EMA Issues Reminder Over Paxlovid Risks

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The agency’s safety committee stressed the risk of potential adverse reactions involved with taking Paxlovid (nirmatrelvir, ritonavir) in combination with certain immunosuppressants.

The European Medicines Agency (EMA) announced on Feb. 9, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) is reminding healthcare professionals that there is a risk of serious adverse events associated with the use of the COVID-19 treatment, Paxlovid (nirmatrelvir, ritonavir), in combination with calcineurin inhibitors and mechanistic target of rapamycin (mTOR) inhibitors, which are immunosuppressants that have a narrow safe dosage range. A drug–drug interaction may reduce the body’s ability to eliminate the medicines, according to EMA.

Calcineurin inhibitors (tacrolimus, ciclosporin) and mTOR inhibitors (everolimus, sirolimus) are used to treat autoimmune disorders or for preventing rejection of transplanted organs. CHMP warns that Paxlovid should only be given with these drugs if blood levels can be closely monitored. “Healthcare professionals need to consult with a multidisciplinary group of specialists to manage the complexity of taking these medicines together,” the agency stated in a press release.

“Paxlovid must not be given in combination with medicines for which elimination from the body is highly reliant on a set of liver enzymes (proteins), known as CYP3A, and that also have a narrow safe dosage range. This includes the immunosuppressant called voclosporin. Before starting the treatment with Paxlovid, healthcare professionals should carefully weigh the potential benefits of Paxlovid treatment against the risks of serious adverse reactions in case of administration together with immunosuppressants,” the agency stated in the release.


This warning comes after PRAC reviewed reports of adverse events that included deaths believed to be the result of drug-–drug interactions between the specific immunosuppressants and Paxlovid. Reports of blood levels rapidly increasing to toxic levels were found.

Source: EMA