Antialcoholic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest High Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Although no published reports describing the use of acamprosate in human pregnancy have been located, there are human data from a Teratology Information Service (TIS) in France. The animal data suggest high risk, but the very limited human pregnancy experience prevents an assessment of the embryo–fetal risk. However, the use of ethanol (alcohol) in pregnancy is well known to cause dose-related developmental toxicity (see Ethanol). Even in the absence of obvious structural defects, alcohol use during gestation is associated with marked neurotoxicity in the offspring. Therefore, in pregnant women with alcohol dependency, the risk:benefit ratio may favor the use of acamprosate.
FETAL RISK SUMMARY
The synthetic compound acamprosate has a chemical structure similar to that of the endogenous amino acid homotaurine, a structural analog of the amino acid neurotransmitter γ-aminobutyric acid and the amino acid neuromodulator taurine. Acamprosate is indicated to maintain abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. The mechanism of action is not completely understood, but acamprosate is thought to act differently than disulfiram, another agent in the class. Moreover, acamprosate and disulfiram have completely different chemical structures. Acamprosate is not metabolized and protein binding is negligible. It has a long elimination half-life ranging from about 20 to 33 hours (1).
Reproduction studies have been conducted in rats, rabbits, and mice. In rats, acamprosate was teratogenic at doses about equal to the maximum recommended human daily dose based on BSA (MRHDD). The dose-related defects were hydronephrosis, malformed iris, retinal dysplasia, and retroesophageal subclavian artery. The no-effect dose in rats was about 0.2 times the MRHDD. In Burgundy Tawny rabbits, hydronephrosis was observed at about 3 times the MRHDD. However, no defects were observed in New Zealand white rabbits at doses about 8 times the MRHDD. In mice, a dose about 2 times the MRHDD administered from day 15 of gestation through the end of lactation on postnatal day 28 was associated with an increased incidence of stillbirths. The no-effect dose in mice was about 0.5 times the MRHDD (1).
No carcinogenicity was observed in studies with rats, and no evidence of mutagenicity or clastogenicity was noted in several tests and assays. Acamprosate had no effect on the fertility of male and female rats at doses up to about 4 times the MRHDD, or in female mice at doses up to about 5 times the MRHDD (1).
It is not known ifacamprosate crosses the human placenta. The molecular weight (about 400), lack of metabolism and protein binding, and long elimination half-life suggest that it will cross to the embryo and/or fetus.
A TIS in France has gathered information on 18 pregnancies exposed to acamprosate during the 1st trimester (T. Vial, personal communication, Teratology Information Service, Lyon, France, 2010). The outcomes of these pregnancies included 2 spontaneous abortions, 3 elective abortions, 10 normal newborns (1 premature and 1 died at 1 month of age probably from sudden infant death syndrome), 1 newborn with minor facial anomalies, and a fetus and a newborn with major malformations. The fetus was electively aborted because of an omphalocele and found also to have microretrognathism, cleft palate, and a ventricular septal defect. The major defect in the infant was a cleft lip. Concomitant exposure to alcohol and other drugs occurred in several of the pregnancies.
BREASTFEEDING SUMMARY
No reports describing the use of acamprosate during human lactation have been located. The molecular weight (about 400), lack of metabolism and protein binding, and prolonged elimination half-life (20–33 hours) suggest that the drug will be excreted in breast milk. The effect on a nursing infant from exposure in milk is unknown. However, alcohol is excreted into milk and is known to be a neurotoxin (see Ethanol). Thus, if a lactating woman requires acamprosate to refrain from drinking, the benefit to the nursing infant appears to outweigh the unknown risk from the drug.
Reference
1.Product information. Campral. Forest Pharmaceuticals, 2012.