Risk Factor: B
Class: Antilipemic agents
Fetal Risk Summary
Cholestyramine is a resin used to bind bile acids in a nonabsorbable complex. In a reproductive study involving rats and rabbits, the resin was given in doses up to 2 g/kg/day without evidence of fertility impairment or adverse fetal effects (1). In a comparison between pregnant and nonpregnant rats, administration of cholestyramine failed to lower the plasma cholesterol concentration or to increase bile acid synthesis (2). The drug therapy had no effect, in comparison to control animals, on maternal weight gain, number of fetuses, and fetal weight.
Cholestyramine has been used for the treatment of cholestasis of pregnancy (3,4,5,6 and 7). Except for the case described below, no adverse fetal effects were observed in these studies. One review recommended the resin as first-line therapy for the pruritus that accompanies intrahepatic cholestasis of pregnancy (6). Cholestyramine also binds fat-soluble vitamins, and long-term use could result in deficiencies of these agents in either the mother or the fetus (8). In one study, treatment with 9 g daily up to a maximum duration of 12 weeks was not associated with fetal or maternal complications (3).
A 31-year-old woman in her third pregnancy was treated with cholestyramine (8 g/day) beginning at 19 weeks’ gestation for intrahepatic cholestasis of pregnancy (7). At 22 weeks’, the dose was increased to 16 g/day. Four weeks later, she was clinically jaundiced and at 29 weeks’ gestation, she was admitted to the hospital for reduced fetal movements. Fetal ultrasound scans over the next week revealed expanding bilateral subdural hematomas with hydrocephalus, an enlarged liver, and bilateral pleural effusions (7). The mother’s prothrombin ratio was markedly elevated but responded to two doses of IV vitamin K. One week later, following labor induction for fetal distress, a 1660-g infant was delivered who died at 15 minutes of age. It was thought that the fetal subdural hematomas were the result of vitamin K deficiency caused by the cholestyramine, cholestasis, or both (7).
A 1989 report described the use of cholestyramine and other agents in the treatment of inflammatory bowel disease during pregnancy (9). Seven patients were treated during gestation with the resin. One of the seven delivered prematurely (
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, four newborns had been exposed to cholestyramine during the 1st trimester (10). Thirty-three other newborns were exposed after the 1st trimester. None of the infants had congenital malformations.
Breast Feeding Summary
Cholestyramine is a nonabsorbable resin. No reports describing its use during lactation have been located. Because it binds fat-soluble vitamins, prolonged use may result in deficiencies of these vitamins in the mother and her nursing infant.
- Koda S, Anabuki K, Miki T, Kahi S, Takahashi N. Reproductive studies on cholestyramine. Kiso to Rinsho 1982;16:204094. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:90.
- Innis SM. Effect of cholestyramine administration during pregnancy in the rat. Am J Obstet Gynecol 1983;146:136.
- Lutz EE, Margolis AJ. Obstetric hepatosis: treatment with cholestyramine and interim response to steroids. Obstet Gynecol 1969;33:6471.
- Heikkinen J, Maentausta O, Ylostalo P, Janne O. Serum bile acid levels in intrahepatic cholestasis of pregnancy during treatment with phenobarbital or cholestyramine. Eur J Obstet Gynecol Reprod Biol 1982;14:15362.
- Shaw D, Frohlich J, Wittmann BAK, Willms M. A prospective study of 18 patients with cholestasis of pregnancy. Am J Obstet Gynecol 1982;142:6215.
- Schorr-Lesnick B, Lebovics E, Dworkin B, Rosenthal WS. Liver disease unique to pregnancy. Am J Gastroenterol 1991;86:65970.
- Sadler LC, Lane M, North R. Severe fetal intracranial haemorrhage during treatment with cholestyramine for intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol 1995;102:16970.
- American Hospital Formulary Service. Drug Information 1997. Bethesda, MD:American Society of Health-System Pharmacists, 1997:13304.
- Fedorkow DM, Persaud D, Nimrod CA. Inflammatory bowel disease: a controlled study of late pregnancy outcome. Am J Obstet Gynecol 1989;160:9981001.
- Rosa F. Anticholesterol agent pregnancy exposure outcomes. Presented at the 7th International Organization for Teratogen Information Services, Woods Hole, MA, April 1994.