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Trichlormethiazide Pregnancy and Breastfeeding Warnings

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

References for breastfeeding information

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

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