Mandatory generic substitution continues to be questioned

"We are seeing a growing trend to require physician or patient approval of certain generic substitutions, primarily for epilepsy (drugs)," said Carmen Catizone, R.Ph., D.Ph., executive director of the National Association of Boards of Pharmacy. "It's being pushed by the Epilepsy Foundation and some transplant organizations. And some pressure is coming from the manufacturers."

Two drug classes are under particular scrutiny with regard to mandatory substitution-antiepilepsy drugs (AEDs) and immunosuppressant drugs used for transplant patients. Recently concerns have been raised about antiarrhythmic drugs. Some states are also fine-tuning their Medicaid preferred drug lists for treatment of mental illnesses, AIDS, and cancer.

For example, the National Kidney Foundation has repeatedly expressed concern that generic bioequivalency is lacking for many of the immunosuppressants. The American Heart Association has expressed similar concerns about the antiarrhythmic drugs used in tachyarrhythmia management. And so have some cancer and AIDS patient advocacy groups.

However, the primary area of concern for state legislatures is AEDs, said Richard Cauchi, program director, health program at the National Conference of State Legislatures. "AEDs are where most of the legislative action remains," he said. "The whole area of mandatory generic substitutions remains contentious. Occasionally bills are passed on both sides of the issue. There's been a lot of lobbying."

The American Academy of Neurology (AAN) joined the Epilepsy Foundation last year in actively seeking state legislation that would disallow generic substitution of AEDs "without the full knowledge and consent of both the treating physician and the patient," according to a recent position statement.

Such substitutions place patients with epilepsy at "undue risk for breakthrough seizures in the name of reducing health costs," according to the statement, because the Food & Drug Administration "allows for significant differences between name-brand and generic drugs." And, for some patients with epilepsy, minor differences in the composition of anticonvulsant drugs can be dangerous, according to the AAN.

The AAN quoted two studies that showed that switchback rates between brands and generics is much higher than for many drugs that treat other chronic conditions. One study compared switchback rates from generic to brand-name AEDs and compared them with drugs for other chronic conditions, including hypercholesterolemia and depression. The switchback rate from generic AEDs was 12% to 19%, compared with just 2% to 3% in drugs for depression or hypercholesterolemia. The study was funded by GlaxoSmithKline, manufacturer of the brand-name AED Lamictal (lamotrigine).

"Epilepsy is unlike other disorders. Unlike a condition such as hypertension, where, if you make a change in dose, you can monitor blood pressure to determine whether it's working or not, with epilepsy you have an all-or-nothing phenomenon: you're either seizure free or you're not," according to Gregory Barkley, M.D., of Wayne State University in Detroit, an author of the AAN position statement.

Whether the apparently politically effective actions by the epilepsy organizations spreads to other therapeutic classes of drugs remains an open question. "While we are closely monitoring legislation that would prohibit pharmacies from making generic substitutions for drug categories, we have not seen any legislation of this kind except for AEDs and immunosuppressants," said Kevin Nicholson, R.Ph., J.D., VP for pharmacy regulatory affairs for the National Association of Chain Drug Stores. "We have seen the greatest amount of legislation for the AEDs."

THEAUTHOR is a writer based in Gettysburg, Pa.