Can a Patient Take Oxycodone HCL IR 5mg with Lyrica 75mg?
Yes, a patient can safely take oxycodone HCL IR 5mg with Lyrica (pregabalin) 75mg together, as this combination is supported by clinical evidence and guidelines for managing pain, particularly neuropathic pain. 1, 2
Evidence Supporting Combination Therapy
Guideline-Based Recommendations
The combination of opioids with pregabalin is explicitly recommended in established pain management guidelines:
- For neuropathic pain management, opioid agonists (including oxycodone) can be used alone or in combination with first-line medications like pregabalin when prompt pain relief is needed or for acute exacerbations of severe pain 1
- The NCCN cancer pain guidelines recommend providing rescue doses of short-acting opioids (10-20% of 24-hour dose) for breakthrough pain in patients on maintenance therapy, which can include pregabalin as adjuvant therapy 1, 3
Clinical Evidence of Safety and Efficacy
Research demonstrates this combination is both safe and potentially synergistic:
- A randomized phase II trial (N=75) showed that 76% of patients achieved ≥33% pain reduction using oxycodone and pregabalin combination therapy for neuropathic cancer pain 2
- A case report documented rapid relief (within 30 minutes) of acute neuropathic cancer pain using immediate-release oxycodone 5mg with pregabalin 75mg simultaneously 4
- A controlled study in healthy volunteers found that pregabalin 75mg combined with oxycodone 10mg altered some subjective effects but did not increase abuse liability or produce dangerous interactions 5
Important Safety Considerations
Monitor for Additive CNS Depression
Both medications can cause sedation and dizziness, which may be additive:
- Pregabalin produces dose-dependent dizziness and sedation, which can be reduced by starting with lower dosages 1
- Common opioid side effects include drowsiness and dizziness 1
- The combination may increase drowsiness (44.4-55.6% in clinical trials) and confusion (16.7-27.8%) compared to either agent alone 2
Dose Adjustments for Renal Impairment
Both medications require dosage reduction in renal insufficiency:
- Pregabalin requires dosage adjustments based on creatinine clearance 1
- Oxycodone should be carefully titrated in renal impairment, though it is safer than morphine or codeine in this population 1
Respiratory Monitoring
Watch for respiratory depression, particularly in opioid-naive patients:
- Pregabalin decreased respiration rate in controlled studies 5
- Opioids carry inherent respiratory depression risk 1
- Use lower starting doses in older, frail patients, or those with COPD 1
Practical Prescribing Approach
Starting These Medications Together
If initiating both simultaneously:
- Start oxycodone IR 5mg every 4-6 hours as needed for pain 1
- Start pregabalin 75mg twice daily (150mg/day total), which is an established starting dose 1
- Assess response after 3-7 days and titrate pregabalin up to 300mg/day if needed for better pain control 1
If Adding One to the Other
If pregabalin is already established:
- Add oxycodone IR 5mg as needed for breakthrough pain 3
- Monitor for increased sedation in the first 24-48 hours 5
If oxycodone is already established:
- Add pregabalin 75mg twice daily as adjuvant therapy 1, 2
- This strategy (fixed oxycodone with escalating pregabalin) showed superior pain control (76% response rate) in clinical trials 2
Common Pitfalls to Avoid
Do not assume this combination is contraindicated - unlike benzodiazepines with high-dose olanzapine (which can be fatal), the oxycodone-pregabalin combination has established safety data 1, 5, 2
Do not neglect constipation prophylaxis - constipation occurred in 52.8-66.7% of patients on combination therapy 2
Do not use codeine or tramadol instead of oxycodone - these are prodrugs with CYP2D6 variability and are less desirable alternatives 1
Do not exceed pregabalin 600mg/day - higher doses are not consistently more effective than 300mg/day and cause more adverse effects 1