Clinical Information

Posaconazole interferes with fungal cytochrome P450 (CYP) lanosterol-14 alpha demethylase activity, thereby decreasing synthesis of ergosterol, the principal sterol in fungal cell membrane, and inhibiting fungal cell membrane formation.(1,2)

Posaconazole has been approved for prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients (eg, hematopoietic stem cell transplant recipients with graft-versus-host disease [GVHD] or those with prolonged neutropenia secondary to chemotherapy for hematologic malignancies) and treatment of oropharyngeal candidiasis (including patients refractory to itraconazole or fluconazole).(1,3) It also is approved for ocular administration (drug monitoring not required for this use).

Posaconazole has a variable absorption. Food and liquid nutritional supplements increase absorption, and fasting states do not provide sufficient absorption to ensure adequate plasma concentrations.(4,5) The drug has a high volume of distribution (Vd=465-1774 L) and is highly protein bound (≥97%), predominantly to albumin.(1,3) The drug does not undergo significant metabolism; approximately 15% to 17% undergoes non-CYP-mediated metabolism, primarily via hepatic glucuronidation into metabolites.(1) The half-life elimination is approximately 35 hours (range: 20-66 hours); steady state is achieved after about 5 to 7 days. Time to maximum concentration is approximately 3 to 5 hours, but due to the highly variable absorption, trough level monitoring is recommended.

Therapeutic drug monitoring should be considered in the following situations:

-To document optimal absorption when used for prophylaxis or active treatment of a fungal infection

Consider rechecking a level even if initial level was in the goal range if the patient:

-Is unable to meet optimal nutritional intake

-Is receiving continuous tube feeding

-Is receiving a proton pump inhibitor (decreased posaconazole levels in some studies)

-Has mucositis, diarrhea, vomiting, GVHD, or other reason that the drug may not be absorbed well