Prospecto: information for the user

IMUKIN 100 micrograms injectable solution

Human recombinant interferon gamma-1b

Read this prospectus carefully before starting to use the medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospectus. See section 4.

1.What is IMUKIN and for what it is used

2.What you need to know before starting to use IMUKIN

3.How to use IMUKIN

4.Possible adverse effects

5.Storage of IMUKIN

6.Contents of the package and additional information

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

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

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

IMUKIN is also used in patients with malignant severe marble bone disease (osteopetrosis). This consists of a hereditary defect in bone cells that produces excessive and abnormal bone growth. It also affects the bone marrow and blood cells that are normally formed there. As a result, patients with osteopetrosis also have a risk of severe infections.

No use IMUKIN

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

Ask your doctor or pharmacist if you are unsure if you are allergic to interferons.

Warnings and precautions

Consult your doctor or pharmacist before starting to use IMUKIN.

Be especially careful with IMUKIN

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

Consult your doctor if any of the above-mentioned circumstances occur in the present or have occurred at any time.

You must avoid using IMUKIN with other medications that contain proteins. You must also avoid using IMUKIN while receiving a vaccine. Consult your doctor if you have any doubts.

You must continue to undergo the tests used in the treatment of EGC and severe malignant osteopetrosis. Your blood cell count, urine, liver, and kidney function must be closely monitored both before and during treatment.

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

Other medications and IMUKIN

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

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

Medications that affect the liver or kidneys may affect the elimination of IMUKIN from the body. IMUKIN may prolong the activity of other medications that are broken down and eliminated from the body by the liver.

If you use IMUKIN with medications or vaccines that affect the heart, blood, bone marrow, nervous system, or immune system, it may increase the risk of adverse effects.

Pregnancy, breastfeeding, and fertility

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

Based on the available information, there is no known effect on fertility, but it cannot be ruled out. IMUKIN should not be used during pregnancy unless your doctor considers it essential. Breastfeeding is not recommended during IMUKIN treatment. Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

IMUKIN may cause fatigue, seizures, confusion, disorientation, or distorted or imaginary sensations (hallucinations). These adverse effects may decrease your reaction time, so you may have a negative effect on your ability to drive and operate machinery. Do not drive or use machinery if you notice that your reaction time is decreased.

IMUKIN contains sodium

This medication 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 individuals with high blood pressure and others who wish to maintain a low-sodium diet.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

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

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

You must 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 (for example, 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.

• No use IMUKIN if you can see small particles or discoloration of the solution.

• Do not mix IMUKIN with other medications.

• 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 indicatedor call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the packaging and the leaflet to the healthcare professional.

The symptoms after administering too much IMUKIN may include the following:

• central nervous system adverse effects such as difficulty thinking, difficulty walking, and dizziness
• If you have a heart disease, it may worsen for a short period of time
• Abnormalities in the blood may occur during treatment with IMUKIN. These include:
• Temporary changes in the number of some blood cells
• Increased levels of certain substances (liver enzymes and triglycerides) in the blood.

Your doctor may detect these alterations through a blood test.

These symptoms disappear with the reduction of the dose or the interruption of IMUKIN treatment.

If you forget to use IMUKIN

Do not take a double dose to compensate for the missed 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 too long without administering a dose.

If you interrupt IMUKIN treatment

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Inform your doctor if you interrupt IMUKIN treatment.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. The risk of side effects depends on the dose and administration schedule that has been indicated to you.

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

These may decrease in severity over time as you continue treatment. Some of these symptoms may be minimized by administering IMUKIN just before bedtime. You may use a medication such as paracetamol to reduce some of these side effects.

Some patients taking IMUKIN may experience skin problems in the short term,such as a temporary skin rash, rash with spots, sudden appearance of blisters on the skin, and skin redness at the injection site.For example,these have rarely been severe enough to interrupt treatment with IMUKIN.

However, the following side effects are listed below grouped by the probability of their occurrence.

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

• fever
• headache
• chills
• pain at the injection site
• vomiting
• nausea (sensation of illness)
• diarrhea
• fatigue
• high levels of liver enzymes
• skin rash

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

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

Unknown frequency (cannot be estimated from available data):

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

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

The following side effects have been reported in clinical trials with patients who presented with disorders/diseases other than EGC or osteopetrosis. The usual doses used in these studies were higher than those recommended for the treatment of EGC and osteopetrosis. Therefore, it cannot be precisely estimated their frequency of occurrence.

Unknown frequency (cannot be estimated from available data):

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

The following nervous system disorders have been observed:

• confusion
• disorientation
• effects on walking, such as parkinsonian gait
• shakiness
• convulsions
• distorted or imaginary sensations (hallucinations)

Also, the following heart disorders have been observed:

• extra and irregular heartbeats
• alterations in heart rhythm, such as an increase or decrease in rhythm
• heart problems that may cause difficulty breathing or inflammation of the ankle (heart failure)
• heart attack

Also, the following blood disorders have been reported:

• low blood pressure
• syncope
• mild ischemic 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 may be fatal
• liver damage that affects its function (hepatic failure)
• kidney damage that affects its function but can be effectively treated (reversible renal failure)
• chest pain
• aggravation of a skin disease called dermatomyositis (presented as a skin rash accompanied by muscle weakness)
• development of a long-term disease called systemic lupus erythematosus (the patient's own immune system attacks various parts of the body)
• autoimmune reaction (auto-antibody response)

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and vial after “CAD”. The expiration date is the last day of the month indicated.

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

The IMUKIN injectable vials must be used once. IMUKIN does not contain preservatives.

Once opened, use the contents of a vial immediately. Dispose of any remaining solution.

Do not use this medication if you observe the presence of particles or discoloration before its use.

Medications should not be disposed of through drains or in the trash. Deposit containers and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of IMUKIN

• The active ingredient is human recombinant interferon gamma-1b. Each vial (0.5 ml) contains 100 micrograms (2 x 106UI) of human recombinant interferon gamma-1b. It is produced by a modified E.coli bacterium using genetic engineering.
• The other components are D-mannitol, disodium succinate hexahydrate, polisorbate 20, succinic acid, and water for injection preparations.

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

Appearance of the product and contents of the packaging

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

Packaging sizes: 1, 3, 5, 6, and 12 vials in a cardboard box. Some packaging sizes may not be commercially available.

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:

Last review date of this leaflet: November 2022

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