IMUKIN 100 micrograms INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

IMUKIN 100 micrograms solution for injection

Recombinant human interferon gamma-1b

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.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is IMUKIN and what is it used for

IMUKIN contains the active substance recombinant human interferon gamma-1b. Interferons are also known as immunomodulators. These are small proteins capable of stimulating the body's defense mechanisms. They protect against microorganisms (such as bacteria, viruses, and fungi) that can cause diseases.

IMUKIN is used in patients with chronic granulomatous disease (CGD). CGD is a deficiency in the metabolism of neutrophils, a type of white blood cell that normally eradicates bacteria or fungi that invade the body. The deficient alteration of CGD makes neutrophils less capable of preventing infections.

IMUKIN is used to reduce the frequency of severe infections that can occur with this disease.

IMUKIN is also used in patients with severe malignant osteopetrosis. This is a hereditary defect in bone cells that produces excessive and abnormal bone growth. It also affects the bone marrow and the blood cells that are normally formed in it. Consequently, patients with osteopetrosis also have a risk of severe infections.

2. What you need to know before you use IMUKIN

Do not use IMUKIN

• if you are allergic to interferon gamma or other related interferons or to some of the other ingredients of this medicine (listed in section 6).

Ask your doctor or pharmacist if you are not sure if you are allergic to interferons.

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with IMUKIN.

Be careful with IMUKIN

• if you have heart disease, as doses higher than the usual doses may worsen your heart disease (see section 3 for dosage)
• if you have seizure disorders and/or alterations in central nervous system function
• if your liver does not function normally (liver failure)
• if your kidney does not function normally (kidney failure)
• if your bone marrow does not produce blood cells in normal quantities (myelosuppression)
• if you are allergic to latex, as the rubber stopper of the glass vial contains natural rubber (a latex derivative) that can cause allergic reactions.

Consult your doctor if any of the above circumstances apply to you now or have applied to you in the past.

You should avoid using IMUKIN with other medicines that contain proteins. You should also avoid using IMUKIN at the same time as you are given a vaccine. Consult your doctor if you have any doubts about this.

You should continue to undergo the tests used in the treatment of CGD and severe malignant osteopetrosis. You should be carefully monitored, with your blood cell count, urine, and liver and kidney function being checked both before and during treatment.

High levels of interferon gamma-1b in the body can damage fertility in men and women.

Other medicines and IMUKIN

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

You may need antibiotics to treat infections that still occur while you are using IMUKIN for the treatment of CGD. It has not been shown that IMUKIN affects the efficacy of antibiotics or corticosteroids, medicines commonly used in patients with CGD and severe malignant osteopetrosis.

Medicines that affect the liver or kidneys may affect the elimination of IMUKIN from the body. IMUKIN may prolong the activity of other medicines that are broken down and eliminated from the body through the liver.

If you use IMUKIN with medicines or vaccines that have effects on the heart, blood, bone marrow, nervous system, or immune system, the risk of side effects may increase.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Based on available information, the effects on fertility are not known, but they cannot be excluded. IMUKIN should not be used during pregnancy unless your doctor considers it essential. Breastfeeding is not recommended during treatment with IMUKIN. Consult your doctor or pharmacist before using any medicine.

Driving and using machines

IMUKIN may cause fatigue, seizures (convulsions), confusion, disorientation, or distorted or imaginary sensations (hallucinations). These side effects can reduce your reaction ability, which may have a negative effect on your ability to drive and use machines. Do not drive or use machines if you notice that your reaction ability is reduced.

IMUKIN contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 0.5 ml vial, so it is considered essentially "sodium-free".

This may be important for people with high blood pressure and others who want to maintain a low-sodium diet.

3. How to use IMUKIN

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist again.

IMUKIN should be administered by subcutaneous injection. IMUKIN can be administered by a doctor or a nurse and also by you or a family member, provided they have been previously instructed by a doctor or a nurse.

The recommended dose of IMUKIN for the treatment of patients with CGD or severe malignant osteopetrosis is 50 micrograms/m2 in those patients whose body surface area is greater than 0.5 m2 and 1.5 micrograms/kg for patients whose body surface area is less than or equal to 0.5 m2.

Your doctor will decide how much IMUKIN you need to use for the treatment of CGD or severe malignant osteopetrosis.

You should inject (or should be injected) under your skin the exact amount of IMUKIN that your doctor has indicated you need. You should administer the injections 3 times a week (e.g., Monday, Wednesday, and Friday), preferably at night. The recommended injection sites are the upper arm or the upper thigh.

• Before administering the injection, always check the amount of IMUKIN solution.

• Do not use IMUKIN if you can see small particles or discoloration of the solution.

• Do not mix IMUKIN with other medicines.

• Do not shake the IMUKIN vials vigorously.

If you use more IMUKIN than you should

Consult your doctor immediately if you have administered more IMUKIN than your doctor has indicated or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken. It is recommended to take the package and leaflet to the healthcare professional.

The symptoms after administration of too much IMUKIN may include:

• central nervous system side effects such as difficulty thinking, difficulty walking, and dizziness
• if you have heart disease, it may worsen for a short period
• blood disorders may occur during treatment with IMUKIN, including:
• temporary changes in the amount of some blood cells
• increased levels of certain substances (liver enzymes and triglycerides) in the blood.

Your doctor may detect these changes with a blood test.

These symptoms disappear with a decrease in the dose or interruption of treatment with IMUKIN.

If you forget to use IMUKIN

Do not take a double dose to make up for forgotten doses.

Administer your injections according to the schedule recommended by your doctor. You can still administer it on the same day or the next day. Consult your doctor if you think you have been without administering a dose for too long.

If you stop treatment with IMUKIN

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

Tell your doctor if you stop treatment with IMUKIN.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The risk of side effects depends on the dose and administration schedule indicated by your doctor.

The most common side effects are flu-like symptoms such as fever, headache, chills, and fatigue.

These may decrease in severity over time as treatment continues. Some of these symptoms can be minimized by administering IMUKIN just before bedtime. A medicine like paracetamol can be used to reduce some of these effects.

Some patients who use IMUKIN may experienceshort-term skin problems, such asa temporary skin rash, spotted rashes, sudden appearance of blisters on the skin, and redness of the skin at the injection site.

However, they have rarely been severe enough to interrupt treatment with IMUKIN.

The following side effects are grouped by frequency:

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

• fever
• headache
• chills
• pain at the injection site
• vomiting
• nausea (feeling sick)
• diarrhea
• fatigue
• high liver enzyme levels
• skin rash

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

• muscle pain
• joint pain
• back pain
• stomach pain
• depression

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

• decrease in white blood cells (neutropenia)
• decrease in blood platelets (thrombocytopenia) that may be associated with the appearance of bruises and tendency to bleed
• proteins in the urine

Side effects have also been observed in patients with diseases other than CGD and severe malignant osteopetrosis. These side effects have not been observed in clinical trials related to CGD or severe malignant osteopetrosis.

The following side effects have been reported in clinical trials with patients who had disorders/diseases other than CGD or severe malignant osteopetrosis. The usual doses used in these studies were higher than those recommended for the treatment of CGD and severe malignant osteopetrosis. For this reason, their frequency of occurrence cannot be precisely determined.

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

• low sodium levels in the blood, which can cause fatigue and confusion, muscle contractions, seizures, or coma (hyponatremia)
• high levels of a sugar called glucose (hyperglycemia)
• high levels of fatty acids called triglycerides (hypertriglyceridemia) in the blood

The following nervous system disorders have been observed:

• confusion
• disorientation
• effects on walking ability, such as parkinsonian gait
• tremors
• seizures
• distorted or imaginary sensations (hallucinations)

The following heart disorders have also been observed:

• extra and irregular heartbeats
• changes in heart rhythm, such as increased or decreased heart rate
• heart problems that can cause difficulty breathing or swelling of the ankle (heart failure)
• heart attack

The following blood system disorders have also been reported:

• low blood pressure
• fainting
• temporary mild stroke (transient ischemic attack)
• blood clots or blockage of a lung artery (deep vein thrombosis and pulmonary embolism); symptoms may include difficulty breathing

The following respiratory disorders have been observed:

• rapid breathing
• chest tightness (bronchospasm or interstitial lung disease)

• bleeding in the digestive system
• inflammation of the pancreas, which can cause death
• liver damage that affects its function (liver failure)
• kidney damage that affects its function but can be effectively treated (reversible kidney failure)
• chest pain
• worsening of a skin disease called dermatomyositis (presenting as a skin rash accompanied by muscle weakness)
• development of a long-term disease called systemic lupus erythematosus (the patient's immune system attacks several parts of the body)
• autoimmune reaction (auto-antibody response)

Reporting of side effects

If you experience 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 through the Spanish Medicines Monitoring System: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing IMUKIN

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 carton and vial after "EXP". The expiry date is the last day of the month stated.

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

The IMUKIN solution for injection vials should be used once only. IMUKIN does not contain preservatives.

Once opened, the contents of a vial should be used immediately. Discard the leftover solution.

Do not use this medicine if you notice the presence of particles or discoloration before use.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the SIGRE collection point at the pharmacy. If you are in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of IMUKIN

• The active substance is recombinant human interferon gamma-1b. Each vial (0.5 ml) contains 100 micrograms (2 x 10^6 IU) of recombinant human interferon gamma-1b. It is produced by the bacterium E. colimodified by genetic engineering.
• The other ingredients are D-mannitol, disodium succinate hexahydrate, polysorbate 20, succinic acid, and water for injections.

The rubber stopper of the glass vial contains natural rubber (a latex derivative).

Appearance and packaging

IMUKIN is a clear and colorless solution for injection. It is available in 4 ml vials containing 0.5 ml of solution.

Package sizes: 1, 3, 5, 6, and 12 vials in a cardboard box. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Clinigen Healthcare B.V.

Schiphol Boulevard 359

WTC Schiphol Airport, D Tower 11th floor

1118BJ Schiphol

Netherlands

Manufacturer

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk,

Co. Louth

A91 P9KD

Ireland

or

Almac Pharma Services Limited

Seagoe Industrial Estate

BT63 5UA Craigavon

Northern Ireland, United Kingdom

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of this leaflet: November 2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/