Methylnaltrexone methobromide: the first peripherally active, centrally inactive opioid receptor-antagonist.

Objective: To review the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, indications, and dosing and administration of methylnaltrexone methobromide, the first approved peripherally selective opioid receptor-antagonist.

Data Source: MEDLINE/PUBMED and EMBASE searches (January 1966-February 2009) were conducted to identify pertinent English-language studies.

Study Selection And Data Extraction: All studies evaluating any aspect of methylnaltrexone methobromide.

Data Synthesis: Subcutaneous methylnaltrexone methobromide is the first opioid receptor-antagonist to be approved for the treatment of opioid receptor-agonist-induced constipation (subset with advanced disease, receiving palliative care, with an inadequate response to laxative therapy). This agent lacks meaningful activity in the central nervous system and, hence, will not compromise centrally mediated analgesia or precipitate centrally mediated signs/symptoms of opioid receptor-agonist withdrawal. There are no published comparative trials with traditional pharmacologic/nonpharmacologic laxation regimens.

Conclusion: Methylnaltrexone methobromide is administered into the upper arm, abdomen, or thigh once every other day, with the frequency of dosing being increased, if needed, to a maximum of once daily. Recommended doses are 8 mg, 12 mg, or 0.15 mg/kg, depending on patient weight. For creatinine clearances less than 30 mL/min, the dose should be reduced by 50%. The average wholesale price is $83.33 for a 12 mg single-use vial (Medispan, accessed December 4, 2008). Clearly, parenteral agents are not as useful as oral agents and results of ongoing studies with new oral formulations of this product are eagerly awaited.