RELISTOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RELISTOR (RELISTOR).
Peripherally acting mu-opioid receptor antagonist that blocks opioid-induced constipation without affecting central analgesia.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6 isoenzymes; also undergoes gut wall metabolism. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 16% of the dose; biliary/fecal excretion is the major route (approximately 54% recovered in feces). |
| Half-life | Terminal elimination half-life is approximately 8-10 hours in patients with normal renal function. In patients with end-stage renal disease, half-life is prolonged (~14-18 hours). |
| Protein binding | Approximately 11-15% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 1.1 L/kg (central volume ~0.3 L/kg); indicates extensive extravascular distribution. |
| Bioavailability | Subcutaneous: approximately 82-100% (mean ~97%); oral: approximately 6% (low due to first-pass metabolism). |
| Onset of Action | Subcutaneous injection: Onset of laxation within 1-4 hours; intravenous: within 1-30 minutes. |
| Duration of Action | Duration of effect for bowel movement typically up to 4-6 hours after subcutaneous administration; may be shorter with IV. Clinical duration may be limited by dosing interval. |
0.15 mg/kg subcutaneously once daily, maximum 16 mg per dose; for opioid-induced constipation, 8 mg subcutaneously once daily.
| Dosage form | TABLET |
| Renal impairment | For creatinine clearance <30 mL/min: 0.075 mg/kg subcutaneously every other day, maximum 8 mg per dose; not recommended in patients with end-stage renal disease requiring dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; use caution due to potential for renal impairment, monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RELISTOR (RELISTOR).
| Breastfeeding | Excreted in human milk at low concentrations; M/P ratio approximately 0.6. No reported adverse effects in breastfeeding infants. Caution advised due to potential for gastrointestinal effects. |
| Teratogenic Risk | Animal studies show no teratogenic effects at doses up to 300 mg/kg/day in rats and rabbits. No adequate human data; risk cannot be excluded in first trimester. Second and third trimester: limited data, potential for gastrointestinal effects in fetus if exposed transplacentally. |
| Fetal Monitoring |
■ FDA Black Box Warning
Gastrointestinal perforation: Cases of gastrointestinal perforation have been reported in patients with conditions that may result in impaired structural integrity of the gastrointestinal tract.
| Serious Effects |
["Known or suspected mechanical gastrointestinal obstruction","Known hypersensitivity to methylnaltrexone or any component of the formulation"]
| Precautions | ["Risk of gastrointestinal perforation","Opioid withdrawal symptoms including diarrhea, nausea, vomiting, abdominal pain","Disruption of analgesic effect if used with opioids crossing the blood-brain barrier (theoretical)","Not recommended in patients with known or suspected mechanical gastrointestinal obstruction"] |
Loading safety data…
| Monitor for opioid withdrawal symptoms in mother (e.g., abdominal pain, nausea, diarrhea) and fetal heart rate monitoring if opioid withdrawal suspected. No specific fetal monitoring required. |
| Fertility Effects | No known effect on fertility. Animal studies show no impairment at doses up to 100 mg/kg/day. Use in opioid-induced constipation may improve quality of life; however, caution due to potential interference with opioid analgesia if used in labor. |