Interferon Gamma

Biologic response modifier; biosynthetic (recombinant DNA origin) form of endogenous human interferon gamma.1 5 6 7

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).1 5 10 13 20 21 22 24

Osteopetrosis

Treatment to delay the time to disease progression in patients with severe, malignant osteopetrosis (designated an orphan drug by FDA for this use).1 6 7 13

Idiopathic Pulmonary Fibrosis

Interferon gamma-1b was investigated in patients with idiopathic pulmonary fibrosis† (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.26 Interim analysis also indicated that 14.5% of patients receiving interferon gamma 1-b died compared with 12.7% of those receiving placebo.26

Interferon gamma-1b is not approved for use in patients with IPF.26 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.26

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

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

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

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

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

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

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

Adults

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

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

Contraindications

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

Warnings/Precautions

Warnings

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

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

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

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

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

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

Specific Populations

Category C.1

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

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

• Importance of advising patients not to administer the drug until their clinician has thoroughly trained them on proper administration methods (including aseptic technique) and proper disposal of used needles and syringes.1 27

• Advise patients to notify their clinician if injection site reactions (e.g., persistent lumps, swelling, bruising, signs of infection or inflammation [pus, redness, pain]) occur.27

• Risk of myelosuppression and adverse hepatic effects.1

• Importance of taking interferon gamma-1b as prescribed.1

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Commonly reported side effects of interferon gamma-1b include: fever, flu-like symptoms, headache, chills, erythema at injection site, and tenderness at injection site. See below for a comprehensive list of adverse effects.

Applies to interferon gamma-1b: solution

Along with its needed effects, interferon gamma-1b may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking interferon gamma-1b:

• Chills
• fever

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• confusion
• cough or hoarseness
• loss of balance control
• lower back or side pain
• mask-like face
• painful or difficult urination
• pinpoint red spots on the skin
• shuffling walk
• sore throat
• stiffness of the arms or legs
• trembling and shaking of the hands and fingers
• trouble breathing
• trouble speaking or swallowing
• trouble thinking or concentrating
• trouble walking
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach pain or tenderness
• change in walking and balance
• clay colored stools
• clumsiness or unsteadiness
• dark urine
• decreased appetite
• decreased frequency or amount of urine
• general feeling of discomfort or illness
• headache
• increased thirst
• itching or skin rash
• joint or muscle pain
• loss of appetite
• lower back or side pain
• muscle aches and pains
• nausea and vomiting
• numbness or tingling of the face, hands, or feet
• painful or difficult urination
• pale skin
• redness and soreness of the eyes
• runny nose
• shivering skin
• sweating
• swelling of the face, fingers, or lower legs
• trouble sleeping
• weight gain
• yellow eyes or skin

Some side effects of interferon gamma-1b may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• redness or tenderness at the injection site

• Back pain
• dizziness
• weight loss

BSA: greater than 0.5 m2
50 mcg/m2 (1 million intl units/m2) subcutaneously three times weekly.

BSA: less than or equal to 0.5 m2
1.5 mcg/kg/dose subcutaneously three times weekly.