METHYLNALTREXONE BROMIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Peripherally acting mu-opioid receptor antagonist; blocks opioid binding at mu-receptors in the gastrointestinal tract, reducing opioid-induced constipation without affecting central analgesia.
| Metabolism | Primarily metabolized by reduction of the ketone group to methylnaltrexol; minor pathways include demethylation and hydroxylation; metabolism is not primarily cytochrome P450-dependent. |
| Excretion | Primarily renal (approximately 50% unchanged) and biliary/fecal (approximately 40% as metabolites and unchanged) |
| Half-life | Terminal elimination half-life is approximately 8 hours; clinical context: dosing interval is every 48 hours for opioid-induced constipation, and renal impairment may prolong half-life |
| Protein binding | Approximately 11-15%, primarily to albumin |
| Volume of Distribution | Approximately 1.1 L/kg; indicates distribution into total body water and limited tissue binding |
| Bioavailability | Subcutaneous: approximately 82%; oral: approximately 1% (extensive first-pass metabolism); intravenous: 100% |
| Onset of Action | Subcutaneous: 0.5 to 1 hour; intravenous: <0.5 hour; oral: 1.5 to 3 hours (though not available in US, used in some settings) |
| Duration of Action | Subcutaneous: duration of laxation effect up to 48 hours; clinical note: effect may wane with repeated dosing; intravenous: up to 24 hours |
0.15 mg/kg subcutaneously once daily as needed, not to exceed 1 dose in 24 hours. Alternatively, 450 mg orally once daily for opioid-induced constipation in adults with chronic non-cancer pain.
| Dosage form | SOLUTION |
| Renal impairment | For creatinine clearance <30 mL/min: reduce dose to 0.075 mg/kg subcutaneously once daily; use with caution. No adjustment for oral dosing specified. |
| Liver impairment | No adjustment recommended for mild to moderate hepatic impairment (Child-Pugh Class A and B). Not studied in severe hepatic impairment (Child-Pugh Class C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. No recommended pediatric dose. |
| Geriatric use | No specific dose adjustment required; however, consider potential renal impairment in elderly and adjust dosing accordingly per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| Breastfeeding | Unknown if excreted in human milk; low oral bioavailability suggests minimal infant exposure; use with caution; M/P ratio not established. |
| Teratogenic Risk | No evidence of teratogenicity in animal studies; limited human data in pregnancy; FDA Pregnancy Category B; risk cannot be excluded but appears low across all trimesters. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: PERFORATION OF GASTROINTESTINAL TRACT; cases of gastrointestinal perforation have been reported in patients with conditions that may result in impaired structural integrity of the GI tract (e.g., advanced cancer, peptic ulcer disease, Crohn's disease, diverticular disease, Ogilvie's syndrome). Use caution in patients with known or suspected GI lesions.
| Common Effects | opioid use disorder |
| Serious Effects |
["Known or suspected mechanical gastrointestinal obstruction","Patients at risk for recurrent bowel obstruction","Hypersensitivity to methylnaltrexone bromide or any component of the formulation"]
| Precautions | ["Risk of gastrointestinal perforation (see black box warning)","Severe or persistent diarrhea during treatment may be a sign of bowel obstruction or perforation","May cause opioid withdrawal symptoms (e.g., hyperhidrosis, chills, abdominal pain, diarrhea) in patients with disruption of blood-brain barrier","Use with caution in patients with renal impairment (dose adjustment for CrCl <60 mL/min)","Not recommended in patients with known or suspected mechanical gastrointestinal obstruction"] |
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| Monitor maternal bowel function and opioid withdrawal symptoms; fetal monitoring only if clinically indicated for maternal complications. |
| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment. |