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Trichlormethiazide Pregnancy and Breastfeeding Warnings

Brand names: Aquacot, Diurese, Metahydrin, Naqua

Trichlormethiazide Pregnancy Warnings

Trichlormethiazide has been assigned to pregnancy category C by the FDA. Animal studies have not been reported. There are no controlled data in human pregnancy, but retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. Trichlormethiazide should only be given during pregnancy when there are no alternatives and benefit outweighs risk.

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 the same 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, and are considered pertinent to other thiazide diuretics.

Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

See references

Trichlormethiazide Breastfeeding Warnings

Thiazide diuretics are excreted into human milk in low concentrations. While a rare case of thrombocytopenia has been reported in one nursing infant whose mother was taking a related drug, chlorothiazide, adverse effects in the nursing infant are unlikely.

See references

References for pregnancy information

  1. Lammintausta R, Erkkola R, Eronen M. Effect of chlorthiazide treatment on renin-aldosterone system during pregnancy. Acta Obstet Gynecol Scand. 1978;57:389-92.
  2. Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de. Effect of chlorothiazide on intravenous glucose tolerance in pregnancy. Am J Obstet Gynecol. 1969;105:556-60.
  3. Bird CC, Reeves BD. Effect of diuretic administration on urinary estriol levels in late pregnancy. Am J Obstet Gynecol. 1969;105:552-5.
  4. Aneckstein AG, Weingold AB. Chlorothiazide-induced hepatic coma in pregnancy. Am J Obstet Gynecol. 1966;95:136-7.
  5. Anderson GG, Hanson TM. Chronic fetal bradycardia: possible association with hypokalemia. Obstet Gynecol. 1974;44:896-8.
  6. Heinonen O, Shapiro S; Kaufman DW ed., Slone D. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, Inc. 1977;297.
  7. Rodriguez SU, Sanford LL, Hiller MC. Neonatal thrombocytopenia associated with ante-partum administration of thiazide drugs. N Engl J Med. 1964;270:881-4.
  8. Lindheimer MD, Katz AI. Sodiuim and diuretics in pregnancy. N Engl J Med. 1973;288:891-4.
  9. Gjonnaess H. Thiazide treatment in pregnancy with special reference to maternal and foetal electrolytes. Acta Obstet Gynecol Scand. 1968;47:404-19.
  10. Zuspan FP, Bell JD, Barnes AC. Balance-ward and double-blind diuretic studies during pregnancy. Obstet Gynecol. 1960;16:543-9.
  11. Tatum HJ, Waterman EA. The prophylactic and therapeutic use of the thiazides in pregnancy. GP. 1961;24:101-5.
  12. Weseley AC, Douglas GW. Continuous use of chlorothiazide for prevention of toxemia of pregnancy. Obstet Gynecol. 1962;19:355-8.
  13. Gray MJ. Use and abuse of thiazides in pregnancy. Clin Obstet Gynecol. 1968;11:568-78.
  14. Watt JD. Oral diuretics in pregnancy toxaemia. Br Med J. 1960;1:1807.
  15. Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Am J Obstet Gynecol. 1984;150:831-5.
  16. Shoemaker ES, Gant NF, Madden JD, MacDonald PC. The effect of thiazide diuretics on placental function. Tex Med. 1973;69:109-15.
  17. Garnet JD. Placental transfer of chlorothiazide. Obstet Gynecol. 1963;21:123-5.
  18. 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. 1978;13:129-31.
  19. Menzies DN. Controlled trial of chlorothiazide in treatment of early pre-eclampsia. Br Med J. 1964;1:139-42.
  20. Ladner CN, Pearson JW, Herrick CN, Harrison HE. The effect of chlorothiazide on blood glucose in the third trimester of pregnancy. Obstet Gynecol. 1964;23:555-60.
  21. Harley JD, Robin H, Robertson SE. Thiazide-induced neonatal haemolysis? Br Med J. 1964;1:696-7.
  22. Leikin SL. Thiazide and neonatal thrombocytopenia. N Engl J Med. 1964;271:161.
  23. Prescott LF. Neonatal thrombocytopenia and thiazide drugs. J Pediatr. 1965;67:681-2.
  24. Finnerty FA. Thiazide and neonatal thrombocytopenia. N Engl J Med. 1964;271:160-1.
  25. Pritchard JA, Walley PJ. Severe hypokalemia due to prolonged administration of chlorothiazide during pregnancy. Am J Obstet Gynecol. 1961;81:1241-4.
  26. Crosland DM, Flowers CE. Chlorothiazide and its relationship to neonatal jaundice. Obstet Gynecol. 1963;22:500-4.
  27. Minkowitz S, Soloway HB, Hall JE, Yermakov V. Fatal hemorrhagic pancreatitis following chlorothiazide administration in pregnancy. Obstet Gynecol. 1964;24:337-42.
  28. Product Information. Metahydrin (trichlormethiazide). Hoechst Marion Roussel. 2001.

References for breastfeeding information

  1. Werthmann MW, Krees SV. Excretion of chlorothiazide in human breast milk. J Pediatr. 1972;81:781-3.
  2. Miller ME, Cohn RD, Burghart PH. Hydrochlorothiazide disposition in a mother and her breast-fed infant. J Pediatr. 1982;101:789-91.
  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. 1978;13:129-31.
  4. Product Information. Metahydrin (trichlormethiazide). Hoechst Marion Roussel. 2001.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.