terfenadine

Terfenadine is a selective antagonist of the peripheral H1 receptor used as a second-generation antihistamine for relief of allergic symptoms such as sneezing, runny nose, itching, and urticaria. It was marketed under the brand name Seldane and was regarded as a non-sedating option due to limited penetration of the central nervous system.

Pharmacology and metabolism: Terfenadine is rapidly absorbed and extensively metabolized in the liver by the cytochrome P450 3A4 system to its active metabolite, fexofenadine. Much of the clinical effect is mediated by fexofenadine, while terfenadine itself has relatively low central nervous system penetration, contributing to a lower risk of sedation compared with first-generation antihistamines. Nevertheless, both terfenadine and its metabolite can influence cardiac repolarization under certain conditions.

Safety concerns and regulation: In the late 1990s, reports linked terfenadine to QT interval prolongation and torsades de pointes when taken with potent CYP3A4 inhibitors (such as certain macrolide antibiotics and azole antifungals) or with substances like grapefruit juice. These interactions can lead to dangerous arrhythmias. As a result, terfenadine was withdrawn from the U.S. market and from many other jurisdictions, and its use has largely been superseded by its active metabolite, fexofenadine, or by other antihistamines.

Indications and adverse effects: When used, terfenadine was indicated for relief of seasonal allergic rhinitis and chronic idiopathic urticaria. Adverse events are typically mild and may include headache, fatigue, nausea, or drowsiness, though sedation is uncommon. See also fexofenadine.