Neither fosinopril nor the active fosinoprilat was mutagenic in the Ames microbial mutagen test, the mouse lymphoma forward mutation assay, or a mitotic gene conversion assay. Fosinopril was also not genotoxic in a mouse micronucleus test in vivo and a mouse bone marrow cytogenetic assay in vivo. In the Chinese hamster ovary cell cytogenetic assay, fosinopril increased the fre-quency of chromosomal aberrations when tested without metabolic activation at a concentration that was toxic to the cells. However, there was no increase in chro-mosomal aberrations at lower drug concentrations without metabolic activation or at any concentration with metabolic activation. There were no adverse reproductive effects in male and female rats treated with 15 or 60 mg/ kg daily. On a body weight basis, the high dose of 60 mg/ kg is about 38 times the maximum recommended human dose. On a body surface area basis, this dose is 6 times the maximum recommended human dose. There was no effect on pairing time prior to mating in rats until a daily dose of 240 mg/ kg, a toxic dose, was given; at this dose, a slight increase in pairing time was observed. On a body weight basis, this dose is 150 times the maximum recommended human dose. On a body surface area basis, this dose is 24 times the maximum recommended human dose. Pregnancy Categories C (first trimester) and D (second and third trimesters) See WARNINGS: Fetal/ Neonatal Morbidity and Mortality. Nursing Mothers Ingestion of 20 mg daily for three days resulted in detectable levels of fosinoprilat in breast milk. MONOPRIL should not be administered to nursing mothers. Geriatric Use Clinical studies of MONOPRIL did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Pediatric Use Safety and effectiveness in pediatric patients have not been established. | ||||
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