Can you take Lyrica (pregabalin) with morphine and oxy (oxycodone)?

Concurrent Use of Pregabalin (Lyrica) with Morphine and Oxycodone

Taking pregabalin (Lyrica) concurrently with both morphine and oxycodone is not recommended due to the increased risk of respiratory depression, sedation, and other serious adverse effects from the combination of multiple CNS depressants. 1, 2

Pharmacological Interactions

• Pregabalin has no significant pharmacokinetic interactions with oxycodone, meaning it doesn't affect the metabolism or blood levels of oxycodone 2
• However, pregabalin does have important pharmacodynamic interactions with opioids like morphine and oxycodone, causing additive effects on cognitive and gross motor functioning 2
• The combination of pregabalin with multiple opioids increases the risk of central nervous system (CNS) toxicity including drowsiness, cognitive impairment, confusion, and hallucinations 1

Specific Risks of This Combination

• Concurrent use of pregabalin with both morphine and oxycodone significantly increases the risk of respiratory depression, which can be life-threatening 1, 3
• Research in animal models has shown that pregabalin can reverse tolerance to morphine's respiratory depressant effects, potentially leading to unexpected overdose even in opioid-tolerant patients 3
• The FDA label for pregabalin specifically warns about increased side effects when combined with opioid pain medicines such as oxycodone 2
• Using multiple opioids together (morphine and oxycodone) already increases overdose risk, and adding pregabalin further compounds this risk 1

Alternative Approaches

• Instead of using multiple opioids concurrently, consider using a single opioid at an appropriate dose 4
• For neuropathic pain management, pregabalin can be effectively combined with a single opioid rather than multiple opioids 4, 5
• If you're currently taking both morphine and oxycodone, consider transitioning to just one of these medications before adding pregabalin 1
• For patients with neuropathic pain requiring opioid therapy, a single opioid plus pregabalin has shown efficacy in clinical studies 5

If Concurrent Use Is Absolutely Necessary

• Start with reduced doses of all medications to account for potential additive effects 1
• Monitor respiratory rate, sedation level, and other vital signs more frequently 1
• Use this combination for the shortest duration possible to minimize risks 1
• Exercise additional caution if you have kidney or liver problems, as decreased clearance can lead to accumulation of medications to toxic levels 1, 2

Important Considerations for Pregabalin Use

• Pregabalin requires dose adjustment in patients with renal impairment 4
• Pregabalin can cause dose-dependent dizziness and sedation, which would be worsened by concurrent use of multiple opioids 4
• Pregabalin should be started at lower dosages and titrated gradually to minimize side effects 4
• Abrupt discontinuation of pregabalin should be avoided as it can cause withdrawal symptoms 2

Common Pitfalls to Avoid

• Failure to account for the additive sedative effects of multiple CNS depressants can lead to dangerous oversedation 1, 3
• Using multiple opioids together significantly complicates pain management and increases the risk of dosing errors 1
• The practice of concurrent use of multiple opioids with pregabalin should generally be limited to specialists familiar with complex pain management 1