Percocet 5/325 Dosing
For opioid-naïve adults with acute moderate-to-severe pain, start with one tablet of Percocet 5/325 (5 mg oxycodone/325 mg acetaminophen) every 4-6 hours as needed, not exceeding 6 doses (30 mg oxycodone/1950 mg acetaminophen) in 24 hours. 1
Standard Dosing Regimen
The recommended starting dose is 5-15 mg of oxycodone (the opioid component) every 4-6 hours as needed for pain. 1 For Percocet 5/325 specifically, this translates to:
- Initial dose: 1 tablet (5 mg oxycodone/325 mg acetaminophen) every 4-6 hours as needed 1
- Dosing frequency: Every 4-6 hours PRN (as needed), NOT scheduled around-the-clock 1
- Maximum daily oxycodone: 30 mg (6 tablets) to stay within the conservative 20-30 MME/day starting range for opioid-naïve patients 1
- Maximum daily acetaminophen: Must not exceed 4000 mg from ALL sources, though 3000 mg/day is increasingly recommended for safety 1, 2
Critical Dosing Principles
Prescribe "as needed" rather than scheduled dosing (e.g., "one tablet every 4-6 hours as needed for moderate to severe pain" rather than "one tablet every 4 hours"). 1 This approach minimizes opioid exposure and reduces risk of respiratory depression, particularly during the first few days when patients are most vulnerable. 1
The lowest starting dose for opioid-naïve patients is typically 5-10 MME per single dose or 20-30 MME/day total. 1 Since 5 mg oxycodone equals approximately 7.5 MME, one Percocet 5/325 tablet (7.5 MME) falls within this safe starting range. 1
Duration of Therapy
Limit opioid prescriptions for acute pain to 3-7 days maximum. 1 The 2022 CDC guidelines emphasize that opioids should be prescribed "for no longer than the expected duration of pain severe enough to require opioids." 1 Most acute pain conditions resolve within this timeframe, and longer durations increase risk of dependence and adverse outcomes.
If opioids are taken around-the-clock for more than a few days, encourage and recommend an opioid taper back to as-needed use or discontinuation. 1
Dose Escalation Cautions
Avoid dose increases for acute pain treated for only a few days. 1 Rapid dosage increases put patients at greater risk for sedation, respiratory depression, and overdose. 1 For outpatients with acute pain, dosage increases are usually unnecessary and should not be attempted without close monitoring. 1
If considering increasing beyond 50 MME/day (approximately 7 tablets of Percocet 5/325), pause and carefully reassess benefits versus risks. 1 Dosage increases beyond 50 MME/day are unlikely to provide substantially improved pain control while overdose risk increases progressively. 1
Special Populations Requiring Dose Reduction
Elderly patients (≥65 years): Start with lower doses due to smaller therapeutic window between safe dosages and respiratory depression. 1 Consider starting with half a tablet (2.5 mg oxycodone) or using the 2.5 mg/325 mg formulation if available. 1
Patients with hepatic or renal insufficiency: Use additional caution and consider lower starting doses because of potentially decreased drug clearance and accumulation to toxic levels. 1
Patients with chronic alcohol use or liver disease: Limit total daily acetaminophen to 2000-3000 mg maximum (6-9 tablets of Percocet 5/325). 2
Acetaminophen Safety Monitoring
Counsel patients explicitly to avoid ALL other acetaminophen-containing products including over-the-counter cold remedies, sleep aids, and other prescription combinations. 1, 2 Unintentional acetaminophen overdose from multiple sources is a common and preventable cause of hepatotoxicity. 2
The acetaminophen component in Percocet is now limited to 325 mg per tablet (reduced from previous 500-650 mg formulations) to minimize hepatotoxicity risk. 1
Clinical Context for Appropriate Use
Opioids like Percocet should only be prescribed when:
- Nonopioid therapies (NSAIDs, acetaminophen alone) are contraindicated, ineffective, or insufficient 1
- Pain is moderate to severe and anticipated benefits outweigh risks 1
- The condition warrants opioid use (e.g., severe traumatic injuries, invasive surgeries, severe acute pain when NSAIDs contraindicated) 1
Nonopioid therapies are at least as effective as opioids for many common acute pain conditions including low back pain, neck pain, musculoskeletal injuries, minor surgeries, dental pain, and kidney stones. 1 Maximize nonopioid approaches first. 1
Common Pitfalls to Avoid
Do not prescribe scheduled around-the-clock dosing for acute pain. 1 This increases total opioid exposure unnecessarily and elevates risk of respiratory depression and dependence.
Do not prescribe for longer than 3-7 days for acute pain. 1 Extended prescriptions beyond the expected duration of severe pain increase risk of long-term use and adverse outcomes.
Do not increase dose without reassessing pain severity, functional improvement, and risk factors. 1 Most acute pain improves with time; dose escalation is rarely needed and increases overdose risk.
Do not forget to account for acetaminophen from other sources. 1, 2 Patients may inadvertently exceed 4000 mg/day by combining Percocet with OTC products containing acetaminophen.
Do not use in patients already on chronic opioid therapy without adjusting for tolerance. 1 These patients require different dosing considerations and are not "opioid-naïve."
Monitoring and Follow-Up
For short-term use (≤7 days), monitor for:
- Pain relief adequacy 1
- Adverse effects (nausea, vomiting, constipation, drowsiness, respiratory depression) 1
- Need for continued opioid therapy versus transition to nonopioid alternatives 1
Provide naloxone and overdose prevention education if prescribing to patients at increased risk (concurrent benzodiazepines, sleep apnea, substance use history, or doses approaching 50 MME/day). 1