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. |
| Molecular Weight | 389.47 |
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 | Fetal risk cannot be ruled out; avoid use unless clearly needed. |
| 2nd trimester | May cause fetal harm; limited data. |
| 3rd trimester | May cause neonatal withdrawal or respiratory depression; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for MOTPOLY XR (MOTPOLY XR).
| Placental transfer | Crosses placenta; detected in fetal circulation at 50-70% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations; use caution, monitor infant for sedation and poor feeding. |
| Lactation Rating | L3 (Moderately Safe) |
■ 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 |
Hypersensitivity to motpolineSevere respiratory insufficiencyConcurrent MAO inhibitor useMyasthenia gravisAcute narrow-angle glaucoma
| 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 |
| Food/Dietary | Avoid alcohol; may increase risk of hypotension and bradycardia. No specific food restrictions, but maintain consistent dietary sodium intake to avoid blood pressure fluctuations. Grapefruit juice has minimal effect. |
Loading safety data…
| 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. |
| Fertility Effects | No significant impairment of fertility in animal studies. In humans, reversible reduction in sperm motility and count reported. |
| Clinical Pearls | MOTPOLY XR (metoprolol tartrate extended-release) is a beta-1 selective adrenergic blocker. Dose adjustments required in hepatic impairment. Do not crush or chew tablets. Monitor heart rate and blood pressure regularly. Avoid abrupt discontinuation to prevent rebound hypertension or angina exacerbation. Use with caution in patients with asthma, diabetes, or peripheral vascular disease. May mask signs of hypoglycemia and hyperthyroidism. |
| Patient Advice | Take at the same time each day with or without food. · Do not crush, chew, or split the extended-release tablet. · Do not stop taking without consulting your doctor; sudden stop may cause chest pain or high blood pressure. · Monitor for slow heartbeat, dizziness, or lightheadedness. · Avoid alcohol as it can increase side effects. · Inform your doctor if you have asthma, diabetes, or thyroid problems. · May cause drowsiness; avoid driving until you know how it affects you. |