FDA backs NTIs, again

For the second time in nine months, the U.S. Food and Drug Administration has defended publicly its approval process for, and the use of, generic substitutions for narrow therapeutic index (NTI) drugs.

In what's become a public relations and lobbying effort fought state by state, the debate's ground zero is warfarin, pitting DuPont Merck's Coumadin against Barr Labs' generic equivalent. With state legislatures increasingly putting up roadblocks for NTI generics, the FDA last April supported their safety and potency in a letter to the National Association of Boards of Pharmacy, only to repeat the process this year to individual state pharmacy boards.

Still, North Carolina, Texas, and Virginia lawmakers have passed legislation making it mandatory for pharmacists to get physician and patient approval before making a switch, while legislators in Alabama, Indiana, Nebraska, New Jersey, New York, and Missouri have introduced similar bills. Along with warfarin, North Carolina's 1997 state law includes lithium, phenytoin, carbamazepine, digoxin, theophylline, and levothyroxine as NTIs that can't be switched without approval.

Pharmacy groups have lined up against the bills, saying they inhibit a pharmacist's time, formulary control, financial decision making, and clinical status. The FDA simply states its testing and approval process can be trusted.

"There are no documented examples of a generic product manufactured to meet its approved specifications that could not be used interchangeably with the corresponding brand-name drug," states the FDA's latest letter, which speaks to patient fears this way: "Because patients may pay closer attention to their symptoms when the substitution of one drug product for another occurs, an increase in symptoms may be reported. . . . Upon investigation by FDA, no problems attributed to substitution of one approved drug product for another have occurred."

The FDA goes on to state that no additional testing is needed outside its own pre- and post-market analysis, and special precautions or patient warnings also are unnecessary.