Efavirenz and Nirmatrelvir and ritonavir interaction
Efavirenz 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 Nirmatrelvir and ritonavir (Paxlovid) label · effective 2026-02-19
…contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.
…Sedative/hypnotics: triazolam, oral midazolam • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin • Vasopressin receptor antagonists: tolvaptan ➢ Drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.
PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer [see Drug Interactions (7.3) ] : • Anticancer drugs: apalutamide, enzalutamide • Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin • Antimycobacterials: rifampin, rifapentine • Cystic…
• Co-administration with potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.
Medications that induce CYP3A may decrease concentrations of PAXLOVID.
From the Efavirenz label · effective 2024-03-31
Protease inhibitor: Lopinavir/ritonavir ↓ lopinavir * Lopinavir/ritonavir once daily dosing is not recommended when coadministered with efavirenz.
No change in the ritonavir dose is required when efavirenz is administered with fosamprenavir plus ritonavir twice daily.
Protease inhibitor: Atazanavir ↓ atazanavir * Treatment-naive patients: When coadministered with efavirenz, the recommended dose of atazanavir is 400 mg with ritonavir 100 mg (together once daily with food) and efavirenz 600 mg (once daily on an empty stomach, preferably at bedtime).
The dose of lopinavir/ritonavir must be increased when coadministered with efavirenz.
See the lopinavir/ritonavir prescribing information for dose adjustments of lopinavir/ritonavir when coadministered with efavirenz in adult and pediatric patients.
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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.