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Interferon Gamma-1b


General


Pronunciation

(in ter FEER on GAM ah won bee)


Brand Names: U.S.

  • Actimmune

Indications


Use: Labeled Indications

Chronic granulomatous disease: Reduction in the frequency and severity of serious infections associated with chronic granulomatous disease

Malignant osteopetrosis (severe): To delay time to disease progression in patients with severe, malignant osteopetrosis


Contraindications


Hypersensitivity to interferon gamma, E. coli derived products, or any component of the formulation


Dosing and Administration


Dosing: Adult

Note: Dosing expressed in mcg; 50 mcg is equivalent to 1 million units (50 mcg/m2 is equivalent to 1 million units/m2).

Chronic granulomatous disease: SubQ: 50 mcg/m2 (1 million units/m2) 3 times/week; doses above 50 mcg/m2 are not recommended.

Malignant osteopetrosis (severe): SubQ: 50 mcg/m2 (1 million units/m2) 3 times/week; doses above 50 mcg/m2 are not recommended.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Note: Dosing expressed in mcg; 50 mcg is equivalent to 1 million units (50 mcg/m2 is equivalent to 1 million units/m2).

Chronic granulomatous disease: Children and Adolescents: SubQ:

Body surface area (BSA) ≤0.5 m2: 1.5 mcg/kg/dose 3 times/week

BSA >0.5 m2: 50 mcg/m2 (1 million units/m2) 3 times/week; doses above 50 mcg/m2 are not recommended.

Malignant osteopetrosis (severe): Infants, Children, and Adolescents: SubQ:

Body surface area (BSA) ≤0.5 m2: 1.5 mcg/kg/dose 3 times/week

BSA >0.5 m2: 50 mcg/m2 (1 million units/m2) 3 times/week; doses above 50 mcg/m2 are not recommended.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling; drug accumulation may occur in patients with severe renal insufficiency.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling; drug accumulation may occur in patients with advanced hepatic disease. If severe transaminase elevations occur during treatment, interrupt and reduce the dose upon resolution.


Reconstitution

Do not mix with other drugs in the same syringe. Vials are intended for single use (does not contain preservative); discard unused portion of the vial.


Administration

Administer by SubQ injection into the right and left deltoid or anterior thigh. Consider premedication with acetaminophen and/or bedtime administration to minimize adverse reactions (eg, flu-like symptoms).


Storage

Store intact vials at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze. Avoid excessive or vigorous agitation; do not shake. Discard if intact vial is left at room temperature for >12 hours prior to use.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Actimmune: 2,000,000 units/0.5 mL (0.5 mL)


Drug Interactions

Theophylline Derivatives: Interferons may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Monitor therapy


Monitoring Parameters

CBC with differential, platelets, LFTs (monthly in children <1 year), electrolytes, BUN, creatinine, and urinalysis prior to therapy and at 3-month intervals


Adverse Reactions


Based on 50 mcg/m2 dose administered 3 times weekly for chronic granulomatous disease

>10%:

Central nervous system: Fever (52%), headache (33%), chills (14%), fatigue (14%)

Dermatologic: Rash (17%)

Gastrointestinal: Diarrhea (14%), vomiting (13%)

Local: Injection site erythema or tenderness (14%)

1% to 10%:

Central nervous system: Depression (3%)

Gastrointestinal: Nausea (10%), abdominal pain (8%)

Neuromuscular & skeletal: Myalgia (6%), arthralgia (2%), back pain (2%)

Postmarketing and/or case reports: Alkaline phosphatase elevated, atopic dermatitis, granulomatous colitis, hepatomegaly, hypersensitivity reactions, hypokalemia, neutropenia, Stevens-Johnson syndrome

Additional adverse reactions noted at doses >100 mcg/m2 administered 3 times weekly: ALT increased, AST increased, autoantibodies increased, bronchospasm, chest discomfort, confusion, dermatomyositis exacerbation, disorientation, DVT, gait disturbance, GI bleeding, hallucinations, heart block, heart failure, hepatic insufficiency, hyperglycemia, hypertriglyceridemia, hyponatremia, hypotension, interstitial pneumonitis, lupus-like syndrome, MI, neutropenia, pancreatitis (may be fatal), Parkinsonian symptoms, PE, proteinuria, renal insufficiency (reversible), seizure, syncope, tachyarrhythmia, tachypnea, thrombocytopenia, TIA


Warnings/Precautions


Concerns related to adverse effects:

- Bone marrow suppression: Dose-related reversible neutropenia and thrombocytopenia (may be severe) have been reported; use caution in patients with myelosuppression.

- CNS effects: Neurologic disorders (ie, decreased mental status, gait disturbances, dizziness) have been noted at the higher doses (>250 mcg/m2/day); most of these abnormalities were reversible within a few days after dose reduction or discontinuation. Use with caution in patients with a history of seizure disorder or compromised CNS function.

- Flu-like symptoms: Acute and transient flu-like symptoms (eg, fever, headache, chills, myalgia, fatigue) have been noted at the higher doses (>250 mcg/m2/day) and may exacerbate preexisting cardiovascular disorders; some of the flu-like symptoms may be minimized by bedtime administration.

- Hepatotoxicity: Elevations of AST and/or ALT (up to 25-fold) have been observed and were reversible with dose reduction or interruption of treatment. Incidence may be increased in children <1 year of age; perform monthly liver function assessments in this age group; modify dosage if severe elevations of liver enzyme develop.

- Hypersensitivity reactions: Acute serious hypersensitivity reactions have been reported (case reports); transient cutaneous rashes may occur, although treatment interruption has rarely been necessary. Discontinue therapy immediately if an acute reaction occurs.

Disease-related concerns:

- Cardiovascular disease: Use with caution in patients with preexisting cardiovascular disease, including ischemia, heart failure, or arrhythmia.

- Hepatic function impairment: Drug accumulation may occur in patients with advanced hepatic disease.

- Renal function impairment: Drug accumulation may occur in patients with severe renal insufficiency; renal toxicity has been reported.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Latex: The vial stopper may contain dry natural rubber and may cause allergic reactions.


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.


Actions


Pharmacology

Interferon gamma participates in immunoregulation by enhancing the oxidative metabolism of macrophages; it also enhances antibody dependent cellular cytotoxicity, activates natural killer cells and has a role in the expression of Fc receptors and major histocompatibility antigens.


Absorption

IM, SubQ: >89%


Time to Peak

Plasma: IM: ~4 hours (1.5 ng/mL); SubQ: ~7 hours (0.6 ng/mL)


Half-Life Elimination

IM: ~3 hours, SubQ: ~6 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience injection site irritation, flu-like symptoms, diarrhea, nausea, vomiting, muscle pain, or loss of strength and energy. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine, black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), confusion, change in balance, abnormal gait, severe dizziness, passing out, seizures, or hallucinations (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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