Risk Factor: CM
Class: Antilipemic agents
Fetal Risk Summary
The reproductive effects of the serum lipid-lowering agent, gemfibrozil, have been studied in rats and rabbits. In male and female rats, gemfibrozil was tumorigenic (benign liver nodules, liver carcinoma, and benign Leydig cell tumors) at 0.2 and 1.3 times the human exposure (based on AUC) (1). Treatment of female rats before and during gestation with 0.6 and 2 times the human dose (based on surface area) produced dose-related decreases in the conception rate, birth weight, and pup growth during lactation, and increased skeletal variations (1). Anophthalmia was observed rarely. The highest dose also resulted in an increased rate of stillbirths. Pregnant rabbits given 1 and 3 times the human dose during organogenesis had a decreased litter size and, at the highest dose, an increased incidence of parietal bone variations (1). Two other studies have found no evidence of reproductive or teratogenic effects in rats and rabbits (2,3).
A 1992 report described the use of gemfibrozil starting at 20 weeks’ gestation in a 33-year-old woman with eruptive xanthomas (4). The patient had a similar condition in her first pregnancy that included hypertriglyceridemia, fulminant pancreatitis, and acute respiratory distress syndrome (4). A dose of 600 mg 4 times daily for 2 months lowered the triglyceride level from 7530 to 4575 mg/dL, and the total cholesterol level from 1515 to 1325 mg/dL, but the xanthomas persisted throughout her pregnancy. A healthy, term infant (birth weight and sex not specified) was eventually delivered.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 8 newborns had been exposed to gemfibrozil during the 1st trimester and 7 in the 2nd or 3rd trimesters (5). One defect, a structural brain anomaly, was observed in an infant delivered from a mother who took the agent after the 1st trimester. In a separate case included in this report, an infant with Pierre Robin syndrome, suspected of being associated with 1st-trimester exposure to gemfibrozil, was reported retrospectively to the FDA (5).
Breast Feeding Summary
No reports describing the use of gemfibrozil during lactation have been located. The relatively low molecular weight (about 250) probably indicates that the drug will be excreted into milk. Gemfibrozil should probably not be used in breast feeding women because of the potential for severe toxicity, including tumors, in the nursing infant.
- Product information. Lopid. Parke-Davis, 2000.
- Kurtz SM, Fitzgerald JE, Fisken RA, Schardein JL, Reutner TF, Lucas JA. Toxicological studies on gemfibrozil. Proc R Soc Med 1976;69(Suppl 2):1523. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY:Marcel Dekker, 1993:81.
- Fitzgerald JE, Petrere JA, De La Iglesia FA. Experimental studies on reproduction with the lipid-regulating agent gemfibrozil. Fund Appl Toxicol 1987;8:45464. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:188.
- Jaber PW, Wilson BB, Johns DW, Cooper PH, Ferguson JE II. Eruptive xanthomas during pregnancy. J Am Acad Dermatol 1992;27:3002.
- Rosa F. Anti-cholesterol agent pregnancy exposure outcomes. Presented at the 7th International Organization for Teratogen Information Services, Woods Hole, MA, April 1994.