OXYMORPHONE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OXYMORPHONE HYDROCHLORIDE (OXYMORPHONE HYDROCHLORIDE).

How it works

Oxymorphone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the central nervous system, inhibiting ascending pain pathways and altering pain perception and response. It also has affinity for kappa and delta opioid receptors.

What the body does with it

Metabolism	Primarily hepatic via glucuronidation (UGT2B7) to oxymorphone-3-glucuronide; minor CYP450 involvement (CYP3A4 and CYP2C9).
Excretion	Primarily renal (90% as parent drug and metabolites); <1% fecal. Unchanged oxymorphone accounts for ~30% of urinary recovery.
Half-life	Terminal elimination half-life: 7-9 hours (range 4-12 h in elderly/renal impairment). Clinically, steady-state achieved within 24-36 hours.
Protein binding	Approximately 10-12%; primarily bound to albumin.
Volume of Distribution	Vd: 1.5-3.7 L/kg; indicates extensive tissue distribution (e.g., brain, adipose). Higher Vd may require dose adjustment in obese patients.
Bioavailability	Oral (immediate-release): 10-15% (extensive first-pass metabolism); Oral (extended-release): 10-15%; Intramuscular: equivalent to IV (100% relative to IV but with slower absorption).
Onset of Action	Intravenous: 5-10 min; Intramuscular: 10-15 min; Oral (immediate-release): 15-30 min; Oral (extended-release): 1-2 h.
Duration of Action	Analgesic duration: 3-6 h (IV/IM/immediate-release oral); 12 h (extended-release oral). Clinical note: Duration prolonged in renal impairment.

Classification & Brands

Dosing & administration

Initial: 1 mg IV/IM every 3-4 hours as needed for moderate to severe pain; titrate to effect. For patient-controlled analgesia (PCA), 0.5 mg IV loading dose, then 0.25-0.5 mg every 6-15 minutes with lockout. Rectal suppository: 5 mg every 4-6 hours.

Dosage form	TABLET
Renal impairment	CrCl 30-59: Administer 75% of normal dose; CrCl 15-29: Administer 50% of normal dose; CrCl <15: Avoid use or administer 25% of normal dose with extended dosing interval (e.g., every 6-8 hours).
Liver impairment	Child-Pugh Class A: No adjustment necessary; Child-Pugh Class B: Reduce initial dose by 50% and titrate cautiously; Child-Pugh Class C: Avoid use or administer 25% of normal dose with prolonged interval.
Pediatric use	Not FDA-approved for pediatric use. Limited data: IV/IM 0.1-0.2 mg/kg every 4-6 hours as needed (max 3 mg/dose).
Geriatric use	Initiate at 0.5-1 mg IV/IM every 4-6 hours; titrate slowly. Consider 50% dose reduction due to increased sensitivity and risk of respiratory depression.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OXYMORPHONE HYDROCHLORIDE (OXYMORPHONE HYDROCHLORIDE).

Breastfeeding	Oxymorphone is excreted into breast milk. M/P ratio not determined. The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for signs of respiratory depression and sedation. Use lowest effective dose for shortest duration.
Teratogenic Risk	Opioid analgesics cross the placenta. First trimester: Limited data, but no clear evidence of major malformations; however, use associated with neural tube defects in some studies. Second and third trimesters: Chronic use may lead to fetal dependence and neonatal opioid withdrawal syndrome (NOWS) after delivery. Use during labor may cause respiratory depression in the newborn.

Warnings & precautions

■ FDA Black Box Warning

Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion (especially in children); neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to oxymorphone or any component; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting; known or suspected paralytic ileus; gastrointestinal obstruction; postpartum analgesia (for the injection form).

Clinical Precautions

Precautions

Respiratory depression; CNS depression; addiction potential; hypotension; seizures; increased intracranial pressure; biliary tract disease; pancreatitis; severe renal impairment; elderly and debilitated patients; adrenal insufficiency; severe hepatic impairment; concurrent use with MAOIs or serotonergic drugs.

Clinical Tips & Counseling

Drug interactions

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OXYMORPHONE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OXYMORPHONE HYDROCHLORIDE (OXYMORPHONE HYDROCHLORIDE).

How it works

What the body does with it

Metabolism	Primarily hepatic via glucuronidation (UGT2B7) to oxymorphone-3-glucuronide; minor CYP450 involvement (CYP3A4 and CYP2C9).
Excretion	Primarily renal (90% as parent drug and metabolites); <1% fecal. Unchanged oxymorphone accounts for ~30% of urinary recovery.
Half-life	Terminal elimination half-life: 7-9 hours (range 4-12 h in elderly/renal impairment). Clinically, steady-state achieved within 24-36 hours.
Protein binding	Approximately 10-12%; primarily bound to albumin.
Volume of Distribution	Vd: 1.5-3.7 L/kg; indicates extensive tissue distribution (e.g., brain, adipose). Higher Vd may require dose adjustment in obese patients.
Bioavailability	Oral (immediate-release): 10-15% (extensive first-pass metabolism); Oral (extended-release): 10-15%; Intramuscular: equivalent to IV (100% relative to IV but with slower absorption).
Onset of Action	Intravenous: 5-10 min; Intramuscular: 10-15 min; Oral (immediate-release): 15-30 min; Oral (extended-release): 1-2 h.
Duration of Action	Analgesic duration: 3-6 h (IV/IM/immediate-release oral); 12 h (extended-release oral). Clinical note: Duration prolonged in renal impairment.

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	CrCl 30-59: Administer 75% of normal dose; CrCl 15-29: Administer 50% of normal dose; CrCl <15: Avoid use or administer 25% of normal dose with extended dosing interval (e.g., every 6-8 hours).
Liver impairment	Child-Pugh Class A: No adjustment necessary; Child-Pugh Class B: Reduce initial dose by 50% and titrate cautiously; Child-Pugh Class C: Avoid use or administer 25% of normal dose with prolonged interval.
Pediatric use	Not FDA-approved for pediatric use. Limited data: IV/IM 0.1-0.2 mg/kg every 4-6 hours as needed (max 3 mg/dose).
Geriatric use	Initiate at 0.5-1 mg IV/IM every 4-6 hours; titrate slowly. Consider 50% dose reduction due to increased sensitivity and risk of respiratory depression.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OXYMORPHONE HYDROCHLORIDE (OXYMORPHONE HYDROCHLORIDE).

Breastfeeding	Oxymorphone is excreted into breast milk. M/P ratio not determined. The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for signs of respiratory depression and sedation. Use lowest effective dose for shortest duration.
Teratogenic Risk	Opioid analgesics cross the placenta. First trimester: Limited data, but no clear evidence of major malformations; however, use associated with neural tube defects in some studies. Second and third trimesters: Chronic use may lead to fetal dependence and neonatal opioid withdrawal syndrome (NOWS) after delivery. Use during labor may cause respiratory depression in the newborn.