Terfenadine: profile and news

Other information

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.

Drug Category
Antiarrhythmic Agents; Anti-allergic Agents; Antihistamines; ATC:R06AX12

Brand Names/Synonyms
Aldaban; Allerplus; Cyater; MDL-9918; Nebralin; RMI 9918; Seldane; Teldane; Teldanex; Terdin; Terfenadine; Terfex; Ternadin; Triludan

Dosage Forms
Oral tablets

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%

Interactions
-->Interactions for Terfenadine:

Ketoconazole

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.

Itraconazole

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.

Macrolides

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.

Chemical IUPAC Name
4-[4-(hydroxy-diphenyl-methyl)-1-piperidyl]-1-(4-tert-butylphenyl)-butan-1-ol

Chemical Formula
C32H41NO2

Half Life
3.5 hours

Drug Type
Approved Drug

# Accession No
APRD00606

CAS Registry Number
50679-08-8