Interferon Gamma-1B

FDA Drug Information • Also known as: Actimmune, Guna-Inf Gamma

Brand Names: Actimmune, Guna-Inf Gamma
Drug Class: Interferon gamma [EPC]
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 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 (2 × 10 6 International Units/0.5 mL) which is equivalent to 30 million units/mg. ACTIMMUNE is a sterile, clear, colorless solution filled in a single-dose 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).

What Is Interferon Gamma-1B Used For?

1 INDICATIONS AND USAGE 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). ACTIMMUNE is an interferon gamma indicated for: Reducing the frequency and severity of serious infections associated with Chronic Granulomatous Disease (CGD) ( 1 ) Delaying time to disease progression in patients with severe, malignant osteopetrosis (SMO) ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For subcutaneous use only ( 2.1 ) The recommended dose is 50 mcg/m 2 for patients whose body surface area is greater than 0.5 m 2 and 1.5 mcg/kg/dose for patients whose body surface area is equal to or less than 0.5 m 2 three times weekly. ( 2.1 ) Monitor hematology, blood chemistries and urinalysis prior to the beginning of treatment and at 3-month intervals. ( 2.1 ) If severe reactions occur, reduce dose by 50 percent or discontinue therapy until the adverse reaction abates. ( 2.3 ) 2.1 Dosing Information The recommended dosage of ACTIMMUNE administered subcutaneously, for the treatment of patients with CGD and SMO is shown in Table 1 below: Table 1: Recommended Dosage for ACTIMMUNE for the Treatment of Patients with CGD and SMO Body Surface Area (m 2 ) Dose (mcg/m 2 ) Dose (International Units/m 2 ) 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). Frequency Greater than 0.5 m 2 50 mcg/m 2 1 million International Units/m 2 Three times weekly (For example, Monday, Wednesday and Friday) Equal to or less than 0.5 m 2 1.5 mcg/kg/dose ------------ Three times weekly (For example, Monday, Wednesday and Friday) Prior to the beginning of treatment and at three-month intervals during treatment the following laboratory tests are recommended for all patients on ACTIMMUNE (interferon gamma-1b) therapy [see Warnings and Precautions (5.3 , 5.4 , 5.6) ] : Hematologic tests – including complete blood counts, differential and platelet counts Blood chemistries – including renal and liver function tests. In patients less than 1 year of age, liver function tests should be measured monthly [see Adverse Reactions (6.2) ] . Urinalysis 2.2 Important Administration Instructions The optimum sites of subcutaneous injection are the right and left deltoid and anterior thigh. ACTIMMUNE can be administered by a physician, nurse, family member or patient when appropriately counseled in the administration of subcutaneous injections. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ACTIMMUNE is a clear, colorless solution. ACTIMMUNE is for a single dose only. Discard any unused portion. ACTIMMUNE does not contain a preservative. ACTIMMUNE should not be mixed with other drugs in the same syringe. Administer ACTIMMUNE using either sterilized glass or plastic disposable syringes. 2.3 Dose Modification If severe reactions occur, the dosage should be reduced by 50 percent or therapy should be interrupted until the adverse reaction abates. Safety and efficacy has not been established for ACTIMMUNE given in doses greater or less than the recommended dose of 50 mcg/m 2 . Higher doses (i.e., greater than 50 mcg/m 2 ) are not recommended. The minimum effective dose of ACTIMMUNE has not been established.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the warnings and precautions section of the labeling: Cardiovascular Disorders [see Warnings and Precautions (5.1) ] Neurologic Disorders [see Warnings and Precautions (5.2) ] Bone Marrow Toxicity [see Warnings and Precautions (5.3) ] Hepatic Toxicity [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Renal Toxicity [see Warnings and Precautions (5.6) ] Common adverse reactions (incidence rate 2% or greater) for ACTIMMUNE include fever, headache, rash, chills, injection site erythema or tenderness, fatigue, diarrhea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc.at 1 800 77 AMGEN (1 800 772 6436)or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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/m 2 , 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,...

Drug Interactions

7 DRUG INTERACTIONS Concomitant use of drugs with neurotoxic, hematotoxic or cardiotoxic effects may increase the toxicity of interferons. ( 7.2 ) Avoid simultaneous administration of ACTIMMUNE with other heterologous serum protein or immunological preparations (e.g., vaccines). ( 7.3 ) 7.1 Myelosuppressive Agents When administering ACTIMMUNE in combination with other potentially myelosuppressive agents, monitor neutrophil and platelet counts [see Warnings and Precautions (5.3) ] . 7.2 Drugs with Neurotoxic, Hematoxic or Cardiotoxic Effects The concurrent use of drugs having neurotoxic (including effects on the central nervous system), hematotoxic, or cardiotoxic effects may increase the toxicity of interferons in these systems. It is theoretically possible that hepatotoxic and/or nephrotoxic drugs might have an effect on the clearance of ACTIMMUNE. 7.3 Immunological Preparations Simultaneous administration of ACTIMMUNE with other heterologous serum protein preparations or immunological preparations (e.g., vaccines) should be avoided due to the risk of an unexpected, or amplified, immune response. 7.4 Effects on Cytochrome P-450 Pathways Preclinical studies in rodents using species-specific interferon gamma have demonstrated a decrease in hepatic microsomal cytochrome P-450 concentrations. This could potentially lead to a depression of the hepatic metabolism of certain drugs that utilize this degradative pathway.

Contraindications

4 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. Known hypersensitivity to interferon gamma, E. coli derived products, or any component of the product ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. ACTIMMUNE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data ACTIMMUNE has shown an increased incidence of abortions in primates when given from gestation day 20 to 80 in doses approximately 100 times the human dose. A study in pregnant primates treated with subcutaneous doses 2 – 100 times the human dose failed to demonstrate teratogenic activity for ACTIMMUNE. Female mice treated subcutaneously with recombinant murine IFN-interferon gamma (rmuIFN-gamma) at 280 times the maximum recommended clinical dose of ACTIMMUNE from shortly after birth through puberty but not during pregnancy had offspring which exhibited decreased body weight during the lactation period. The clinical significance of this finding observed following treatment of mice with rmuIFN-gamma is uncertain. For lower doses, there is no evidence of maternal toxicity, embryotoxicity, fetotoxicity or teratogenicity in preclinical studies.

Overdosage

10 OVERDOSAGE Central nervous system adverse reactions including decreased mental status, gait disturbance and dizziness have been observed, particularly in patients receiving doses greater than 100 mcg/m 2 /day by intravenous or intramuscular administration. These abnormalities were reversible within a few days upon dose reduction or discontinuation of therapy. Reversible neutropenia, elevation of hepatic enzymes and of triglycerides, and thrombocytopenia have also been observed.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied ACTIMMUNE (interferon gamma-1b) is a sterile, clear, colorless solution filled in a single-dose vial for subcutaneous injection. Each vial permits the extraction of up to 0.5 mL of ACTIMMUNE with additional volume to facilitate solution withdrawal. Each 0.5 mL of ACTIMMUNE contains: 100 mcg (2 million International Units) of interferon gamma-1b. NDC Number Size 75987-111-10 One vial 75987-111-11 Cartons of 12 vials 16.2 Storage and Handling Store vials in the refrigerator at 2 to 8 °C (36 °F – 46 °F). Do Not Freeze. Avoid excessive or vigorous agitation. Do Not Shake . An unused vial of ACTIMMUNE can be stored at room temperature up to 12 hours prior to use. Discard vials if not used within the 12 hour period. Do not return to the refrigerator. 16.1 How Supplied ACTIMMUNE (interferon gamma-1b) is a sterile, clear, colorless solution filled in a single-dose vial for subcutaneous injection. Each vial permits the extraction of up to 0.5 mL of ACTIMMUNE with additional volume to facilitate solution withdrawal. Each 0.5 mL of ACTIMMUNE contains: 100 mcg (2 million International Units) of interferon gamma-1b. NDC Number Size 75987-111-10 One vial 75987-111-11 Cartons of 12 vials

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.