Hukyndra: detailed information

Package leaflet: Information for the patient

Hukyndra 20 mg solution for injection in pre-filled syringe

adalimumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you observe while your child is receiving this medicine. See the end of section 4 for information on how to report side effects.
Please read 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 provide you with a Patient Reminder Card containing important safety information that you need to know before your child starts taking Hukyndra and during treatment with Hukyndra. You or your child should keep this Patient Reminder Card during your child’s treatment and for 4 months after the last injection of Hukyndra to your child.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for your child only. Do not give it to others, even if their symptoms are the same as your child’s, because it may be harmful.
If your child experiences any side effects, including those not listed in this leaflet, contact your paediatrician or pharmacist. See section 4.

Contents of this leaflet

What Hukyndra is and what it is used for
What you need to know before your child uses Hukyndra
How to use Hukyndra
Possible side effects
How to store Hukyndra
Contents of the pack and other information
Instructions for use

1. What Hukyndra is and what it is used for

Hukyndra contains the active substance adalimumab.
Hukyndra is indicated for the treatment of the following inflammatory diseases:

Polyarticular juvenile idiopathic arthritis
Enthesitis-related arthritis
Pediatric plaque psoriasis
Crohn’s disease in pediatric patients
Pediatric uveitis

The active substance in Hukyndra, adalimumab, is a human monoclonal antibody.
Monoclonal antibodies are proteins that bind to a specific target.
Adalimumab’s target is a protein called tumour necrosis factor (TNFα), which is involved in the immune (defence) system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hukyndra reduces the inflammatory process in these diseases.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints that usually begins during childhood.
Hukyndra is used to treat polyarticular juvenile idiopathic arthritis in patients aged 2 years and older. Initially, other disease-modifying drugs such as methotrexate may be given to your child. If these medicines are not effective enough, your child will be given Hukyndra to treat polyarticular juvenile idiopathic arthritis.
Your doctor will decide whether Hukyndra should be taken with methotrexate or on its own.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the sites where tendons attach to bones.
Hukyndra is used to treat enthesitis-related arthritis in patients from 6 years of age.
Initially, other disease-modifying drugs such as methotrexate may be given to your child. If these medicines are not sufficiently effective, your child will be given Hukyndra to treat enthesitis-related arthritis.

Pediatric plaque psoriasis
Plaque psoriasis is a skin condition that causes red, scaly, thickened patches of skin covered with silvery scales.
Plaque psoriasis can also affect the nails, causing them to crumble, thicken, or detach from the nail bed, which may 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.
Hukyndra is used for the treatment of severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapies have not worked adequately or are not suitable.

Crohn’s disease in pediatric patients
Crohn’s disease is an inflammatory disease of the digestive tract.
Hukyndra is used to treat moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.
Your child may initially be given other medicines. If these medicines are not sufficiently effective, your child will be given Hukyndra to reduce the signs and symptoms of the disease.

Pediatric uveitis
Non-infectious uveitis is an inflammatory disease affecting certain parts of the eye.
Hukyndra is used to treat children with chronic non-infectious uveitis from the age of 2 years, with inflammation of the front part of the eye.
This inflammation may lead to reduced vision and/or the presence of floaters in the eye (black spots or thread-like lines moving across the visual field). Hukyndra works by reducing this inflammation.
Your child may initially be given other medicines. If these medicines are not sufficiently effective, your child will be given Hukyndra to reduce the signs and symptoms of the disease.

2. What you should know before your child uses Hukyndra

Do not use Hukyndra

If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
If your child has active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform your doctor if your child has symptoms of infection, such as fever, wounds, feeling tired, or dental problems.
If your child has moderate or severe heart failure. It is important to inform your doctor if there has been or is currently a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hukyndra.
Allergic reactions

If your child experiences allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling, or rash, do not administer Hukyndra again and contact your doctor immediately, as in rare cases these reactions may be life-threatening.

Infections

If your child has an infection, including long-term infections or localized infections (e.g., leg ulcers), consult your doctor before starting treatment with Hukyndra. If you are unsure, contact your doctor.
Your child may be more likely to get infections while being treated with Hukyndra. This risk may increase if your child has lung problems. These infections can be serious and may include:
o tuberculosis
o infections caused by viruses, fungi, parasites, or bacteria
o serious blood infections (sepsis)

In rare cases, these infections can be life-threatening. It is important to inform your doctor if your child develops symptoms such as fever, wounds, feeling tired, or dental problems. Your doctor may instruct you to temporarily stop Hukyndra.

Inform your doctor if your child lives in or travels to regions where fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic.
Inform your doctor if your child has had recurrent infections or if they have conditions that increase the risk of infection.
Your child and doctor should pay particular attention to signs of infection while your child is being treated with Hukyndra. It is important to inform your doctor if symptoms of infection occur, such as fever, wounds, feeling tired, or dental problems.

Tuberculosis

Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check whether your child shows signs or symptoms typical of tuberculosis before starting treatment with Hukyndra. This will involve a thorough medical evaluation of your child’s medical history and appropriate clinical tests (e.g., a chest X-ray and tuberculin test). The performance and results of these tests must be recorded in your child’s Patient Reminder Card.
o It is very important to inform your doctor if your child has ever had tuberculosis or has been in contact with someone who had tuberculosis. If your child has active tuberculosis, Hukyndra must not be used.
o Tuberculosis may develop during treatment even if your child has received preventive treatment for tuberculosis.
o Contact your doctor immediately if symptoms of tuberculosis (e.g., persistent cough, weight loss, lack of energy, low-grade fever) or other infections occur during or after treatment.

Hepatitis B

It is very important to inform your doctor if your child is a carrier of the hepatitis B virus (HBV), has an active hepatitis B infection, or if you think they may be at risk of contracting hepatitis B.
o Your doctor must test your child for hepatitis B virus infection. In individuals who are HBV carriers, Hukyndra may reactivate the virus.
o In rare cases, particularly if the patient is also being treated with other medicines that suppress the immune system, reactivation of hepatitis B virus can be life-threatening.

Surgery or dental procedures

If your child is scheduled for surgery or dental procedures, inform your doctor that your child is taking Hukyndra. Your doctor may recommend temporarily stopping Hukyndra.

Demyelinating diseases

If your child has or develops a demyelinating disease (a disease affecting the insulating layer around nerves, such as multiple sclerosis), your doctor will decide whether treatment with Hukyndra should be started or continued. Inform your doctor immediately if your child develops symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccinations

Certain vaccines may cause infections and must not be given during treatment with Hukyndra.
o Consult your doctor before vaccinating your child.
o It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Hukyndra.
o If a woman has taken Hukyndra during pregnancy, the baby may have an increased risk of infection for up to approximately 5 months after the last dose the woman received during pregnancy. It is important that you inform the pediatrician or other healthcare provider about the use of Hukyndra during pregnancy so they can determine when the baby should receive any vaccinations.

Heart failure

If your child has mild heart failure and is being treated with Hukyndra, their heart condition must be closely monitored by the doctor. It is important to inform your doctor about any past or current heart problems. If new symptoms of heart failure develop or if existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether your child can continue taking Hukyndra.

Fever, bruising, bleeding, or paleness

In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. Your doctor may decide to stop treatment. If your child has persistent fever, develops easy bruising or bleeding, or appears pale, contact your doctor immediately.

Tumors

Very rarely, certain types of tumors have occurred in patients, both children and adults, treated with adalimumab or other anti-TNF medicines.
o Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumor affecting the lymphatic system) and leukemia (a tumor affecting blood and bone marrow).
o If your child takes Hukyndra, the risk of developing lymphomas, leukemia, or other tumors may increase. In rare cases, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or 6-mercaptopurine.
o Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Hukyndra.
o Cases of non-melanoma skin cancer have been observed in patients taking adalimumab.
o If new skin lesions appear during or after treatment, or if the appearance of existing lesions changes, inform your doctor.
Cases of malignancies other than lymphoma have occurred in patients with a specific type of lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If your child has COPD or is a heavy smoker, discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

Rarely, treatment with Hukyndra may lead to the development of a lupus-like syndrome. Inform your doctor if symptoms such as unexplained persistent skin rash, fever, joint pain, or fatigue occur.

Other medicines and Hukyndra
Inform your doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines.
Your child must not use Hukyndra with medicines containing the following active substances due to an increased risk of serious infections:

anakinra
abatacept

Hukyndra may be taken with:

methotrexate
other disease-modifying antirheumatic drugs (e.g., sulfasalazine, hydroxychloroquine, leflunomide, and parenteral gold salts)
corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.

Pregnancy and breastfeeding

A woman should use an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after the last dose of Hukyndra.
If a woman is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor about taking this medicine.
Hukyndra should be used during pregnancy only if necessary.
According to a pregnancy study, no increased risk of birth defects was observed when mothers received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
Hukyndra may be used during breastfeeding.
If a woman has taken Hukyndra during pregnancy, her baby may have an increased risk of infection.
It is important to inform the pediatrician and other healthcare providers about the use of Hukyndra during pregnancy before the baby receives any vaccinations. For more information on vaccinations, see the section "Warnings and precautions".

Driving and using machines
Hukyndra may affect, although only slightly, your child’s ability to drive, ride a bicycle, or operate machinery. After taking Hukyndra, visual disturbances or a sensation that the surroundings are spinning may occur.

Hukyndra contains sodium and polysorbate 80
This medicine contains less than 1 mmol (23 mg) of sodium per 0.2 ml, i.e., essentially 'sodium-free'.
This medicine contains 1 mg of polysorbate 80 per ml. Polysorbates may cause allergic reactions. Inform your doctor if your child has known allergies.

3. How to use Hukyndra

Use this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The recommended doses of Hukyndra for each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hukyndra if your child requires a different dose.

Juvenile idiopathic polyarticular arthritis
Age or body weight	What dose should be taken and how often?	Notes
Children, adolescents, and adults from 2 years of age and weighing 30 kg or more	40 mg every other week	Not applicable
Children and adolescents from 2 years of age and weighing between 10 kg and less than 30 kg	20 mg every other week	Not applicable
Enthesitis-related arthritis
Age or body weight	What dose should be taken and how often?	Notes
Children, adolescents, and adults from 6 years of age and weighing 30 kg or more	40 mg every other week	Not applicable
Children and adolescents from 6 years of age and weighing between 15 kg and less than 30 kg	20 mg every other week	Not applicable
Pediatric plaque psoriasis
Age or body weight	What dose should be taken and how often?	Notes
Children and adolescents aged between 4 and 17 years and weighing 30 kg or more	An initial dose of 40 mg, followed by 40 mg after one week. Subsequently, the usual dose is 40 mg every other week.	Not applicable
Children and adolescents aged between 4 and 17 years and weighing between 15 kg and less than 30 kg	An initial dose of 20 mg, followed by 20 mg after one week. Subsequently, the usual dose is 20 mg every other week.	Not applicable
Crohn's disease in pediatric patients
Age or body weight	What dose should be taken and how often?	Notes
Children and adolescents aged between 6 and 17 years weighing 40 kg or more	An initial dose of 80 mg, followed by 40 mg after two weeks. If a faster response is needed, the pediatrician may prescribe an initial dose of 160 mg, followed by 80 mg after two weeks. Subsequently, the usual dose is 40 mg every other week.	The pediatrician may increase the dosage to 40 mg weekly or 80 mg every other week.
Children and adolescents aged between 6 and 17 years and weighing less than 40 kg	An initial dose of 40 mg, followed by 20 mg after two weeks. If a faster response is needed, the pediatrician may prescribe an initial dose of 80 mg, followed by 40 mg after two weeks. Subsequently, the usual dose is 20 mg every other week.	The pediatrician may increase the dosing frequency to 20 mg weekly.

Pediatric uveitis

Age or body weight	What amount should be taken and how often?	Notes
Children and adolescents from 2 years of age and body weight below 30 kg	20 mg every other week	Your doctor may prescribe an initial dose of 40 mg to be administered one week before starting the regular dose of 20 mg every other week. The use of Hukyndra is recommended in combination with methotrexate.
Children and adolescents from 2 years of age and body weight equal to or above 30 kg	40 mg every other week	Your doctor may prescribe an initial dose of 80 mg to be administered one week before starting the regular dose of 40 mg every other week. The use of Hukyndra is recommended in combination with methotrexate.

Method and route of administration
Hukyndra is administered by subcutaneous injection (for subcutaneous injection).
Detailed instructions for Hukyndra injection are provided in section 7 “Instructions for use”.

If you use more Hukyndra than you should
If you accidentally inject Hukyndra more frequently than prescribed by your doctor or pharmacist, contact your doctor or pharmacist and inform them that your child has received an excess of the medicine. Always keep the medicine packaging, even if empty.

If you forget to use Hukyndra
If you forget to give your child an injection, administer the next dose of Hukyndra as soon as you remember. After that, give your child the following dose regularly according to the prescribed dosing schedule.

If you stop treatment with Hukyndra
The decision to stop using Hukyndra should be discussed with your doctor. Your child's symptoms may return if treatment with Hukyndra is stopped.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicinal product can cause side effects, although not everyone experiences them. Most side effects are mild to moderate in severity. However, some may be serious and require treatment. Side effects may occur up to 4 months after the last injection of Hukyndra.

Contact your doctor immediately if you notice any of the following reactions

severe rash, hives or other signs of allergic reaction
swelling of the face, hands or feet
difficulty breathing, difficulty swallowing
shortness of breath during physical activity or when lying down, or swollen feet

Contact your doctor as soon as possible if you notice any of the following reactions

signs of infection such as fever, feeling unwell, wounds, dental problems, burning sensation when urinating
fatigue or weakness
cough
tingling
numbness
double vision
weakness in arms or legs
swelling or open wound that does not heal
signs and symptoms suggesting disorders of the haematopoietic system, such as persistent fever, bruising, bleeding, paleness

The symptoms described above may be signs of the following side effects, 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, sinusitis, pneumonia)
headache
abdominal pain
nausea and vomiting
rash
musculoskeletal pain

Common (may affect up to 1 in 10 people)

serious infections (including sepsis and influenza)
intestinal infections (including gastroenteritis)
skin infections (including cellulitis and herpes zoster infection)
ear infections
oral infections (including dental infections and herpes simplex)
reproductive system infections
urinary tract infections
fungal infections
joint infections
benign tumours
skin cancer
allergic reactions (including seasonal allergies)
dehydration
mood changes (including depression)
anxiety
sleep disorders
sensory disturbances such as tingling, stabbing sensations or numbness
migraine
nerve root compression (including lower back pain and leg pain)
visual disturbances
eye inflammation
eyelid inflammation and eye swelling
dizziness (feeling of dizziness or spinning)
sensation of rapid heartbeat
high blood pressure
hot flushes
haematoma (accumulation of blood outside blood vessels)
cough
asthma
shortness of breath
gastrointestinal bleeding
dyspepsia (indigestion, bloating, heartburn)
acid reflux disorder
dryness syndrome (including dry eyes and dry mouth)
itching
itchy rash
bruising
skin inflammation (such as eczema)
nail breakage in fingers and toes
increased sweating
hair loss
onset or worsening of psoriasis
muscle spasms
blood in urine
kidney problems
chest pain
oedema (swelling)
fever
reduced platelet count in blood, increasing the risk of bleeding or bruising
poor wound healing

Uncommon (may affect up to 1 in 100 people)

opportunistic infections (including tuberculosis and other infections occurring when immune defences are reduced)
neurological infections (including viral meningitis)
eye infections
bacterial infections
diverticulitis (inflammation and infection of the large intestine)
tumours
lymphatic system tumours
melanoma
immune system disorders affecting lungs, skin and lymph nodes (most commonly presenting as sarcoidosis)
vasculitis (inflammation of blood vessels)
tremor (shaking)
neuropathy (nerve disorder)
stroke
hearing loss, ringing in the ears
sensation of irregular heartbeat such as palpitations
heart problems that may cause shortness of breath or swelling in the ankles
acute myocardial infarction
formation of a sac in the wall of a major artery, inflammation and clot in a vein, blockage of a blood vessel
lung disease causing shortness of breath (including inflammation)
pulmonary embolism (blockage of a pulmonary artery)
pleural effusion (abnormal fluid accumulation in the pleural space)
pancreatitis causing severe abdominal and back pain
difficulty swallowing
facial oedema (facial swelling)
gallbladder inflammation, gallstones
fatty liver
night sweats
scarring
abnormal muscle catabolism
systemic lupus erythematosus (including inflammation of the skin, heart, lungs, joints and other organs)
disrupted sleep
impotence
inflammations

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

leukaemia (a cancer affecting blood and bone marrow)
severe allergic reaction with shock
multiple sclerosis
neurological disorders (such as optic neuritis and Guillain-Barré syndrome, which may cause muscle weakness, abnormal sensations, tingling in arms and upper body)
cardiac arrest
pulmonary fibrosis (lung scarring)
intestinal perforation (hole in the intestine)
hepatitis
reactivation of hepatitis B
autoimmune hepatitis (liver inflammation caused by the body’s own immune system)
cutaneous vasculitis (inflammation of blood vessels in the skin)
Stevens-Johnson syndrome (early symptoms include malaise, fever, headache and rash)
facial oedema (facial swelling) associated with allergic reactions
erythema multiforme (inflammatory skin rash)
lupus-like syndrome
angioedema (localized skin swelling)
lichenoid skin reaction (pruritic red-violet rash)

Not known (frequency cannot be estimated from the 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 form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly presents with purple lesions on the skin
liver failure
worsening of a condition called dermatomyositis (characterized by skin rash accompanied by muscle weakness)
weight gain (in most patients, weight gain has been low)

Some of the effects observed with adalimumab may be asymptomatic and detectable only through blood tests. These include:

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

low white blood cell count
low red blood cell count
increased blood lipids
increased liver enzymes

Common (may affect up to 1 in 10 people)

increased white blood cell count
decreased platelet count
increased blood uric acid
altered blood sodium levels
decreased blood calcium
decreased blood phosphorus
increased blood glucose
increased blood lactate dehydrogenase
presence of autoantibodies in blood
decreased blood potassium

Uncommon (may affect up to 1 in 100 people)

elevated bilirubin levels in blood (liver blood test)

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

low white blood cell, red blood cell and platelet counts

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, talk to your paediatrician or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hukyndra

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label/blister/box after the word "Exp". The expiry date refers to the last day of that month.
Store in the refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.

Alternative storage conditions:
If necessary (e.g. during travel), a single pre-filled syringe of Hukyndra may be stored at a temperature between 20°C and 25°C for a maximum period of 30 days, taking care to protect it from light. Once removed from the refrigerator for storage at a temperature between 20°C and 25°C, the syringe must be used within 30 days or discarded, even if it is returned to the refrigerator.
It is necessary to record the date when the syringe was first removed from the refrigerator and the date after which it must be discarded.
Do not use this medicine if the liquid is cloudy, discoloured, or contains flakes or particles.
Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hukyndra contains

The active substance is adalimumab.
The excipients are sodium chloride, sucrose, polysorbate 80, water for injections, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment).

Description of the appearance of Hukyndra and contents of the pack
Hukyndra 20 mg solution for injection in pre-filled syringe with needle protection for paediatric use is supplied as a sterile solution containing 20 mg of adalimumab dissolved in 0.2 ml of solution.
Hukyndra pre-filled syringe consists of a solution of adalimumab contained in a glass syringe.
Each pack contains 2 pre-filled syringes packaged in blisters with 2 alcohol-impregnated swabs.

Marketing Authorisation Holder
STADA Arzneimittel AG
Stadastrasse 2–18
61118 Bad Vilbel
Germany

Manufacturers
Ivers-Lee CSM
Marie-Curie-Str.8
79539 Lörrach
Germany
Alvotech Hf
Sæmundargata 15-19
Reykjavik, 101
Iceland
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
EG (Eurogenerics) NV UAB „STADA Baltics“
Tél/Tel: +32 24797878 Tel: +370 52603926

България Luxembourg/Luxemburg
STADA Bulgaria EOOD EG (Eurogenerics) NV
Teл.: +359 29624626 Tél/Tel: +32 24797878

Česká republika Magyarország
STADA PHARMA CZ s.r.o. STADA Hungary Kft
Tel: +420 25788111 Tel.: +36 18009747

Danmark Malta
STADA Nordic ApS Pharma.MT Ltd
Tlf: +45 44859999 Tel: +356 21337008

Deutschland Nederland
STADAPHARM GmbH Centrafarm B.V.
Tel: +49 61016030 Tel.: +31 765081000

Eesti Norge
UAB „STADA Baltics“ STADA Nordic ApS
Tel: +370 52603926 Tlf: +45 44859999

Ελλάδα Österreich
RAFARM A.E.B.E. STADA Arzneimittel GmbH
Τηλ: +30 2106776550 Tel: +43 136785850

España Polska
Laboratorio STADA, S.L. STADA Pharm Sp. z.o.o.
Tel: +34 934738889 Tel: +48 227377920

France Portugal
EG LABO - Laboratoires EuroGenerics Stada, Lda.
Tél: +33 146948686 Tel: +351 211209870

Hrvatska România
STADA d.o.o. STADA M&D SRL
Tel: +385 13764111 Tel: +40 213160640

Ireland Slovenija
Clonmel Healthcare Ltd. Stada d.o.o.
Tel: +353 526177777 Tel: +386 15896710

Ísland Slovenská republika
STADA Arzneimittel AG STADA PHARMA Slovakia, s.r.o.
Sími: +49 61016030 Tel: +421 252621933

Italia Suomi/Finland
EG SpA STADA Nordic ApS, Suomen sivuliike
Tel: +39 028310371 Puh/Tel: +358 207416888

Κύπρος Sverige
STADA Arzneimittel AG STADA Nordic ApS
Τηλ: +30 2106664667 Tel: +45 44859999

Latvija
UAB „STADA Baltics“
Tel: +370 52603926

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
Detailed information on this medicinal product, including a video on how to use the pre-filled syringe, is available by scanning the QR code included below or on the outer packaging with a smartphone. The same information is also available at the following URL: hukyndrapatients.com
Insert QR code

7 Instructions for use
INSTRUCTIONS FOR USE
Hukyndra (adalimumab) pre-filled syringe
20 mg/0.2 ml solution for injection, for subcutaneous use
Read these instructions for use carefully before using the Hukyndra single-use pre-filled syringe

Hukyndra pre-filled syringe

Important information you should know before injecting Hukyndra single-use pre-filled syringe
Important information:

For subcutaneous injection only
Do not use the syringe and contact your doctor or pharmacist if:
- The liquid appears cloudy, discoloured, or contains flakes or particles,
- The expiry date has been exceeded,
- The solution has been frozen (even if thawed) or exposed to direct sunlight,
- The pre-filled syringe has been dropped or damaged.
Remove the needle cap only immediately before injection. Keep Hukyndra out of the reach of children.
See section 5 of the package leaflet for instructions on how to store the Hukyndra single-use pre-filled syringe.

Before injection:
Your doctor should show you how to use the Hukyndra single-use pre-filled syringe before you use it for the first time.
Current use of adalimumab syringe:
Even if you have previously used other marketed adalimumab syringes, please read these instructions completely to understand how to correctly use this device before injection.
Questions about using Hukyndra pre-filled syringe?
Talk to your doctor if you have any questions.

Preparing for Hukyndra pre-filled syringe injection
STEP 1: Remove the syringe from the refrigerator and allow it to reach room temperature (20°C to 25°C) for 15–30 minutes
1.1 Remove Hukyndra from the refrigerator (see Figure A).
1.2 Allow Hukyndra to warm to room temperature (20°C to 25°C) for 15–30 minutes before injection (see Figure B).

Do not remove the grey needle cap while waiting for Hukyndra to reach 20°C–25°C.
Do not warm Hukyndra by other means. For example, do not warm in a microwave or in hot water.
Do not use the pre-filled syringe if the solution has been frozen (even if thawed).

A hand holds a white container while a black arrow indicates the insertion movement toward the

Figure A

Circular clock with white dial and black border showing a time interval highlighted in red between 15 and 30 minutes

Figure B
STEP 2: Check the expiry date and the liquid medicine
2.1 Check the expiry date on the label of the pre-filled syringe (see Figure C).

Do not use the pre-filled syringe if the expiry date (Exp.) has passed.

2.2 Check the liquid medicine in the syringe to ensure it is clear and colourless (see Figure C).

Do not use the syringe and contact your doctor or pharmacist if the liquid appears cloudy, discoloured, or contains flakes or particles.

A hand holds a syringe to check the solution and expiration date marked with the text Exp MM/YYYY

Figure C
STEP 3: Gather what you need and wash your hands
3.1 Place the following items on a clean, flat surface (see Figure D):

1 single-use pre-filled syringe and 1 alcohol-impregnated swab.
1 cotton ball or gauze (not included).
A puncture-resistant sharps disposal container (not included). See Step 9.

3.2 Wash and dry your hands (see Figure E).

Drawing of an alcohol-soaked swab, a cotton ball, and a red and yellow container with biohazard symbol

Figure D

Two hands under an open faucet emitting a stream of

Figure E
Injecting Hukyndra pre-filled syringe
STEP 4: Choose and clean the injection site
4.1 Select an injection site (see Figure F):

on the front of the thigh, or
on the abdomen (stomach), at least 5 cm from the navel;
different from your last injection site (at least 3 cm away from the previous injection site).

4.2 Wipe the injection site in a circular motion with the alcohol-impregnated swab (see Figure G).

Do not inject through clothing.
Do not inject into areas where the skin appears tender, bruised, red, hard, scarred, or has stretch marks or psoriasis.

Diagram of a male body with three yellow areas highlighted for the

Figure F

A hand with dark skin pressing a white cotton swab onto the skin surface of an arm or leg

Figure G
STEP 5: Remove the needle cap
5.1 Hold the pre-filled syringe in one hand (see Figure H).
5.2 Gently remove the needle cap with the other hand (see Figure H).

Discard the needle cap.
Do not reuse the needle cap.
Do not touch the needle with your fingers and ensure the needle does not come into contact with anything.
Hold the pre-filled syringe with the needle pointing upwards. You may see air in the pre-filled syringe. Slowly push the plunger to expel the air through the needle.
You may see a drop of liquid at the tip of the needle. This is normal.

A hand lifts a protective cap upward toward the

Figure H
STEP 6: Hold the syringe and lift the skin
6.1 Hold the body of the pre-filled syringe between your thumb and index finger with one hand, like a pencil (see Figure I). Do not pull back the plunger at any time.
6.2 With the other hand, gently pinch (lift) the cleaned skin area at the injection site (abdomen or thigh) (see Figure J). Hold the skin firmly.

A hand firmly holds a syringe with needle pointing downward to prepare the

Figure I

Two hands gently pressing the skin of the abdominal area to prepare the

Figure J
STEP 7: Inject the medicine
7.1 Insert the needle into the lifted skin at an angle of approximately 45 degrees with a quick, dart-like motion (see Figure K).

Once the needle is inserted, release the skin.

7.2 Slowly push the plunger until all the solution has been injected and the pre-filled syringe is empty (see Figure L).

Figure K

A hand holds an auto-injector at an angle while the

Figure L
STEP 8: Allow the pre-filled syringe to retract the needle from the skin
8.1 Slowly remove your finger from the plunger. The plunger will rise with your finger and retract the needle into the needle protection device (see Figure M).

The needle will not retract unless the full solution has been injected. Contact your doctor, pharmacist, or nurse if you think you did not administer a complete dose.
It is normal to see a spring around the plunger after the needle has retracted.

8.2 After completing the injection, place a cotton ball or gauze pad on the skin over the injection site.

Do not rub.
Mild bleeding at the injection site is normal.

A hand holds an injection pen tilted while the

Figure M
Disposal of Hukyndra pre-filled syringe
STEP 9: Dispose of the used syringe in a sharps disposal container
9.1 Immediately after use, place used needles, syringes, and other sharp objects into a sharps disposal container (see Figure N).

Do not throw loose needles or syringes into household waste.

9.2 The needle cap, alcohol swab, cotton ball or gauze, and packaging may be disposed of in household waste.

A hand holds a transparent medical device to insert it into a red and yellow container with biohazard symbol

Figure N
Additional information on disposal

If you do not have a sharps disposal container, you may use a household container that is:
- made of heavy-duty plastic,
- closed with a tight-fitting, puncture-resistant lid so that sharp objects cannot leak out,
- kept upright and stable during use,
- leak-proof, and
- properly labelled to warn of hazardous waste inside.

When the sharps disposal container is nearly full, follow local guidelines for proper disposal of the container.
Do not throw used sharps disposal containers into household waste. Do not recycle used sharps disposal containers.
If you have any questions, contact your doctor for assistance.

Patient information leaflet

Hukyndra 40 mg solution for injection in pre-filled syringe

adalimumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will provide you with a Patient Reminder Card containing important safety information you need to know before starting treatment with Hukyndra and during treatment. Keep this Patient Reminder Card throughout your treatment and for 4 months after your last injection of Hukyndra.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

What Hukyndra is and what it is used for
What you need to know before using Hukyndra
How to use Hukyndra
Possible side effects
How to store Hukyndra
Contents of the pack and other information
Instructions for use

1. What Hukyndra is and what it is used for

Hukyndra contains the active substance adalimumab.
Hukyndra is used to treat:

Rheumatoid arthritis
Polyarticular juvenile idiopathic arthritis
Enthesitis-related arthritis
Ankylosing spondylitis
Axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
Psoriatic arthritis
Plaque psoriasis
Hidradenitis suppurativa
Crohn's disease
Ulcerative colitis
Non-infectious uveitis

The active substance in Hukyndra, adalimumab, is a human monoclonal antibody.
Monoclonal antibodies are proteins that bind to a specific target.
Adalimumab's target is a protein called tumour necrosis factor (TNFα), which is involved in the (defence) immune system and is present at higher concentrations in the inflammatory diseases listed above. By binding to TNFα, Hukyndra reduces the inflammatory process in these diseases.

Rheumatoid arthritis
Rheumatoid arthritis is an inflammatory disease affecting the joints.
Hukyndra is used to treat moderate to severe rheumatoid arthritis in adults.
Initially, other disease-modifying drugs such as methotrexate may be used. If the response to these drugs is not satisfactory, you will be given Hukyndra.
Hukyndra may also be used to treat severe, active and progressive rheumatoid arthritis without prior treatment with methotrexate.
Hukyndra can slow down the progression of joint damage caused by the inflammatory disease and may help you move more freely.
Your doctor will decide whether Hukyndra should be taken with methotrexate or alone.

Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints.
Hukyndra is used to treat polyarticular juvenile idiopathic arthritis in patients aged 2 years and older. Initially, other disease-modifying drugs such as methotrexate may be used. If the response to these drugs is not adequate, you will be given Hukyndra.
Your doctor will decide whether Hukyndra should be taken with methotrexate or alone.

Enthesitis-related arthritis
Enthesitis-related arthritis is an inflammatory disease affecting the joints and the areas where tendons attach to bones.
Hukyndra is used to treat enthesitis-related arthritis in patients aged 6 years and older. Initially, other disease-modifying drugs such as methotrexate may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis are inflammatory conditions of the spine.
Hukyndra is used to treat severe ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing spondylitis in adults. Initially, other medications may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

Psoriatic arthritis
Psoriatic arthritis is an inflammatory disease of the joints, usually associated with psoriasis.
Hukyndra is used to treat psoriatic arthritis in adults. Hukyndra can slow down joint damage caused by the disease and may help you move more freely. Initially, other medications may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

Plaque psoriasis
Plaque psoriasis is a skin condition causing reddish, scaly, thickened patches of skin covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken, or lift from the nail bed, which may be painful.
Hukyndra is used to treat:

moderate to severe chronic plaque psoriasis in adults, and
severe chronic plaque psoriasis in children and adolescents aged 4 to 17 years when topical therapy and phototherapy have not worked well or are not suitable.

Hidradenitis suppurativa
Hidradenitis suppurativa (sometimes called inverse acne) is a chronic inflammatory skin disease and is often painful. Symptoms may include painful nodules and abscesses (cysts) that may drain pus. It most commonly affects specific skin areas such as the under-breast region, armpits, inner thighs, groin, and buttocks. Scarring may also develop in affected areas.
Hukyndra is used to treat:

moderate to severe hidradenitis suppurativa in adults, and
moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hukyndra can reduce the number of nodules and abscesses caused by the disease. Initially, other medications may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

Crohn's disease
Crohn's disease is an inflammation of the gastrointestinal tract.
Hukyndra is used to treat:

moderate to severe Crohn's disease in adults, and
moderate to severe Crohn's disease in children and adolescents aged 6 to 17 years.

Initially, other medications may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

Ulcerative colitis
Ulcerative colitis is an inflammation of the large intestine (colon).
Hukyndra is used to treat:

moderate to severe ulcerative colitis in adults, and
moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

Initially, other medications may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

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

This inflammation can lead to reduced vision and/or the presence of floaters in the eye (black spots or thin lines moving across the visual field). Hukyndra works by reducing this inflammation.
Initially, other medications may be used. If the response to these drugs is not adequate, you will be given Hukyndra.

2. What you should know before using Hukyndra

Do not use Hukyndra

If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
If you have active tuberculosis or other serious infections (see "Warnings and precautions"). It is important to inform your doctor if you have signs or symptoms of infection, for example, fever, wounds, feeling tired, dental problems.
If you have moderate or severe heart failure. It is important to inform your doctor if you have had or currently have a serious heart condition (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before using Hukyndra.
Allergic reactions

If you experience allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or skin rash, do not take Hukyndra again and contact your doctor immediately, as these reactions may, in rare cases, be life-threatening.

Infections

If you have an infection, including long-term infections or localized infections in one part of the body (for example, leg ulcers), consult your doctor before starting treatment with Hukyndra. If you are unsure, contact your doctor.
You may be more likely to get infections while being treated with Hukyndra. This risk may increase if you have lung problems. These infections can be serious and may include:
tuberculosis
infections caused by viruses, fungi, parasites or bacteria
serious blood infections (sepsis)

In rare cases, these infections may be life-threatening. It is important to inform your doctor if you have symptoms such as fever, wounds, feeling tired or dental problems.
Your doctor may instruct you to temporarily stop taking Hukyndra.

Inform your doctor if you live or travel in areas where fungal infections are common (for example, histoplasmosis, coccidioidomycosis or blastomycosis).
Inform your doctor if you have had recurring infections or if you have other medical conditions that increase your risk of infection.
If you are over 65 years old, you may be more likely to get infections while taking Hukyndra. You and your doctor should pay particular attention to signs of infection during treatment with Hukyndra. It is important to inform your doctor if you develop symptoms of infections such as fever, wounds, feeling tired or dental problems.

Tuberculosis

It is very important to inform your doctor if you have ever had tuberculosis or if you have been in contact with someone who had tuberculosis. You must not take Hukyndra if you have active tuberculosis.
Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will check for signs and symptoms of tuberculosis before starting treatment with Hukyndra. This will include a detailed medical evaluation including your medical history and appropriate clinical tests (for example, a chest X-ray and tuberculin skin test). The performance and results of these tests must be recorded in the Patient Reminder Card.
Tuberculosis may develop during treatment even if you have received treatment to prevent tuberculosis.
Contact your doctor immediately if you develop symptoms of tuberculosis (for example, a persistent cough, weight loss, lack of energy, low-grade fever) or other infections during or after treatment.

Hepatitis B

Inform your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active hepatitis B virus infection, or if you think you may be at risk of contracting the hepatitis B virus.
Your doctor should test you for hepatitis B virus infection. In HBV carriers, taking adalimumab may cause the virus to reactivate.
In some rare cases, especially if the patient is also taking other medicines that suppress the immune system, reactivation of the hepatitis B virus may be life-threatening.

Surgery or dental procedures

Before any surgery or dental procedures, inform your doctor that you are taking Hukyndra. Your doctor may recommend temporarily stopping Hukyndra.

Demyelinating diseases

If you have or develop a demyelinating disease (a disease affecting the protective covering around nerves, such as multiple sclerosis), your doctor will decide whether you should start or continue treatment with Hukyndra. Inform your doctor immediately if you experience symptoms such as changes in vision, weakness in arms or legs, or numbness or tingling in any part of the body.

Vaccinations

Certain vaccines may cause infections and must not be given during treatment with Hukyndra.
Consult your doctor before receiving any vaccinations.
It is recommended, if possible, that children receive all age-appropriate vaccinations before starting treatment with Hukyndra.
If you have taken Hukyndra during pregnancy, your baby may have an increased risk of infection for up to about 5 months after your last dose of Hukyndra. It is important that you inform the paediatrician or other healthcare provider about your use of Hukyndra during pregnancy, so they can decide when your baby should receive any type of vaccination.

Heart failure

If you have mild heart failure and are being treated with Hukyndra, your doctor should carefully evaluate and monitor your heart condition. It is important to inform your doctor about any past or current heart problems. If new symptoms of heart failure appear or if existing symptoms worsen (for example, shortness of breath or swelling of the feet), contact your doctor immediately. Your doctor will decide whether you can continue using Hukyndra.

Fever, bruising, bleeding or paleness

In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. Your doctor may decide to stop treatment. If you have persistent fever, bruising, easy bleeding or paleness, contact your doctor immediately.

Tumours

Very rarely, certain types of tumours have occurred in patients, both children and adults, treated with adalimumab or other anti-TNF medicines.
Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma (a tumour affecting the lymphatic system) and leukaemia (a tumour affecting blood and bone marrow).
If you take Hukyndra, your risk of developing lymphomas, leukaemia or other tumours may increase. In rare cases, a rare and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or 6-mercaptopurine.
Inform your doctor if you are taking azathioprine or 6-mercaptopurine with Hukyndra.
Cases of non-melanoma skin cancer have been observed in patients taking adalimumab.
If new skin lesions appear during or after treatment, or if existing lesions change in appearance, inform your doctor.
Cases of malignancies other than lymphoma have been reported in patients with a specific type of lung disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another anti-TNF medicine. If you have COPD or are a heavy smoker, you should discuss with your doctor whether treatment with an anti-TNF medicine is appropriate.

Autoimmune disease

Rarely, treatment with Hukyndra may lead to the development of a lupus-like syndrome. Inform your doctor if you develop symptoms such as a persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

Vaccinations: if possible, children should have received all age-appropriate vaccinations before using Hukyndra.

Other medicines and Hukyndra
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Do not use Hukyndra with medicines containing the following active substances due to an increased risk of serious infections:

anakinra
abatacept

Hukyndra may be taken with:

methotrexate
other disease-modifying antirheumatic drugs (for example, sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts)
corticosteroids or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).

If you have any doubts, consult your doctor.
Pregnancy and breastfeeding

You should consider using an effective contraceptive method to prevent pregnancy and continue using it for at least 5 months after your last dose of Hukyndra.
If you are pregnant, think you may be pregnant or are planning to become pregnant, ask your doctor for advice regarding the use of this medicine.
Hukyndra should be used during pregnancy only if necessary.
According to a pregnancy study, no increased risk of birth defects was observed in mothers who received adalimumab during pregnancy compared to mothers with the same condition who did not receive adalimumab.
Hukyndra may be used during breastfeeding.
If you take Hukyndra during pregnancy, your baby may have an increased risk of infection.
It is important that you inform the paediatrician or other healthcare provider about your use of Hukyndra during pregnancy before your baby receives any vaccinations. For further information on vaccinations, see the section "Warnings and precautions".

Driving and using machines
Hukyndra may have a minor influence on your ability to drive, ride a bicycle or use machines. After taking Hukyndra, you may experience visual disturbances or a sensation that your surroundings are spinning.
Hukyndra contains sodium and polysorbate 80
This medicine contains less than 1 mmol (23 mg) of sodium per 0.4 ml, i.e. essentially 'sodium-free'.
This medicine contains 1 mg of polysorbate 80 per ml. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.