NUMORPHAN
Clinical safety rating
cautionComprehensive clinical and safety monograph for NUMORPHAN (NUMORPHAN).
Opioid agonist; binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception.
| Metabolism | Primarily hepatic via glucuronidation; involves UGT2B7; active metabolite (hydromorphone-3-glucuronide) may accumulate in renal impairment. |
| Excretion | Primarily renal (approximately 70% as unchanged drug, <5% as noroxymorphone and other conjugates); biliary/fecal excretion accounts for ~20%. |
| Half-life | Terminal elimination half-life is 2–3 hours in adults; prolonged to 3–4 hours in elderly and up to 15 hours in patients with severe hepatic impairment. |
| Protein binding | Approximately 10–20% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 2.5–3.5 L/kg; indicates extensive tissue distribution, with high affinity for brain and other tissues. |
| Bioavailability | Intravenous: 100%; Intramuscular: approximately 85–95%; Subcutaneous: approximately 75–85%; Oral: approximately 10–20% due to extensive first-pass metabolism. |
| Onset of Action | Intravenous: 1–2 minutes; Intramuscular: 10–15 minutes; Subcutaneous: 15–30 minutes; Oral: 30–60 minutes. |
| Duration of Action | Intravenous: 3–4 hours; Intramuscular/Subcutaneous: 4–6 hours; Oral: 4–6 hours; duration is dose-dependent and prolonged in hepatic impairment. |
| Molecular Weight | 357.5 |
Intravenous or subcutaneous: 0.5-2 mg (0.1-0.2 mg/kg for severe pain) every 2-3 hours as needed; not to exceed 20 mg/day.
| Dosage form | SUPPOSITORY |
| Renal impairment | CrCl 10-50 mL/min: administer 75% of dose; CrCl <10 mL/min: administer 50% of dose, use with caution, consider extended dosing intervals. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: reduce dose by 75% or avoid use; start at lowest dose and titrate carefully. |
| Pediatric use | Children >2 years: 0.1-0.2 mg/kg intravenously, subcutaneously, or intramuscularly every 2-4 hours as needed; not to exceed 15 mg/day. |
| Geriatric use | Start at low end of dosing range (0.5 mg), extend dosing interval to 3-4 hours, monitor for respiratory depression and constipation, use non-opioid alternatives when possible. |
| 1st trimester | Avoid due to risk of neural tube defects and other malformations; limited data show possible association with congenital anomalies. |
| 2nd trimester | Use only if clearly needed; may cause fetal dependence and withdrawal; monitor for fetal growth restriction. |
| 3rd trimester | Use only if clearly needed; risk of neonatal respiratory depression, opioid withdrawal syndrome, and long-term neurobehavioral effects. |
Clinical note
Comprehensive clinical and safety monograph for NUMORPHAN (NUMORPHAN).
| Placental transfer | Readily crosses placenta; fetal concentrations may approach maternal levels due to high lipid solubility and low molecular weight. |
| Breastfeeding | Excreted into breast milk in low concentrations; may cause infant sedation and respiratory depression; avoid or use caution, especially in preterm infants or with prolonged use. |
| Lactation Rating | L3 (Moderately Safe) - use with caution |
| Teratogenic Risk | First trimester: Limited data, but opioid use is associated with neural tube defects and congenital heart defects in some studies. Second and third trimesters: Chronic use may lead to fetal opioid dependence and neonatal withdrawal syndrome. No specific malformation pattern attributed to Numorphan. Avoid prolonged use, especially in first trimester. |
| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, and sedation level. Fetal monitoring: Non-stress test or biophysical profile if chronic use. Neonatal monitoring for signs of opioid withdrawal (e.g., tremors, irritability, poor feeding) for at least 48 hours postpartum. Avoid abrupt discontinuation; taper if needed. |
| Fertility Effects | Opioid use may disrupt hypothalamic-pituitary-gonadal axis, leading to decreased libido, amenorrhea, or anovulation. No specific data on oxymorphone. In males, may reduce testosterone levels. Effects are likely reversible upon discontinuation. |
■ FDA Black Box Warning
Risk of respiratory depression, especially in elderly, cachectic, or debilitated patients; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death; abuse potential leading to addiction; neonatal opioid withdrawal syndrome with prolonged use during pregnancy.
| Serious Effects |
Hypersensitivity to morphine or any componentAcute or severe bronchial asthmaRespiratory depression (in absence of resuscitative equipment)Paralytic ileusConcurrent use of MAOIs (within 14 days)
| Precautions | Respiratory depression; CNS depression; serotonin syndrome (with serotonergic drugs); adrenal insufficiency; hypotension; seizures; opioid-induced hyperalgesia; impaired ability to drive/operate machinery; risk of overdose with alcohol or other CNS depressants. |
| Food/Dietary | Avoid alcohol and grapefruit juice. Grapefruit juice may inhibit CYP3A4 metabolism of oxymorphone, leading to increased plasma concentrations and risk of toxicity. High-fat meals may delay absorption but not significantly alter overall exposure. Maintain adequate hydration to prevent constipation. |
| Clinical Pearls | Numorphan (oxymorphone) is a potent semisynthetic opioid agonist approximately 10 times more potent than morphine. Avoid in patients with severe respiratory depression, paralytic ileus, or acute asthma. Caution in elderly, cachectic, or debilitated patients due to increased risk of respiratory depression. Monitor for hypotension and bradycardia. Use with extreme caution in patients with head injury or increased intracranial pressure. Abrupt discontinuation may precipitate withdrawal; taper gradually. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Numorphan may cause dizziness, drowsiness, or blurred vision; avoid driving or operating heavy machinery until you know how the drug affects you. · Avoid alcohol and other central nervous system depressants (e.g., sedatives, tranquilizers) as they may increase the risk of serious side effects like respiratory depression. · If you miss a dose, skip it and take the next dose at the scheduled time; do not double up. · Do not suddenly stop taking this medication; a gradual reduction under medical supervision is needed to prevent withdrawal symptoms. · Store securely away from children and pets; dispose of unused medication via a drug take-back program. |
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