Introduction

Biologic response modifier; biosynthetic (recombinant DNA origin) form of endogenous human interferon gamma.

Uses for Interferon Gamma

Chronic Granulomatous Disease

Reduction of the frequency and severity of serious infections in patients with chronic granulomatous disease (designated an orphan drug by FDA for this use).

Osteopetrosis

Treatment to delay the time to disease progression in patients with severe, malignant osteopetrosis (designated an orphan drug by FDA for this use).

Idiopathic Pulmonary Fibrosis

Interferon gamma-1b was investigated in patients with idiopathic pulmonary fibrosis^{† [off-label]} (IPF) with mild-to-moderate lung function impairment in the INSPIRE study; the study was terminated early when interim data analysis indicated lack of benefit in patients receiving the drug. Interim analysis also indicated that 14.5% of patients receiving interferon gamma 1-b died compared with 12.7% of those receiving placebo.

Interferon gamma-1b is not approved for use in patients with IPF. FDA suggests that health-care professionals should discuss the results of this trial with their patients receiving the drug for IPF and carefully consider whether they should continue to receive treatment with interferon gamma-1b.

Interferon Gamma 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.

Administration

Sub-Q Administration

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

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

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

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

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).

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.

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

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.

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

Adults

Chronic Granulomatous Disease

Sub-Q

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

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

Osteopetrosis

Sub-Q

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

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

Prescribing Limits

Pediatric Patients

Chronic Granulomatous Disease

Sub-Q

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

Osteopetrosis

Sub-Q

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

Adults

Chronic Granulomatous Disease

Sub-Q

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

Osteopetrosis

Sub-Q

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

Contraindications

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

Warnings/Precautions

Warnings

Cardiac Effects

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

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

CNS Effects

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

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

Hematologic Effects

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

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

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

Renal Effects

Proteinuria reported rarely.

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

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). Reversible with dosage reduction or interruption of therapy.

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. If severe hepatic enzyme elevations occur, modify dosages. (See Dosage under Dosage and Administration.)

Sensitivity Reactions

Hypersensitivity Reactions

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

Specific Populations

Pregnancy

Category C.

Lactation

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

Pediatric Use

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

Possibly reversible alkaline phosphatase elevation and hypokalemia.

Common Adverse Effects

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

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.

Administration

Sub-Q Administration

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

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

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

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

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).

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.

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

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.

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

Adults

Chronic Granulomatous Disease

Sub-Q

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

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

Osteopetrosis

Sub-Q

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

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

Prescribing Limits

Pediatric Patients

Chronic Granulomatous Disease

Sub-Q

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

Osteopetrosis

Sub-Q

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

Adults

Chronic Granulomatous Disease

Sub-Q

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

Osteopetrosis

Sub-Q

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

No formal drug interaction studies to date.

Specific Drugs