What are the guidelines for prescribing oxymorphone (opioid analgesic) for pain management?

Oxymorphone Prescribing Guidelines for Pain Management

Oxymorphone is a mu-opioid receptor agonist available in immediate-release formulation for moderate to severe pain, but it is not a preferred first-line strong opioid—morphine remains the gold standard for initiating opioid therapy in opioid-naïve patients. 1, 2

Clinical Positioning and Role

Oxymorphone is considered a second-line or alternative strong opioid option when morphine, oxycodone, or hydromorphone are not suitable or have failed. 1

• Oxymorphone acts primarily at the mu-opioid receptor and is available only in immediate-release oral formulation (extended-release formulations were discontinued). 1
• Evidence shows oxymorphone has comparable efficacy to other strong opioids like morphine and oxycodone for moderate to severe pain, but offers no unique clinical advantages. 1, 3, 4
• A meta-analysis demonstrated that oxymorphone 40-100 mg daily was superior to placebo with a pain intensity reduction of -17.08 to -8.69 on visual analog scale. 1

Dosing Guidelines

For Opioid-Naïve Patients

Start with 10-20 mg orally every 4-6 hours; initiation with doses higher than 20 mg is not recommended due to serious adverse reaction risk. 5

• For patients with renal impairment, hepatic impairment, or elderly patients, start at the lowest dose of 5 mg. 5
• Oxymorphone must be taken on an empty stomach—at least 1 hour before or 2 hours after eating—as food increases absorption rate by up to 50%. 5, 6

For Patients Converting from Other Opioids

Use published equianalgesic conversion ratios, but start with half the calculated total daily dose divided into 4-6 equally divided doses every 4-6 hours. 5

• When converting from parenteral oxymorphone to oral oxymorphone, multiply the total daily parenteral dose by 10 (due to ~10% oral bioavailability), then divide into 4-6 doses. 5, 6
• Example: A patient on 4 mg total daily IM oxymorphone would require approximately 10 mg oral oxymorphone four times daily. 5

Dose Titration and Maintenance

Titrate dose based on individual response to achieve mild or no pain while monitoring for adverse effects. 5

• Provide immediate-release breakthrough medication during titration periods. 5
• If significant adverse events occur before achieving pain control, treat the adverse events aggressively before continuing upward titration. 5

Special Population Considerations

Renal Impairment

Oxymorphone bioavailability increases by 57-65% in moderate to severe renal impairment; use reduced doses cautiously in patients with creatinine clearance <50 mL/min. 5, 4

Hepatic Impairment

Oxymorphone is contraindicated in moderate to severe hepatic impairment (Child-Pugh class B or C). 5

• In mild hepatic impairment (Child-Pugh class A), start with 5 mg and titrate slowly while carefully monitoring side effects. 5, 4

Elderly Patients

Start at the low end of dosing range (5 mg) in elderly patients, as they experience approximately 40% increase in plasma concentrations. 5, 6, 4

Comparative Tolerability Data

Oxymorphone has a higher rate of treatment discontinuation due to adverse effects compared to other opioids. 1

• In a systematic review, tapentadol had significantly fewer discontinuations than oxymorphone (OR 4.27), as well as compared to morphine (OR 2.03), oxycodone (OR 2.31), and hydromorphone (OR 2.38). 1
• Common adverse effects include nausea, vomiting, pruritus, constipation, sedation, somnolence, dizziness, and headache—similar to other opioids. 1, 6, 7

Potency Considerations

Clinical equianalgesic estimates may not reflect actual pharmacodynamic effects—oxymorphone appears less potent than oxycodone at identical doses on most measures. 8

• At identical doses, oxymorphone produced approximately twofold less potent effects on miosis compared to oxycodone. 8
• Oxymorphone also produced lesser magnitude effects on respiratory depression and experimental pain models compared to oxycodone at the same doses. 8
• However, at the highest dose tested (40 mg), oxymorphone's abuse liability was similar to 40 mg oxycodone. 8

Risk Mitigation and Universal Precautions

Assess potential risks and benefits before initiating long-term opioid therapy, and incorporate universal precautions to minimize abuse, addiction, and adverse consequences. 1

• Exercise caution when prescribing doses ≥90-200 mg morphine equivalents per day. 1
• Avoid coprescribing with benzodiazepines or other centrally acting drugs due to increased risk of respiratory depression and opioid-related deaths. 1
• Use opioid risk assessment tools, written treatment agreements, and urine drug testing when prescribing for long-term use. 1
• Understand that oxymorphone is not detected by standard enzyme-linked immunoassays; gas chromatography or mass spectrometry is required for specific identification. 1

Drug Interactions

Reduce oxymorphone dose to 1/3 to 1/2 of usual dose when used with CNS depressants (sedatives, hypnotics, general anesthetics, phenothiazines, tranquilizers, alcohol) due to risk of respiratory depression, hypotension, profound sedation, coma, or death. 5

• Oxymorphone is not recommended within 14 days of MAO inhibitor use, although no specific interaction has been observed. 5
• Oxymorphone undergoes extensive liver metabolism but has no clinically significant CYP3A4, 2C9, or 2D6-mediated drug interactions. 6

Cessation of Therapy

Never stop opioids abruptly—taper doses gradually by 30-50% over approximately one week to prevent withdrawal symptoms in physically dependent patients. 1, 5

Critical Pitfalls to Avoid

• Do not administer oxymorphone with food or alcohol—food increases absorption by 50%, and alcohol causes "dose-dumping" with increased intersubject variability. 5, 6, 4
• Do not use in moderate to severe hepatic impairment—this is an absolute contraindication. 5
• Do not assume published equianalgesic ratios are precise—start conservatively at half the calculated dose when rotating opioids. 5
• Do not initiate with doses >20 mg—this increases risk of serious adverse reactions without established benefit. 5
• Do not choose oxymorphone as first-line therapy—morphine remains the preferred initial strong opioid with superior evidence and clinical experience. 2