[Posted 01/04/2016]

AUDIENCE: Internal Medicine, Infectious Disease

ISSUE: The FDA is cautioning that differences in dosing regimens between the two oral formulations of the antifungal Noxafil (posaconazole) have resulted in dosing errors.  To help prevent additional medication errors, the drug labels were revised to indicate that the two oral formulations cannot be directly substituted for each other but require a change in dose.  Direct mg for mg substitution of the two formulations can result in drug levels that are lower or higher than needed to effectively treat certain fungal infections. 

Since the approval of Noxafil delayed-release tablets in November 2013, FDA received eleven reports of the wrong oral formulations being prescribed and/or dispensed to patients.  One case resulted in death, and an additional case resulted in hospitalization.  According to the reports, these outcomes were a result of health care professionals not knowing that the two oral formulations cannot be substituted for each other without adjusting the dose due to differences in how the medicine is absorbed and handled by the body. 

In addition to changes to the outer carton of Noxafil (see Photos in Drug Safety Communication), its manufacturer Merck revised the prescribing information and the patient information in the drug label to alert patients and their health care professionals that the two oral formulations of Noxafil cannot be substituted for each other.    

BACKGROUND: Noxafil is approved in two oral formulations: an oral suspension and a delayed-release tablet.  It is also approved as an intravenous solution for injection.  Noxafil is used to help prevent certain invasive fungal infections caused by fungi called Aspergillus and Candida.  Noxafil is used in patients who have an increased chance of getting these infections due to weakened immune systems.  Noxafil oral suspension is also used to treat a fungal infection called thrush caused by Candida in the mouth or throat area. 

RECOMMENDATION: Prescribers should specify the dosage form, strength, and frequency on all prescriptions they write for Noxafil.  Pharmacists should request clarification from prescribers when the dosage form, strength, or frequency is not specified. Patients should talk to their health care professional before they switch from one oral formulation to the other. For additional information for health care professionals, patients and caregivers, refer to the Drug Safety Communication.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[01/04/2016 - Drug Safety Communication - FDA]