Posaconazole

Category: pharmacological

Aliases: Noxafil

Pharmacological Mechanism

Broad-spectrum triazole (mucormycosis coverage). Strong CYP3A4 inhibitor without significant CYP2C9/2C19 effect — narrower DDI profile than voriconazole. Delayed-release tablet improved absorption over the older suspension formulation.

Half-Life (t½)

PO: 35h, IV: 35h

Dosing Guidelines

PO: Typical 300 mg (Range: 100–400 mg)

Target Organ Systems

digestive

Interactions

Midazolam (major): CYP3A4 inhibition. Krishna 2009 (PMID:19302901) healthy volunteers, posaconazole 200/400 mg BID + oral and IV midazolam: AUCtf increased up to 4.6× (200 mg BID) and 6.2× (400 mg BID); Cmax 1.3×/2.4×. Ki ≈ 2/5.2 = 0.38 µM at 400 mg BID Cp_perp 2 µM. Strong CYP3A4 inhibitor (slightly weaker than ketoconazole).
Tacrolimus (major): CYP3A4 inhibition. Sansone-Parsons 2007 (PMID:17542765) open-label PK in healthy volunteers, single tacrolimus + posaconazole: tacrolimus Cmax +121%, AUC +358% (ratio 4.58). Ki ≈ 2/3.58 = 0.56 µM. Reduce tacrolimus dose substantially with TDM.
Sirolimus (contraindicated): CYP3A4 inhibition. Moton 2009 (PMID:19196220) n=12 healthy, single sirolimus ± posaconazole: sirolimus Cmax 6.7×, AUC 8.9×. Ki ≈ 2/7.9 = 0.25 µM. Coadministration generally not recommended per posaconazole label. Slug "rapamycin" in v8 catalog = sirolimus generic.

Pathways It Modulates

Fungal ergosterol biosynthesis (inhibitor) — fungal CYP51 (+ CYP3A4)

Chemical Identifiers

PubChem CID: 468595
Formula: C37H42F2N8O4
Molecular weight: 700.79 g/mol
InChIKey: RAGOYPUPXAKGKH-XAKZXMRKSA-N
SMILES: CC[C@@H]([C@H](C)O)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@H]5C[C@](OC5)(CN6C=NC=N6)C7=C(C=C(C=C7)F)F