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Chlorothiazide Pregnancy and Breastfeeding Warnings

Chlorothiazide is also known as: Diuril, Diuril Sodium

Chlorothiazide Pregnancy Warnings

Chlorothiazide readily crosses the human placenta, with umbilical cord blood levels approximately equivalent to maternal plasma. 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, although the fact that the population studied had underlying cardiovascular disease makes implication of drug use alone difficult. 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. The Michigan Medicaid surveillance study showed no association between some thiazide diuretics and congenital defects (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). This report is a summary of information from two studies, one in which 390 of 104,000 pregnant women from 1980 to 1983, and one in which 567 of 229,000 pregnant women from 1985 to 1992 received a related drug, hydrochlorothiazide (HCTZ). In the first study 28 total defects and 6 cardiovascular defects were observed (25 and 4 were expected, respectively). In the second study, 24 total defects and 7 cardiovascular defects were observed (22 and 6 were expected, respectively). Cleft palate was not observed in either study. These data do not support an association between HCTZ and congenital defects. These data are considered pertinent to other thiazide diuretics, although the number of exposures to chlorothiazide is too small to make definitive conclusions relative to this drug, per se. Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

Chlorothiazide has been assigned to pregnancy category C by the FDA. Animal data have failed to reveal evidence of teratogenicity, but the data are considered limited since visceral or skeletal abnormalities were not sought. There are no controlled data from human pregnancy. Some retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. The routine use of chlorothiazide during pregnancy in patients without heart disease is considered contraindicated by some experts.

See references

Chlorothiazide Breastfeeding Warnings

Chlorothiazide is secreted into human milk in low concentrations. While a rare case of thrombocytopenia has been reported in one nursing infant whose mother was taking chlorothiazide, adverse effects in the nursing infant are unlikely. Chlorothiazide is considered compatible with breast-feeding by the American Academy of Pediatrics; however, 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.

In one case, a single chlorothiazide 500 mg dose resulted in milk drug concentrations of less than 1 mcg per mL at 1, 2, and 3 hours. This usually represents an insignificant amount of chlorothiazide to the infant such that adverse effects in the nursing infant are unlikely.

See references

References for pregnancy information

  1. Tatum HJ, Waterman EA "The prophylactic and therapeutic use of the thiazides in pregnancy." GP 24 (1961): 101-5
  2. Anderson GG, Hanson TM "Chronic fetal bradycardia: possible association with hypokalemia." Obstet Gynecol 44 (1974): 896-8
  3. Harley JD, Robin H, Robertson SE "Thiazide-induced neonatal haemolysis?" Br Med J 1 (1964): 696-7
  4. Finnerty FA "Thiazide and neonatal thrombocytopenia." N Engl J Med 271 (1964): 160-1
  5. Lammintausta R, Erkkola R, Eronen M "Effect of chlorthiazide treatment on renin-aldosterone system during pregnancy." Acta Obstet Gynecol Scand 57 (1978): 389-92
  6. Mulley BA, Parr GD, Pau WK, Rye RM, Mould JJ, Sidle NC "Placental transfer of chlorthalidone and its elimination in maternal milk." Eur J Clin Pharmacol 13 (1978): 129-31
  7. Leikin SL "Thiazide and neonatal thrombocytopenia." N Engl J Med 271 (1964): 161
  8. Lindheimer MD, Katz AI "Sodiuim and diuretics in pregnancy." N Engl J Med 288 (1973): 891-4
  9. Menzies DN "Controlled trial of chlorothiazide in treatment of early pre-eclampsia." Br Med J 1 (1964): 139-42
  10. Rodriguez SU, Sanford LL, Hiller MC "Neonatal thrombocytopenia associated with ante-partum administration of thiazide drugs." N Engl J Med 270 (1964): 881-4
  11. Bird CC, Reeves BD "Effect of diuretic administration on urinary estriol levels in late pregnancy." Am J Obstet Gynecol 105 (1969): 552-5
  12. Jerkner K, Kutti J, Victorin L "Platelet counts in mothers and their newborn infants with respect to ante-partum administration of oral diuretics." Acta Med Scand 194 (1973): 473-5
  13. Gray MJ "Use and abuse of thiazides in pregnancy." Clin Obstet Gynecol 11 (1968): 568-78
  14. Shoemaker ES, Gant NF, Madden JD, MacDonald PC "The effect of thiazide diuretics on placental function." Tex Med 69 (1973): 109-15
  15. Watt JD "Oral diuretics in pregnancy toxaemia." Br Med J 1 (1960): 1807
  16. Heinonen O, Slone D, Shapiro S; Kaufman DW ed. "Birth Defects and Drugs in Pregnancy." Littleton, MA: Publishing Sciences Group, Inc. (1977): 297
  17. Aneckstein AG, Weingold AB "Chlorothiazide-induced hepatic coma in pregnancy." Am J Obstet Gynecol 95 (1966): 136-7
  18. Garnet JD "Placental transfer of chlorothiazide." Obstet Gynecol 21 (1963): 123-5
  19. Minkowitz S, Soloway HB, Hall JE, Yermakov V "Fatal hemorrhagic pancreatitis following chlorothiazide administration in pregnancy." Obstet Gynecol 24 (1964): 337-42
  20. Ladner CN, Pearson JW, Herrick CN, Harrison HE "The effect of chlorothiazide on blood glucose in the third trimester of pregnancy." Obstet Gynecol 23 (1964): 555-60
  21. Crosland DM, Flowers CE "Chlorothiazide and its relationship to neonatal jaundice." Obstet Gynecol 22 (1963): 500-4
  22. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  23. Sibai BM, Grossman RA, Grossman HG "Effects of diuretics on plasma volume in pregnancies with long-term hypertension." Am J Obstet Gynecol 150 (1984): 831-5
  24. Zuspan FP, Bell JD, Barnes AC "Balance-ward and double-blind diuretic studies during pregnancy." Obstet Gynecol 16 (1960): 543-9
  25. Weseley AC, Douglas GW "Continuous use of chlorothiazide for prevention of toxemia of pregnancy." Obstet Gynecol 19 (1962): 355-8
  26. Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de "Effect of chlorothiazide on intravenous glucose tolerance in pregnancy." Am J Obstet Gynecol 105 (1969): 556-60
  27. Pritchard JA, Walley PJ "Severe hypokalemia due to prolonged administration of chlorothiazide during pregnancy." Am J Obstet Gynecol 81 (1961): 1241-4
  28. Prescott LF "Neonatal thrombocytopenia and thiazide drugs." J Pediatr 67 (1965): 681-2

References for breastfeeding information

  1. Werthmann MW, Krees SV "Excretion of chlorothiazide in human breast milk." J Pediatr 81 (1972): 781-3
  2. "Product Information. Diuril (chlorothiazide)." Merck & Co, Inc, West Point, PA.
  3. Mulley BA, Parr GD, Pau WK, Rye RM, Mould JJ, Sidle NC "Placental transfer of chlorthalidone and its elimination in maternal milk." Eur J Clin Pharmacol 13 (1978): 129-31
  4. Miller ME, Cohn RD, Burghart PH "Hydrochlorothiazide disposition in a mother and her breast-fed infant." J Pediatr 101 (1982): 789-91

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