LD50 values

The estimated dermal LD50 of dutasteride in rabbits is > 2,000 mg/kg.^L6256

Overdose

In studies of volunteers receiving single doses of dutasteride up to 40 mg (which is 80 times the therapeutic dose) for 7 days, there were no reports of clinically significant adverse events.^L10568 Low incidences of impotence, reduced libido, gynecomastia, and ejaculation disorder occurred significantly more often in dutasteride than placebo recipients.^A178345 There are no known antidotes for dutasteride. In case of overdose, appropriate symptomatic and supportive treatment should be given.^L10568

Nonclinical Toxicology

In a 2-year carcinogenicity mouse study, there was an increased incidence of benign hepatocellular adenomas in female mice receiving 250 mg/kg/day.^L10568 An increased incidence of Leydig cell hyperplasia was observed in male rats receiving doses of 7.5 mg/kg/day and greater. At tumorogenic doses, the luteinizing hormone (LH) levels in rats were increased by 167%. There was no demonstrated a genotoxic potential of dutasteride or its metabolites in a bacterial mutagenesis assay, a chromosomal aberration assay in CHO cells, and a micronucleus assay in rats.^L10568 At much higher doses than the maximum recommended human dose (MRHD) in sexually mature male rats, dutasteride caused a dose- and time-dependent decrease in fertility, reduced cauda epididymal (absolute) sperm counts but not sperm concentration (at 50 and 500 mg/kg/day), reduced weights of the epididymis, prostate, and seminal vesicles, and microscopic changes in the male reproductive organs.^L10568 At exposures 425- and 315-fold the expected clinical exposure of dutasteride in rats and dogs, respectively, there were some signs of non-specific, reversible, centrally-mediated toxicity without associated histopathological changes. ^L10568

Pregnancy and Lactation

As DHT is a necessary hormone for the development of male genitalia, exposure to dutasteride in pregnant women bearing male fetuses may cause fetal harm.^L10568 In animal reproduction and developmental toxicity studies, dutasteride inhibited normal development of external genitalia in male fetuses.^L10568 Although it is not known whether dutasteride is excreted in human milk, the use of dutasteride in women of childbearing potential, including nursing women.^L10568 In elderly patients, the half-life of dutasteride may increase. As the renal elimination of dutasteride is very minimal, the use of dutasteride in patients renal insufficiency is reported to be safe.^L6256 There are no specific dosage adjustment recommendations for use in elderly patients or patients with renal impairment.^L10568