indication

Astemizole was indicated for use in the relieving allergy symptoms, particularly rhinitis and conjunctivitis. It has been withdrawn from the market however due to concerns of arrhythmias.

pharmacology

Astemizole is a second generation H₁-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses.

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.

toxicity

LD₅₀=2052mg/kg in mice

biotransformation

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

absorption

Rapidly absorbed from the gastrointestinal tract.

half life

1 day

drug interactions

Amprenavir: Increased risk of cardiotoxicity and arrhythmias

Aprepitant: Increased risk of cardiotoxicity and arrhythmias

Bepridil: 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

Delavirdine: Increased risk of cardiotoxicity and arrhythmias

Efavirenz: Increased risk of cardiotoxicity and arrhythmias

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Fluoxetine: 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

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

Mibefradil: Increased risk of cardiotoxicity and arrhythmias

Nefazodone: Increased risk of cardiotoxicity and arrhythmias

Nelfinavir: Increased risk of cardiotoxicity and arrhythmias

Posaconazole: Contraindicated co-administration

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

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Telithromycin: 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 Astemizole. Concomitant therapy is contraindicated.

Troleandomycin: Increased risk of cardiotoxicity and arrhythmias

Voriconazole: Increased risk of cardiotoxicity and arrhythmias