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| Clinical data | |
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| Trade names | Seldane, Triludan, Teldane |
| AHFS/Drugs.com | Multum Consumer Information |
| MedlinePlus | a600034 |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Protein binding | 70% |
| Metabolism | Hepatic (CYP3A4) |
| Metabolites | Fexofenadine |
| Eliminationhalf-life | 3.5 hours |
| Identifiers | |
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| CAS Number | |
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| DrugBank |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.051.537 |
| Chemical and physical data | |
| Formula | C32H41NO2 |
| Molar mass | 471.685 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Terfenadine is anantihistamine formerly used for the treatment ofallergic conditions. It was brought to market byHoechst Marion Roussel (nowSanofi) and was marketed under various brand names, includingSeldane in theUnited States,Triludan in theUnited Kingdom, andTeldane inAustralia.[1] It was superseded byfexofenadine in the 1990s due to the risk of a particular type of disruption of the electrical rhythms of the heart (specificallycardiac arrhythmia caused byQT interval prolongation) and has been withdrawn from markets worldwide.[2]: 53
Terfenadine acts as aperipherally-selectiveantihistamine, orantagonist of thehistamineH1 receptor.[3] It is aprodrug, generally completelymetabolized to the active formfexofenadine in theliver by theenzymecytochrome 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, iscardiotoxic at higher doses, while its majoractive metabolite is not. Terfenadine, in addition to its antihistamine effects, also acts as apotassium channel blocker (Kv11.1 encoded by the genehERG). Since its active metabolite is not a potassium channel blocker, no cardiotoxicity is associated withfexofenadine.[4] Sudden toxicity is possible even after years of use without problems as a result of an interaction with other medications such aserythromycin, or foods such asgrapefruit. 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 andtorsades de pointes).
Terfenadine was synthesized by chemists atRichardson–Merrell in 1973 as a potentialtranquilizer.[3] However, it was found to be inactive for such purposes as it did not cross theblood–brain barrier or enter thecentral nervous system.[3] Pharmacologist Richard Kinsolving noticed that terfenadine showed a structural resemblance to the antihistaminediphenhydramine, so terfenadine was tested as an antihistamine.[3] It was found to be a non-sedating antihistamine and was the first such drug to be discovered.[3]
In the United States, terfenadine as Seldane was brought to market in 1985 as the firstnon-sedating antihistamine for the treatment ofallergic rhinitis.[1][5] In June 1990, evidence of seriousventricular arrhythmias among those taking Seldane prompted the FDA to issue a report on therisk factors associated withconcomitant use of the drug withmacrolide antibiotics andketoconazole.[1] Two months later, the FDA required the manufacturer to send a letter to all physicians, alerting them to the problem; in July 1992, the existing precautions were elevated to ablack box warning[1] and the issue attracted mass media attention in reports that people with liver disease or who took ketoconazole, an antifungal agent, or the antibioticerythromycin, could suffercardiac arrhythmia if they also took Seldane.[5]
In January 1997, the same month when the U.S.Food and Drug Administration (FDA) had earlier approved a generic version of Seldane made byIVAX Corporation of Miami, the FDA recommended terfenadine-containing drugs be removed from the market and physicians consider alternative medications for their patients.[5] Seldane (and Seldane-D, terfenadine combined with the decongestantpseudoephedrine) were removed from the U.S. market by their manufacturer in late 1997 after the FDA approval of Allegra-D (fexofenadine/pseudoephedrine).[6] Terfenadine-containing drugs were subsequently removed from the Canadian market in 1999,[7] and are no longer available for prescription in the UK.[8]