Actimmune (Interferon Gamma-1B) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Carcinogenesis, Mutagenesis and Impairment of Fertility

Carcinogenesis

ACTIMMUNE has not been tested for its carcinogenic potential.

Mutagenesis

Ames tests using five different tester strains of bacteria with and without metabolic activation revealed no evidence of mutagenic potential. ACTIMMUNE was tested in a micronucleus assay for its ability to induce chromosomal damage in bone marrow cells of mice following two intravenous doses of 20 mg/kg. No evidence of chromosomal damage was noted.

Impairment of Fertility

Female cynomolgus monkeys treated with daily subcutaneous doses of 30 or 150 mcg/ kg ACTIMMUNE (approximately 20 and 100 times the human dose) exhibited irregular menstrual cycles or absence of cyclicity during treatment. Similar findings were not observed in animals treated with 3 mcg/kg ACTIMMUNE.

Female mice receiving recombinant murine IFN-gamma (rmuIFN-gamma) at 32 times the maximum recommended clinical dose of ACTIMMUNE for 4 weeks via intramuscular injection exhibited an increased incidence of atretic ovarian follicles.

Male cynomolgus monkeys treated intravenously for 4 weeks with 8 times the maximum recommended clinical dose of ACTIMMUNE exhibited decreased spermatogenesis. The impact of this finding on fertility is not known. Male mice receiving rmuIFN-gamma at 32 times the maximum recommended clinical dose of ACTIMMUNE for 4 weeks via intramuscular injection exhibited decreased spermatogenesis.

Male mice treated subcutaneously with rmuIFNgamma from shortly after birth through puberty, with 280 times the maximum recommended clinical dose of ACTIMMUNE exhibited profound yet reversible decreases in sperm counts and fertility, and an increase in the number of abnormal sperm.

The clinical significance of these findings observed following treatment of mice with rmuIFN-gamma is uncertain.

OVERDOSAGE

Central nervous system adverse reactions including decreased mental status, gait disturbance and dizziness have been observed, particularly in cancer patients receiving doses greater than 100 mcg/m²/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.

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.

REFERENCES

1. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med 324: 509–516, 1991.
2. Beard CJ, Key L, Newburger PE, Ezekowitz RAB, et al. Neutrophil defect associated with malignant infantile osteopetrosis. J Lab Clin Med 108: 498–505, 1986.
3. Shankar L, Gerritsen EJA, and Key LL. Osteopetrosis: pathogenesis and rationale for the use of interferon-γ-1b. Biodrugs 7: 23–29, 1997.
4. Key LL, Rodriguiz RM, Willi SM. Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med 24: 1594–1599, 1995.

Manufactured for:
Vidara Therapeutics Research Ltd.
Dublin, Ireland
Marketed by:
Vidara Therapeutics Inc.
Roswell, Georgia 30076

U.S. License No. 1905
Revised June 2013

PH0100301.00

© 2013 Vidara Therapeutics
302660-01