Agency strikes another blow for malaria agents’s use against Covid-19

WASHINGTON — Hydroxychloroquine and chloroquine were dealt a one-two punch by the FDA, when on the same day, not only did the agency retract its emergency use authorization (EUA) for the two drugs as treatments for Covid-19, it also warned of drug-drug interactions when paired with remdesivir.

The agency noted that the drugs may reduce the antiviral activity of remdesivir and updated its fact sheet for health care providers. Under section 5.3, the FDA states:

“Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.”

Under section 10:

“Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans. Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine phosphate or hydroxychloroquine sulfate is not recommended.”

And under Section 15:

“Remdesivir exhibited cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary human airway epithelial (HAE) cells with a 50% effective concentration (EC50) of 9.9 nM after 48 hours of treatment. The EC50 values of remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 nM at 48 hours post-treatment. The antiviral activity of remdesivir was antagonized by chloroquine phosphate in a dose-dependent manner when the two drugs were co-incubated at clinically relevant concentrations in HEp-2 cells infected with respiratory syncytial virus (RSV). Higher remdesivir EC50 values were observed with increasing concentrations of chloroquine phosphate. Increasing concentrations of chloroquine phosphate reduced formation of remdesivir triphosphate in normal human bronchial epithelial cells.” [Emphasis added]

“Over the course of this unprecedented pandemic, the FDA has issued emergency use authorizations for a variety of medical products after evaluating the available scientific evidence and carefully balancing any known or potential risks against the benefits of making these products available during the current public health emergency. We understand that, as we learn more about these products, changes may be necessary based on new data — such as today’s updates for health care providers about a potential drug interaction and other important information about using remdesivir to treat Covid-19 patients,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research. “As we have done throughout the pandemic, the FDA continues to evaluate all of the emergency use authorizations issued and their related materials and will continue to make changes as appropriate based on emerging science and data.”

Remdesivir was granted EUA in May for use in the U.S. “to be administered intravenously by health care providers, as appropriate, to treat suspected or laboratory-confirmed Covid-19 in adults and pediatric patients hospitalized with severe disease.”

Candace Hoffmann, Managing Editor, BreakingMED™

Cat ID: 190

Topic ID: 79,190,254,930,570,574,190,926,192,927,151,928,925,934