OXYMORPHONE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OXYMORPHONE HYDROCHLORIDE (OXYMORPHONE HYDROCHLORIDE).
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.
| 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. |
| Molecular Weight | 337.8 |
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. |
| 1st trimester | Avoid use; associated with neural tube defects and congenital anomalies in early pregnancy. |
| 2nd trimester | Use only if clearly needed; risk of fetal dependence and respiratory depression. |
| 3rd trimester | Avoid; high risk of neonatal respiratory depression, withdrawal, and opioid withdrawal syndrome. |
Clinical note
Comprehensive clinical and safety monograph for OXYMORPHONE HYDROCHLORIDE (OXYMORPHONE HYDROCHLORIDE).
| Placental transfer | Crosses the placenta readily; detectable in fetal plasma and amniotic fluid. |
| Breastfeeding | Excreted into breast milk. Use caution; monitor infant for respiratory depression and sedation. Infant exposure is generally low but may accumulate with high maternal doses. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to oxymorphone or any componentSignificant respiratory depressionAcute or severe bronchial asthma (in unmonitored setting or without resuscitation equipment)Known or suspected gastrointestinal obstruction (including paralytic ileus)Concurrent use of MAO inhibitors or within 14 days of such therapy
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 metabolism, increasing oxymorphone levels and risk of adverse effects. Alcohol should be strictly avoided due to additive CNS depression and increased risk of respiratory depression. No other clinically significant food interactions are reported. |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and bowel function. Fetal monitoring: assess fetal heart rate patterns during labor. Neonatal monitoring: observe for NOWS (irritability, hypertonia, tremors, poor feeding, respiratory distress) for 48-72 hours after delivery if maternal use was prolonged. |
| Fertility Effects | Endogenous opioid system modulates reproductive hormones. Chronic oxymorphone use may suppress gonadotropin-releasing hormone (GnRH) leading to hypogonadism, decreased libido, and impaired fertility in both sexes. Reversible upon discontinuation. |
| Clinical Pearls | Oxymorphone is approximately 10 times more potent than morphine. It has no ceiling effect for analgesia but dose-limiting adverse effects include respiratory depression and CNS depression. Use with extreme caution in patients with impaired renal function because the drug is primarily excreted unchanged in urine. Avoid use within 14 days of MAO inhibitor therapy. Monitor for opioid-induced constipation and consider prophylactic bowel regimen. For breakthrough pain, immediate-release formulations have an onset of 5-10 minutes intravenously and 15-30 minutes orally. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not crush, chew, or break extended-release tablets; swallow whole. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of fatal respiratory depression. · Do not stop abruptly; withdrawal symptoms may occur. Work with your provider to taper if needed. · Store securely out of reach of children and others. Dispose of unused medication via take-back programs. · Report any signs of respiratory depression (slow/shallow breathing), severe sedation, or constipation immediately. · This medication may impair your ability to drive or operate machinery. Do not perform such tasks until you know how it affects you. · Inform all healthcare providers that you are taking this medication. · If you are pregnant, plan to become pregnant, or are breastfeeding, discuss risks with your doctor. · Avoid grapefruit and grapefruit juice while taking oxymorphone as it may increase side effects. |