Monitoring posaconazole therapy
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Noxafil (Posaconazole)
Posaconazole (Noxafil)
Serum Red
Collection Container/Tube: Red top (serum gel/SST are not acceptable)
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL
Collection Instructions: Centrifuge and aliquot serum into plastic vial within 2 hours of collection.
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
0.6 mL
Gross hemolysis | OK |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum Red | Refrigerated (preferred) | 28 days | |
Ambient | 28 days | ||
Frozen | 28 days |
Monitoring posaconazole therapy
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 (> or =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
>700 ng/mL (trough)
Levels greater than 700 ng/mL (0.7 mcg/mL) have been suggested for prophylaxis.
Levels greater than or equal to 1250 ng/mL (1.25 mcg/mL) were shown to be optimal in a salvage trial for treatment of invasive Aspergillus infections.
Toxic range has not been established.
No significant cautionary statements
1. Noxafil (posaconazole). Package insert: Schering Corporation; 2006
2. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 10th ed. McGraw-Hill Professional; 2001
3. Physicians' Desk Reference (PDR). 61st ed. Thomson PDR; 2007
4. Courtney R, Wexler D, Radwanski E, Lim J, Laughlin M: Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol. 2004 Feb;57(2):218-222. doi: 10.1046/j.1365-2125.2003.01977.x
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 Mar;48(3):804-808. doi: 10.1128/AAC.48.3.804-808.2004
6. Rifai N, Horvath AR, Wittwer CT, eds: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018
Posaconazole is extracted by mixing serum samples with acetonitrile to precipitate proteins. The supernatant is removed and analyzed by a liquid chromatography-tandem mass spectrometry method.(Unpublished Mayo method)
Monday through Saturday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
80187
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
POSA | Posaconazole, S | 53731-6 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
89591 | Posaconazole, S | 53731-6 |