Just as good?

As generics move into Americans' medicine chests in growing numbers, two things are likely, say experts: There will be copycat medications that work differently -- and sometimes less effectively -- than originals; and there will be patients who do not respond as well to them. Patients and doctors should be alert to variations in a new prescription's effectiveness, they advise, and report their concerns to the FDA's adverse-events monitoring system, called MedWatch ( www.fda.gov/medwatch).

"The generics industry is highly successful, and it wouldn't be if it was always failing patients," said R. William Soller, a professor of pharmacology at UC San Francisco. But, he added, "it's pretty hard to think you have an absolutely perfect system."

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'Pandora's box'

In recent years, the system by which generic prescription drugs are approved as "bioequivalent" to their brand-name counterparts has come in for criticism from many quarters. FDA's regulation of generics is most vulnerable to criticism in cases where a medicine must be administered in very precise doses and on a precise schedule to be safe and effective. These drugs have what pharmacologists call a "narrow therapeutic index": There's a fine line between a dose that's ineffective and one that could be dangerous.

Typically, a patient's response to such medicine must be carefully monitored, and the consequences of failure could be dire: a seizure, dangerously erratic heartbeat, soaring blood pressure, blood clots or uncontrolled bleeding.

But FDA regulators have been "very categorical" in their insistence that no differences exist between generics and the pioneer drugs they follow, said Kowey. As a result, the agency has resisted studies that might call that into question with any single class of drugs, fearing that consumers will come to question the equal effectiveness of all generics. "They don't want to open the Pandora's box," said Kowey.

Dr. Gary Buehler, director of the FDA's office of generic drugs, declined an interview request. But FDA spokeswoman Sandy Walsh told The Times the "FDA cannot offer any examples where generics have been shown to not perform as expected."

The "FDA has many years of experience in the review of generic drugs and has great confidence in the quality and equivalence of generic drug products," added Walsh.