Imukin

Package leaflet: Information for the user

IMUKIN 2 x 10 UI (0.1 mg) injection solution

Recombinant human interferon gamma-1b
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any 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, as it may be harmful.
• If any adverse reaction occurs, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What IMUKIN is and what it is used for

IMUKIN contains a substance called recombinant human interferon gamma-1b. Interferons are so-called immunomodulators, small proteins capable of stimulating the body's immune defence system. They protect it against microorganisms (e.g. bacteria, viruses and fungi) that can cause disease.
IMUKIN is indicated for use in patients with chronic granulomatous disease (CGD). CGD is a metabolic defect of neutrophils, a type of white blood cells in the blood. These normally kill bacteria or fungi. The defect associated with CGD makes neutrophils less able to prevent infections.
IMUKIN is used to reduce the number of serious infections that may occur with this disease.
IMUKIN is also used in patients with severe, progressive osteopetrosis (marble bone disease). This is an inherited defect of bone cells that leads to excessive, abnormal bone growth. This disease also affects the bone marrow and the blood cells normally produced within it. As a consequence, patients with osteopetrosis are also at risk of developing serious infections.

2. What you need to know before using IMUKIN

Do not use IMUKIN

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

Consult your doctor or pharmacist if you are unsure whether you are allergic to interferons.
Warnings and precautions
Talk to your doctor or pharmacist before using IMUKIN.
Exercise caution with IMUKIN, especially if

• you have heart disease, as doses higher than usual may worsen your cardiac condition (see section 3 for dosing information)
• you suffer from epileptic seizures and/or impaired central nervous system function
• your liver is not functioning properly (hepatic insufficiency)
• your kidneys are not functioning properly (renal insufficiency)
• your bone marrow does not produce enough blood cells (myelosuppression)
• if you are allergic to latex, because the rubber stopper of the glass vial contains natural rubber (a derivative of latex) which may cause allergic reactions. Consult your doctor if any of the above warnings apply to you or have applied in the past. You should avoid using IMUKIN concurrently with other types of protein-based medicines. You should also avoid taking IMUKIN together with vaccines. If you have any doubts about this, consult your doctor. You should continue regular monitoring tests for CGD and severe progressive osteopetrosis. Blood counts, urine tests, and liver and kidney function should be carefully monitored both before and during treatment. High levels of interferon gamma-1b in the body may impair male and female fertility.

Other medicines and IMUKIN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any
other medicine.
You may need to take antibiotics to treat infections that may still occur while you are receiving IMUKIN for the treatment of CGD. There is no evidence that IMUKIN affects the efficacy of antibiotics or corticosteroids, which are commonly used in CGD and malignant osteopetrosis.
Medicines that affect the liver or kidneys may influence the elimination of IMUKIN from the body. IMUKIN may prolong the activity of other medicines that are metabolized and eliminated by the liver.
Concurrent use of IMUKIN with medicines or vaccines that affect the heart, blood, bone marrow, nervous system, or immune system may increase the risk of adverse effects.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Based on currently available information, effects on fertility are not known, but cannot be ruled out.
You should not use IMUKIN during pregnancy unless your doctor considers it necessary. Breastfeeding is not recommended during treatment with IMUKIN.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
IMUKIN may cause fatigue, seizures, confusion, disorientation, or distorted or imaginary sensations (hallucinations). These side effects may slow your reflexes and therefore may negatively affect your ability to drive or operate machinery. Do not drive or operate machinery if you experience reduced alertness.
IMUKIN contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.5 mL vial, i.e. essentially “sodium-free”. This information may be important for people with high blood pressure or those who must follow a low-sodium diet for other reasons.

3. How to take IMUKIN

Use this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
IMUKIN is administered by subcutaneous injection (injection under the skin) and may be given by a
doctor or nurse. You or a family member may also administer IMUKIN yourself, provided you have been
properly trained by a doctor or nurse in the correct technique for this type of injection.
The recommended dose of IMUKIN for the treatment of patients with CGD or severe, malignant
osteopetrosis is 50 mcg/m² in patients whose body surface area is greater than 0.5 m², and 1.5 mcg/kg in
patients with a body surface area equal to or less than 0.5 m².
Your doctor will determine how much IMUKIN you need to treat CGD or severe, progressive osteopetrosis.
You must inject, or have injected, the exact amount of IMUKIN prescribed by your doctor under the skin.
Injections should be given three times a week (e.g., Monday, Wednesday, and Friday), preferably in the
evening. The optimal injection sites are the upper arm or the upper thigh.

• Always check the exact amount of IMUKIN solution before administering the injection.
• Do not use IMUKIN if you notice small particles or changes in the colour of the solution.
• Do not mix IMUKIN with other medicines.
• Do not shake IMUKIN vials vigorously.

If you use more IMUKIN than you should
Contact your doctor immediately if you have administered more IMUKIN than prescribed.
In case of overdose, symptoms may include:

• central nervous system side effects such as difficulty concentrating, difficulty walking, and dizziness.
• if you have heart disease, it may worsen temporarily.
• during treatment with IMUKIN, hematological changes may occur. These include:
• temporary changes in the number of certain blood cells
• increased levels of certain substances in the blood (liver enzymes and triglycerides). These changes can be detected by your doctor through a blood test.

These symptoms resolve with dose reduction or discontinuation of IMUKIN.
If you forget to use IMUKIN
Do not take a double dose to make up for the missed dose.
Administer the injection at the time recommended by your doctor. If you miss the prescribed dose, you may still take the missed dose on the same day or the following day. Contact your doctor if you have gone a long time without taking the medicine.
If you stop using IMUKIN
If you have any questions about the use of this medicine, consult your doctor or pharmacist.
Inform your doctor if you stop treatment with IMUKIN.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The likelihood of side effects occurring depends on the dose and treatment regimen administered.
The most common side effects are influenza-like symptoms such as fever, headache, chills, and fatigue.
These symptoms may become less severe with continued treatment. Some may be reduced by administering the dose immediately before going to bed. A medicine such as paracetamol may be used to reduce some of these side effects.
Some people taking IMUKIN may develop skin changes shortly after administration, such as temporary skin redness, patchy skin redness, sudden blistering of the skin, and redness at the injection site.
However, these effects are rarely severe enough to require discontinuation of IMUKIN treatment.
The side effects reported below are grouped according to the likelihood of their occurrence.

Very common side effects (affecting more than 1 in 10 treated patients):

• fever
• headache
• chills
• injection site pain
• vomiting
• nausea (feeling unwell)
• diarrhoea
• fatigue
• increased liver enzymes
• rash

Common side effects (affecting less than 1 in 10 treated patients):

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

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

• reduced number of white blood cells (neutropenia)
• reduced number of platelets (thrombocytopenia), which may be associated with bruising and a tendency to bleed
• protein in the urine

Side effects have also been observed in patients taking IMUKIN for diseases other than CGD or malignant osteopetrosis. These side effects have not been observed in clinical studies involving CGD or malignant osteopetrosis.

The following side effects have been reported in clinical studies conducted in patients with conditions other than CGD or malignant osteopetrosis. Often, the doses administered were higher than those recommended for CGD or malignant osteopetrosis. For this reason, the frequency of occurrence cannot be accurately determined.

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

• low levels of sodium in the blood, which may cause fatigue and confusion, muscle spasms, seizures, or coma (hyponatremia)
• high levels of a sugar called glucose in the blood (hyperglycaemia)
• high levels of fatty acids called triglycerides in the blood (hypertriglyceridaemia)

The following nervous system disorders have been observed:

• confusion
• disorientation
• difficulty walking, with a Parkinsonian gait
• tremor
• seizures
• distorted or imaginary sensations (hallucinations)

The following cardiac disorders have also been observed:

• extra and/or irregular heartbeats
• changes in heart rate, such as increased or decreased rate
• heart problems that may cause shortness of breath or swollen ankles (heart failure)
• heart attack

The following circulatory system disorders have been reported:

• low blood pressure
• fainting
• transient ischaemic attack (temporary stroke-like episode)
• blood clot or blockage of a pulmonary artery (deep vein thrombosis and pulmonary embolism); symptoms may also include shortness of breath

The following respiratory changes have occurred:

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

The following gastrointestinal and other effects have been reported:

• gastrointestinal bleeding
• inflammation of the pancreas, which may be fatal
• liver damage impairing its function (liver failure)
• kidney damage impairing their function, but which may be effectively treated (reversible renal failure)
• chest pain
• worsening of a skin condition called dermatomyositis (manifesting as skin redness accompanied by muscle weakness)
• development of a chronic disease called systemic lupus erythematosus (i.e. the patient's immune system attacks various parts of the body)
• autoimmune reaction (autoantibody response)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store IMUKIN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard carton and on the vial,
following "Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze.
The IMUKIN injection solution vials are for single use only. IMUKIN does not contain preservatives.
Once the vial has been opened, its contents must be used immediately. Any unused medicinal product
or waste material must be discarded.
Do not use this medicine if you notice particles or changes in colour before administration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose
of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What IMUKIN contains

• The active substance is recombinant human interferon gamma-1b. Each vial (0.5 mL) contains 2 x 10 IU (0.1 mg) of recombinant human interferon gamma-1b. This is a substance produced using genetically modified E. coli bacteria.
• The other ingredients are D-mannitol, disodium succinate hexahydrate, polysorbate 20, succinic acid and water for injections. The vial stopper contains natural rubber (a derivative of latex).

Description of the appearance of IMUKIN and contents of the pack
IMUKIN is a clear, colourless injectable solution. IMUKIN is available in 4 mL vials containing 0.5 mL of injectable solution.
Pack sizes: 1, 3, 5, 6 and 12 vials per carton.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Clinigen Healthcare B.V.
Schiphol Boulevard 359
WTC Schiphol Airport, D Tower, 11th floor
1118BJ Schiphol
The Netherlands
Manufacturer
Almac Pharma Services (Ireland) Limited
Finnabair Industrial Estate
Dundalk
Co. Louth
A91 P9KD
Ireland
Almac Pharma Services Limited
Almac House, 20 Seagoe Industrial Estate
Craigavon, BT63 5QD
Northern Ireland, United Kingdom
This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names: