Nirmatrelvir and ritonavir and Sirolimus interaction

Nirmatrelvir and ritonavir and Sirolimus: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

Obtain expert consultation to appropriately manage the complexity of this co-administration [see Warnings and Precautions (5.1) ] . mTOR inhibitors: everolimus, sirolimus ↑ everolimus ↑ sirolimus Avoid concomitant use of everolimus and sirolimus and PAXLOVID.

Drug interactionsnames SirolimusView label on DailyMed
Major

…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:…

Contraindicationsby drug classView label on DailyMed
Major

Immunosuppressants voclosporin ↑ voclosporin Co-administration contraindicated due to potential for acute and/or chronic nephrotoxicity [see Contraindications (4) ] .

Drug interactionsby drug classView label on DailyMed
Major

Immunosuppressants calcineurin inhibitors: cyclosporine, tacrolimus ↑ cyclosporine ↑ tacrolimus Avoid concomitant use of calcineurin inhibitors with PAXLOVID when close monitoring of immunosuppressant concentrations is not feasible.

Drug interactionsby drug classView label on DailyMed
Moderate

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.

Drug interactionsby drug classView label on DailyMed

From the Sirolimus label · effective 2026-03-26

Major

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ].

Warnings and precautionsby drug classView label on DailyMed
Major

• Avoid concomitant use with strong CYP3A4/P-gp inducers or strong CYP3A4/P-gp inhibitors that decrease or increase sirolimus concentrations ( 7.4 , 12.3 ).

Drug interactionsby drug classView label on DailyMed
Major

Strong Inducers and Strong Inhibitors of CYP3A4 and P-gp Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors (e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) of CYP3A4 and P-gp.

Drug interactionsby drug classView label on DailyMed
Moderate

…concentrations: Bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, letermovir, protease inhibitors (e.g., HIV and hepatitis C that include drugs such as ritonavir, indinavir, boceprevir, and telaprevir), metoclopramide, nicardipine, troleandomycin, verapamil • Drugs and other agents that could decrease sirolimus concentrations: Carbamazepine,…

Drug interactionsnames Nirmatrelvir and ritonavirView label on DailyMed
Moderate

Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.

Drug interactionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

Not 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.