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Considerations for Using Tyrosine Kinase Inhibitors in CML During the COVID‐19 Pandemic

By: Sarah Campen, PharmD
Posted: Friday, May 15, 2020

Treatment with tyrosine kinase inhibitors (TKIs) does not appear to increase the risk of COVID-19 infection in patients with chronic myeloid leukemia (CML) in chronic phase, according to an Editorial published in the British Journal of Clinical Pharmacology. According to Ahmet Emre Eşkazan, MD, of Istanbul University-Cerrahpasa, Turkey, the main concern for patients with CML in chronic phase with COVID-19 disease is the potential for drug-drug interactions between TKIs and medications used for the treatment of SARS-CoV-2 infection.

Several drugs that can prolong the QTc interval—including hydroxychloroquine, chloroquine, azithromycin, and favipiravir—have been considered for treatment of COVID-19 disease, although their effectiveness has yet to be confirmed. All TKIs have the capacity to prolong the QTc interval, potentially leading to torsades de pointes and sudden death. Dr. Eşkazan advises close monitoring of the QTc interval with serial ECG analysis and measurement of electrolytes for patients receiving any of these drugs in combination with a TKI.

Because TKIs are metabolized by CYP P450 enzymes, there is a substantial risk of drug-drug interactions with medications that inhibit or induce this pathway; for example, imatinib and chloroquine/hydroxychloroquine are simultaneously inhibitors and substrates of CYP2D6. Drug-drug interactions involving gastrointestinal absorption should also be considered. Dr. Eşkazan noted that checking the plasma levels of TKIs may have clinical valueboth in terms of efficacy and toxicity.

TKI treatment should not be discontinued or disrupted in a patient with CML that contracts COVID-19, the author emphasized. Instead, he concluded, “close monitoring with serial ECGs is necessary, together with prompt and timely dose modifications of these drugs, in patients with CML and COVID-19 disease.”

Disclosure: For full disclosures of the study authors, visit bpspubs.onlinelibrary.wiley.com.



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