Furosemide]]>

Risk Factor: CM*
Class: Diuretics

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References

Fetal Risk Summary

Furosemide is a potent diuretic. The drug has caused maternal deaths and abortions in rabbits at doses 2, 4, and 8 times the maximum recommended human dose of 600 mg/day (1). An increase in the incidence and severity of hydronephrosis (distention of the renal pelvis and in some cases of the ureters) has also been observed in the offspring of mice and rabbits (1). Wavy ribs and some skeletal defects have been observed in the offspring of rats given furosemide during organogenesis (2). These effects appeared to be caused directly or indirectly by the diuretic action of the drug (2).

Cardiovascular disorders, such as pulmonary edema, severe hypertension, or congestive heart failure, are probably the only valid indications for this drug in pregnancy. Furosemide crosses the placenta (3). Following oral doses of 2540 mg, peak concentrations in cord serum of 330 ng/mL were recorded at 9 hours. Maternal and cord levels were equal at 8 hours. Increased fetal urine production after maternal furosemide therapy has been observed (4,5). Administration of furosemide to the mother has been used to assess fetal kidney function by provoking urine production, which is then visualized by ultrasonic techniques (6,7). Diuresis was found more often in newborns exposed to furosemide shortly before birth than in controls (8). Urinary sodium and potassium levels in the treated newborns were significantly greater than in the nonexposed controls.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 350 newborns had been exposed to furosemide during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 18 (5.1%) major birth defects were observed (15 expected). Specific data were available for six defect categories, including (observed/expected) 2/4 cardiovascular defects, 1/1 oral clefts, 0/0 spina bifida, 1/1 polydactyly, 1/1 limb reduction defects, and 3/1 hypospadias. Only with the latter defect is there a suggestion of an association, but other factors, including the mother’s disease, concurrent drug use, and chance, may be involved.

After the 1st trimester, furosemide has been used for edema, hypertension, and toxemia of pregnancy without causing fetal or newborn adverse effects (9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30 and 31). Many investigators now consider diuretics contraindicated in pregnancy, except for patients with cardiovascular disorders, since they do not prevent or alter the course of toxemia and they may decrease placental perfusion (32,33,34 and 35). A 1984 study determined that the use of diuretics for hypertension in pregnancy prevented normal plasma volume expansion and did not change perinatal outcome (36). Thus, diuretics are not recommended for the treatment of pregnancy-induced hypertension because of the maternal hypovolemia characteristic of this disease.

Administration of the drug during pregnancy does not significantly alter amniotic fluid volume (30). Serum uric acid levels, which are increased in toxemia, are further elevated by furosemide (37). No association was found in a 1973 study between furosemide and low platelet counts in the neonate (38). Unlike the thiazide diuretics, neonatal thrombocytopenia has not been reported for furosemide.

[*Risk Factor D if used in pregnancy-induced hypertension.]

Breast Feeding Summary

Furosemide is excreted into breast milk (1,39). No reports of adverse effects in nursing infants have been found. Thiazide diuretics have been used to suppress lactation (see Chlorothiazide).

References

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  1. Product information. Furosemide. Mylan Pharmaceuticals, 2000.
  2. Shepard TH. Catalog of Teratogen Agents. 9th ed. Baltimore, MD:The Johns Hopkins University Press, 1998:215.
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  4. Wladimiroff JW. Effect of furosemide on fetal urine production. Br J Obstet Gynaecol 1975;82:2214.
  5. Stein WW, Halberstadt E, Gerner R, Roemer E. Effect of furosemide on fetal kidney function. Arch Gynekol 1977;224:1145.
  6. Barrett RJ, Rayburn WF, Barr M Jr. Furosemide (Lasix) challenge test in assessing bilateral fetal hydronephrosis. Am J Obstet Gynecol 1983;147:8467.
  7. Harman CR. Maternal furosemide may not provoke urine production in the compromised fetus. Am J Obstet Gynecol 1984;150:3223.
  8. Pecorari D, Ragni N, Autera C. Administration of furosemide to women during confinement, and its action on newborn infants. Acta Biomed (Italy) 1969;40:211.
  9. Pulle C. Diuretic therapy in monosymptomatic edema of pregnancy. Minerva Med 1965;56:16223.
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  30. Votta RA, Parada OH, Windgrad RH, Alvarez OH, Tomassinni TL, Patori AA. Furosemide action on the creatinine concentration of amniotic fluid. Am J Obstet Gynecol 1975;123:6214.
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  36. Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Am J Obstet Gynecol 1984;150:8315.
  37. Carswell W, Semple PF. The effect of furosemide on uric acid levels in maternal blood, fetal blood and amniotic fluid. J Obstet Gynaecol Br Commonw 1974;81:4724.
  38. Jerkner K, Kutti J, Victorin L. Platelet counts in mothers and their newborn infants with respect to antepartum administration of oral diuretics. Acta Med Scand 1973;194:4735.
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