Antihypertensive
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 2nd and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of eprosartan during human pregnancy have been located. The antihypertensive mechanisms of action of eprosartan and angiotensin-converting enzyme (ACE) inhibitors are very close. That is, the former selectively blocks the binding of angiotensin II to AT1 receptors, whereas the latter blocks the formation of angiotensin II itself. Therefore, use of this drug during the 2nd and 3rd trimesters may cause teratogenicity and severe fetal and neonatal toxicity that is identical to that seen with ACE inhibitors (see Captopril or Enalapril). Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth restriction, prematurity, and patent ductus arteriosus. Anuria-associated oligohydramnios may produce fetal limb contractures, craniofacial deformation, and pulmonary hypoplasia. Severe anuria and hypotension, that is resistant to both pressor agents and volume expansion, may occur in the newborn following in utero exposure to eprosartan. Newborn renal function and blood pressure should be closely monitored.
FETAL RISK SUMMARY
Eprosartan is a selective angiotensin II receptor blocker (ARB) that is used, either alone or in combination with other antihypertensive agents, for the treatment of hypertension. Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by preventing angiotensin II from binding to AT1 receptors.
Reproduction studies have been conducted in rats and rabbits (1). No teratogenic effects were observed in either species, but dose-related toxicity occurred in pregnant rabbits. In pregnant rats, no adverse effects on the fetus or on the postnatal development and maturation of offspring were observed at oral doses up to approximately 0.6 times the human exposure based on AUC at the maximum recommended human dose or 800 mg/day (MRHD). Similarly, a dose approximately 0.8 times the MRHD did not result in fetal or maternal toxicity in pregnant rabbits. Increasing the dose to approximately 2.7 times the MRHD in pregnant rabbits, however, caused both maternal (reduced body weight, decreased food consumption, and death) and embryo–fetal (resorptions, abortions, and litter loss) toxicity (1).
It is not known if eprosartan crosses the human placenta. The molecular weight (about 521) is low enough that passage to the fetus should be expected.
A 2012 review of the use of ACE inhibitors and ARBs in the 1st trimester concluded that there may be an elevated teratogenic risk, but the risk appeared to be related to other factors (2). The factors, that typically coexist with hypertension in pregnancy, included diabetes, advanced maternal age, and obesity.
BREASTFEEDING SUMMARY
No reports describing the use of eprosartan during human lactation have been located. The molecular weight (about 521) is low enough that excretion into breast milk should also be expected. The effects of this exposure on a nursing infant are unknown. The American Academy of Pediatrics, however, classifies ACE inhibitors, a closely related group of antihypertensive agents, as compatible with breastfeeding (see Captopril and Enalapril).
References
1.Product information. Teveten. Unimed Pharmaceuticals, 2001.
2.Polifka JE. Is there an embryopathy associated with first-trimester exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence. Birth Defects Res (Part A) 2012;94:576–98.