Generic Name

Percocet

Mechanism

• Oxycodone
• Acts primarily as a mu‑opioid receptor agonist in the central nervous system.
• Activates G‑protein–coupled receptors → inhibition of adenylate cyclase → ↓cAMP → decreased Ca²⁺ influx and increased K⁺ efflux, reducing neuronal excitability.
• Results in strong analgesia, sedation, and respiratory depression.
• Acetaminophen
• Inhibits cyclooxygenase (COX) enzymes in the brain, reducing prostaglandin synthesis.
• Modulates the serotonergic system in the spinal cord, contributing to analgesia without significant peripheral anti‑inflammatory action.

The synergistic effect of oxycodone and acetaminophen optimizes pain control while reducing the required oxycodone dose.

Pharmacokinetics

Indications

• Moderate to severe acute pain (post‑operative, trauma, dental, obstetric).
• Situations where oral opioid therapy is needed with an added non‑opioid component to maximize pain reduction and lower opioid dose.

Contraindications

• Absolute contraindications
• Known hypersensitivity to oxycodone or acetaminophen.
• Severe respiratory depression or uncontrolled hypoxia.
• Severe hepatic insufficiency (ALT/AST > 5× ULN).
• Relative contraindications
• Pediatric patients 4 g.
• Pruritus and constipation are common opioid side effects.
• Drug–drug interactions: SSRIs, CYP3A4 inhibitors, anticoagulants, or other CNS depressants.

Dosing

• Adults
• Typical dose: 5 mg oxycodone + 500 mg acetaminophen every 4–6 h as needed.
• Max daily oxycodone: 60 mg (12 × 5 mg).
• Max daily acetaminophen: 4 g (8 × 500 mg).
• Elderly (≥65 yr) or hepatic impairment
• Start at 2 × 5 mg; titrate cautiously based on tolerance.
• Renal impairment
• No major dose adjustment; monitor for accumulation of metabolites.
• Special Note
• Do not exceed 4 g Acetaminophen per day to avoid hepatic injury.

Adverse Effects

Common (≥10 %):
• Nausea, vomiting
• Constipation
• Sedation
• Dizziness
• Dry mouth

Serious (≤1 %):
• Respiratory depression (especially with dose escalation or concomitant CNS depressants)
• Liver injury (ALT/AST ↑, hyperbilirubinemia)
• Severe pruritus or rash (contact dermatitis)
• Acute opioid withdrawal symptoms (if abrupt cessation)

Monitoring

• Patient‑level
• Observe for sedation, paradoxical agitation, and respiratory rate.
• Laboratory
• Baseline and periodic liver function tests (LFTs) in patients ≥4 weeks of therapy or on high cumulative doses.
• Monitor for weight loss or hypo‑albuminemia (loss of analgesic efficacy).
• Safety
• Check for signs of misuse or diversion (e.g., requests for refills).

Clinical Pearls

1. Comparator with Acetaminophen Alone – Using Percocet allows for lower oxycodone dosing; avoid over‑reliance on opioids alone.

2. Nutritional Impact – Opioid therapy can increase appetite; monitor caloric intake to prevent weight gain or constipation.

3. Tailored Oxycodone – CYP2D6 poor metabolizers may require reduced dosing to limit O‑demethylated metabolite accumulation.

4. Emergency Concomitant Acetaminophen – In acute overdose, promptly consider activated charcoal and N‑acetylcysteine for acetaminophen toxicity.

5. Overdose Awareness – Educate patients on reservoirs of opioid tablets; safe storage reduces accidental ingestion.

6. Patient Education – Reinforce that Percocet is not a sedative; avoid driving or operating machinery until sedation level is assessed.

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• Percocet blends an opioid’s potent analgesic with acetaminophen’s mild systemic effect to control moderate‑to‑severe acute pain while keeping opioid exposure lower. In practice, judicious dosing, vigilant monitoring of hepatic function, and patient‑centered education are key to safe and effective use.