Oxycodone vs Hydrocodone: Key Differences
Oxycodone is 1.5 times more potent than hydrocodone on a milligram-per-milligram basis, meaning 10 mg of oxycodone equals approximately 15 morphine milligram equivalents (MME) while 10 mg of hydrocodone equals 10 MME 1, 2.
Potency and Conversion
The most clinically relevant difference is potency:
- Hydrocodone conversion factor: 1.0
- Oxycodone conversion factor: 1.5
This means if you're converting between these medications, you need 50% more hydrocodone to achieve equivalent analgesia to oxycodone 2. For example, 20 mg of hydrocodone daily = 20 MME, while 20 mg of oxycodone daily = 30 MME 1.
Pharmacokinetics
Both medications have similar pharmacokinetic profiles 3:
- Oxycodone: Half-life 3.5-4 hours, reaches steady state in 18-24 hours, 60-87% oral bioavailability
- Hydrocodone: Similar duration of action and dosing frequency (typically every 4-6 hours for immediate-release formulations)
Both are metabolized primarily by CYP3A4, with oxycodone also metabolized by CYP2D6 to oxymorphone 3.
Abuse Liability and Long-term Use Risk
Critical clinical consideration: Hydrocodone appears associated with substantially higher rates of long-term use compared to oxycodone, despite equivalent analgesia 4. In primary care patients with acute back pain, an estimated 12% of those treated with hydrocodone transitioned to long-term use versus only 2% with oxycodone. Among patients receiving multiple prescriptions, this increased to 23% for hydrocodone versus 5% for oxycodone 4.
However, oxycodone demonstrates higher abuse liability in controlled studies, with higher "likeability" scores and fewer negative subjective effects when abused 5. When administered intravenously by recreational users, oxycodone showed the highest potency among the three opioids tested (oxycodone > morphine > hydrocodone) 6.
Clinical Efficacy
For acute pain management, both medications provide equivalent analgesia at equipotent doses 7. In emergency department patients with fractures, 5 mg of either oxycodone or hydrocodone (both with acetaminophen) produced similar pain relief at 30 and 60 minutes, with the only difference being higher constipation rates with hydrocodone (21% vs 0%) 7.
Recent evidence from joint arthroplasty patients suggests hydrocodone may provide comparable pain control with significantly lower total opioid consumption 8. Among CYP2D6 normal metabolizers, hydrocodone was associated with lower composite pain scores (9.0 vs 9.3) and substantially lower cumulative MME consumption (93.5 vs 154.5 MME over 10 days) compared to oxycodone 8.
Practical Clinical Implications
When choosing between these medications:
- For equivalent analgesia: Prescribe 1.5 times more hydrocodone than oxycodone (e.g., 7.5 mg hydrocodone ≈ 5 mg oxycodone)
- For acute pain: Both are equally effective at equipotent doses 7
- For postoperative pain: Hydrocodone may result in lower total opioid consumption while maintaining pain control 8
- For abuse risk: Oxycodone has higher immediate abuse liability 5, but hydrocodone carries higher risk of transition to long-term use 4
- For side effects: Expect higher constipation rates with hydrocodone 7
Important Caveats
Both medications carry identical FDA warnings regarding addiction, abuse, misuse, and respiratory depression 3. The choice between them should not be viewed as a safety distinction—both are Schedule II controlled substances with significant risks. The conversion factors provided are estimates and cannot account for individual variability in genetics and pharmacokinetics 2. When converting between opioids, always start the new opioid at a substantially lower dose than the calculated MME to avoid overdose due to incomplete cross-tolerance 2.