Antihypertensive
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 2nd and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
The antihypertensive mechanisms of action of telmisartan and angiotensin-converting enzyme (ACE) inhibitors are very close. That is, the former selectively blocks the binding of angiotensin II to AT1receptors, whereas the latter prevents 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 (e.g., 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 are resistant to both pressor agents and volume expansion may occur in the newborn following in utero exposure to telmisartan. Newborn renal function and blood pressure should be closely monitored.
FETAL RISK SUMMARY
Telmisartan 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. Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by preventing angiotensin II from binding to AT1 receptors (1).
Reproduction studies have been conducted in pregnant rats and rabbits. No teratogenicity was observed in either species at oral doses up to about 6.3 and 6.4 times the maximum recommended human dose of 80 mg based on BSA (MRHD), respectively, but embryolethality was noted at the highest dose in rabbits. The highest doses were maternally toxic (reduced body weight gain and food consumption) in both species. In rats, an oral dose approximately 1.9 times the MRHD (also maternal toxic) during late gestation and lactation resulted in neonatal adverse effects, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. The no-observed-effect doses for developmental toxicity in rats and rabbits were 0.64 and 3.7 times the MRHD, respectively. No adverse effects on reproductive performance were noted in male and female rats at a dose about 13 times the MRHD (1).
It is not known if telmisartan crosses the human placenta to the fetus. The drug is found in rat fetuses in late gestation (1). The molecular weight (about 515) is low enough that passage to the human fetus should be expected.
A 2003 case report described transient renal failure in a newborn secondary to maternal use of telmisartan (2). A 35-year-old woman with hypertension was treated with telmisartan throughout pregnancy. Oligohydramnios was diagnosed at 34 weeks’ gestation and a 2.2-kg female infant was delivered by cesarean section. Apgar scores were 9, 10, and 10 at 1, 5, and 10 minutes, respectively. The infant was anuric until the third day of life, but renal function improved thereafter. Telmisartan plasma levels on day 10 and 13 were 20 and 13 ng/L, respectively. The infant’s renal function had normalized by 1.5 months of age (2).
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 (3). The factors, that typically coexist with hypertension in pregnancy, included diabetes, advanced maternal age, and obesity.
BREASTFEEDING SUMMARY
No reports describing the use of telmisartan during human lactation have been located. The molecular weight (515) is low enough that excretion into human breast milk should be expected. The effect of this exposure on a nursing infant is unknown. The American Academy of Pediatrics, however, classifies ACE inhibitors, a closely related group of antihypertensive agents, as compatible with breastfeeding (see Captopril or Enalapril).
References
1.Product information. Micardis. Boehringer Ingelheim Pharmaceuticals, 2000.
2.Pietrement C, Malot L, Santerne B, Roussel B, Motte J, Morville P. Neonatal acute renal failure secondary to maternal exposure to telmisartan, angiotensin II receptor antagonist. J Perinatol 2003;23:254–5.
3.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.