Dexfenfluramine
Risk Factor: CM
Class: CENTRAL NERVOUS SYSTEM DRUGS
/ Stimulants and/or Anorexiants
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
Dexfenfluramine, the dextrorotatory isomer of fenfluramine, is a serotonin reuptake inhibitor and releasing agent used for the treatment of obesity. In reproductive studies with pregnant rats and rabbits at doses up to 10 times the daily human dose on a mg/m2 basis, no treatment-related embryotoxicity or teratogenicity was observed (1). In a three-generation study of pregnant rats given a dose 2.5 and 5 times the daily human dose on a mg/m2 basis, a dose-related significant reduction in maternal body weight and weight gain throughout pregnancy was noted. There were also a reduced number of placental implantations, fetuses, and live young, and delayed ossification in the fetuses (1). No significant treatment-related adverse effects or abnormalities were observed in second- and third-generation rats.
A 1992 report described the effects on brain serotonin of a continuous SC infusion of either 6 or 12 mg/kg/day of dexfenfluramine during the last week of pregnancy in pregnant rats and their offspring (2). Compared to controls, treated mothers had blunted weight gain, but no effect was observed on the number or the birth weight of their offspring. In contrast to the mothers, who had large depletions of serotonin when measured 3 weeks after birth, the amount of brain serotonin of the pups was either not affected or had returned to pretreatment levels within 24 hours.
The fatal course of a 30-year-old woman who had been treated with dexfenfluramine for 6 months immediately prior to pregnancy was described in a 1992 Reference (3). She was delivered by cesarean section at 34 weeks' gestation because of premature labor. She died 4 days later of irreversible primary pulmonary hypertension. The authors concluded that the drug treatment, plus a short stay at an altitude of approximately 2400 feet (800 m) above sea level, and her subsequent pregnancy were the cause of the condition. The condition of the newborn was not mentioned.
Two birth defects have been reported by the WHO International Drug Monitoring System following use of dexfenfluramine during pregnancy (F. Rosa, personal communication, FDA, 1997). One involved a malformation of the hand in 1989 and the second, in 1995, of an infant with multiple birth defects including anencephaly, a spinal anomaly, and a ventricular septal defect. No other details of these cases were available.
Except for the above, no published studies have reported the use of dexfenfluramine during human pregnancy, and the limited animal data appear to indicate a minimal fetal risk. Use of the anorexiant during gestation, however, is not recommended. If weight loss is needed during gestation, then nonpharmacologic methods such as diet control combined with professional assistance should be used.
Breast Feeding Summary
No studies describing the use of dexfenfluramine during human lactation or measuring the amount of drug, if any, excreted into milk have been located. Dexfenfluramine is excreted into rat milk (1). Because of its low molecular weight, about 268, passage into human milk in measurable quantities should be expected.
The use of dexfenfluramine during lactation is not recommended because of its unknown effect on serotonin parameters within the nursing infant's brain and the potential for long-term adverse changes.
References
- Product information. Redux. Wyeth-Ayerst Laboratories, 1997.
- Rowland NE, Robertson RM. Administration of dexfenfluramine in pregnant rats: effect on brain serotonin parameters in offspring. Pharmacol Biochem Behav 1992;42:8558.
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Atanassoff PG, Weiss BM, Schmid ER, Tornic M. Pulmonary hypertension and dexfenfluramine. Lancet 1992;339:436.
