Public Release: 

FDA Approves Safer Seldane Developed By Georgetown Pharmacologist

Georgetown University Medical Center

FDA Approves Safer version of Seldane
Contact: Michael Tebo
(202) 687-5100
tebom@georgetown.gunet.edu

FDA APPROVES SAFER VERSION OF SELDANE DEVELOPED BY GEORGETOWN PHARMACOLOGIST

WASHINGTON, DC -- The Food and Drug Administration (FDA) has approved fexofenadine, a new, safer version of the popular, non-sedating antihistamine Seldane that effectively relieves the symptoms of seasonal allergies without Seldane's potential to cause a deadly heart condition when taken with other commonly prescribed medications.

Discovered and patented by Raymond Woosley, MD, PhD, professor and chairman of pharmacology at Georgetown University Medical Center, fexofenadine is expected to be available by prescription in late August, marketed by Hoechst Marion Roussell (HMR) under the brand name "Allegra."

"Fexofenadine is a major advance in the safe treatment of allergy symptoms," says Woosley, who first demonstrated the mechanism by which Seldane can cause potentially life-threatening heart rhythm disorders. "Patients have died from drug combinations that are often taken to treat common, relatively trivial illnesses. Although these kinds of side effects resulting in death are rare, even one death caused by this kind of interaction is unacceptable."

Introduced in 1985, Seldane was the first drug that relieved the sneezing, watery eyes, and runny nose of seasonal allergies without causing drowsiness that keeps many people from driving or working. With more than 14,000 prescriptions for Seldane written annually in the United States, the FDA was ready to make the medication available to consumers over-the-counter in 1991. But plans were suspended when reports surfaced that many people had suffered serious heart rhythm disorders when taking Seldane with other commonly prescribed drugs.

Woosley initiated his research of Seldane's cardiac side effects when he became aware of a patient at Georgetown University Medical Center who had blacked out from high levels of the medication in her blood. Woosley and fellow Georgetown clinical pharmacologists found that Seldane, but not its breakdown product, fexofenadine, produced the unwanted effects on the heart, and that fexofenadine was actually the active and safer antihistamine. Researchers established that a person's liver normally converts Seldane to fexofenadine, but when the liver conversion of Seldane to fexofenadine is blocked by other drugs or disease, Seldane can build up in the body and cause heart rhythm problems.

Seldane's use then became restricted with warnings for adverse interaction added to its labeling. Interacting medications were eventually identified and include ketoconazole, used to treat a variety of fungal infections, and erythromycin, an antibiotic used to treat respiratory tract infections, middle ear infections, and skin infections.

Subsequently, clinical trials conducted by HMR found that fexofenadine did not interfere with heart function, even when taken in combination with ketoconazole or erythromycin. There were no changes in electrocardiogram parameters for patients taking fexofenadine, and results indicated that the new, improved compound could now be taken with antifungals and antibiotics without the risk for adverse interaction.

"The side effects of prescription drugs are the downside of the medical miracles developed by the pharmaceutical industry," says Woosley. "Very little research is conducted to study adverse drug reactions because most believe there is no economic incentive to systematically evaluate the side effects of drugs. However, our work demonstrates that understanding the mechanism of a side effect can allow you to develop a new drug that is free of that unwanted action."

Woosley patented fexofenadine in collaboration with Sepracor, Inc., a Massachusetts-based drug company that develops improved chemicals similar to marketed drugs to improve efficacy and safety. Sepracor subsequently licensed the patent to HMR for marketing in the United States, and in an exceptionally short period of time, HMR has obtained FDA approval for fexofenadine. The new drug will be available by prescription under the brand name "Allegra" in August of this year.

ABOUT THE RESEARCHER

Raymond Woosley, MD, PhD, is Chairman of the Department of Pharmacology at Georgetown University Medical Center, and Professor of Pharmacology and Medicine at Georgetown's School of Medicine.

Woosley is a leading advocate of expanded education on medications for physicians, pharmacists and patients to increase consumer safety.

In 1991, just before the popular antihistamine Seldane was set to go over-the-counter, Woosley discovered the mechanism by which Seldane can cause fatal heart arrhythmias when taken with the antibiotic erythromycin or the antifungal ketoconazole.

Woosley and colleagues recently authored a study that surveyed 50 Washington area pharmacies and found that, when presented with prescriptions for erythromycin and Seldane, nearly one-third of pharmacies failed to detect the potentially life-threatening error. The study appeared in a letter to the editor in the April 10, 1996 Journal of the American Medical Association.

With more than two billion prescriptions written each year and prescribing errors as the second greatest cause of medical malpractice in the United States today, Woosley has championed the creation of federally-funded Centers for Education and Research in Therapeutics (CERT) that could address the information gap on medications and improve prescribing practices of physicians.


To speak to Dr. Woosley about fexofenadine, contact Michael Tebo in Georgetown University Medical Center's press office at (202) 687-4699.

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