Interaction entre Nirmatrelvir et ritonavir et Rifabutine

…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.

Alternate antimycobacterial drugs such as rifabutin should be considered [see Contraindications (4) ] .

Fosamprenavir/ritonavir 700 mg twice a day plus ritonavir 100 mg twice a day for 2 weeks 150 mg every other day for 2 weeks Healthy subjects (15) ↔ AUC compared to rifabutin 300 mg once a day alone ↓ C max by 15% ↑ AUC by 35% compared to historical control (fosamprenavir/ritonavir 700/100 mg twice a day) , ↑ C max by 36%, ↑ C min by 36% Reduce rifabutin dose…

Lopinavir/ ritonavir 400/100 mg twice a day for 20 days 150 mg once a day for 10 days Healthy subjects (14) ↑ AUC by 203% also taking zidovudine 500 mg once a day ↓ C max by 112% ↔ Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination.

Saquinavir/ritonavir 1000/100 mg twice a day for 14 or 22 days 150 mg every 3 days for 14 or 22 days Healthy subjects ↑ AUC by 53% compared to rifabutin 150 mg once a day alone ↑ C max by 88% (n=11) ↓ AUC by 13%, ↓ C max by 15%, (n=19) Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with saquinavir/ritonavir…

Ritonavir 500 mg twice a day for 10 days 150 mg once a day for 16 days Healthy subjects (5) ↑ AUC by 300%, ↑ C max by 150% ND Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination.

Tipranavir/ritonavir 500/200 twice a day for 15 doses 150 mg single dose Healthy subjects (20) ↑ AUC by 190%, ↑ C max by 70% ↔ Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with tipranavir/ritonavir combination.