PHENTERMINE

Fetal Risk Summary

Phentermine (phenyl-tertiary-butylamine) is a sympathomimetic amine that has activity as a central nervous system stimulant. Similar to other drugs in this class, such as the amphetamines, it is used as an appetite suppressant in the treatment of obesity. In addition to other adverse effects, hypertension has occurred in adults treated with this agent.

Reproduction studies in animals investigating if phentermine is teratogenic have not been conducted. A closely related compound, chlorphentermine (30 mg/kg/day SC), was administered to pregnant rats during the last 5 days of gestation (1). Phospholipidosis was evident in the lungs of the mothers and the newborn rats, and 83% of the latter died within 24 hours of birth. Another group treated with phentermine (30 mg/kg/day SC) in a similar manner did not develop the complication and did not die. A subsequent Reference suggested that the chlorphentermine-induced pup mortality was consistent with retardation of fetal pulmonary maturity (2).

No studies have been located that described the placental transfer of phentermine in animals or humans, but because of its low molecular weight (about 186), exposure of the fetus to the drug should be expected.

A study published in 1962 described the use of phentermine in 118 women who were treated for obesity during the 3rd trimester of pregnancy up to delivery (3). Women weighing less than 200 pounds were given 30 mg each morning, while those more than 200 pounds were given with 30 mg twice daily. The weights of the patients before treatment ranged from 180 to 315 pounds. Adverse outcomes occurred in five women with stillborn infants (three females and two males), one of whom was caused by abruptio placentae. The cause of the other stillborns, whose weights ranged from 9 to 10 pounds, was not mentioned, other than the statement that one mother had mild preeclampsia.

The FDA has received two reports involving the use of the combination fenfluramine and phentermine in early pregnancy (F. Rosa, personal communication, FDA, 1997). A spontaneous abortion occurred in one of the pregnancies. In the other, an infant with bilateral valvular abnormalities, both aortic and pulmonary, with moderate stenosis and displacement was delivered. Because valvular toxicity has been reported in adults taking the combination, a causal relationship in the pregnancy case is potentially possible. No other details of these cases were available.

That any real benefit is derived from the use of phentermine for weight control during pregnancy is doubtful, and its use during gestation, especially during the 1st trimester, should be considered contraindicated. Moreover, although the causes of the stillbirths in the human study cited above were not fully elucidated and may not have been caused by maternal treatment with phentermine, the high incidence is disturbing and is a reason to withhold use of the drug during pregnancy.

Breast Feeding Summary

No reports describing the use of phentermine during lactation have been located. Based on its low molecular weight (about 186), however, the excretion of phentermine into breast milk should be expected. Because central nervous system stimulation and other adverse reactions may occur in a nursing infant exposed to this drug in milk, breast feeding should be considered a contraindication if the mother is taking phentermine.

References

1. Thoma-Laurie D, Walker ER, Reasor MJ. Neonatal toxicity in rats following in utero exposure to chlorphentermine or phentermine. Toxicology 1982;24:85–94.
2. Kacew S, Reasor MJ. Newborn response to cationic amphiphilic drugs. Fed Proc 1985;44:2323–2327.
3. Sands RX. Obesity and pregnancy. Weight control with a resinate. Am J Obstet Gynecol 1962;83:1617–21.