This review is intended primarily for healthcare professionals. It provides a brief summary of key medicinal product safety information published in March 2023 by the Ministry of Health of Canada (Health Canada). The published information is not exhaustive.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, as well as what is known about the use of medicinal products both in Canada and abroad.
New safety information on the medicinal product
Drug interaction between the medicinal product Paxlovid (Paxlovid®) and medicinal products containing tacrolimus
Key messages for healthcare professionals:
- It is recommended to avoid the use of Paxlovid® in patients taking immunosuppressants if careful monitoring of immunosuppressant concentrations is not possible.
- With concomitant use, dose adjustment of the immunosuppressant and monitoring of immunosuppressant concentrations and of adverse reactions associated with immunosuppressants are recommended.
- For additional information, review the instructions for medical use of the medicinal product Paxlovid® and of the individual immunosuppressant, and also consult a specialist in immunosuppressant therapy.
- Before and during therapy with Paxlovid®, the potential risk of interactions with other medicinal products should be taken into account; the use of concomitant medicinal products during therapy with Paxlovid® should be reviewed, and adverse reactions associated with taking concomitant medicinal products should be monitored.
Paxlovid (Paxlovid®) (nirmatrelvir and ritonavir) is a combination oral antiviral medicinal product. Paxlovid (Paxlovid®) is indicated for the treatment of mild to moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk of progression to severe COVID-19, including hospitalization or death.
Paxlovid (Paxlovid®) is an inhibitor of cytochrome P450 (CYP) 3A and may increase the plasma concentrations of medicinal products that are primarily metabolized by CYP3A.
Tacrolimus (tacrolimus) is an immunosuppressant used to treat or prevent transplant rejection and to treat rheumatoid arthritis. Tacrolimus (tacrolimus) is metabolized by CYP3A. It also has a narrow therapeutic index, which means that small differences in dose or blood concentration can lead to serious adverse reactions that may be life-threatening.
Health Canada has received reports of cases of serious adverse reactions of drug interaction between Paxlovid® and tacrolimus in Canada. In some cases, a rapid increase in tacrolimus levels to very high values was observed. High tacrolimus levels can lead to adverse effects such as acute kidney injury and increased susceptibility to severe infections due to excessive immunosuppression. International cases have also been reported in the literature.
The section “Interactions with other medicinal products and other forms of interaction” of the Canadian instructions for medical use of the medicinal product Paxlovid® has been updated with information on the risk of drug interactions with immunosuppressants [including cyclosporine, everolimus, sirolimus, and tacrolimus]. Health Canada will continue to monitor the safety of Paxlovid® and will take appropriate action if new health risks are identified.
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