Short-term pregnancy outcomes and drug interactions after simultaneous exposure to Nematavir/Ritonavir (Paxlovid) and immunosuppressants in pregnant women

Abstract Background In the context of the coronavirus disease 2019 (COVID-19) pandemic, pregnant women, especially those who have been receiving long-term immunosuppressive therapy, are considered at high risk for developing severe COVID-19. However, there are limited available data regarding the safety of Paxlovid for the treatment of novel coronavirus infection during pregnancy. Moreover, it should be noted that the ritonavir component of paxlovid acts as a potent cytochrome P4503A (CYP3A) inhibitor that can significantly increase the blood concentrations of various drugs metabolized by paxlovid. When combined with immunosuppressive agents, this interaction may lead to drug toxicity and other adverse reactions. This article presents three cases illustrating short-term pregnancy outcomes and drug interactions resulting from simultaneous exposure to both paxlovid and immunosuppressive agents. Methods Through an initial series of reports on three pregnant women concurrently exposed to paxlovid and immunosuppressive drugs, such as cyclosporine and tacrolimus, we conducted an analysis of short-term delivery outcomes and discussed potential interactions between paxlovid and immunosuppressive drugs. By integrating pharmacogenomics and therapeutic drug concentration monitoring, this study facilitates the formulation, adjustment, and monitoring of drug therapy while also providing a comprehensive review of the literature. Results After simultaneous exposure to paxlovid and immunosuppressive agents during pregnancy, the short-term pregnancy and neonatal outcomes of the two pregnant women were favourable, consistent with the majority of studies. Unfortunately, one pregnant woman delivered a preterm infant at 26⁺ gestational weeks (GW), resulting in adverse outcomes unrelated to the administration of paxlovid. Furthermore, the use of paxlovid in pregnant women significantly inhibited the metabolism of cyclosporine and tacrolimus, leading to increased drug exposure and potential side effects. This interaction is associated with genetic polymorphisms, such as those in the CYP3A5*3, CYP3A4*18B, and ABCB1 genes, and with a unique physiological state during pregnancy. Conclusions Pregnant women who concurrently use paxlovid, cyclosporine, and tacrolimus should promptly adjust the drug dosage to mitigate potential drug toxicity. Given the distinctive physiological conditions during pregnancy, it is advisable to incorporate genetic testing into pharmacokinetics and therapeutic drug monitoring. The integration of these two strategies constitutes a pivotal approach to achieving precision medicine for pregnant women.