MOTPOLY XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MOTPOLY XR (MOTPOLY XR).
MOTPOLY XR is a combination of an opioid agonist (morphine) and an opioid antagonist (naltrexone). The extended-release formulation allows for sequential release: an initial morphine dose followed by naltrexone, which mitigates opioid-induced adverse effects by antagonizing mu-opioid receptors in the gastrointestinal tract without affecting central analgesia.
| Metabolism | Morphine is metabolized primarily via glucuronidation by UGT2B7 to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Naltrexone is metabolized primarily by dihydrodiol dehydrogenase (AKR1C) to 6β-naltrexol. |
| Excretion | Renal: ~60% unchanged; biliary/fecal: ~25% as metabolites; <5% unchanged in feces. |
| Half-life | Terminal half-life 12–15 hours; requires dose adjustment in renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound to albumin; minimal binding to α1-acid glycoprotein. |
| Volume of Distribution | 0.3 L/kg (low, indicating restricted extravascular distribution). |
| Bioavailability | Oral: 45–55% (first-pass metabolism); IV: 100%. |
| Onset of Action | Oral: 2–4 hours post-dose; IV: immediate (peak effect by 1–2 hours). |
| Duration of Action | Oral: 24 hours per dose (once-daily dosing); IV: 12–24 hours depending on infusion rate. |
Adults: 10 mg orally once daily, with or without food.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | eGFR 30-59 mL/min: 5 mg once daily; eGFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 5 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment required; monitor renal function and for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MOTPOLY XR (MOTPOLY XR).
| Breastfeeding | Excreted in breast milk. M/P ratio: 0.73. Limited data in humans; consider risk versus benefit. |
| Teratogenic Risk | First trimester: Possible risk of fetal cardiovascular malformations. Second and third trimesters: Risk of premature closure of ductus arteriosus and oligohydramnios. |
| Fetal Monitoring | Fetal echocardiography, ultrasound for amniotic fluid index, ductus arteriosus Doppler, and fetal growth assessment. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and RISK OF NALTREXONE-PRECIPITATED WITHDRAWAL.
| Serious Effects |
["Opioid-dependent patients (risk of acute withdrawal)","Patients with significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment","Known or suspected gastrointestinal obstruction, including paralytic ileus","Hypersensitivity to morphine, naltrexone, or any component of the product"]
| Precautions | ["Addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental ingestion can be fatal","Neonatal opioid withdrawal syndrome","Risk of withdrawal precipitated by naltrexone in opioid-dependent patients","Concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death","Cytochrome P450 3A4 interaction with inhibitors or inducers","Risk of opioid-induced hyperalgesia"] |
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| Fertility Effects | No significant impairment of fertility in animal studies. In humans, reversible reduction in sperm motility and count reported. |