Carcinogenesis, mutagenesis, impairment of fertility
Two-year carcinogenicity studies were conducted with leuprolide acetate in rats and mice.
In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group).
In mice, no leuprolide acetate-induced tumors or pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years.
Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities.
No carcinogenicity studies have been conducted with ELIGARD.
Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems and with ELIGARD 7.5 mg in bacterial systems. These studies provided no evidence of a mutagenic potential.