Gastrointestinal Agent (Antiemetic)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of nabilone in human pregnancy have been located. Dose-related developmental toxicity consisting of growth restriction and death was observed in two animal species. In addition, unspecified postnatal toxicity was observed in one species. Nabilone is structurally related to delta-9-tetrahydrocannabinol (delta-9-THC), the active ingredient in marijuana. Although additional studies are needed, there is evidence that marijuana use in pregnancy is associated with developmental toxicity, such as growth restriction, long-term neurobehavioral deficits, and potentiation of the fetal effects of alcohol. (See Marijuana.) Because of the potential for adverse effects in the embryo and fetus, as well as the absence of human pregnancy experience, the best course is to avoid nabilone during gestation. Nevertheless, the use of this drug may be acceptable if other therapies, including hospitalization and treatment with IV antiemetics, have failed.
FETAL RISK SUMMARY
Nabilone is a synthetic cannabinoid that is indicated for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond to other antiemetic regimens. The chemical structure is similar to delta-9-THC, the active ingredient in marijuana. The drug may produce disturbing psychotomimetic reactions and psychological dependence, and has the potential to be abused. Nabilone is extensively metabolized, but the activity of the metabolites has not been characterized. The plasma half-lives of nabilone and its metabolites are 2 and 35 hours, respectively. Terminal elimination, mainly in the feces (67%) with smaller amounts in the urine (22%), occurs within 7 days. Although no accumulation of nabilone after repeated doses has been observed, accumulation of the metabolites may occur (1).
Reproduction studies have been conducted in rats and rabbits. There was no evidence of structural defects in pregnant rats and rabbits receiving oral doses up to about 16 and 9 times, respectively, the human dose based on BSA (HD). However, dose-related developmental toxicity, consisting of embryo death, fetal resorptions, decreased fetal weight, and pregnancy disruptions, was observed. Unspecified postnatal developmental toxicity also was observed in rats (1,2).
Studies for carcinogenicity have not been conducted with nabilone, but assays for genotoxicity were negative (2). Doses up to six times the HD had no effect on fertility or reproductive performance of male and female rats (1,2).
It is not known if nabilone crosses the human placenta. The molecular weight (about 373) and lipid solubility suggest that the drug will cross to the embryo and fetus, but the very short plasma half-life of the parent compound should limit the exposure.
BREASTFEEDING SUMMARY
No reports describing the use of nabilone during human lactation have been located. Nabilone is structurally similar to delta-9-THC, the active ingredient of marijuana (2). Delta-9-THC is known to be excreted into breast milk. (See Marijuana.) The molecular weight (about 373) and lipid solubility of nabilone suggest that it also will be excreted into breast milk, but the very short plasma half-life (2 hours) should limit the amount. The metabolites, whose activity has not been characterized, have a longer plasma half-life (35 hours) and, therefore, a greater potential for clinically significant concentrations in milk. However, the metabolites of delta-9-THC have not been detected in milk; this also could be the case for the metabolites of nabilone. The effects on the nursing infant from exposure to nabilone or its metabolites in the milk are unknown, but are of concern. Although no adverse effects of marijuana exposure from breast milk have been reported, follow-up of exposed infants is inadequate. Because of the potential for long-term toxicity in nursing infants, women taking nabilone should not breastfeed.
References
1.Markham JK, Hanasono GK, Adams ER, Owen NV. Reproduction studies on nabilone, a synthetic 9-keto-cannabinoid (abstract). Toxicol Appl Pharmacol 1979;48:A119.
2.Product information. Cesamet. Valeant Pharmaceuticals, 2007.