Brands, Medical Use, Clinical Data
- Anti-allergic Agents
Brands / Synonyms
Alermizol; Astemisan; Astemisol; Astemison; Hismanal; Histamen; Histaminos; Histazol; Kelp; Laridal; Metodik; Nono-Nastizol A; Paralergin; Retolen; Waruzol
For the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria.
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.
Rapidly absorbed from the gastrointestinal tract.
LD50=2052mg/kg in mice
Biotrnasformation / Drug Metabolism
Almost completely metabolized in the liver and primarily excreted in the feces.
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
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
Ketoconazole/Itraconazole, Macrolides, Including Erythromycin