Risk Factor: CM*
Class: Cardiovascular drugs/ Antihypertensives/ Angiotensin-converting enzyme inhibitors
Fetal Risk Summary
The prodrug, trandolapril, is rapidly metabolized to the active drug, trandolaprilat. It is indicated in the management of hypertension either alone, or in combination with other antihypertensives (e.g., hydrochlorothiazide). Trandolapril is also indicated in the management of stable patients with heart failure or left-ventricular dysfunction after myocardial infarction. The active metabolite, trandolaprilat, is a competitive inhibitor of angiotensin Iconverting enzyme (ACE inhibitor), thus preventing the conversion of angiotensin I to angiotensin II.
Reproduction studies have been conducted in rats, rabbits, and cynomolgus monkeys (1). No teratogenicity was observed in the three species at doses that were 2564, 3, and 108 times, respectively, the maximum projected human dose based on body surface area.
It is not known if trandolapril or trandolaprilat cross the human placenta. The molecular weights (about 431 for trandolapril; about 403 for trandolaprilat) are low enough that transfer to the fetus should be expected.
No reports describing the use of trandolapril during human pregnancy have been located. Based on the human pregnancy experience with other ACE inhibitors, trandolapril exposure during the 1st trimester would not be expected to represent a risk to the fetus. However, use of trandolapril during the 2nd and 3rd trimesters may cause teratogenicity and severe fetal and neonatal toxicity (see Captopril or Enalapril). Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth retardation, 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 ACE inhibitors.
In cases in which the mother’s disease requires trandolapril (or other ACE inhibitor), the lowest possible dose should be used. Close monitoring of amniotic fluid levels and fetal well-being should be conducted during gestation, followed by close observation of renal function and blood pressure in the newborn.
[*Risk Factor DM if used in the 2nd and/or 3rd trimesters according to the manufacturer.]
Breast Feeding Summary
No reports describing the use of trandolapril in human lactation have been located. The molecular weights (about 431 for trandolapril; about 403 for trandolaprilat) suggest that excretion into breast milk should be expected. The effect of this exposure on a nursing infant are unknown. However, other ACE inhibitors are excreted into breast milk and are considered compatible with breast feeding by the American Academy of Pediatrics (see Captopril and Enalapril).
- Product information. Mavik. Knoll Pharmaceutical, 2001.