atazanavir + ritonavir + voriconazole

"atazanavir + ritonavir + voriconazole" is a **combination of three small molecule drugs** used in specific clinical scenarios but **not commercially available as a single co-formulation**. This combination consists of: - **atazanavir**: an HIV-1 protease inhibitor, primarily used in antiretroviral therapy for HIV. - **ritonavir**: a protease inhibitor used mainly as a pharmacokinetic booster to increase atazanavir plasma concentrations by inhibiting CYP3A4. - **voriconazole**: a triazole antifungal that inhibits fungal cytochrome P450-dependent ergosterol synthesis, primarily metabolized by CYP2C19. Mechanistically, **atazanavir blocks HIV protease**, preventing viral polyprotein processing. **Ritonavir inhibits CYP3A4**, thus slowing atazanavir metabolism and boosting its levels. **Voriconazole blocks fungal ergosterol synthesis**. There is a significant drug-drug interaction: **atazanavir/ritonavir affects voriconazole exposure in a manner dependent on CYP2C19 genotype**. In CYP2C19 extensive metabolizers (EM), ritonavir induces CYP2C19 and decreases voriconazole exposure. In CYP2C19 poor metabolizers (PM), atazanavir/ritonavir inhibits CYP3A4, dramatically raising voriconazole levels. Co-administration is generally **not recommended unless benefit-risk assessment supports use**, due to risk of subtherapeutic or toxic voriconazole levels and decreased atazanavir exposure[1][2][4].