gnancy (see Clinical Considerations). In animal reproduction studies, therewas no evidence of adverse developmental effects when pregnant rats and rabbits were treatedorally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times themaximum recommended human dose (MRHD), respectively. However for rats, litter size wassignificantly decreased (by about 50%) and the number of intrauterine deaths was significantlyincreased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and
the duration of labor in rats at this dose [see Data].
The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. All pregnancies have a background risk of birth defect, loss or otheradverse outcomes. In the U.S. general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%,respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes,premature delivery, and delivery complications (e.g., need for cesarean section and post-partumhemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction andintrauterine death. Pregnant women with hypertension should be carefully monitored andmanaged accordingly.
Data
Animal Data
No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats andrabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day(approximately 10 and 20 times the MRHD based on body surface area, respectively) duringtheir respective periods of major organogenesis. However for rats, litter size was significantlydecreased (by about 50%) and the number of intrauterine deaths was significantly increased(about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mgamlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipinemaleate has been shown to prolong both the gestation period and the duration of labor in rats atthis dose.
8.2 Lactation
Risk Summary
Limited available data from a published clinical lactation study reports that amlodipine is presentin human milk at an estimated median relative infant dose of 4.2%. No adverse effects ofamlodipine on the breastfed infant have been observed. There is no available information on theeffects of amlodipine on milk production.
8.4 Pediatric Use
Amlodipine (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years[see Clinical Studies (14.1)].
Effect of amlodipine on blood pressure in patients less than 6 yearsof age is not known.
8.5 Geriatric Use
Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over todetermine whether they respond differently from younger subjects. Other reported clinicalexperience 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 endof the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiacfunction, and of concomitant disease or other drug therapy. Elderly patients have decreasedclearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a loweri |
