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Captopril / hydrochlorothiazide Pregnancy and Breastfeeding Warnings

Captopril / hydrochlorothiazide is also known as: Capozide, Capozide 25/15, Capozide 25/25, Capozide 50/15, Capozide 50/25

Captopril / hydrochlorothiazide 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 only during the first trimester should be informed of the risks. When pregnancy is detected or expected, captopril should be discontinued as soon as possible. The Collaborative Perinatal Project monitored 50,282 mother-child pairs, of whom 233 were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics. Use of thiazides after the first trimester does not seem to carry this risk. Thiazide diuretics may, however pose metabolic risks to the mother and fetus (hyponatremia, hypokalemia, thrombocytopenia, hyperglycemia), and may have a direct effect on smooth muscle, resulting in inhibition of labor. Case reports of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

Captopril has been assigned to pregnancy category D by the FDA for use during the second and third trimesters, and to category C for use in the first trimester. Animal and human data have revealed evidence of embryolethality and teratogenicity associated with captopril. There are no controlled data in human pregnancy. However, fetal and neonatal toxicity and death, as well as congenital anomalies, are reported with the use of ACE inhibitors, including captopril, during pregnancy. Hydrochlorothiazide has been assigned to pregnancy category B by the FDA. There are no data from controlled human studies, but retrospective reviews have show an increased risk of malformations associated with thiazide diuretics. Captopril-hydrochlorothiazide is considered contraindicated during pregnancy.

See references

Captopril / hydrochlorothiazide Breastfeeding Warnings

Both captopril and hydrochlorothiazide are excreted into human milk in small amounts. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

See references

References for pregnancy information

  1. Barr M "Fetal effects of angiotensin converting enzyme inhibitor." Teratology 41 (1990): 536
  2. Lindheimer MD, Katz AI "Sodiuim and diuretics in pregnancy." N Engl J Med 288 (1973): 891-4
  3. Hanssens M, Keirse MJ, Vankelecom F, Assche FA "Fetal and neonatal effects of treatment with angiotensin-converting enzyme inhibitors in pregnancy." Obstet Gynecol 78 (1991): 128-35
  4. Brent RL, Beckman DA "Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors." Teratology 43 (1991): 543-6
  5. 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
  6. 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
  7. Guignard JP, Bergener F, Calame A "Persistent anuria in a neonate: a side effect of captopril?" Int J Pediatr Nephrol 2 (1981): 1981
  8. Lindheimer MD, Katz AI "Hypertension in pregnancy." N Engl J Med 313 (1985): 675-80
  9. Pryde PG, Nugent CE, Sedman AB, Barr M Jr "ACE inihibitor fetopathy." Am J Obstet Gynecol 166 (1992): 348
  10. Rosa FW, Bosco LA, Graham CR, Milstein JB, Dreis M, Creamer J "Neonatal anuria with maternal angiotensin-converting enzyme inhibition." Obstet Gynecol 74 (1989): 371-4
  11. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. "The 1984 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure." Arch Intern Med 144 (1984): 1045-57
  12. Rothberg AD, Lorenz R "Can captopril cause fetal and neonatal renal failure?" Pediatr Pharmacol (New York) 4 (1984): 189-92
  13. Duminy PC, Burger PD "Fetal abnormality associated with the use of captopril during pregnancy ." S Afr Med J 60 (1981): 805
  14. Rodriguez SU, Sanford LL, Hiller MC "Neonatal thrombocytopenia associated with ante-partum administration of thiazide drugs." N Engl J Med 270 (1964): 881-4
  15. Knott PD, Thorpe SS, Lamont CA "Congenital renal dysgenesis possibly due to captopril." Lancet 1 (1989): 451
  16. Koren G, Pastuszak A, Ito S "Drugs in pregnancy." N Engl J Med 338 (1998): 1128-37
  17. Heinonen O, Slone D, Shapiro S; Kaufman DW ed. "Birth Defects and Drugs in Pregnancy." Littleton, MA: Publishing Sciences Group, Inc. (1977): 297
  18. Piper JM, Ray WA, Rosa FW "Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors." Obstet Gynecol 80 (1992): 429-32
  19. Barr M Jr, Cohen MM "ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection." Teratology 44 (1991): 485-95
  20. "Product Information. Capozide (hydrochlorothiazide-captopril)." Bristol-Myers Squibb, Princeton, NJ.
  21. Broude AM "Fetal abnormality associated with captopril during pregnancy." S Afr Med J 61 (1982): 68

References for breastfeeding information

  1. "Product Information. Capozide (hydrochlorothiazide-captopril)." Bristol-Myers Squibb, Princeton, NJ.
  2. Committee on Drugs, 1992 to 1993 "The transfer of drugs and other chemicals into human milk." Pediatrics 93 (1994): 137-50
  3. Werthmann MW, Krees SV "Excretion of chlorothiazide in human breast milk." J Pediatr 81 (1972): 781-3
  4. Roberts RJ, Blumer JL, Gorman RL, et al "American Academy of Pediatrics Committee on Drugs: Transfer of drugs and other chemicals into human milk." Pediatrics 84 (1989): 924-36
  5. Devlin RG, Fleiss PM "Captopril in human blood and breast milk." J Clin Pharmacol 21 (1981): 110-3
  6. Miller ME, Cohn RD, Burghart PH "Hydrochlorothiazide disposition in a mother and her breast-fed infant." J Pediatr 101 (1982): 789-91
  7. Devlin RG, Fleiss PM "Selective resistance to the passage of captopril into human milk." Clin Pharmacol Ther 27 (1980): 250

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