Active ingredient: Astemizole - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anti-allergic Agents
• Antihistamines

Dosage Forms

• Suspension
• Tablet

Brands / Synonyms

Alermizol; Astemisan; Astemisol; Astemison; Hismanal; Histamen; Histaminos; Histazol; Kelp; Laridal; Metodik; Nono-Nastizol A; Paralergin; Retolen; Waruzol

Indications

For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.

Pharmacology

Astemizole, an H₁-receptor antagonist, is similar in structure to terfenadine and haloperidol, a butyrophenone antipsychotic. It has anticholinergic (atropine-like) and antipruritic effects.

Mechanism of Action

Astemizole competes with histamine for binding at H₁-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole 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 and preferentially binds at H1 receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H₃-receptors, producing adverse effects.

Absorption

Rapidly absorbed from the gastrointestinal tract.

Toxicity

LD₅₀=2052mg/kg in mice

Biotrnasformation / Drug Metabolism

Almost completely metabolized in the liver and primarily excreted in the feces.

Contraindications

Concomitant administration of Astemizole with erythromycin is contraindicated because erythromycin is known to impair the cytochrome P450 enzyme system which also influences astemizole metabolism. There have been two reports to date of syncope with Torsades De Pointes, requiring hospitalization, in patients taking combinations of astemizole 10 mg daily with erythromycin. In each case the QT intervals were prolonged beyond 650 milliseconds the time of the event; One patient also received ketoconazole and the other patient also had hypokalemia.

Concomitant administration of astemizole with ketoconazole tablets is contraindicated because available human pharmacokinetic data indicate that oral ketoconazole significantly inhibits the metabolism of astemizole, resulting in elevated plasma levels of astemizole and desmethylastemizole. Data suggest that cardiovascular events are associated with elevation of astemizole and/or astemizole metabolite levels resulting in electrocardiographic QT prolongation.

Concomitant administration with itraconazole is also contraindicated based on the chemical resemblance of itraconazole and ketoconazole. In vitro data suggest that itraconazole has a less pronounced effect on the biotransformation system responsible for the metabolism of astemizole compared to ketoconazole.

Astemizole is contraindicated in patients with known hypersensitivity to astemizole or any of the inactive ingredients.

Drug Interactions

Ketoconazole/Itraconazole, Macrolides, Including Erythromycin