WHO reported serious adverse drug reactions from COVID-19
The World Health Organization, citing the Ministry of Health of Canada, reported the risk of serious adverse events of the antiviral drug nirmatrelvir and ritonavir when taken with immunosuppressants. The drug is approved for the treatment of mild to moderate cases of COVID-19.WHO reported a change by Health Canada to the Paxlovid instructions. The antiviral drug with the active ingredients nirmatrelvir and ritonavir now includes information about the risk of interaction with tacrolimus and other immunosuppressants: cyclosporine, everolimus, sirolimus. Such interactions may result in serious adverse events, including acute kidney injury and severe infections due to excessive immunosuppression.
The information is available in the WHO Pharmaceutical Newsletter, which is published by the WHO.
Paxlovid is a cytochrome (CYP)3A inhibitor and may increase the concentration of drugs metabolized primarily with the enzyme. These drugs include tacrolimus and other immunosuppressants. In addition, tacrolimus has a narrow therapeutic corridor, and an increase in its plasma concentration due to interaction with Paxlovid can lead to serious life-threatening adverse reactions.
Health Canada has received reports describing cases of drug interactions and the development of serious adverse events. In some of these cases, there was a rapid increase in blood levels of tacrolimus to very high levels. The regulator also reports similar cases in other countries described in the literature.
It is recommended to avoid taking nirmatrelvir and ritonavir when monitoring of immunosuppressant concentrations is not available. In case of concomitant administration, dose adjustment, monitoring of immunosuppressant concentrations and adverse reactions are recommended.
The combination antiviral drug nirmatrelvir and ritonavir is approved for the treatment of mild to moderate cases of COVID-19 with risk of disease progression.
According to GRLS data, four nirmatrelvir preparations are registered in Russia. These are Skyvira, Mirobivir, Nirmatrelvir PSC and Arpaxel. They contain an indication on the prohibition of taking together with certain analgesics, antibiotics, statins, FDE5 inhibitors, sedatives and neuroleptics, agents containing St. John's wort.