Actimmune

Name: Actimmune

How should I use Actimmune (interferon gamma-1b)?

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Interferon gamma-1b is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Use only the type of syringe supplied with this medicine, or recommended by your pharmacist. Do not mix interferon gamma-1b in the same syringe with other injectable medicines.

Do not shake the medication bottle. Prepare your dose only when you are ready to give an injection. Do not use if the medicine has changed colors or has particles in it. Call your pharmacist for new medicine.

Each single-use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Interferon gamma-1b can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill.

While using interferon gamma-1b, you may need frequent blood tests. Your kidney function may also need to be checked.

Tell your doctor if you have any changes in height or weight. Interferon gamma-1b doses are based on body surface area (height and weight), and any changes may affect your dose.

Store interferon gamma-1b in the refrigerator, do not freeze.

You may take the medicine out of the refrigerator and allow it to reach room temperature before injecting your dose.

Do not leave the medicine at room temperature for longer than 12 hours. Throw the medicine if it has been at room temperature for more than 12 hours. Do not put it back in the refrigerator.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

What happens if I miss a dose?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What other drugs will affect Actimmune (interferon gamma-1b)?

Other drugs may interact with interferon gamma-1b, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Actimmune Dosage and Administration

General

  • If home use is prescribed, carefully instruct patients and/or their caregivers in appropriate use; provide a puncture-resistant container for proper, safe disposal of used syringes and needles.1

Administration

Sub-Q Administration

Administer by sub-Q injection 3 times weekly (e.g., Monday, Wednesday, Friday).1

Optimum sites for sub-Q injection include right and left deltoid and anterior thigh.1

To minimize risk of flu-like syndrome, administer at bedtime and/or give acetaminophen to prevent or partially alleviate fever and headache.1 5

Vials contain no preservative; discard any residual solution remaining in the vial after administration of the single dose.1

Dosage

Each mg of interferon gamma-1b is approximately equivalent to 20 million international units (equivalent to the amount that formerly was expressed as 30 million units).1

Pediatric Patients

Chronic Granulomatous Disease Sub-Q

50 mcg/m2 (1 million international units per m2) 3 times weekly for patients with body surface area (BSA) >0.5 m2 and 1.5 mcg/kg 3 times weekly for those with body surface area ≤0.5 m2.1

If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1

Osteopetrosis Sub-Q

50 mcg/m2 (1 million international units per m2) 3 times weekly for patients with body surface area >0.5 m2 and 1.5 mcg/kg 3 times weekly for those with body surface area ≤0.5 m2.1

If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1

Adults

Chronic Granulomatous Disease Sub-Q

50 mcg/m2 (1 million international units per m2) 3 times weekly.1

If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1

Osteopetrosis Sub-Q

50 mcg/m2 (1 million international units per m2) 3 times weekly.1

If a severe adverse reaction (e.g., flu-like symptoms) occurs, reduce dosage by 50% or discontinue drug until adverse reaction abates.1

Prescribing Limits

Pediatric Patients

Chronic Granulomatous Disease Sub-Q

Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1

Osteopetrosis Sub-Q

Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1

Adults

Chronic Granulomatous Disease Sub-Q

Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1

Osteopetrosis Sub-Q

Safety and efficacy of dosages >50 mcg/m2 3 times weekly not established.1

Cautions for Actimmune

Contraindications

  • Known hypersensitivity to interferon gamma-1b, products derived from Escherichia coli, or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Cardiac Effects

Acute and transient flu-like syndrome or constitutional symptoms (e.g., chills, fever)20 24 that are associated with daily dosages ≥250 mcg/m2 (>10 times the weekly recommended dosage) may exacerbate preexisting cardiac conditions.1

Use with caution in patients with preexisting cardiac disease (e.g., arrhythmia, CHF, symptoms of ischemia).1

CNS Effects

Possible seizures, decreased mental status, dizziness, and gait disturbance, particularly at daily dosages >250 mcg/m2 (>10 times the weekly recommended dosage).1

Use with caution in patients with known seizure disorders or compromised CNS function.1

Hematologic Effects

Possibly severe, reversible, dose-limiting neutropenia and thrombocytopenia reported rarely.1

Use with caution in patients with myelosuppression and in those receiving drugs that may be myelosuppressive.1

Monitor blood cell and differential counts and platelet counts prior to initiating interferon gamma-1b and at 3-month intervals during therapy.1

Renal Effects

Proteinuria reported rarely.1

Perform urinalysis and monitor appropriate blood chemistry tests prior to initiating interferon gamma-1b and at 3-month intervals during therapy.1

Hepatic Effects

Possibly substantial (up to 25-fold) elevations of AST and/or ALT reported; children <1 year of age most at risk (see Pediatric Use under Cautions).1 Reversible with dosage reduction or interruption of therapy.1

Perform liver function tests prior to initiating interferon gamma-1b and at monthly (for children <1 year of age) or 3-month intervals during therapy.1 If severe hepatic enzyme elevations occur, modify dosages.1 (See Dosage under Dosage and Administration.)

Sensitivity Reactions

Hypersensitivity Reactions

If acute, serious hypersensitivity reactions occur, discontinue immediately and initiate appropriate therapy.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether interferon gamma-1b is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Increased risk of elevations of AST and/or ALT in children <1 year of age.1 May occur as early as 7 days after starting treatment.1 (See Hepatic Effects under Cautions.)

Possibly reversible alkaline phosphatase elevation and hypokalemia.1

Common Adverse Effects

Flu-like syndrome (e.g., headache, fever, chills, myalgia, fatigue),1 3 5 8 10 18 erythema or tenderness at injection site,1 injection site hemorrhage,1 nausea,1 vomiting,1 rash.1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Interferon Gamma-1b (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

100 mcg/0.5 mL (2 million international units)

Actimmune

InterMune

Proper Use of Actimmune

This medicine is given as a shot under your skin, usually in the right and left upper arms, or thighs.

Each package of gamma interferon-1b contains a patient instruction sheet. Read this sheet carefully and make sure you understand:

  • How to prepare the injection.
  • Proper use of disposable syringes.
  • How to give the injection.
  • How long the injection is stable.

If you have any questions about any of this, check with your doctor.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections.

Use each vial only one time. Do not save an open vial. If the medicine in the vial has changed color, or if you see particles in it, do not use it. Do not shake it.

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

You may have fewer side effects (headache, fever, or muscle aches) if you give yourself the shot just before bedtime. Ask your doctor if you can take acetaminophen to prevent or relieve side effects.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For injection dosage form:
    • For chronic granulomatous disease:
      • Adults and children 1 year of age and older—Dose is based on body size and must be determined by your doctor.
        • For patients with more than 0.5 square meter (m[2]) of body size: The dose is 50 microgram (mcg) per square meter (m[2]) of body size injected under your skin 3 times every week.
        • For patients with less than or equal to 0.5 square meter (m[2]) of body size: The dose is 1.50 microgram (mcg) per kilogram (kg) of body size injected under your skin 3 times every week.
      • Children younger than 1 year of age—Use and dose must be determined by your doctor.
    • For severe, malignant osteopetrosis:
      • Adults and children 1 month of age and older—Dose is based on body size and must be determined by your doctor.
        • For patients with more than 0.5 square meter (m[2]) of body size: The dose is 50 microgram (mcg) per square meter (m[2]) of body size injected under your skin 3 times every week.
        • For patients with less than or equal to 0.5 square meter (m[2]) of body size: The dose is 1.50 microgram (mcg) per kilogram (kg) of body size injected under your skin 3 times every week.
      • Children up to 1 month of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

Throw away any unopened vials that are left at room temperature for more than 12 hours.

Uses of Actimmune

  • It is used to fight infections having to do with chronic granulomatous disease.
  • It is used to slow the progress of osteopetrosis.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Actimmune or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Actimmune (interferon gamma-1b). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Indications and Usage for Actimmune

  • Actimmune is indicated for reducing the frequency and severity of serious infections associated with Chronic Granulomatous Disease (CGD).
  • Actimmune is indicated for delaying time to disease progression in patients with severe, malignant osteopetrosis (SMO).

Contraindications

Actimmune is contraindicated in patients who develop or have known hypersensitivity to interferon gamma, E. coli derived products, or any component of the product.

Description

ACTIMMUNE (Interferon gamma-1b), an interferon gamma, is a single-chain polypeptide containing 140 amino acids. Production of ACTIMMUNE is achieved by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes for the recombinant protein. Purification of the product is achieved by conventional column chromatography. ACTIMMUNE is a highly purified sterile solution consisting of non-covalent dimers of two identical 16,465 Dalton monomers; with a specific activity of 20 million International Units/mg (2x106 International Units/0.5 mL) which is equivalent to 30 million units/mg.

ACTIMMUNE is a sterile, clear, colorless solution filled in a single-use vial for subcutaneous injection. Each 0.5 mL of ACTIMMUNE contains: 100 mcg (2 million International Units) of interferon gamma-1b formulated in disodium succinate hexahydrate (0.37 mg), mannitol (20 mg), polysorbate 20 (0.05 mg), succinic acid (0.14 mg) and Sterile Water for Injection. Note that the above activity is expressed in International Units (1 million International Units/50 mcg). This is equivalent to what was previously expressed as units (1.5 million units/50 mcg).

Side effects

The following adverse reactions are described below and elsewhere in the warnings and precautions section of the labeling:

  • Cardiovascular Disorders [see WARNINGS AND PRECAUTIONS]
  • Neurologic Disorders [see WARNINGS AND PRECAUTIONS]
  • Bone Marrow Toxicity [see WARNINGS AND PRECAUTIONS]
  • Hepatic Toxicity [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Renal Toxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following data on adverse reactions are based on the subcutaneous administration of ACTIMMUNE at a dose of 50 mcg/m², three times weekly, in patients with CGD during a clinical trial in the United States and Europe.

The most common adverse reactions observed in patients with CGD are shown in the following table:

Table 2: Adverse Reactions Occurring in 2 % or Greater of CGD Patients Receiving ACTIMMUNE in Clinical Trials

Adverse Reactions Percent of Patients
ACTIMMUNE CGD
(n=63)
Placebo CGD
(n=65)
Fever 52 28
Headache 33 9
Rash 17 6
Chills 14 0
Injection site erythema or tenderness 14 2
Fatigue 14 11
Diarrhea 14 12
Vomiting 13 5
Nausea 10 2
Myalgia 6 0
Arthralgia 2 0

Similar safety data were observed in 34 patients with SMO.

The clinical and laboratory toxicity associated with multiple dose studies of ACTIMMUNE is dose, route and schedule-dependent.

The most common adverse reactions include constitutional symptoms such as fever, headache, chills, myalgia or fatigue which may decrease in severity as treatment continues.

Less Common Adverse Reactions

The following adverse reactions are assessed as potentially related to ACTIMMUNE (interferon gamma-1b) therapy:

Blood and Lymphatic System—neutropenia (reversible), febrile neutropenia, leukopenia, and thrombocytopenia.

Cardiovascular— angina pectoris, arrhythmia, atrial fibrillation, atrioventricular block, cardiac failure (including congestive cardiac failure), tachyarrhythmia, heart block, (acute) myocardial infarction, myocardial ischemia, syncope, and tachycardia.

Gastrointestinal—abdominal pain, dyspepsia, gastrointestinal bleeding, granulomatous colitis, hepatic insufficiency, and pancreatitis, including pancreatitis with fatal outcome.

General Disorders and Administration Site Conditions—asthenia, chest pain/discomfort, influenza-like illness/flu-like symptoms, injection site hemorrhage, injection site pain, malaise, rigors, and weakness.

Hepatobiliary Disorders—hepatic insufficiency and hepatomegaly.

Immunological—hypersensitivity, increased autoantibodies, lupus-like syndrome (including systemic lupus erythematosus-flares and drug-induced lupus erythematosus), and Stevens-Johnson syndrome.

Infections and Infestations—upper respiratory tract infection.

Investigations—blood alkaline phosphatase increased, liver function tests abnormal/ elevation of hepatic enzymes, increased triglycerides, and weight decreased.

Metabolic—hyponatremia, hypokalemia, hyperglycemia, and hypertriglyceridemia.

Musculoskeletal—back pain, clubbing, and muscle spasms.

Nervous System—dizziness (excluding vertigo), gait disturbance, headache, Parkinsonian symptoms, convulsion/seizure (including grand mal convulsions), and transient ischemic attacks.

Psychiatric—confusion, depression, disorientation, hallucinations, mental status changes, and mental status decreased.

Pulmonary—tachypnea, bronchospasm, pulmonary edema, and interstitial pneumonitis.

Renal—acute renal failure (which may be reversible) and, proteinuria.

Skin and Subcutaneous Tissue Disorders—atopic dermatitis, (exacerbation of) dermatomyositis, transient cutaneous rash, and urticaria.

Vascular Disorder—deep venous thrombosis, hypotension, pulmonary embolism.

Abnormal Laboratory Test Values: Elevations of ALT and AST have been observed [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post approval use of ACTIMMUNE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Children With CGD Less Than 3 Years Of Age

Data on the safety and activity of ACTIMMUNE in 37 patients under the age of 3 years was pooled from four uncontrolled postmarketing studies. The rate of serious infections per patient-year in this uncontrolled group was similar to the rate observed in the ACTIMMUNE treatment groups in controlled trials. Developmental parameters (height, weight and endocrine maturation) for this uncontrolled group conformed to national normative scales before and during ACTIMMUNE therapy.

In 6 of the 10 patients receiving ACTIMMUNE therapy before age one year 2-fold to 25-fold elevations from baseline of AST and/or ALT were observed. These elevations occurred as early as 7 days after starting treatment. Treatment with ACTIMMUNE was interrupted in all 6 of these patients and was restarted at a reduced dosage in 4. Liver transaminase values returned to baseline in all patients and transaminase elevation recurred in one patient upon ACTIMMUNE rechallenge. An 11-fold alkaline phosphatase elevation and hypokalemia in one patient and neutropenia (ANC = 525 cells/mm³) in another patient resolved with interruption of ACTIMMUNE treatment and did not recur with rechallenge.

In the postmarketing safety database clinically significant adverse reactions observed during ACTIMMUNE therapy in children under the age of three years (n=14) included: two cases of hepatomegaly, and one case each of Stevens-Johnson syndrome, granulomatous colitis, urticaria, and atopic dermatitis.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. In clinical trials, 8 out of 33 ACTIMMUNE-treated patients developed non-neutralizing antibodies to interferon gamma-1b. No neutralizing antibodies to ACTIMMUNE have been detected in patients. In a Phase 1 study, none of the 38 ACTIMMUNE-treated healthy volunteers developed non-neutralizing antibodies to interferon gamma-1b.

The detection of antibody formation, including neutralizing antibody, in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ACTIMMUNE with the incidence of antibodies to other products may be misleading.

Adverse Effects

>10%

Fever (52%)

Headache (33%)

Rash (17%)

Chills (14%)

Diarrhea (14%)

Injection site erythema/tenderness (14%)

Vomiting (13%)

Nausea (10%)

1-10%

Arthralgia

Myalgia

Pharmacology

Mechanism of Action

Recombinant human interferon gamma-1b, cytokine that confers greater resistance to microbial pathogens and regulates immune processes

Pharmacokinetics

Absorption: 89% (SC, IM)

Half-life: 38 min (IV); 3 hr (IM); 5.9 hr (SC)

Peak plasma time: 4 hr (IM); 7 hr (SC)

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