Darunavir and cobicistat and Nirmatrelvir and ritonavir interaction
Darunavir and cobicistat and Nirmatrelvir and ritonavir: both prescribing labels 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 Darunavir and cobicistat (PREZCOBIX) label · effective 2026-02-01
Post-marketing cases of liver injury, including some fatalities, have also been reported with darunavir co-administered with ritonavir.
PREZCOBIX or PREZCOBIX PED is not recommended in combination with products containing the individual components of PREZCOBIX or PREZCOBIX PED (darunavir and cobicistat) or with ritonavir.
Hepatotoxicity During the darunavir clinical development program (N=3063), where darunavir was co-administered with ritonavir 100 mg once or twice daily, drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) was reported in 0.5% of participants.
When used with concomitant medications, PREZCOBIX or PREZCOBIX PED may result in different drug interactions than those observed or expected with darunavir co-administered with ritonavir.
Switching from darunavir co-administered with ritonavir to PREZCOBIX or PREZCOBIX PED in patients on bosentan : Maintain bosentan dose.
From the Nirmatrelvir and ritonavir (Paxlovid) label · effective 2026-02-19
• HIV-1 Drug Resistance: PAXLOVID use may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
Risk of HIV-1 Resistance Development Because nirmatrelvir is co-administered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection [see Contraindications (4) and Drug Interactions (7) ] .
Monitor for increased PAXLOVID or protease inhibitor adverse events .
Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated.
Potential for PAXLOVID to Affect Other Drugs PAXLOVID (nirmatrelvir co-packaged with ritonavir) is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp and OATP1B1.
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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.