NUMORPHAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NUMORPHAN (NUMORPHAN).

How it works

Opioid agonist; binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for NUMORPHAN (NUMORPHAN).

Breastfeeding	Numorphan (oxymorphone) is excreted into breast milk. The M/P ratio is unknown. Limited data suggest low concentrations, but caution is advised. Monitor infant for drowsiness, respiratory depression, and withdrawal if maternal use is prolonged. American Academy of Pediatrics considers it compatible with breastfeeding with cautious use, but consider risk-benefit.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to hydromorphone or any component; significant respiratory depression; acute or severe bronchial asthma; known or suspected paralytic ileus; concurrent use of MAOIs (or within 14 days).

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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NUMORPHAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NUMORPHAN (NUMORPHAN).

How it works

Opioid agonist; binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for NUMORPHAN (NUMORPHAN).

Breastfeeding	Numorphan (oxymorphone) is excreted into breast milk. The M/P ratio is unknown. Limited data suggest low concentrations, but caution is advised. Monitor infant for drowsiness, respiratory depression, and withdrawal if maternal use is prolonged. American Academy of Pediatrics considers it compatible with breastfeeding with cautious use, but consider risk-benefit.
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.