Pharmacogenetics Research for COVID-19 Drugs Needed to Improve Patient Safety

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Medical bottle with hydroxychloroquine HCQ pills, 3D rendering isolated on white background

Research into the genetics of the metabolism of several drugs being used to treat COVID-19 suggests that variation in certain genes could influence how safe it is for individuals to be given these medications, both individually and in combination.

Many of these drugs are not being used for the indication they were originally designed for and there has been much public debate about how effective or safe some of them, notably hydroxychloroquine, are.

While there is currently not enough information available to make evidence-based decisions, the team, led by Pamala Jacobson, PharmD, a professor at the University of Minnesota College of Pharmacy, believes more research into their pharmacogenetics is needed to ensure patient safety.

“The application of pharmacogenomic tests can help eliminate fatal hypersensitivity for patients prescribed certain drugs,” emphasized Jacobson.

As published in the journal Genomic Medicine, the researchers carried out a review of the available academic literature about the genetics of how drugs being used to treat Covid-19 patients are metabolized.

They found that four gene variants exist that could impact the metabolism and efficacy of hydroxychloroquine or chloroquine, one that impacts azithromycin, three that affect ribavirin; and three that impact lopinavir or ritonavir.

In addition, they also highlighted several gene variants that could contribute to adverse drug reactions. For example, variants in the genes G6PD and ITPA can cause hemolysis in patients given hydroxychloroquine/chloroquine or ribavirin, respectively. Similarly, liver toxicity can occur in some patients given interferon β -1b if they have specific variants in the IRF6 gene.

The fact that many patients with severe Covid-19 are often given several drugs together as well as commonly having underlying comorbidities makes assessing pharmacogenetic safety much harder. There is an added risk for drug-drug interactions on top of genetic interactions.

For instance, combining hydroxychloroquine/chloroquine and azithromycin can increase the risk for electrical heart problems and this risk can increase if the patient has genetic variants that mean higher concentrations of the drugs are circulating in their body.

“While we did not find direct evidence to support use of pharmacogenomic testing for COVID-19, we did identify many actionable genetic markers that may have promise to improve efficacy and safety,” said Jacobson.

“Clinical studies in patients with COVID-19 are needed before routine testing can be recommended.”

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