DRUG INTERACTIONS
Drug/Laboratory Test Interactions
Therapy with histrelin results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after histrelin therapy may be affected.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies were conducted in rats for 2 years at doses of 5, 25 or 150 mcg/kg/day (up to 15 times the human dose) and in mice for 18 months at doses of 20, 200, or 2000 mcg/kg/day (up to 200 times the human dose). As seen with other LH-RH agonists, histrelin acetate injection administration was associated with an increase in tumors of hormonally responsive tissues. There was a significant increase in pituitary adenomas in rats. There was an increase in pancreatic islet-cell adenomas in treated female rats and a non-dose-related increase in testicular Leydig-cell tumors (highest incidence in the low-dose group). In mice, there was significant increase in mammary-gland adenocarcinomas in all treated females. In addition, there were increases in stomach papillomas in male rats given high doses, and an increase in histiocytic sarcomas in female mice at the highest dose.
Mutagenicity studies have not been performed with histrelin acetate. Saline extracts of implants with and without histrelin were negative in a battery of genotoxicity studies. Fertility studies have been conducted in rats and monkeys given subcutaneous daily doses of histrelin acetate up to 180 mcg/kg for 6 months and full reversibility of fertility suppression was demonstrated. The development and reproductive performance of offspring from parents treated with histrelin acetate has not been investigated.
Pregnancy
Teratogenic Effects
Pregnancy Category X
(see CONTRAINDICATIONS).
Major fetal abnormalities were observed in rabbits but not in rats after administration of histrelin acetate throughout gestation. There were increased fetal mortality and decreased fetal weights in rats and rabbits. The effects on fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug. The possibility exists that spontaneous abortion may occur .
|
