|Values are valid only on day of printing.|
Posaconazole interferes with fungal cytochrome P450 (CYP) (lanosterol-14 alpha demethylase) activity, decreasing synthesis of ergosterol, the principal sterol in fungal cell membrane, and inhibiting fungal cell membrane formation.(1,3)
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 and/or fluconazole).(1,2) 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=465-1,774 L) and is highly protein bound (> or =97%), predominantly bound to albumin.(1,2) 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 he/she may not absorb the drug well
Monitoring of posaconazole therapy
Greater than 700 ng/mL (>0.7 mcg/mL) has been suggested for prophylaxis and also in a salvage trial for treatment of invasive Aspergillus infections.
No significant cautionary statements
>700 ng/mL (trough)
1. Package insert: Noxafil (posaconazole), Schering Corporation, Kenilworth, NJ, 2006
2. Physicians' Desk Reference (PDR). 61st edition. Montvale, NJ Thomson PDR, 2007
3. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 10th edition. New York, McGraw-Hill Professional, 2001
4. Courtney R, Wexler D, Radwanski E, et al: Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol 2004;57:218-222
5. Courtney R, Radwanski E, Lim J, Laughlin M: Pharmacokinetics of posaconazole coadministered with antacid in fasting or nonfasting healthy men. Antimicrob Agents Chemother 2004;48(3):804-808