Methotrexate and Nirmatrelvir and ritonavir interaction
Methotrexate and Nirmatrelvir and ritonavir: the Nirmatrelvir and ritonavir prescribing label flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Nirmatrelvir and ritonavir (Paxlovid) label · effective 2026-02-19
…methylergonovine • HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use [see Table 2 , Drug Interactions (7.3) ] ) • Immunosuppressants: voclosporin • Microsomal triglyceride transfer protein inhibitor: lomitapide • Migraine medications: eletriptan, ubrogepant • Mineralocorticoid receptor antagonists:…
Immunosuppressants voclosporin ↑ voclosporin Co-administration contraindicated due to potential for acute and/or chronic nephrotoxicity [see Contraindications (4) ] .
Immunosuppressants calcineurin inhibitors: cyclosporine, tacrolimus ↑ cyclosporine ↑ tacrolimus Avoid concomitant use of calcineurin inhibitors with PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible.
If co-administered, dose adjustment of the immunosuppressant and close and regular monitoring for immunosuppressant concentrations and adverse reactions are recommended during and after treatment with PAXLOVID.
Refer to the individual immunosuppressant prescribing information and latest guidelines for further information.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.