We are now seeing more and more generics for “extended-release” drugs, i.e., diltiazem XT, metformin ER, and others. Can we rely on these to be pharmacokinetically equivalent to the original brand-name products?
—Lawrence M. Markman, MD, Wilmington, Del.
The FDA rates a multisource drug product’s bioequivalence as “A” or “B.” “A”-rated drugs have demonstrated bioequivalence in human bioavailability studies (known as “AB”-rated) or are considered unlikely to have bioavailability problems (known as “AA”-rated).
“B”-rated drugs have not demonstrated bioequivalence in human testing. The second letter of the “B” rating describes the reason for the “B.” For example, “BC” is assigned to extended-release products for which bioequivalence data have not been submitted; “BX” is assigned to products with insufficient data to determine bioequivalence.
The active ingredients in delayed-release dosage forms are subject to significant differences in absorption and represent a potential bioequivalence problem. In the absence of any in vivo studies that demonstrate bioequivalence, these products are rated by the FDA as “BE.” If in vivo studies have demonstrated bioequivalence of specific delayed-release products (i.e., those made by an individual manufacturer), those products are rated “AB.”
An extended-release dosage form—to be distinguished from the delayed-release form—is one that allows at least a twofold reduction in dosing frequency as compared with the conventional or prompt-releasing dosage form. These drug products are also subject to significant differences in absorption. Unless otherwise noted, they are considered to present potential bioequivalence problems and are rated “BE.” If adequate in vivo studies have demonstrated the bioequivalence of specific extended-release products, those products would then be “AB”-rated.
Individual products that demonstrate bioequivalence through appropriate bioavailability studies and have therefore been rated “AB” may be safely substituted for a brand-name product.
The ratings are listed in the FDA Center for Drug Evaluation and Research Approved Drug Products with Therapeutic Equivalence Evaluations (known as “the list” or the “Orange Book”). The publication, which presents an explanation of the rating system and the bioequivalence rating of various drugs, is available online (. Accessed March 12, 2008).
—Lorraine A. Cicero, MS, PharmD, associate professor of pharmacy practice, Long Island University, Brooklyn, N.Y. (114-14)