 225 775 111

Magyarország

Sandoz Hungária Kft.

Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige

Sandoz A/S

Tlf: +45 63 95 10 00

Malta

Sandoz Pharmaceuticals d.d.

Tel: +356 21222872

Deutschland

Hexal AG

Tel: +49 8024 908 0

Nederland

Sandoz B.V.

Tel: +31 36 52 41 600

Eesti

Sandoz d.d. Eesti filiaal

Tel: +372 665 2400

Österreich

Sandoz GmbH

Tel: +43 5338 2000

EZZaöa

Novartis (Hellas) A.E.B.E.

Tql: +30 210 281 17 12

Polska

Sandoz Polska Sp. z o.o.

Tel.: +48 22 209 70 00

España

Sandoz Farmacéutica, S.A.

Tel: +34 900 456 856

Portugal

Sandoz Farmacéutica Lda.

Tel: +351 21 196 40 00

France

Sandoz SAS

Tél: +33 1 49 64 48 00

Romania

Sandoz SRL

Tel: +40 21 407 51 60

Hrvatska

Slovenija

Sandoz d.o.o.

Lek farmacevtska družba d.d.

Tel: +386 1 580 21 11

Tel: +385 1 23 53 111

Ireland

Rowex Ltd.

Tel: + 353 27 50077

Slovenská republika

Sandoz d.d. – organizačná zložka

Tel: +421 2 48 200 600

Italia

Sandoz S.p.A.

Tel: +39 02 96541

Suomi/Finland

Sandoz A/S

Puh/Tel: +358 10 6133 400

Kvnpog

Sandoz Pharmaceuticals d.d.

Tql: +357 22 69 0690

United Kingdom (Northern Ireland)

Sandoz GmbH

Tel: +43 5338 2000

Latvija

Sandoz d.d. Pârstâvniecïba Latvija

Tel: +371 67 892 006

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

Instructions for use

To help avoid possible infections and to ensure that you use the medicine correctly, it is important that you follow these instructions.

Be sure that you read, understand, and follow these Instructions for Use before injecting Hefiya. Your healthcare provider should show you how to prepare and inject Hefiya properly using the pre-filled syringe before you use it for the first time. Talk to your healthcare provider if you have any questions.

Your Hefiya single-use pre-filled syringe with needle guard and add-on finger flange

Figure A: Hefiya pre-filled syringe with needle guard and add-on finger flange

It is important that you:

do not open the outer box until you are ready to use the syringe.
do not use the syringe if the seals of the blister are broken, as it may not be safe for you to use.
never leave the syringe unattended where others might tamper with it.
if you drop your syringe, do not use it if it looks damaged, or if you dropped it with the needle

cap removed.

do not remove the needle cap until just before you give the injection.
be careful not to touch the needle guard wings before use. Touching them may cause the needle guard to be activated too early. Do not remove the finger flange before the injection.
inject Hefiya 15–30 minutes after taking it out of the refrigerator for a more comfortable injection.
throw away the used syringe right away after use. Do not re-use a syringe. See “4. Disposing of used syringes” at the end of these Instructions for Use.

How should you store Hefiya?

Store your outer carton of syringes in a refrigerator, between 2°C to 8°C.
When needed (for example when you are travelling), Hefiya may be stored at room temperature

Keep the syringes in the original carton until ready to use to protect from light.
Do not store the syringes in extreme heat or cold.
Do not freeze the syringes.

Keep Hefiya and all medicines out of the reach of children.

What do you need for your injection?

Place the following items on a clean, flat surface.

Included in your carton is:

Hefiya pre-filled syringe/s (see Figure A). Each syringe contains 40 mg/0.8 ml of Hefiya.

Not included in your carton are (see Figure B ):

Alcohol wipe
Cotton ball or gauze
Sharps disposal container

See “4. Disposing of used syringes” at the end of these Instructions for Use.

Before your injection

Figure C: needle guard is not activated – the syringe is ready for use

Figure D: needle guard is activated – do not use

o In this configuration the needle guard is NOT ACTIVATED.

o The syringe is ready for use (see Figure C ).

o In this configuration the needle guard is ACTIVATED.

o DO NOT USE the syringe (see Figure D ).

Preparing the syringe

For a more comfortable injection, take the blister containing the syringe out of the refrigerator and leave it unopened on your work surface for about 15 to 30 minutes so that it reaches room temperature.
Take the syringe out of the blister.
Look through the viewing window. The solution should be colourless to slightly yellowish as well as clear to slightly opalescent. Do not use if any particulates and / or discolorations are observed. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.
Do not use the syringe if it is broken or the needle guard is activated. Return the syringe and the package it came in to the pharmacy.
Look at the expiration date (EXP) on your syringe. Do not use the syringe if the expiration date has passed.

Contact your pharmacist if the syringe fails any of the above mentioned checks.

1. Choosing your injection site:

The recommended injection site is the front of your thighs. You may also use the lower abdomen, but not the area 5 cm around your navel (belly button) (see Figure E ).

Choose a different site each time you give yourself an injection.

2. Cleaning your injection site:

Wash your hands well with soap and water.

Using a circular motion, clean the injection site with an alcohol wipe. Leave it to dry before injecting (see Figure F ).

Do not touch the cleaned area before injecting.

3. Giving your injection:

Carefully pull the needle cap straight off to remove it from the syringe (see Figure G ).

Discard the needle cap.

You may see a drop of liquid at the end of the needle. This is normal.

Figure E: choose your injection site

Figure F: clean your injection site

Figure G: pull the needle cap off

Gently pinch the skin at the injection site (see Figure H ).

Insert the needle into your skin as shown.

Push the needle all the way in to ensure that the medication can be fully administered

Hold the syringe as shown (see Figure I ).

Slowly press down on the plunger as far as it will go, so that the plunger head is completely between the needle guard wings.

Keep the plunger pressed fully down while you hold the syringe in place for 5 seconds.

Keep the plunger fully pressed down while you carefully lift the needle straight out from the injection site and let go of your skin (see Figure J).

Slowly release the plunger and allow the needle safety guard to automatically cover the exposed needle (see Figure K ).

Figure H: insert the needle

Figure I: hold the syringe

Figure J: lift the needle straight out

Figure K: slowly release the plunger

4. Disposing of used syringes:

Dispose of the used syringe in a sharps container (closable, puncture-resistant container). For the safety and health of you and others, needles and used syringes must never be re-used.

If you have any questions, please talk to a doctor, pharmacist or nurse who is familiar with Hefiya.

Package leaflet: Information for the patient

Hefiya 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 Hefiya and during treatment with Hefiya. Keep this Patient Reminder Card with you during your treatment and for 4 months after your (or your child’s) last injection of Hefiya.
– If you have any further questions, please 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 Hefiya is and what it is used for
2. What you need to know before you use Hefiya
3. How to use Hefiya
4. Possible side effects
5. How to store Hefiya
6. Contents of the pack and other information
7. Instructions for use

1. What Hefiya is and what it is used for

Hefiya contains the active substance adalimumab, a medicine that acts on your body’s immune (defence) system.

Hefiya 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 and
non-infectious uveitis.