FLUVASTATIN

Fetal Risk Summary

The cholesterol-lowering agent, fluvastatin, has the same mechanism of action (i.e., inhibition of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase) as some other agents in this class (e.g., see Lovastatin, Pravastatin, and Simvastatin). It differs from these other agents in that it is entirely synthetic and is not derived from fungal sources.

Fluvastatin was not teratogenic in rats and rabbits at doses up to 36 and 10 mg/kg/day, respectively (1,2). Moreover, at the highest doses tested in rats for effects on fertility and reproductive performance, 20 mg/kg/day in males and 6 mg/kg/day in females, no adverse effects were observed (2). Significant maternal body weight loss and an increase in stillborns, neonatal morbidity, and maternal morbidity, however, were observed with fluvastatin doses of either 12 or 24 mg/kg/day administered to pregnant rats from the 15th day after coitus through weaning (2). The maternal morbidity was attributed to the occurrence of cardiomyopathy in the affected animals. The adverse effects of fluvastatin were lessened or prevented by the co-administration of mevalonic acid, a product produced by the enzyme HMG-CoA reductase, indicating that the toxicity was a result of inhibition of this enzyme.

Rosa reported finding no recipients of this drug in his 1994 presentation on the outcome of pregnancies following exposure to anticholesterol agents (3). However, a 1999 case report described the pregnancy outcome of a 28-year-old woman who had taken fluvastatin (20 mg/day) for 18 months before conception and during the first 9 weeks of pregnancy (4). The patient, who had a kidney transplantation 6 years before pregnancy, took prednisone, cyclosporine, azathioprine, cephalexin, and ranitidine throughout gestation. She delivered a healthy, 2901-g female infant at term with Apgar scores of 4 and 9 at 1 and 5 minutes, respectively. Except for transient tachypnea, no other complications were noted. At age 19 months, the infant's growth (weight, height, and head circumference all at the 50th percentile or higher) and development were normal (4).

Because the interruption of cholesterol-lowering therapy during pregnancy should have no effect on the long-term treatment of hyperlipidemia, and because cholesterol and other products synthesized from cholesterol are required for fetal development, the use of fluvastatin is contraindicated during pregnancy.

Breast Feeding Summary

No published reports describing the use of fluvastatin during lactation have been located. The manufacturer reports that fluvastatin is present in breast milk at a milk:plasma ratio of 2 (1). Because of the potential for adverse effects in the nursing infant, the drug should not be used during lactation.

References

1. Product information. Lescol. Sandoz Pharmaceuticals, 1995.
2. Hrab RV, Hartman HA, Cox RH Jr. Prevention of fluvastatin-induced toxicity, mortality, and cardiac myopathy in pregnant rats by mevalonic acid supplementation. Teratology 1994;50:19–26.
3. Rosa F. Anti-cholesterol agent pregnancy exposure outcomes. Presented at the 7th International Organization for Teratogen Information Services, Woods Hole, MA, April 1994.
4. Seguin J, Samuels P. Fluvastatin exposure during pregnancy. Obstet Gynecol 1999;93:847.