Introduction
Percocet is a prescription combination analgesic medication containing oxycodone hydrochloride (a semi-synthetic opioid agonist) and acetaminophen (a non-opioid analgesic and antipyretic). This fixed-dose combination product is classified as a Schedule II controlled substance due to its high potential for abuse and dependence. Percocet is formulated to provide additive analgesic effects through two distinct mechanisms of action.
Mechanism of Action
Oxycodone component: Binds primarily to mu-opioid receptors in the central nervous system, altering the perception of and response to pain through G-protein coupled receptor mechanisms. It produces analgesia, sedation, and euphoria through activation of descending inhibitory pathways. Acetaminophen component: Exact mechanism remains incompletely understood but likely involves central inhibition of prostaglandin synthesis, with weak inhibition of peripheral prostaglandin synthesis. It may also activate descending serotonergic pathways and inhibit nitric oxide synthesis.Indications
- Management of acute pain severe enough to require an opioid analgesic
- Treatment of pain that is not adequately controlled by non-opioid analgesics alone
- FDA-approved for short-term treatment of moderate to moderately severe pain
Dosage and Administration
Standard adult dosing:- Percocet 2.5/325: 1-2 tablets every 6 hours as needed for pain
- Percocet 5/325, 7.5/325, 10/325: 1 tablet every 6 hours as needed for pain
- Oxycodone: No specific maximum, but should be titrated to lowest effective dose
- Acetaminophen: ≤ 4,000 mg daily (reduced to ≤ 3,000 mg daily in certain populations)
- Renal impairment: Use with caution; consider reduced frequency
- Hepatic impairment: Contraindicated in severe hepatic impairment
- Geriatric: Start with lowest possible dose
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption:- Oxycodone: Oral bioavailability 60-87%
- Acetaminophen: Rapid and nearly complete gastrointestinal absorption
- Tmax: 1-2 hours for both components
- Oxycodone: Vd ~2.6 L/kg; 38-45% protein bound
- Acetaminophen: Vd ~0.9 L/kg; 10-25% protein bound
- Both cross placenta and are excreted in breast milk
- Oxycodone: Primarily hepatic via CYP3A4 (N-demethylation) and CYP2D6 (O-demethylation)
- Acetaminophen: Hepatic conjugation (90%) and CYP450 oxidation (10%)
- Oxycodone: Half-life 3-5 hours; renal excretion of metabolites
- Acetaminophen: Half-life 1-4 hours; renal excretion of conjugates
Contraindications
- Significant respiratory depression
- Acute or severe bronchial asthma
- Known or suspected gastrointestinal obstruction
- Hypersensitivity to oxycodone, acetaminophen, or any component
- Moderate to severe hepatic impairment
Warnings and Precautions
Boxed Warning:- Addiction, abuse, and misuse risk
- Life-threatening respiratory depression
- Accidental ingestion can be fatal
- Neonatal opioid withdrawal syndrome
- Risks from concomitant use with benzodiazepines
- Acetaminophen hepatotoxicity
- Increased intracranial pressure
- Seizure disorders
- Adrenal insufficiency
- Elderly or debilitated patients
- Patients with CNS depression
- Biliary tract disease
- Acute abdominal conditions
Drug Interactions
Major interactions:- Benzodiazepines and other CNS depressants: Additive CNS depression
- CYP3A4 inhibitors (ketoconazole, macrolides): Increased oxycodone levels
- CYP3A4 inducers (rifampin, carbamazepine): Decreased oxycodone efficacy
- Anticholinergics: Increased risk of urinary retention and constipation
- Monoamine oxidase inhibitors: Risk of serotonin syndrome
- Warfarin: Slight increase in INR
- Isoniazid: Increased hepatotoxicity risk
- Chronic alcohol use: Increased hepatotoxicity risk
Adverse Effects
Common (≥10%):- Nausea (30%)
- Constipation (25%)
- Drowsiness (15%)
- Vomiting (12%)
- Dizziness (10%)
- Respiratory depression
- Hypotension
- Adrenal insufficiency
- Severe hepatotoxicity (acetaminophen-related)
- Anaphylaxis
- Serotonin syndrome
- Withdrawal symptoms with abrupt discontinuation
Monitoring Parameters
- Pain intensity and relief scores
- Respiratory rate and oxygen saturation
- Blood pressure and heart rate
- Bowel function (constipation management)
- Signs of misuse or addiction
- Hepatic function tests (with long-term use)
- Mental status changes
- Signs of hypogonadism with chronic use
Patient Education
- Take exactly as prescribed; do not crush or chew tablets
- Never share medication with others
- Avoid alcohol consumption during therapy
- Be aware of acetaminophen content in all medications
- Report any difficulty breathing or excessive sedation
- Maintain adequate hydration and fiber intake
- Do not abruptly stop medication
- Store securely away from children and others
- Dispose of unused medication properly
- Understand risks of dependence and addiction
References
1. FDA Prescribing Information: Percocet (oxycodone and acetaminophen) tablets 2. American Pain Society. (2016). Guidelines on the Management of Postoperative Pain. 3. Chou R, et al. (2015). CDC Guideline for Prescribing Opioids for Chronic Pain. 4. Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information. 5. Micromedex Solutions, Truven Health Analytics. 6. Raffa RB, et al. (2012). The basic pharmacology of opioids informs the opioid discourse about misuse and abuse. Pain Medicine. 7. Dart RC, et al. (2015). Acetaminophen (paracetamol) overdose. New England Journal of Medicine.
Note: This monograph is for educational purposes only. Healthcare providers should consult current prescribing information and clinical guidelines before making treatment decisions.