Methylnaltrexone Disease Interactions

Peripheral opioid receptor antagonists are contraindicated in patients with known or suspected gastrointestinal obstruction, and in patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. Cases of gastrointestinal perforation have been reported in patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structure integrity in the wall of the GI tract such as peptic ulcer, diverticular disease, Crohn's disease, infiltrative GI tract malignancies or peritoneal metastases. It is recommended to monitor for the development of severe, persistent, or worsening abdominal pain and to discontinue treatment in patients who develop symptoms. The overall risk- benefit profile should be carefully evaluated before using these agents in patients with these conditions.

Studies have shown a significant increase in systemic exposure of methylnaltrexone in patients with moderate and severe hepatic impairment, compared to subjects with normal hepatic function. A dosage reduction is recommended in these patients. No dose adjustment is needed in patients with mild hepatic impairment.

Patients with moderate, severe and end-stage renal disease have shown to exhibit markedly higher systemic exposure to peripheral opioid receptor antagonists such as methylnaltrexone and naloxegol, compared to subjects with normal renal function. A dose reduction is recommended for these patients. No dosage adjustment is needed in patients with mild renal impairment.