Narcotic Antagonist
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Published human pregnancy experience with methylnaltrexone has not been located. The animal reproduction data suggest low risk, but the absence of human data prevents a complete assessment of the embryo–fetal risk. Orthostatic hypotension, an effect that could decrease placental perfusion, is a potential risk if the drug is inadvertently given IV. Close attention to the dose and SC administration technique is warranted.
FETAL RISK SUMMARY
Methylnaltrexone, a selective antagonist of opioid binding at the mu-opioid receptor, is given by SC injection. It is a quaternary amine that because of its restricted ability to cross the blood–brain barrier acts peripherally without affecting opioid-mediated analgesic effects in the central nervous system. Methylnaltrexone is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. The drug undergoes partial metabolism before elimination. Plasma protein binding is about 15% or less and the elimination half-life is about 8 hours (1).
Reproduction studies have been conducted in pregnant rats and rabbits. In these species, IV doses up to about 14 and 17 times, respectively, the maximum recommended human SC dose of 0.3 mg/kg based on BSA (MRHD) revealed no evidence of impaired fertility or fetal harm. There were no effects on the mother, labor, delivery, offspring survival, or growth in rats (1).
Carcinogenicity studies have not been conducted, but the drug was not mutagenic in multiple assays. SC doses up to 81 times the MRHD had no adverse effect on fertility or reproductive performance in male or female rats (1).
It is not known if methylnaltrexone crosses the human placenta. The molecular weight (about 436), minimal plasma protein binding, and long elimination half-life suggest that the drug will cross. However, quaternary amines cross biological membranes poorly; this should limit the exposure of the embryo or fetus.
Orthostatic hypotension, an effect that could decrease placental perfusion if it occurred in pregnancy, has been noted in healthy volunteers given an IV bolus of 0.64 mg/kg. However, this dose is twice the recommended maximum SC dose. Moreover, a 0.5 mg SC dose was well tolerated by healthy volunteers (1).
BREASTFEEDING SUMMARY
No reports describing the use of methylnaltrexone, a quaternary amine, during human lactation have been located. The molecular weight (about 436), minimal plasma protein binding (<15%), and long elimination half-life (about 8 hours) suggest that the drug will be excreted into breast milk. The effects of this exposure on a nursing infant are unknown, but are probably clinically insignificant.
Reference
1.Product information. Relistor. Progenics Pharmaceuticals, 2009.