Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel (now Sanofi) and was marketed under various brand names, including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia.
Medical uses
Terfenadine is still used in some countries for reliving the symptoms of asthma, allergic rhinitis, acute and chronic urticaria, and hay fever.
Pharmacology
Terfenadine acts as a peripherally-selective antihistamine, or antagonist of the histamine H<sub>1</sub> receptor. It is a prodrug, generally completely metabolized to the active form fexofenadine in the liver by the enzyme cytochrome P450 3A4. Due to its near complete metabolism by the liver immediately after leaving the gut, terfenadine normally is not measurable in the plasma. Terfenadine itself, however, is cardiotoxic at higher doses, while its major active metabolite fexofenadine is not. Terfenadine, in addition to its antihistamine effects, also acts as a potassium channel blocker (K<sub>v</sub>11.1 encoded by the gene hERG). Since its active metabolite is not a potassium channel blocker, no cardiotoxicity is associated with fexofenadine. The addition of, or a dosage increase in, these CYP3A4 inhibitors makes it harder for the body to metabolize and remove terfenadine. In larger plasma concentrations, it may lead to toxic effects on the heart's rhythm (e.g. ventricular tachycardia and torsades de pointes). Terfenadine also inhibits CYP2J2.
History
Terfenadine was synthesized by chemists at Richardson–Merrell in 1973 as a potential tranquilizer.
In the United States, terfenadine as Seldane was brought to market in 1985 as the first non-sedating antihistamine for the treatment of allergic rhinitis. Terfenadine-containing drugs were subsequently removed from the Canadian market in 1999, and are no longer available for prescription in the UK.
Tefenadine is still available in China and listed on the 2020 edition of the Pharmacopoeia of the People's Republic of China, but has become largely obsolete.