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Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE inhibitor exposure. Animal Data Lisinopril was not teratogenic in mice treated on days 6-15 of gestation with up to 1000 mg/ kg/ day (625 times the maximum recommended human dose). There was an increase in fetal resorptions at doses down to 100 mg/ kg; at doses of 1000 mg/ kg this was prevented by saline supplementation. There was no fetotoxicity or teratogenicity in rats treated with up to 300 mg/ kg/ day (188 times the maximum recommended dose) of lisinopril at days 6-17 of gestation. Text Continues Below
In rats receiving lisinopril from day 15 of gestation through day 21 postpartum, there was an increased incidence in pup deaths on days 2-7 postpartum and a lower average body weight of pups on day 21 postpartum. The increase in pup deaths and decrease in pup weight did not occur with maternal saline supplementation. Lisinopril, at doses up to 1 mg/ kg/ day, was not teratogenic when given throughout the organogenic period in saline supplemented rabbits. Saline supplementation (physiologic saline in place of tap water) was used to eliminate maternotoxic effects and enable evaluation of the teratogenic potential at the highest possible dosage level. The rabbit has been shown to be extremely sensitive to angiotensin-converting enzyme inhibitors (captopril and enalapril) with maternal and fetotoxic effects apparent at or below the recommended therapeutic dosage levels in man. Fetotoxicity was demonstrated in rabbits by an increased incidence of fetal resorptions at an oral dose of lisinopril of 1 mg/ kg/ day and by an increased incidence of incomplete ossification at the lowest dose tested (0.1 mg/ kg/ day). A single intravenous dose of 15 mg/ kg of lisinopril administered to pregnant rabbits on gestation days 16, 21 or 26 resulted in 88% to 100% fetal death. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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