Pharmacogenomics and Opioid Efficacy in Sickle Cell Disease: Is the Field Ready for Precision Prescribing?

Pain is a leading cause of morbidity and healthcare utilization in sickle cell disease (SCD), and opioids remain central to treating vaso-occlusive and chronic pain. Yet opioid response varies widely, raising the question of whether pharmacogenetic testing should inform opioid prescribing. Our review examined the PubMed literature on pharmacogenomics and opioid efficacy in SCD. We focus on CYP2D6 as the clearest current pharmacogenetic signal for codeine and tramadol, and assess SCD-specific implementation studies, preemptive testing, and African pharmacoequity. The current evidence supports targeted CYP2D6-informed prescribing in selected contexts rather than universal testing for all opioids, while highlighting the need to integrate genotype with pain phenotype, drug–drug interactions, liver function, and clinically grounded implementation studies, and better characterize African and African-ancestry pharmacogene variation.