Substitution of Anti-Epileptic Drugs Under Review

28 June 2007

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Epilepsy is a neurologic condition involving unprovoked and recurring seizures that can cause mental and physical disability and dysfunction. In the United States, approximately 2.7 million people are affected by epilepsy, with 200,000 new cases diagnosed each year. By 20 years of age, 1% of the general population will be expected to have epilepsy, and about 10% of patients will have at least one seizure in their lifetime. Treatment for epilepsy involves individual titration of one or more anti-seizure medications to prevent future seizures, minimize or prevent adverse drug effects, and enable seizure patients to lead active lives.

Pharmacist's Letter is a subscription service that provides recommendations for pharmacists on new developments in drug therapy, and trends in pharmacy practice. Pharmacist's Letter started in 1985 and currently serves most pharmacists in the United States and Canada. The service consists of a monthly letter, plus Detail-Documents available 24 hours a day.

Therapeutic Research is a completely independent research and publishing organization that provides evidence-based information for physicians, pharmacists, and other medical professionals. In addition to Pharmacist's Letter, Therapeutic Research publishes Prescriber's Letter, a similarly formatted advisory service for prescribers, as well as Natural Medicines Comprehensive Database, Ident-A-Drug Reference, and a variety of continuing medical education courses including live courses. Therapeutic Research accepts no advertising and provides objective information for subscribers.

The $20 billion dollar practice of substituting generic antiepileptic drugs for their brand name equivalents will soon be under review by law and policy makers. Therapeutic Research Center, the publisher of Pharmacist's Letter and Prescriber's Letter, informs patients, pharmacists and prescribers on both sides of the argument and provides recommendations on how to provide the best drug care to patients. A growing controversy over substituting generic antiepileptic drugs (AEDs) for their brand name counterparts will impact pharmacists, prescribers, and patients with epilepsy. Almost all older anti-epilepsy drugs are already available generically.

Many newer agents have recently gone generic, and nearly all epilepsy drugs will be available generically over the next few years. Generic substitution in pharmacies is common, legal, well accepted, and can save patients and insurers a lot of money. Manufacturers of the newer anti-epilepsy drugs stand to lose a lot of money if generic equivalents are dispensed instead of the brand name medicines. Expect both insurance providers and drug manufacturers to try to sway practices to their benefit.

The practice of switching to therapeutically equivalent generics could save more than $20 billion a year. This figure represents revenue that the manufactures don't want to lose and the insurance providers don't want to spend. Critics of generic substitution for epilepsy drugs point out that epilepsy is different than other conditions. Many anti-epilepsy drugs must be used at very precise doses. Experts call this a "narrow therapeutic window."

These narrow blood levels are required because slightly too little of the medicine may not control the patient's seizures, and slightly too much of the drug can lead to toxicity. These critics point to potential variability among the many available generic products and say this increases the likelihood of a problem. For example, Zonegran went generic in 2005 and there are now over 15 different generic zonisamide products. The FDA does allow a slight variability between generic and brand medications...and among generics...but this usually isn't a problem.

Despite this, some experts worry that this small variability is too much in epilepsy, where the effectiveness of drugs is heavily dependent on consistency, and argue that generic substitution guidelines for anti-epilepsy drugs should be stricter than with other medications. There are cases of drug toxicity or breakthrough seizures in patients switching to generic versions of older AEDs like phenytoin (Dilantin), carbamazepine (Tegretol), and others.

Breakthrough seizures can be devastating to epilepsy patients and may lead to loss of driving or work privileges. But most epilepsy experts say that similar equivalency problems aren't likely with generics of the newer meds because of different drug characteristics. Most experts agree it is safe and economical to switch to a generic version of a drug when it is therapeutically equivalent. Any variability allowed by the FDA is very small and highly unlikely to impact a patient's therapy.

Many states refer to the FDA's Orange Book rating for bioequivalence and authorize substituting "A-rated" drugs. Experts say generic substitution can save money for patients and provides equal therapeutic effects when bioequivalent and therapeutically equivalent products are substituted. "The key for health professionals is to focus on the needs of the patient." says Kristin Weitzel, PharmD, CDE, Assistant Editor for Pharmacist's Letter.

"Pharmacists are in an ideal position to help epilepsy patients by using their clinical judgment and following their state's substitution laws for epilepsy drugs. For example, there are many AB-rated generics for phenytoin, but it's probably a good idea to keep phenytoin patients on the same product if you can from refill to refill. This can help to decrease any potential variability among epilepsy patients that may have problems."

"Keep in mind you don't necessarily need to do this with every epilepsy medication, but it may help some patients on older agents like phenytoin and carbamazepine." Experts at Pharmacist's Letter indicate that many of the anti-seizure drugs are used for many purposes other than treating epilepsy.

In these instances, the slight variations in the drug products are even less likely to be noticed in a patient. If a blanket requirement to avoid therapeutic substitution were to apply to all anti-seizure drugs, many patients without seizure problems would pay significantly higher prices for products that offered no increase in benefit.