Posaconazole (PO)

Criteria & Principles

Posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy (i.e. AML patients).  

Refer to prophylaxis guidelines and educational documents below for more information:

DUH Adult Hematologic Malignancy Anti-Infective Prophylaxis Guideline for High Risk Patients,

Duke Adult Stem Cell Transplant Infection Prophylaxis Guidelines, OR

DUH Adult Lung and Heart Transplant Antifungal Prophylaxis Guidelines (Policy Center #6685)

DUH Broad Spectrum Anti-Infective Prophylaxis Guidelines for High Risk Pediatric Hematology-Oncology Patients

Spectrum of activity

Antifungal Therapeutic Drug Monitoring

Usual Dose & Administration

Posaconazole DR tablets

300 mg PO BID on day 1, THEN

300 mg PO daily

Adjustment of Dose & Administration

Indication-Specific Adjustment

Dosing: dependent on formulation and indication

1. Prophylaxis of invasive fungal infections (>=13 years of age)
   • Delayed-release tablet: 300 mg PO q12h on day 1, then 300 mg PO q24h  **preferred product d/t better absorption & cost**
   • Oral suspension: 200 mg PO q8h
   • Intravenous: 300 mg IV q12h on day 1, then 300 mg IV q24h
2. Serious systemic mycoses, empiric doses (>=13 years of age)
   • Delayed-release tablet: 300 mg PO q12h on day 1, then 300 mg PO q24h
   • Oral suspension: 200 mg PO q6h
   • Intravenous: 300 mg IV q12h on day 1, then 300 mg IV q24h

Serum Concentration Monitoring

• For patients with invasive disease, monitoring is recommended
• When being used for prophylaxis, monitoring is recommended for HSCT, HOA, and lung transplant patients
• Target Concentration (prophylaxis): Trough > 0.7 mcg/mL
• Target Concentration (treatment): > 1 mcg/mL (may consider > 1.25 mcg/mL in select clinical cases)

Protocol for serum monitoring

• Trough should be drawn immediately prior to a dose on day 5-7 of therapy

Note:

• Limited data to support target concentrations for treatment
• High intrasubject PK variability
• See the attached PDF for a literature summary describing available data crushing posaconazole DR tablets for via tube administration.

Drug-Specific Information

Oral suspension bioavailability - because of poor oral absorption, each dose of posaconazole oral suspension should be administered with a full meal, liquid nutritional supplement, or acidic, carbonated beverage

Delayed release tablet - each dose of posaconazole should be administered with food if possible

General Notes

1. Up-to-date cost information, click here 
2. IV antimicrobials outpatient (OPAT) dosing, click here
3. Obesity dosing weight recommendations here
4. Helpful drug-drug interaction check website here 
5. When dosing guidance is provided it is important to note the following:

Fixed (ie non weight-based) doses in adults are historically based on a 70 kg patient. Specific disease states or individual patients may warrant dosages that differ from the above recommendations. Since product-specific criteria for dose adjustment based on creatinine clearance exist, consult product information regarding specific recommendations for dosage adjustment based on estimated creatinine clearance.