Seldane was the first non-sedating antihistamine — it caused fatal heart arrhythmias

Terfenadine, marketed as Seldane in the US, was the first non-sedating antihistamine, launched in 1985. It was a revolution in allergy treatment — patients could take it without the drowsiness caused by older antihistamines. The drug became a blockbuster almost immediately, with millions of prescriptions worldwide. It was developed by Richardson-Merrell and later acquired by Hoechst Marion Roussel through a series of mergers.

The problem was that terfenadine itself is cardiotoxic. The drug blocks potassium channels in heart muscle cells, causing QT interval prolongation — a disruption of the heart's electrical rhythm that can lead to torsades de pointes, a potentially fatal ventricular arrhythmia. Normally, the drug is rapidly metabolised by the liver enzyme CYP3A4 into a safe metabolite. But when patients took other drugs that inhibited CYP3A4 — such as the antibiotic erythromycin or the antifungal ketoconazole — the metabolism was blocked, terfenadine accumulated in the blood, and the heart toxicity emerged.

The FDA added a black box warning in 1992, but deaths continued. By 1997, Hoechst Marion Roussel had developed fexofenadine (Allegra), the active metabolite of terfenadine, which is not cardiotoxic. The company voluntarily withdrew Seldane from the US market in late 1997 and replaced it with Allegra. The Seldane case became a landmark in drug development for demonstrating that a drug's active metabolite could be a safer replacement, and it triggered a widespread review of QT prolongation risks across the entire pharmaceutical industry.