Dr. Jasmine Luzum Publishes Review of Pharmacogenomics for COVID-19 Therapies
The COVID-19 pandemic continues to impact global health and safety. Numerous drugs are under expedited investigations, without well-established safety or efficacy data. Jasmine Luzum, PharmD, PhD, BCPS, assistant professor of clinical pharmacy, has published a review of pharmacogenomics for COVID-19 therapies in a Nature journal.
The goal of Dr. Luzum’s research is to use precision medicine, particularly genetics, to improve cardiovascular outcomes from medications. Adverse cardiac outcomes from drugs used to treat COVID-19 have recently been a major concern.
“Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety,” explains Dr. Luzum. “In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids.”
Dr. Luzum and collaborators found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). They also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β -1b (IRF6; liver toxicity).
The team describes in the paper the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors.
“Although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies,” notes Dr. Luzum. “Clinical studies in COVID-19 patients are warranted to assess potential roles of these markers.”