The Role of Clinical Pharmacogenetics and Opioid Interactions in Pain Management: Current Evidence and Future Perspectives

TL;DR

This paper reviews how genetic differences and drug interactions affect how people respond to opioids, aiming to improve pain management.

Contribution

It provides a comprehensive review of pharmacogenetic and interaction factors influencing opioid response, offering a framework for future approaches.

Findings

Genetic polymorphisms in CYP2D6 and CYP3A4 genes influence opioid metabolism and safety.

Drug interactions with enzyme inducers or inhibitors can significantly alter opioid response.

Pharmacogenetics and interaction awareness can help explain variability in patient responses to opioids.

Abstract

Introduction: Opioids are the most commonly used analgesic drugs for acute and chronic severe pain and are metabolized in the liver via cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs). Methods: A narrative review of the literature was conducted by searching the PubMed database up to December 2025, with English as the only language restriction. Relevant studies were identified using the keywords “opioids,” “pharmacogenetic,” “cytochrome mutations,” and “interactions.” Results: Polymorphisms in CYP2D6 and CYP3A4 genes can affect the pharmacokinetics, clinical effect, and safety of opioids. Furthermore, enzyme induction and inhibition by concomitant drugs or compounds (herbal products or food) are sources of variability factors in drug response that may be predictable. Conclusions: This review article summarizes current evidence on the role of pharmacogenetics and opioid-related interactions, offering a framework to better understand interindividual variability in opioid response and to inform future multimodal approaches.