Psychotherapeutic (Miscellaneous)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
One report describing the use of sodium oxybate in human pregnancy has been located. The animal data suggest low risk, but the near absence of human pregnancy experience prevents a more complete assessment of the embryo–fetal risk. However, the indication suggests that the maternal benefit, under close medical supervision, may outweigh the unknown risk to the embryo–fetus.
FETAL RISK SUMMARY
Sodium oxybate, gamma hydroxybutyrate (GHB), is a CNS depressant that is available as an oral solution. It is indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. Because it is a known drug of abuse, sodium oxybate is only available through the Xyrem Success Program, using a centralized pharmacy. The drug is mainly eliminated by metabolism with <5% of unchanged drug appearing in the urine within 6–8 hours after dosing. Plasma protein binding is <1% and the half-life is 0.5–1 hour (1).
Reproduction studies have been conducted in rats and rabbits. Doses in these species that were about equal to and three times, respectively, the maximum recommended human dose based on BSA (MRHD) revealed no evidence of teratogenicity. In rats, a dose that was about equal to the MRHD given from day 6 of gestation through day 21 postpartum caused slight decreases in pup and maternal weight gains. No other drug effects on development were observed (1).
Sodium oxybate was not carcinogenic in long-term studies in male and female rats. A test for mutagenicity and a chromosomal aberration assay were negative. Doses that were about equal to the MRHD did not impair fertility in rats (1).
It is not known if sodium oxybate, or its acid, cross the human placenta. The molecular weight of 4-hydroxybutyric acid (about 104) and the minimal plasma protein binding suggest that it will cross to the embryo–fetus, but the extensive, rapid metabolism and short half-life should limit the exposure.
A brief 2004 case report described a woman in labor who developed mild respiratory depression (2). The event was initially thought to be due to the opioid used for spinal–epidural analgesia. The depression was treated with face mask oxygen and 2 hours later she delivered a healthy newborn with a good Apgar score (scores not specified). Routine toxicology screening revealed the presence of GHB, also known as liquid ecstasy, and the mother admitted that she had used the drug (2).
BREASTFEEDING SUMMARY
No reports describing the use of sodium oxybate (GBH) during human lactation have been located, but such use is unlikely because of the drug’s rapid action. The molecular weight of the acid form (4-hydroxybutyric acid) (about 104) and the minimal plasma protein binding (<1%) suggest that it will be excreted into breast milk, but the extensive, rapid metabolism and short half-life (0.5–1 hour) should limit the amount excreted. The effect of this exposure on a nursing infant is unknown, but sedation and confusion are potential complications. However, because the drug is taken immediately before bedtime, nursing no sooner than 5 hours after a dose to just before the next dose should prevent clinically significant exposure of an infant.
References
1.Product information. Xyrem. Jazz Pharmaceuticals, 2009
2.Kuczkowski KM. Liquid ecstasy during pregnancy. Anaesthesia 2004;59:926.