Paxlovid (nirmatrelvir; ritonavir): reminder of life-threatening and fatal drug-drug interactions with certain immunosuppressants, including tacrolimus.

Summary

• Co-administration of Paxlovid with certain immunosuppressants with narrow therapeutic index such as calcineurin inhibitors (ciclosporin, tacrolimus) and mTOR inhibitors (everolimus, sirolimus) can result in life-threatening and fatal reactions due to pharmacokinetic interactions.
• Due to the risk of serious interactions, co-administration with these immunosuppressants should only be considered if close and regular monitoring of immunosuppressant serum concentrations is possible. 
• Monitoring should be performed not only during co-administration with Paxlovid but also after treatment.
• Paxlovid is contraindicated in patients using medicines with highly CYP3A dependent clearance and for which elevated plasma concentrations can lead to serious and/or life-threatening reactions, including the calcineurin inhibitor voclosporin. 
• Consultation with a multidisciplinary group of specialists is required to manage the complexity of co-administration.
• The potential benefit of treatment with Paxlovid should be carefully weighed against the serious risks if the drug-drug interactions are not appropriately managed.