M-10: Pharmacogenomics in Opioid Use Disorder Managment
Poster Presenter
Casey Walker
Pharmacist
Jushi Holdings, Inc United States
Objectives
Our aim is determine associations between CYP3A4 genotype, rate of relapse to unauthorized substances, and presence of withdrawal symptoms in African American patients being managed on buprenorphine.
ORAL PRESENTATION: 2:35PM
Method
A case series was conducted with 5 patients from an OUD management clinic in Washington DC. Demographic data, medication history, and social history were collected from each patient. Pharmacogenomic test reports were reviewed to determine CYP3A4 genotype information.
Results
All five patients were African American males with an average age of 58 years. Four patients had the CYP3A4*1/*1B genotype and one patient had the CYP3A4*1B/*1B genotype. All five patients required daily buprenorphine doses above the 24 mg/day maximum in order to reduce withdrawal symptoms and relapse to unauthorized substances. At a daily dose of 24 mg buprenorphine, the patients had multiple relapses with unauthorized substances. Pharmacogenomic testing revealed that the patients exhibited a cytochrome P450 3AA4 ultrarapid metabolizer phenotype, which necessitated a higher than recommended daily dose of buprenorphine for adequate OUD management. Four out of the five patients exhibited a reduction in the number of relapses on the pharmacogenetic-based dose reduction. The past medical history and social history of the patients were compared. As a result of OUD, two of the patients contracted HIV, and four patients were previously infected with hepatitis C (HCV), three patients have comorbid depression, and all the patients are cigarette smokers. Only one patient is married and employed. All of the patients has been previously incarcerated on drug-related offenses.
Conclusion
Clinical pharmacogenomic testing may help to improve OUD management outcomes for patients being managed on buprenorphine. There is conflicting evidence in the literature regarding the phenotype associated with the CYP3A4*1B genotype; some studies have associated the CYP3A4*1B allele with an EM phenotype, while other studies have purported that the CYP3A4*1B correlates to an UM phenotype. In these cases, the presence of the CYP3A4*1B allele appears to be consistent with an UM phenotype, as higher doses of buprenorphine were required for successful maintenance therapy. These cases support existing evidence patients that have at least one copy of the CYP3A4*1B allele metabolize buprenorphine at an accelerated rate compared to the EM phenotype (CYP3A4*1/*1). This accelerated rate of metabolism may have resulted in suboptimal therapeutic levels of buprenorphine prior to the next scheduled dose. Sub-optimal therapeutic medication levels may have subsequently resulted in the patients relapsing to unauthorized substances to supplement the reduced buprenorphine dose.
The clinical trials used to derive the standard dosing recommendations for buprenorphine/naloxone did not take into account for possible genetic effects on buprenorphine/naloxone use. Considering that buprenorphine/naloxone is metabolized primarily via CYP3A4, the inclusion of pharmacogenomic testing during the clinical trials may have elucidated a need for variable dosing based on phenotypic presentation. The package insert makes no mention of pharmacogenomic considerations in the dosing of buprenorphine/naloxone. UMs could exhibit a sub-therapeutic clinical response and require dosing that exceeds the maximum daily recommended maintenance dose for buprenorphine/naloxone. These limitations should be addressed in order to further enable pharmacogenetic testing implementation for OUD management.
