Pharmacogenetic Evaluation of Hospitalized Patients Requiring Naloxone for Reversal of Acute Opioid Toxicity

Abstract

Background: Opioids are utilized for acute pain in hospitalized patients and carry the risk of unintentional toxicity. The relationship between unintentional toxicity within a hospital setting and genetic polymorphisms has not been fully evaluated within the literature to date. Assessment and utilization of pharmacogenetic data may be a way to prevent unintentional toxicity in hospitalized patients and reduce the need for naloxone administration. Objective: This study aimed to provide proof of concept for the comparison of allele frequencies of hospitalized patients who received naloxone for opioid reversal with lab control data allele frequencies to identify variations between groups. Methods: This single-center, exploratory, pilot study enrolled 15 patients. Genotype samples were collected via buccal swab and analyzed using a custom 13 gene panel of genes which impact opioid metabolism. Genes assessed include CYP1A2, CYP3A4/A5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, UGT2B7, UGT1A3, ABCB1, COMT, OPRM1. The 15 patients were compared to an internal lab control group of 100 patients and separated into preventable and not preventable events for further analysis. Results: CYP3A5 genotype was found to be statistically significantly different between the experimental and control groups (P = .004). This statistically significant difference was also seen in CYP3A5 phenotypes (P = .038). When comparing preventable and not preventable events, a statistically significant difference was found in both the genotype (P = .030) and phenotype (P = .029) of CYP2C19. Other assessed risk factors included mean MME in the 24 hours preceding naloxone being higher among preventable events and hospital or emergency department admission percent risk being higher among not preventable events. Conclusion: Factors other than pharmacogenetics, including opioid route of administration, medication formulation, and overall hospital admission risk, may play an additive role in unintentional toxicity risk. Future research of genotype-guided opioid dosing in pain management services further adds to calculating the risk of unintentional opioid-related adverse effects with standard dosing of this drug class.