Co-Diovan Use In Pregnancy & Lactation

Pregnancy: Risk summary: As for any drug that acts directly on the RAAS, Co-Diovan must not be used during pregnancy (see Contraindications).
Due to the mechanism of action of angiotensin II antagonists, a risk for the fetus cannot be excluded. In utero exposure to angiotensin converting enzyme (ACE) inhibitors (a specific class of drugs acting on the renin-angiotensin-aldosterone system - RAAS) given to pregnant women during the second and third trimesters has been reported to cause injury and death to the developing fetus. 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.
Intrauterine exposure to thiazide diuretics, including hydrochlorothiazide, is associated with fetal or neonatal jaundice or thrombocytopenia, and may be associated with other adverse reactions that have occurred in adults.
If pregnancy is detected during therapy, Co-Diovan should be discontinued as soon as possible (see Pharmacology: Toxicology: Non-Clinical Safety Data under Actions).
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 should be closely observed for hypotension.
Animal data: 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 18 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).
Hydrochlorothiazide: Hydrochlorothiazide was not teratogenic and had no effects on fertility and conception. No teratogenic potential was revealed in 3 animal species tested. There was no dose-related fetotoxicity at oral dose levels of 0, 100, 300, and 1000 mg/kg in rats. A decrease in weight gain in suckling rat pups was attributed to the high dose and diuretic effects of hydrochlorothiazide, with subsequent effects on milk production.
Lactation: Risk summary: It is not known whether valsartan is transferred into human milk. Valsartan was transferred into the milk of lactating rats. Hydrochlorothiazide crosses the placenta and is transferred into human milk. Thus, it is not advisable to use Co-Diovan in breast-feeding mothers.
Females and males of reproductive potential: As for any drug that acts directly on the RAAS, Co-Diovan should 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 valsartan or hydrochlorothiazide on human fertility. Studies in rats did not show any effects of valsartan or hydrochlorothiazide on fertility (see Pharmacology: Toxicology: Non-Clinical Safety Data under Actions).