indication

For the treatment of allergic rhinitis, hay fever, and allergic skin disorders.

pharmacology

Terfenadine, an H1-receptor antagonist antihistamine, is similar in structure to astemizole and haloperidol, a butyrophenone antipsychotic. The active metabolite of terfenadine is fexofenadine.

mechanism of action

Terfenadine competes with histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of terfenadine to H1-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier, CNS depression is minimal.

toxicity

Mild (e.g., headache, nausea, confusion), but adverse cardiac events including cardiac arrest, ventricular arrhythmias including torsades de pointes and QT prolongation have been reported. LD₅₀=mg/kg (orally in mice)

biotransformation

Hepatic

absorption

On the basis of a mass balance study using 14C labeled terfenadine the oral absorption of terfenadine was estimated to be at least 70%

half life

3.5 hours

drug interactions

Acetophenazine: Increased risk of cardiotoxicity and arrhythmias

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Amitriptyline: Increased risk of cardiotoxicity and arrhythmias

Amoxapine: Increased risk of cardiotoxicity and arrhythmias

Amprenavir: Increased risk of cardiotoxicity and arrhythmias

Aprepitant: Increased risk of cardiotoxicity and arrhythmias

Bepridil: Increased risk of cardiotoxicity and arrhythmias

Chlorpromazine: Increased risk of cardiotoxicity and arrhythmias

Cimetidine: Increased risk of cardiotoxicity and arrhythmias

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Clarithromycin: Increased risk of cardiotoxicity and arrhythmias

Clomipramine: Increased risk of cardiotoxicity and arrhythmias

Delavirdine: Increased risk of cardiotoxicity and arrhythmias

Desipramine: Increased risk of cardiotoxicity and arrhythmias

Diltiazem: Increased risk of cardiotoxicity and arrhythmias

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Doxepin: Increased risk of cardiotoxicity and arrhythmias

Efavirenz: Increased risk of cardiotoxicity and arrhythmias

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Flecainide: Increased risk of cardiotoxicity and arrhythmias

Fluconazole: Increased risk of cardiotoxicity and arrhythmias

Fluoxetine: Increased risk of cardiotoxicity and arrhythmias

Fluphenazine: Increased risk of cardiotoxicity and arrhythmias

Fluvoxamine: Increased risk of cardiotoxicity and arrhythmias

Fosamprenavir: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Imipramine: Increased risk of cardiotoxicity and arrhythmias

Indinavir: Increased risk of cardiotoxicity and arrhythmias

Itraconazole: Increased risk of cardiotoxicity and arrhythmias

Josamycin: Increased risk of cardiotoxicity and arrhythmias

Ketoconazole: Increased risk of cardiotoxicity and arrhythmias

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methdilazine: Increased risk of cardiotoxicity and arrhythmias

Methotrimeprazine: Increased risk of cardiotoxicity and arrhythmias

Mexiletine: Increased risk of cardiotoxicity and arrhythmias

Mibefradil: Increased risk of cardiotoxicity and arrhythmias

Nefazodone: Increased risk of cardiotoxicity and arrhythmias

Nelfinavir: Increased risk of cardiotoxicity and arrhythmias

Nicardipine: Increased risk of cardiotoxicity and arrhythmias

Nortriptyline: Increased risk of cardiotoxicity and arrhythmias

Perphenazine: Increased risk of cardiotoxicity and arrhythmias

Posaconazole: Contraindicated co-administration

Procainamide: Increased risk of cardiotoxicity and arrhythmias

Prochlorperazine: Increased risk of cardiotoxicity and arrhythmias

Promazine: Increased risk of cardiotoxicity and arrhythmias

Promethazine: Increased risk of cardiotoxicity and arrhythmias

Propafenone: Increased risk of cardiotoxicity and arrhythmias.

Propericiazine: Increased risk of cardiotoxicity and arrhythmias

Propiomazine: Increased risk of cardiotoxicity and arrhythmias

Protriptyline: Increased risk of cardiotoxicity and arrhythmias

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Quinine: Increased risk of cardiotoxicity and arrhythmias

Quinupristin: This combination presents an increased risk of toxicity

Ritonavir: Increased risk of cardiotoxicity and arrhythmias

Saquinavir: Increased risk of cardiotoxicity and arrhythmias

Sotalol: Increased risk of cardiotoxicity and arrhythmias

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Telithromycin: Increased risk of cardiotoxicity and arrhythmias

Thiethylperazine: Increased risk of cardiotoxicity and arrhythmias

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Terfenadine. Concomitant therapy is contraindicated.

Tocainide: Increased risk of cardiotoxicity and arrhythmias

Trifluoperazine: Increased risk of cardiotoxicity and arrhythmias

Triflupromazine: Increased risk of cardiotoxicity and arrhythmias

Trimeprazine: Increased risk of cardiotoxicity and arrhythmias

Trimipramine: Increased risk of cardiotoxicity and arrhythmias

Troleandomycin: Increased risk of cardiotoxicity and arrhythmias

Verapamil: Increased risk of cardiotoxicity and arrhythmias

Voriconazole: Increased risk of cardiotoxicity and arrhythmias