Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about Imukin.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you using Imukin against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist. This leaflet was last updated on the date at the end of this leaflet. More recent information may be available. The latest Consumer Medicine Information is available from your pharmacist, doctor, or from www.medicines.org.au and may contain important information about the medicine and its use of which you should be aware.

Keep this leaflet with your medicine. You may need to read it again.

What Imukin is used for

Interferons are substances which are normally produced by the body and which play a role in the body's response to infection. Interferon gamma-1b is just one of several types of interferon. Imukin contains interferon gamma-1b which is produced in the laboratory by recombinant technology. It modifies the body's response to infection in the same way as naturally-occurring interferon gamma.

Chronic Granulomatous Disease (CGD) is a rare disorder in which the body's own natural defence against infection is not working properly.

Imukin is used with other treatments to reduce the frequency of serious infections in people with CGD.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you use Imukin

When you must not use it

Do not use Imukin if you have an allergy to:

• any medicine containing interferons
• any of the ingredients listed at the end of this leaflet
• any other similar medicines.

Some of the symptoms of an allergic reaction may include:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin.

Do not use this medicine if you are pregnant. It may affect your developing baby if you use it during pregnancy.

Do not breast-feed if you are using this medicine. Imukin is not recommended in women who are breast-feeding.

Do not use Imukin after the expiry date printed on the vials or carton or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

Do not use it if the solution contains any solid particles or if it is cloudy, hazy or discoloured.

If you are not sure whether you should start using this medicine, talk to your doctor.

Before you start to use it

Tell your doctor if you are allergic to latex. The stopper of the Imukin glass vial contains natural rubber (a derivative of latex).

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes. Your response to Imukin may vary depending on a number of things.

It is essential that your doctor knows your medical history before prescribing Imukin.

Your doctor will do some blood tests before starting you on Imukin.

Tell your doctor if you have or have had any of the following medical conditions:

• heart disease including angina or irregular heart beats
• epilepsy or other nervous system conditions
• any condition which affects blood cell production in the bone marrow
• liver disease
• kidney disease.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start using Imukin.

Using other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Imukin may interfere with each other. These include:

• medicines for vaccinations
• medicines that affect blood cell production in the bone marrow.

These medicines may be affected by Imukin or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

Do not mix Imukin with other medicines in the same syringe.

How to use Imukin

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the carton, ask your doctor or pharmacist for help.

How much to use

Your doctor will advise you what volume of solution is required in order to achieve the required dose.

For most people the dosage is calculated on the basis of body surface area (BSA).

For people with a BSA greater than 0.5 square metres the recommended dose is 1 million international units (IU) or 50 micrograms per square metre of BSA.

For people with a BSA less than or equal to 0.5 square metres the recommended dose is 30,000 IU or 1.5 micrograms per kilogram bodyweight.

Ask your doctor for more information if you have been prescribed a dose that is different to that recommended above.

How to use it

Follow the Directions for Use at the end of this leaflet on how to use Imukin.

Imukin should be injected immediately after it is withdrawn from the vial and any unused portion of the vial should be thrown away.

Injections are administered under the skin (subcutaneously).

The best sites for injection are the upper arms or fronts of the thighs.

When to use it

Injections are usually administered under the skin three times a week (for example, Monday, Wednesday, Friday) and can be given by a doctor, nurse, family member or by the patient once they are trained in giving the injections correctly.

How long to use it

Continue using Imukin for as long as your doctor tells you.

This medicine helps to control your condition, but does not cure it. It is important to keep using your medicine even if you feel well.

Tell your doctor or pharmacist if any illness occurs during treatment with Imukin. Your doctor will tell you whether treatment with Imukin should continue or stop temporarily.

If you forget to inject it

If it is less than 12 hours before your next dose, skip the dose you missed and administer your next dose when you are meant to.

Otherwise, administer it as soon as you remember, and then go back to using your medicine as you would normally.

Do not inject a double dose to make up for the dose that you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (Australia 13 11 26; New Zealand 0800 764 766), or go to Emergency at your nearest hospital, if you think that you or anyone else may have used too much Imukin. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of overdose may include:

• confusion
• disturbance in the manner of walking and dizziness
• frequent signs of infection such as fever, severe chills, sore throat or mouth ulcers
• bleeding or bruising may occur more easily than normal.

With a large overdose, blood cells, the liver and kidneys can be affected. A laboratory can detect changes in the blood and urine. Very high doses of Imukin may worsen pre-existing heart disease.

While you are using Imukin

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Imukin.

Tell any other doctors, dentists, and pharmacists who treat you that you are using this medicine.

Tell your doctor if, for any reason, you have not used Imukin exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

If you become pregnant while using Imukin, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor will do regular blood and urine tests while you are using Imukin.

Things you must not do

Do not give Imukin to anyone else, even if they have the same condition as you.

Do not stop using your medicine or lower the dosage without checking with your doctor. If you stop using it suddenly, your condition may worsen or you may have unwanted side effects.

Things to be careful of

Be careful driving or operating machinery until you know how Imukin affects you. Imukin may alter your ability to drive or operate machinery and this may be made worse by alcohol.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while using Imukin.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

• fever
• headache
• chills
• muscle pain or tiredness.

These effects may decrease in severity as treatment continues. Using Imukin just before you go to bed at night may reduce these effects or you can take paracetamol to treat them.

Other side effects of Imukin include the following:

• nausea
• vomiting
• joint pain
• diarrhoea
• back pain
• stomach pain or discomfort
• feeling depressed
• tenderness at the injection site
• temporary skin rashes.

Occasionally a problem may develop at the injection site.

Tell your doctor as soon as possible if you notice any of the following:

• a lump or swelling that doesn't go away
• bruising that doesn't go away
• any signs of infection or inflammation at an injection site (pus, persistent redness, surrounding skin that is hot to touch, persistent pain after the injection)
• worsening of signs of a heart condition such as swelling in the legs, shortness of breath, chest pain or irregular heartbeat
• bleeding or bruising that may occur more easily than normal.

Tell your doctor as soon as possible if you experience any side effects during or after using Imukin, so that these may be properly treated. Other side effects not listed above may also occur in some patients.

After using Imukin

Storage

Keep Imukin in the refrigerator where the temperature stays between 2-8°C.

Do not freeze Imukin.

Imukin should not be left for more than 12 hours at room temperature (25°C).

Avoid exposing Imukin to high temperatures during transport e.g. use an insulated container.

Do not shake the vials.

Imukin should not be used if the solution contains any solid particles or if it is cloudy, hazy or discoloured.

Keep Imukin where children cannot reach it.

Disposal

If your doctor tells you to stop using Imukin or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product Description

What it looks like

Imukin is the brand name of your medicine.

Imukin comes as a sterile, clear, colourless solution in clear glass vials which are packed into cartons containing 1 vial* or 6 vials each.

* Not currently distributed in Australia.

Ingredients

Imukin is an injection and each vial contains 2 million IU or 100 micrograms of interferon gamma-1b (recombinant) in 0.5 mL of solution. The solution also contains:

• mannitol
• sodium succinate hexahydrate
• succinic acid
• polysorbate 20
• water for injections.

Supplier

Imukin is supplied in Australia by:

Link Medical Products Pty Ltd.
5 Apollo Street
Warriewood NSW 2102

This leaflet was updated in April 2021

Australian Registration Number

AUST R 48404

Imukin®

Interferon gamma-1b

Directions for Use

Before using Imukin

1. Wash hands with soap and water and dry thoroughly to help prevent infection.
2. Check that the Imukin solution is clear. NEVER SHAKE THE VIAL. Shaking can cause the solution to become cloudy or hazy. If the solution is cloudy, hazy or discoloured or if it contains any solid particles, do not inject it, but return it to your doctor or pharmacist.
3. Check the expiry date on the Imukin vial to ensure it has not passed.
4. Remove the protective cap from the vial and wipe the rubber stopper on the top of the vial with a cotton ball saturated with rubbing alcohol, or with an alcohol swab.
5. Leaving the needle cap in place, pull back on the plunger of the syringe until you have drawn an amount of air into the syringe equal to the volume of Imukin your doctor has ordered for each dose.
6. Remove and save the needle cap from the syringe. Holding the syringe by the side of the plastic tube, slowly insert the needle straight through the centre of the rubber stopper of the Imukin vial to be used.
7. Gently push the plunger to discharge the air into the vial.
8. Turn the vial upside down with the syringe needle still in it and hold it in one hand. Be sure the tip of the needle is in the solution. Using your other hand, slowly pull on the plunger in a continuous motion until the correct amount of Imukin solution is in the syringe. Avoid injecting the solution back into the vial as this may cause the formation of small colourless particles.
9. With the syringe and vial still held upside down in one hand, gently tap the syringe with your hand to dislodge any large air bubbles. The bubbles will rise to the top of the syringe and can be pushed back into the vial by gently pushing in the plunger. Make sure the correct amount of Imukin solution remains in the syringe. You may need to withdraw more Imukin solution if there were a lot of bubbles in the syringe.
10. Remove the needle from the Imukin vial and carefully replace the needle cap until time of administering the injection. Place the needle and syringe on a clean surface.

Selecting the injection site

11. The best sites for injection are the upper arms or fronts of the thighs. It is very important that you alternate the site of injection every time you give the medication. The exact same spot within each area should not be used time after time.

Injecting the dose

Needles and syringes should be used only once to ensure they remain sterile.

12. Applying firm pressure, clean the injection site with an alcohol-saturated cotton ball or cotton swab using a circular motion and working outward from the inside of the circle. Once you have cleaned the centre of the circle, do not go back to it with the same swab. Allow the alcohol to dry before inserting the needle. This will reduce the stinging sensation.
13. Remove the needle cap from the syringe filled with the proper dose of Imukin and hold the syringe the way you would hold a pencil. Double check the correct amount of Imukin solution is in the syringe.
14. Gently pinch up the skin surrounding the site of injection and hold firmly with your other hand. Insert the needle into the skin at a 45 degree angle with a quick, firm motion. This hurts less than slowly pushing the needle in.
15. Once the needle has been inserted into the skin, you can release your hold of the skin. Inject the solution by gently pushing the plunger until the syringe is empty.
16. Withdraw the needle quickly, pulling it straight out, and apply pressure over the injection site with a dry gauze or cotton ball. A drop of blood may appear. Put a dressing on the injection site if desired.
17. Any unused portion of Imukin remaining in the vial should be thrown away.
18. Dispose of the needle and syringe in a sharps container. These are available from your pharmacist.

Published by MIMS June 2021

1 Name of Medicine

Interferon gamma-1b recombinant human.

2 Qualitative and Quantitative Composition

Vials containing 2 x 10⁶ IU (100 microgram) interferon gamma-1b (rbe) per 0.5 mL.
Imukin (interferon gamma - 1b [rbe]), a biologic response modifier, is a single-chain polypeptide containing 140 amino acids. Production of Imukin is achieved by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes the human protein. Purification of the product is achieved by conventional column chromatography.
Imukin is a highly purified sterile solution consisting of noncovalent dimers of two identical 16,465 dalton monomers, with a specific activity of 20 million IU/mg.

List of excipients.

3 Pharmaceutical Form

Solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Imukin is indicated as an adjunct for reduction of the frequency of serious infections in patients with chronic granulomatous disease (CGD).
The benefits of Imukin have been most marked in children with CGD although Imukin may be used in adult patients.

4.2 Dose and Method of Administration

The recommended dosage of Imukin for injection for the treatment of patients with CGD is 1 x 10⁶ IU (50 microgram)/m² for patients whose body surface area is greater than 0.5 m², and 3 x 10⁴ IU (1.5 microgram)/kg/dose for patients whose body surface area is equal to or less than 0.5 m².
Care should be taken to ensure accurate adjustment of the volume of solution drawn into the syringe prior to injection. Injections should be administered subcutaneously three times weekly (for example, Monday, Wednesday, Friday). The optimum sites of injection are the right and the left deltoid region and anterior thigh. Imukin can be administered by a physician, nurse, family member or patient once they are trained in the administration of subcutaneous injections.
Treatment with Imukin should continue in the event of infectious complications related to CGD. In the event of other intercurrent illness, the treating physician should decide if and for how long Imukin should be discontinued. If severe reactions occur, therapy should be discontinued until the reaction abates.
There are limited data available to adequately characterise the patient population most likely to benefit from Imukin. However, there is some evidence to suggest that Imukin may be most effective in the young, in those with X-linked disease and in those with a history of more serious prior infection. In adult patients, a significant difference between Imukin and placebo has not been demonstrated.
Higher doses are not recommended. The optimum dose of Imukin has not been established. Safety and efficacy have not been established for Imukin given in doses greater or less than the recommended dose of 1 x 10⁶ IU (50 microgram)/m² three times weekly.
Available data indicate that Imukin is well tolerated and patients continue to benefit through 12 months of therapy. It is not known how long treatment with Imukin should continue since the safety and efficacy of a longer duration of treatment are unknown.

4.3 Contraindications

Imukin is contraindicated in patients who develop or have known acute hypersensitivity to interferon gamma, known hypersensitivity to closely related interferons or to any component of the product.

4.4 Special Warnings and Precautions for Use

Imukin should be used with caution in patients with pre-existing cardiac disease, including symptoms of ischaemia, congestive heart failure or arrhythmia. No direct cardiotoxic effect has been demonstrated, but it is possible that acute and transient "flu-like" or constitutional symptoms such as fever and chills, frequently associated with Imukin administration at doses of 5 x 10⁶ IU (250 microgram)/m²/day or higher, may exacerbate pre-existing cardiac conditions.
Caution should be exercised when treating patients with known seizure disorders and/or compromised central nervous system function. Central nervous system reactions including decreased mental status, gait disturbance and dizziness have been observed, particularly in patients receiving doses greater than 5 x 10⁶ IU (250 microgram)/m²/day. Most of these abnormalities were mild and reversible within a few days upon dose reduction or discontinuation of therapy.
Reversible neutropenia and thrombocytopenia which have been observed during Imukin therapy can be severe and may be dose related. Caution should be exercised when administering Imukin to patients with myelosuppression.
Use of Imukin should be restricted to physicians experienced in the management of patients with CGD.
Patients being treated with Imukin, and their parents, should be informed regarding the potential benefits and risks associated with treatment. If home use is considered to be desirable by the physician, instructions on appropriate use should be given.
In addition to tests normally required for monitoring patients with CGD, patients should have the following tests performed before beginning Imukin therapy and at appropriate periods during treatment: haematological tests, including complete blood counts, differential and platelet counts; blood chemistries, including renal and liver function tests; urinalysis.
Interferon gamma 1b, the active ingredient of Imukin, is an exogenous protein, which may lead to the occurrence of antibodies during the course of treatment. More than 900 patients treated with Imukin in single agent clinical trials have been tested for the presence of antibody to interferon gamma by a sensitive radioimmunoprecipitation assay which detects neutralising as well as non-neutralising antibody. All assays performed to date have been negative, with the exception of one patient, whose subsequent samples were negative. However, since the interferon gamma present in Imukin is not identical to the corresponding endogenous interferon, it would be prudent to monitor patients periodically for the presence of antibodies against Imukin.
The stopper of the glass vial with Imukin contains natural rubber (a derivative of latex) which may cause allergic reactions.

Use in hepatic and renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Simultaneous administration of interferon gamma with other heterologous serum protein preparations or immunological preparations (e.g. vaccines) should be avoided because of the risk of unexpected amplified immune response.
Caution should be exercised in concomitant administration of Imukin with other myelosuppressive drugs.
Imukin does not reduce the efficacy of antibiotics or glucocorticoids in CGD patients.
Drug interactions seen with Imukin are similar to those seen with other interferons in animal experiments.
It is theoretically possible that hepatotoxic and/or nephrotoxic drugs might have effects on the clearance of Imukin. Also, the effects of anti-inflammatory drugs, NSAIDs, theophylline, immunosuppressive and cytostatic drugs on the acute cellular effects of Imukin and its therapeutic effects in CGD patients when such drugs are used concomitantly in chronic conditions, are not known.
Imukin potentially can alter the half-lives of simultaneously administered drugs which are metabolised by the cytochrome P450 system.
Concurrent use of drugs having neurotoxic (including effects on the central nervous system), haemotoxic, myelosuppressive or cardiotoxic effects may increase the toxicity of interferons in these systems.
Imukin should not be mixed with other drugs in the same syringe.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effect on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as fatigue, convulsion, confusional state, disorientation or hallucination during treatment. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience any of these events, they should avoid potentially hazardous tasks such as driving or operating machinery.
Even when given at the recommended dosage of 1 x 10⁶ IU (50 microgram)/m² by subcutaneous injection, Imukin may affect reactions such that the ability to drive a vehicle or to operate machinery is impaired. This effect may be enhanced by alcohol.

4.8 Adverse Effects (Undesirable Effects)

The clinical and laboratory toxicities associated with multiple dose Imukin therapy are dose, route and schedule dependent.
Serious adverse reactions have not been observed in patients receiving the recommended dose of Imukin 1 x 10⁶ IU (50 microgram)/m² by subcutaneous injection.
The most common adverse experiences occurring with Imukin therapy are constitutional symptoms such as fever, headache, chills, myalgia or fatigue, which may decrease in severity as treatment continues. Some of these symptoms can be minimised by bedtime administration. Paracetamol may also be used to ameliorate these effects. Anorexia and weight loss have been observed in clinical trials at a similar incidence to placebo.
The following definitions apply to the frequency terminology used hereafter: very common (≥ 1/10); common (≥ 1/100 - < 1/10); uncommon (≥ 1/1,000 - < 1/100); rare (≥ 1/10,000 - < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

Blood and lymphatic system disorders.

Metabolism and nutrition disorders.

Psychiatric disorders.

Nervous system disorders.

Cardiac disorders.

Vascular disorders.

Respiratory, thoracic and mediastinal disorders.

Gastrointestinal disorders.

Hepatobiliary disorders.

Skin and subcutaneous tissue disorders.

Musculoskeletal and connective tissue disorders.

Renal and urinary disorders.

General disorders and administration site conditions.

Investigations.

Reporting suspected adverse events.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
Imukin has been administered at higher doses (> 2 x 10⁶ IU (100 microgram)/m²) to patients with advanced malignancies by the intravenous or intramuscular route.
Central nervous system adverse reactions, including decreased mental status, gait disturbance and dizziness, have been observed, particularly in cancer patients receiving doses greater than 2 x 10⁶ IU (100 microgram)/m²/day. These abnormalities were reversible within a few days upon dose reduction or discontinuation of therapy. Reversible neutropenia, elevation of hepatic enzymes, raised triglycerides and thrombocytopenia have also been observed.
In patients with pre-existing cardiac disease, including symptoms of ischaemia, congestive heart failure or arrhythmia, no direct cardiotoxic effect has been demonstrated, but at very high doses (5 x 10⁶ IU (250 microgram)/m²/day or higher), it is possible that acute, self-limited constitutional toxicities may exacerbate pre-existing cardiac conditions.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mannitol, sodium succinate hexahydrate, succinic acid, polysorbate 20, water for injections.

6.2 Incompatibilities

Imukin should not be mixed with other drugs in the same syringe (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

6.3 Shelf Life

3 years.
The formulation does not contain a preservative. Once opened, the contents of a vial should be used immediately. Each vial is for use in one patient on one occasion only. The unused portion of any vial should be discarded.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.

6.4 Special Precautions for Storage

Vials of Imukin must be placed in a refrigerator (2 - 8°C), but must not be frozen or shaken vigorously.
An unused vial of Imukin should not be left at room temperature for a total time exceeding 12 hours prior to use.

6.5 Nature and Contents of Container

Packs of 6 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes