The Pharmacy and Therapeutics Committee voted to add posaconazole to the inpatient formulary with Antimicrobial Restrictions, effective April 27, 2007. In order to make this medication available as a formulary agent for the general medical staff and to ensure appropriate usage, the Pharmacy and Therapeutics Committee has approved the following requirements for posaconazole use:

1. Any use will require review and approval by the Infectious Disease (ID) Service or the Hematology/Oncology Service. The ordering physician is responsible for contacting the ID or Hem/Onc service. The drug will be started with a 24-hour stop date unless approval for continued use is obtained; therefore, the approval must be received within 24 hours of the original order.
   1. If use is approved, the ID or Hem/Onc service will relay this information to the ordering physician as well as to the pharmacy for continued administration of posaconazole. If posaconazole is thought to be inappropriate, the ID or Hem/Onc service will provide alternative recommendations and communicate these recommendations to the physician originating the posaconazole order.

If you have any questions regarding this policy, please direct them to the Antimicrobial Stewardship Program (ASP) by contacting Elizabeth D. Hermsen, Pharm.D., M.B.A., BCPS-ID via email at ehermsen@nebraskamed.com or telephone at 402-559-4287.

Posaconazole Review

Posaconazole is a triazole antifungal agent that inhibits the enzyme lanosterol 14α-demethylase. This enzyme is needed for the synthesis of ergosterol, a key fungal cell membrane component.

Posaconazole has a mean half-life of approximately 35 hours. Posaconazole should be administered with food (preferable high fat) or a nutritional supplement to assure adequate plasma concentrations. Posaconazole is highly protein bound (>98%) and predominantly eliminated in the feces (71%).

Posaconazole is indicated for patients 13 years of age and older who are at risk of developing invasive Aspergillus and Candida infections due to being severely immunocompromised. The recommended dose for posaconazole is 200 mg (5mL) three times a day. Posaconazole is also approved for treatment of oropharyngeal candidiasis at a dose of 100 mg once daily after an initial load of 100 mg twice daily for the first day.

The most commonly reported adverse events with posaconazole include nausea, diarrhea, vomiting, and abdominal pain. Serious adverse events include hepatotoxicity, prolonged QTc interval, and seizures. Patients receiving posaconazole should have baseline liver function tests done before and during the course of therapy.

Similar to other drugs in its class, a number of drug-drug interactions exist with posaconazole. The potential for drug-drug interactions should be assessed prior to administration of posaconazole.