Enteric-coated ddI Approved: FDA Letter

On October 31, 2000 the FDA approved a new once-daily formulation of ddI which is easier and less complicated to take, avoids certain drug interactions, and may reduce diarrhea or other gastrointestinal side effects. But the overall safety and efficacy of the drug remain about the same.

ddI (didanosine) is destroyed by acid in the stomach. So the original drug had to be taken with a powerful antacid to protect it -- which had other disadvantages, including causing diarrhea in some patients, and preventing absorption of certain other drugs which require an acid stomach to work properly. The new drug uses an enteric coating -- a substance which does not dissolve in the acid environment of the stomach but does dissolve in the alkaline environment of the small intestines, releasing the drug there. We do not know why it took many years to develop this improvement.

Here is a November 1, 2000 letter from the FDA describing the new formulation:

Yesterday, October 31, 2000, FDA approved a new formulation of the nucleoside reverse transcriptase inhibitor, ddI, called VIDEX EC.

VIDEX EC is an enteric-coated, once-daily formulation, which, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in adults whose management requires once-daily administration of didanosine or an alternative didanosine formulation.

In VIDEX EC, the active ingredient, didanosine, is protected against degradation by stomach acid by the use of an enteric coating on the beadlets in the capsule. The enteric coating dissolves when the beadlets empty into the small intestine, the site of drug absorption.

In earlier, buffered formulations of didanosine, administration with an antacid (buffer) provides protection from degradation by stomach acid.

The peak plasma concentration (CMAX) of didanosine, administered as VIDEX EC, is reduced approximately 40% relative to didanosine buffered tablets.

The time to the peak concentration (TMAX) increases from approximately 0.67 hours for didanosine buffered tablets to 2.0 hours for VIDEX EC.

The enteric-coated capsule was approved because of advantages related to not being buffered, since drug interactions with ciprofloxacin, ketoconazole and indinavir, that were caused by the buffer, are avoided.

Additionally, VIDEX EC can be swallowed without being chewed or dispersed in water.

The previous formulation (which is buffered) was approved last year for use in a once daily regimen.

The preferred didanosine regimen is twice daily with the older buffered formulation because there is more efficacy data with this regimen. There are limited data to date to support the long-term durability of response with a once-daily dosing regimen of didanosine.

The safety profile of the enteric coated and the buffered products are the same.

ISSN # 1052-4207

Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.

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