FDA Warns About Posaconazole Prescribing Errors

January 04, 2016

Clinicians cannot substitute two different oral formulations of the antifungal posaconazole (Noxafil, Merck) for each other on a milligram per milligram basis lest patients experience adverse events, including death, the US Food and Drug Administration (FDA) warned today.

The two oral formulations are dosed differently, with the delayed-release tablet having a higher bioavailability than its oral suspension counterpart. Direct milligram to milligram substitution can result in underdoses or overdoses, the agency said in a safety communication.

The FDA has revised the labels of the two posaconazole formulations to highlight this potential problem. It said that prescribers should specify the dosage form, strength, and frequency on all scripts for posaconazole, and that pharmacists should request this information when it is not specified.

The agency approved the oral suspension version of the antifungal in 2006 and the delayed-release tablet in November 2013. Both are indicated to prevent invasive infections caused by the fungi Aspergillus and Candida in patients aged 13 years and older with weakened immune systems. The oral suspension version also is approved to treat thrush, a fungal infection of the mouth or throat caused by Candida.

Since the approval of the delayed-release tablet in November 2013, the agency has received 11 reports of the wrong oral formulation being prescribed or dispensed. In the most serious case, a patient was taking the tablet to prevent invasive Aspergillus and Candida infections, but died of a stroke related to an Aspergillus infection after a pharmacist substituted the oral suspension at the same dose and frequency without realizing that it amounted to an underdose.

In the 10 other cases, posaconazole levels were too high because patients switched from the oral suspension to the tablet without an adjustment to dose and frequency. "For example, one patient received two 100 mg delayed-released tablets taken three times per day, which is twice the recommended Noxafil dose of three 100 mg delayed-release tablets taken once per day for prophylaxis of invasive Aspergillus and Candida infections," the FDA said.

Some of these overtreated patients experienced vomiting and nausea. One such patient, presenting at the hospital, was diagnosed with a low serum potassium level.

More information about today's announcement is available on the FDA website.

To report any problems with posaconazole, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at https://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.


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