Tacrolimus (major): CYP3A4 inhibition. Vanhove 2019 (PMID:31152598): voriconazole at steady state raised IR-tacrolimus AUC 6.02× (Cmax 2.7×) and PR-tacrolimus AUC 2.62× (Cmax 2.02×) in healthy volunteer crossover. Reduce tacrolimus dose ~66% empirically and follow trough levels.
Cyclosporine (major): CYP3A4 inhibition. Romero 2002 (PMID:11956505) n=7 stable kidney transplant on CsA 150-375 mg/d, voriconazole 200 mg q12h × 7.5d randomized double-blind crossover: CsA AUCτ ratio 1.7× (90% CI 1.47-1.96). Ki ≈ 8/0.7 = 11.4 µM. Halve CsA dose on voriconazole initiation.
Midazolam (major): CYP3A4 inhibition (gut + liver). Saari 2006 (PMID:16580904) n=10 healthy crossover: voriconazole raises oral midazolam Cmax 3.8×, AUC 10.3×; IV CL −72%; oral F 31%→84%. Ki ≈ 8/9.3 = 0.86 µM. Avoid oral midazolam or use markedly reduced doses.
Alfentanil (major): CYP3A4 inhibition. Saari 2006 (PMID:17112806) verbatim: "Voriconazole decreased the mean plasma clearance of intravenous alfentanil by 85% ... The area under the alfentanil plasma concentration-time curve was increased by 6-fold by voriconazole (P<.001)". 12 healthy, randomized 3-phase crossover, oral vori (400 mg bid d1, 200 mg bid d2) + 20 µg/kg IV alfentanil. t½ 1.5 → 6.6 h. Ki ≈ 5/5 = 1.0 µM. Profound respiratory depression risk.
Omeprazole (warn): CYP2C19 inhibition (label-only DDI, no indexed primary PMID). Vfend label Section 7 verbatim: "Cmax and AUCτ of omeprazole an average of 2 times (90% CI: 1.8, 2.6) and 4 times (90% CI: 3.3, 4.4), respectively" with vori 200 mg q12h × 6d + omep 40 mg/d × 7d. AUC 4×; label recommends halving omep dose ≥40 mg when starting vori.
Sirolimus (contraindicated): CYP3A4 inhibition (label-only DDI, no indexed primary PMID). Vfend label Section 7 verbatim: "increased the Cmax and AUC of sirolimus (2 mg single dose) an average of 7-fold (90% CI: 5.7, 7.5) and 11-fold (90% CI: 9.9, 12.6), respectively, in healthy male subjects". Vori 200 mg q12h × 8d + 2 mg sirolimus single dose. Label CONTRAINDICATED — sirolimus toxicity risk.