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Trandolapril / verapamil Pregnancy and Breastfeeding Warnings

Trandolapril / verapamil is also known as: Tarka

Trandolapril / verapamil Pregnancy Warnings

Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered during pregnancy. A committee of the National Institutes of Health has recommended that these drugs be avoided during pregnancy. Limited data have shown an association between major congenital malformations and the use of ACE inhibitors during the first trimester. In addition, the use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug. Mothers whose embryos and fetuses are exposed to an ACE inhibitor during the first trimester should be informed of the risks. When pregnancy is detected or expected, trandolapril-verapamil should be discontinued as soon as possible. With regard to "verapamil" alone, there are no specific reports linking verapamil to congenital defects in humans. Data from the Michigan Medicaid Birth Defects Study failed to show an association between the use of verapamil and birth defects (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). Orally administered verapamil monotherapy has been used safely and successfully to treat maternal hypertension and both maternal and fetal tachyarrhythmias during pregnancy.

Trandolapril-verapamil has been assigned to pregnancy category D by the FDA for use during the second and third trimesters and to category C during the first trimester. Animal and human data have revealed evidence of embryolethality and teratogenicity associated with ACE inhibitors. Animal studies with verapamil have failed to reveal evidence of teratogenicity; however, there was evidence of embryolethality and fetotoxicity at doses that were associated with maternal toxicity. There are no controlled data in human pregnancy. Congenital malformations have been reported with the use of ACE inhibitors during the first trimester of pregnancy, while fetal and neonatal toxicity, death, and congenital anomalies have been reported with the use of ACE inhibitors during the second and third trimesters of pregnancy. If the patient becomes pregnant, trandolapril-verapamil should be discontinued as soon as possible. Trandolapril-verapamil is considered contraindicated during pregnancy.

See references

Trandolapril / verapamil Breastfeeding Warnings

There are no data on the excretion of trandolapril into human milk. Verapamil is excreted into human milk in small amounts. The manufacturer states that trandolapril-verapamil should not be given to nursing mothers.

With regard to verapamil, there are two case studies that have shown that between 23% and 60% of the maternal serum verapamil concentration appears in human milk at steady state. In one study, the authors calculated that the nursing infant would receive less than 0.01% of the mother's dose. This represents a miniscule amount of drug to the nursing infant.

See references

References for pregnancy information

  1. Cunniff C, Jones KL, Phiullipson J, Benirschke K, Short S, Wujek J "Oligohydramnios sequence and renal tubular malformation associated with maternal enalapril use." Am J Obstet Gynecol 162 (1990): 187-9
  2. Kreft-Jais C, Plouin PF, Tchobroutsky C "Angiotensin-converting enzyme inhibitors during pregnancy: a survey of 22 patients given captopril and nine given enalapril." Br J Obstet Gynaecol 95 (1988): 420-2
  3. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al "Major congenital malformations after first-trimester exposure to ACE inhibitors." N Engl J Med 354 (2006): 2443-51
  4. Thorpe-Beeston JG, Armar NA, Dancy M, Cochrane GW, Ryan G, Rodeck CH "Pregnancy and ACE inhibitors." Br J Obstet Gynaecol 100 (1993): 692-3
  5. "Product Information. Tarka (trandolapril-verapamil)." Knoll Pharmaceutical Company, Whippany, NJ.
  6. Smith AM "Are Ace inhibitors safe in pregnancy?" Lancet 2 (1989): 750-1
  7. Schubiger G, Flury G, Nussberger J "Enalapril for pregnancy-induced hypertension: acute renal failure in a neonate." Ann Intern Med 108 (1988): 215-6
  8. Shotan A, Widerhorn J, Hurst A, Elkayam U "Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use." Am J Med 96 (1994): 451-6
  9. Mehta N, Modi N "Ace inhibitors in pregnancy." Lancet 2 (1989): 96
  10. Koren G, Pastuszak A, Ito S "Drugs in pregnancy." N Engl J Med 338 (1998): 1128-37

References for breastfeeding information

  1. "Product Information. Tarka (trandolapril-verapamil)." Knoll Pharmaceutical Company, Whippany, NJ.
  2. Anderson P, Bondesson U, Mattiasson I, Johansson BW "Verapamil and norverapamil in plasma and breast milk during breast feeding." Eur J Clin Pharmacol 31 (1987): 625-7

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