Oxycodone

1. Drug Name

• Generic Name: Oxycodone

• Brand Names: OxyContin, Roxicodone, Percocet (combination with acetaminophen), Percodan (combination with aspirin), Xtampza ER

2. Drug Classification

• Class: Opioid analgesic

• Subclass: Semisynthetic opioid

3. Mechanism of Action

• Primary Action: Oxycodone functions as an agonist primarily at the μ-opioid receptor in the central nervous system (CNS). This binding inhibits the transmission of pain signals, leading to analgesia and sedation. Oxycodone also has partial κ-opioid receptor affinity, contributing to its analgesic effects.

• Additional Effects: As with other opioids, oxycodone affects respiratory centers, potentially leading to respiratory depression at higher doses.

4. Pharmacokinetics

• Absorption: High oral bioavailability (60-87%), with extended-release formulations designed for controlled release over 12-24 hours.

• Distribution: Volume of distribution (Vd) is approximately 2.6 L/kg; moderately protein-bound (45%).

• Metabolism: Extensively metabolized in the liver, mainly by CYP3A4 to noroxycodone (inactive) and by CYP2D6 to oxymorphone (active). The latter is a potent analgesic, though it contributes minimally to the clinical effects.

• Excretion: Elimination half-life (t½) is about 3-4 hours for immediate-release formulations and approximately 8-12 hours for extended-release. Excretion is primarily renal.

• Special Considerations: Altered metabolism and elimination in hepatic and renal impairment; caution and dose adjustment recommended.

5. Indications

• Primary Indications: Management of moderate to severe pain requiring continuous, long-term opioid treatment when other treatments are insufficient.

• Off-label Uses: Occasionally used for chronic pain management in cases such as cancer pain.

• Beneficial Populations: Patients with chronic, severe pain conditions or post-operative pain that require an opioid analgesic.

6. Dosage and Administration

• Adult Dosing:

  • Immediate-Release for Pain Relief: 5-15 mg orally every 4-6 hours as needed.

  • Extended-Release for Chronic Pain: Start with 10 mg every 12 hours; titrate based on response and tolerance.

• Pediatric Dosing: Not recommended for children under 18, though specific cases may be managed with appropriate formulations under close supervision.

• Routes: Oral tablets (immediate and extended-release), oral solution, capsules, and combinations with acetaminophen or aspirin.

• Renal/Hepatic Adjustments: Caution in moderate-to-severe hepatic/renal impairment with potential dosage reductions and extended monitoring.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to oxycodone or components of the formulation.

  • Severe respiratory depression or asthma in an unmonitored setting.

  • Paralytic ileus or GI obstruction.

• Relative Contraindications: Moderate-to-severe hepatic or renal impairment; use with caution in elderly or debilitated patients.

8. Warnings and Precautions

• Black Box Warnings: High potential for addiction, abuse, and misuse; risk of life-threatening respiratory depression; accidental ingestion can be fatal; neonatal opioid withdrawal syndrome may occur with prolonged use during pregnancy.

• Pregnancy and Lactation: Prolonged use during pregnancy may cause neonatal withdrawal syndrome; oxycodone passes into breast milk and may affect infants.

• Monitoring Parameters: Respiratory rate, sedation levels, liver and kidney function tests, pain control, and signs of misuse or addiction.

• Special Considerations: Increased risk of respiratory depression in elderly, debilitated, and opioid-naïve patients.

9. Adverse Effects

• Common Adverse Effects (≥10%): Nausea, vomiting, constipation, somnolence, dizziness, pruritus.

• Less Common but Clinically Significant: Urinary retention, orthostatic hypotension, dry mouth, headache.

• Serious Adverse Reactions: Severe respiratory depression, anaphylaxis, serotonin syndrome (in combination with serotonergic agents), and seizures in rare cases.

10. Drug Interactions

• Major Drug Interactions:

  • CNS Depressants (e.g., benzodiazepines, alcohol): Heightened risk of sedation, respiratory depression, coma, and death.

  • CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Increased plasma concentrations of oxycodone, leading to heightened risk of toxicity.

  • CYP3A4 Inducers (e.g., rifampin): Reduced plasma concentrations, which may decrease analgesic effect.

  • CYP2D6 Inhibitors (e.g., paroxetine, fluoxetine): Reduced conversion to oxymorphone, potentially affecting analgesic efficacy.

• Food-Drug Interactions: Absorption rates can be affected by high-fat meals with certain extended-release formulations.

• Lab Test Interference: Can yield positive results for opiates in some urine drug screens.

11. Clinical Pharmacology

• Pharmacodynamic Profile: Oxycodone’s μ-receptor agonist activity provides effective pain relief but carries a risk of dependence, respiratory depression, and sedation. The active metabolite oxymorphone contributes to analgesia in CYP2D6-expressing patients.

• Additional Effects: Effects on respiratory and gastrointestinal function are dose-dependent, with greater impairment at higher doses.

12. Special Populations

• Pregnancy: Category C; use only if potential benefits justify risks to the fetus. Long-term use can lead to neonatal withdrawal syndrome.

• Lactation: Oxycodone is excreted in breast milk; use with caution as it may cause sedation or respiratory depression in the infant.

• Geriatric Use: Elderly patients may experience increased sensitivity; lower starting doses with careful titration are recommended.

• Renal/Hepatic Impairment: Dose adjustments and close monitoring required in moderate-to-severe renal or hepatic impairment.

13. Therapeutic Uses

• First-Line Use: Effective for moderate to severe pain where opioid therapy is appropriate, particularly in chronic and cancer-related pain.

• Combination Therapy: Frequently combined with acetaminophen or NSAIDs for enhanced pain relief and reduced opioid requirements.

• Clinical Trials and Efficacy: Demonstrated efficacy in chronic pain management settings, but dependence potential limits prolonged use.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Baseline liver and renal function tests, with follow-up as needed during extended treatment.

• Patient Symptom Checklists: Regular assessment for respiratory rate, sedation, pain relief, and signs of misuse or dependency.

• Therapeutic and Toxic Levels: Monitor for therapeutic effects while observing for early toxicity signs, particularly in long-term therapy.

15. Overdose Management

• Symptoms of Overdose: Respiratory depression, miosis, extreme drowsiness leading to stupor or coma, bradycardia, and cyanosis.

• Treatment Protocols:

  • Naloxone Administration: Effective as an opioid antagonist; repeat dosing may be needed given the duration of oxycodone’s effects.

  • Supportive Care: Maintain open airway, provide oxygen, and ventilate if necessary.

• Monitoring in Overdose: Continuous monitoring of respiratory, cardiovascular, and neurologic status.

16. Patient Counseling Information

• Key Counseling Points:

  • Educate on correct usage, especially with extended-release formulations, to avoid overdose.

  • Warn against using alcohol or other CNS depressants during therapy.

  • Discuss the risks of dependence and importance of adherence to prescribed dosages.

  • Instruct patients to report signs of respiratory depression, severe constipation, or confusion promptly.

• Signs Requiring Immediate Attention: Difficulty breathing, extreme drowsiness, confusion, severe allergic reactions, and overdose symptoms.