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. |
| Molecular Weight | 499.6 |
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 | Limited human data; animal studies show no evidence of harm at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | Limited human data; no teratogenic effects reported. Consider risk-benefit. |
| 3rd trimester | Use with caution near term due to potential for opioid withdrawal in neonate if mother is opioid-dependent. |
Clinical note
Comprehensive clinical and safety monograph for RELISTOR (RELISTOR).
| Placental transfer | Expected to cross placenta due to molecular weight <500 Da; however, specific data not available. |
| Breastfeeding | Minimal excretion into breast milk expected due to low oral bioavailability and high molecular weight. However, no specific data available. Use with caution in nursing mothers. |
■ 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 |
Hypersensitivity to methylnaltrexone or any componentGastrointestinal obstruction (or risk thereof)
| 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 |
| Food/Dietary | No specific food interactions reported with methylnaltrexone. No dietary restrictions necessary. However, to optimize bowel function, patients should maintain adequate fluid intake and dietary fiber as tolerated, unless contraindicated due to underlying illness. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| 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 | 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. |
| Clinical Pearls | Relistor (methylnaltrexone) is a peripherally acting mu-opioid receptor antagonist (PAMORA) used for opioid-induced constipation (OIC) in patients with advanced illness or chronic pain. It does not cross the blood-brain barrier, thus does not reverse central opioid analgesia. Administer subcutaneously; onset typically within 1-4 hours. Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Use with caution in renal impairment (CrCl <30 mL/min) as dose reduction recommended. Monitor for gastrointestinal perforation, especially in patients with underlying GI pathology. Coadministration with other opioid antagonists may precipitate opioid withdrawal. |
| Patient Advice | Relistor is used to treat constipation caused by opioid pain medications without affecting pain relief. · Inject the medication exactly as prescribed; do not use more often than every other day. · You should have a bowel movement within a few hours of receiving the injection; if not, contact your doctor. · Common side effects include abdominal pain, nausea, diarrhea, and flatulence. · Stop Relistor and seek immediate medical attention if you experience severe abdominal pain, vomiting, or signs of intestinal obstruction (e.g., inability to pass gas). · Tell your doctor if you have kidney problems, as the dose may need adjustment. · Do not take other medicines for constipation without your doctor's approval. |