Exforge Use In Pregnancy & Lactation

amlodipine + valsartan




Full Prescribing Info
Use In Pregnancy & Lactation
Pregnancy: Risk summary: As for any drug that acts directly on the RAAS, Exforge must not be used during pregnancy (see CONTRAINDICATIONS). Due to the mechanism of action of angiotensin II antagonists, a risk to the foetus cannot be excluded. Administration of angiotensin converting enzyme (ACE) inhibitors (a specific class of drugs acting on the renin-angiotensin-aldosterone system, RAAS) to pregnant women during the second and third trimesters has been reported to cause injury and death to the developing foetus. In addition, in retrospective data, first trimester use of ACE inhibitors has been associated with a potential risk of birth defects. There have been reports of spontaneous abortion, oligohydramnios and newborn renal dysfunction when pregnant women have inadvertently taken valsartan.
There are no adequate clinical data with amlodipine in pregnant women. Animal studies with amlodipine have shown reproductive toxicity at dose 8 times the maximum recommended dose of 10 mg (see Pharmacology: Toxicology: NON-CLINICAL SAFETY DATA under Actions). The potential risk to humans is unknown.
If pregnancy is detected during therapy, Exforge must be discontinued as soon as possible (see ANIMAL DATA as follows).
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-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Fetal/Neonatal Risk: Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death.
In case of accidental exposure to ARB therapy, appropriate fetal monitoring should be considered.
Infants whose mothers have taken ARB therapy in the first trimester, should be closely observed for hypotension.
Animal data: Valsartan and amlodipine: In an oral embryo-fetal development study in rats with dose levels of 5:80 mg/kg/day, amlodipine:valsartan, 10:160 mg/kg/day amlodipine:valsartan, and 20:320 mg/kg/day amlodipine:valsartan, treatment-related maternal and fetal effects (developmental delays and alterations noted in the presence of significant maternal toxicity) were noted with the high dose combination. The no-observed-adverse-effect level (NOAEL) for embryo-fetal effects was 10:160 mg/kg/day amlodipine:valsartan. These doses are, respectively, 4.3 and 2.7 times the systemic exposure in humans receiving the MRHD (10/320 mg/60 kg).
Valsartan: In embryofetal development studies in mice, rats and rabbits, fetotoxicity was observed in association with maternal toxicity in rats at valsartan doses of 600 mg/kg/day approximately 6 times the maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient) and in rabbits at doses of 10 mg/kg/day approximately 0.6 times the maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient). There was no evidence of maternal toxicity or fetotoxicity in mice up to a dose level of 600 mg/kg/day approximately 9 times the maximum recommended human dose on a mg/m2 basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient).
Amlodipine: No evidence of teratogenicity or embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose.
Lactation: It is not known whether valsartan is excreted in human milk. It is reported that amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3 - 7%, with a maximum of 15%. The effect of amlodipine on infants is unknown. Valsartan was excreted in the milk of lactating rats. It is therefore not advisable for women who are breast-feeding to use Exforge.
Females and males of reproductive potential: As for any drug that acts directly on the RAAS, Exforge must not be used in women planning to become pregnant. Healthcare professionals prescribing any agents acting on the RAAS should counsel women of childbearing potential about the potential risk of these agents during pregnancy.
Infertility: There is no information on the effects of amlodipine or valsartan on human fertility. Studies in rats did not show any effects of amlodipine or valsartan on fertility (see Pharmacology: Toxicology: NON-CLINICAL SAFETY DATA under Actions).
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