New Drug of the day : Methylnaltrexone

New Pharmacological Drug Classes Introduced in 2008 

Methylnaltrexone is a peripherally acting μ-opioid receptor antagonist FDA approved for the treatment of refractory opioid-induced constipation in patients with advanced illness (e.g., cancer, AIDS) who are receiving palliative care.

Administered subcutaneously no more frequently than once per day, methylnaltrexone stimulates laxation within 4 hours in approximately 60% of patients. 

Clinical experience confirms a much more rapid onset of action in patients who are opioid tolerant. Methylnaltrexone is a quaternary amine derivative of naltrexone with a limited ability to penetrate into the central nervous system. Side effects are largely extensions of normal gastrointestinal functions: abdominal pain, flatulence, nausea, and diarrhea. The drug is a weak CYP2D6 inhibitor with no known drug-drug interactions. Methylnaltrexone undergoes hepatic metabolism; however, N-demethylation to naltrexone is not thought to be a significant pathway.

Renal excretion of unchanged drug is the dominant route of elimination. The usual dose of methylnaltrexone is 8-12 mg, depending on body weight. Therapy for longer than 4 weeks in the target population of patients with terminal illness is unstudied. Methylnaltrexone was investigated as a treatment for postoperative ileus, but with disappointing results.