What are the differences between oxycodone and hydrocodone for pain management?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: September 25, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Comparison of Oxycodone and Hydrocodone for Pain Management

Oxycodone and hydrocodone have comparable efficacy for pain management, but oxycodone is approximately 1.5 times more potent than hydrocodone, with oxycodone showing potentially better efficacy for neuropathic pain components while hydrocodone may have a slightly better side effect profile. 1

Pharmacological Properties and Potency

  • Mechanism of Action: Both are semi-synthetic opioid agonists that act primarily on μ-opioid receptors, but oxycodone also has activity at κ-opioid receptors which may contribute to its efficacy in visceral pain 1, 2
  • Potency: Oxycodone is approximately 1.5 times more potent than hydrocodone, requiring lower doses for equivalent analgesia 1
  • Metabolism: Both medications undergo metabolism through the CYP2D6 enzyme system, but oxycodone has less reliance on this pathway compared to codeine, making it less susceptible to genetic polymorphisms affecting efficacy 1

Efficacy Comparison

  • For moderate to severe pain, both medications provide effective analgesia when used at appropriate doses 3
  • In comparative studies, oxycodone 5mg/ibuprofen 400mg combinations showed superior analgesia compared to hydrocodone 7.5mg/acetaminophen 500mg in acute pain models 4
  • For cancer-related pain, both medications are considered effective options in the WHO pain ladder for moderate to severe pain 3
  • Limited evidence exists for long-term efficacy of both hydrocodone and oxycodone in chronic non-cancer pain beyond 6 months 5

Side Effect Profiles

  • Common side effects for both medications include:

    • Constipation
    • Nausea/vomiting
    • Sedation
    • Respiratory depression
    • Risk of dependence and addiction 1
  • Comparative side effects:

    • Hydrocodone may cause slightly less nausea and vomiting than oxycodone in some patients 4
    • Oxycodone may cause more dizziness in some patients
    • Both medications carry similar risks for respiratory depression when used at equianalgesic doses 1

Clinical Applications

Acute Pain Management

  • Both medications are commonly used in combination with acetaminophen or NSAIDs for moderate to severe acute pain 1
  • For opioid-naïve patients with moderate pain:
    • Start with hydrocodone/acetaminophen 5mg/325mg, 1 tablet every 4-6 hours as needed
    • For patients requiring stronger analgesia, oxycodone/acetaminophen 5mg/325mg may be used 1

Chronic Pain Management

  • Evidence for long-term efficacy (>6 months) is limited for both medications 5
  • When used for chronic pain:
    • Regular assessment of pain relief, function, and side effects is essential
    • Risk of tolerance and dependence should be monitored
    • Consider rotation between opioids if tolerance develops 3

Cancer Pain

  • Both medications are effective for moderate to severe cancer pain
  • Oxycodone may be particularly useful for mixed nociceptive-neuropathic pain due to its κ-receptor activity 3, 2

Risk of Abuse and Addiction

  • Both medications are Schedule II controlled substances with similar abuse potential
  • Patients with history of substance abuse are at higher risk of misusing both medications 6
  • Research indicates that individuals with history of opioid abuse will self-administer oxycodone regardless of pain condition, while non-abusers tend to self-administer only when in pain 6

Special Populations

Elderly Patients

  • Both medications should be initiated at 25-50% of standard adult doses in elderly patients
  • Slower titration and closer monitoring for side effects is recommended 1

Renal Impairment

  • Both medications require dose adjustment in renal impairment
  • Consider alternative opioids like hydromorphone or fentanyl in severe renal impairment 1

Practical Prescribing Considerations

  • For moderate pain in opioid-naïve patients:

    • Hydrocodone/acetaminophen 5mg/325mg is often the first choice
    • Limit acetaminophen to <4000mg daily to prevent hepatotoxicity 1
  • For more severe pain or patients with prior opioid exposure:

    • Oxycodone/acetaminophen 5mg/325mg or hydrocodone/acetaminophen 7.5mg/325mg may be more appropriate 1
  • For patients with visceral pain components:

    • Oxycodone may provide better relief due to its κ-receptor activity 2

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.