Brands, Medical Use, Clinical Data
- Antiarrhythmic Agents
- Anti-allergic Agents
Brands / Synonyms
Aldaban; Allerplus; Cyater; Nebralin; Seldane; Teldane; Teldanex; Terdin; Terfex; Ternadin; Triludan
For the treatment of allergic rhinitis, hay fever, and allergic skin disorders.
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.
On the basis of a mass balance study using 14C labeled terfenadine the oral absorption of terfenadine was estimated to be at least 70%
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)
Biotrnasformation / Drug Metabolism
CONCOMITANT ADMINISTRATION OF TERFENADINE WITH KETOCONAZOLE (NIZORAL) OR ITRACONAZOLE (SPORONOX) IS
CONTRAINDICATED. TERFENADINE IS ALSO CONTRAINDICATED IN PATIENTS WITH DISEASE STATES OR OTHER CONCOMITANT MEDICATIONS
KNOWN TO IMPAIR ITS METABOLISM, INCLUDING SIGNIFICANT HEPATIC DYSFUNCTION, AND CONCURRENT USE OF CLARITHROMYCIN,
ERYTHROMYCIN, OR TROLEANDOMYCIN. QT PROLONGATION HAS BEEN DEMONSTRATED IN SOME PATIENTS TAKING TERFENADINE IN THESE
SETTINGS, AND RARE CASES OF SERIOUS CARDIOVASCULAR EVENTS, INCLUDING DEATH, CARDIAC ARREST, AND TORSADES DE POINTES,
HAVE BEEN REPORTED IN THESE PATIENT POPULATIONS..
Terfenadine is contraindicated in patients with a known hypersensitivity to terfenadine or any of its
Spontaneous adverse reaction reports of patients taking concomitant ketoconazole with recommended doses of
terfenadine demonstrate QT interval prolongation and rare serious cardiac events, e.g. death, cardiac arrest, and
ventricular arrhythmia including torsades de pointes. Pharmacokinetic data indicate that ketoconazole markedly
inhibits the metabolism of terfenadine, resulting in elevated plasma terfenadine levels. Presence of unchanged
terfenadine is associated with statistically significant prolongation of the QT and QTc intervals.Concomitant
administration of ketoconazole and terfenadine is contraindicated.
Torsades de pointes and elevated parent terfenadine levels have been reported during concomitant use of
terfenadine and itraconazole in clinical trials of itraconazole and from foreign post-marketing sources. One death
has also been reported from foreign post- marketing sources. Concomitant administration of itraconazole and
terfenadine is contraindicated.
Due to the chemical similarity of other azole-type antifungal agents (including fluconazole, metronidazole, and
miconazole) to ketoconazole, and itraconazole, concomitant use of these products with terfenadine is not recommended
pending full examination of potential interactions.
Clinical drug interaction studies indicate that erythromycin and clarithromycin can exert an effect on terfenadine
metabolism by a mechanism which may be similar to that of ketoconazole, but to a lesser extent. Although erythromycin
measurably decreases the clearance of the terfenadine acid metabolite, its influence on terfenadine plasma levels is
still under investigation. A few spontaneous accounts of QT interval prolongation with ventricular arrhythmia
including torsades de pointes, have been reported in patients receiving erythromycin or troleandomycin.
Concomitant administration of terfenadine with clarithromycin, erythromycin, or troleandomycin is
contraindicated: Pending full characterization of potential interactions, concomitant administration of
terfenadine with other macrolide antibiotics, including azithromycin, is not recommended. Studies to evaluate
potential interactions of terfenadine with azithromycin are in progress.