Loratadine arrhythmia with

In vitro studies have shown that ketoconazole inhibits the metabolism of astemizole. Ketoconazole, and to a lesser extent itraconazole and miconazole, also appear to reduce the metabolism of terfenadine by inhibition of the cytochrome P450 isoenzyme CYP3A. " High serum levels of astemizole and terfenadine (but not its metabolites) block cardiac potassium channels leading to prolongation of the QT interval, which may precipitate the development of torsade de pointes arrhythmia (see Table 15.2 , (p.583)). The risk of cardiac arrhythmias with other non-sedating antihistamines appears to be non-existent or very much lower (see Table 15.2 , (p.583)), so any pharmacokinetic interactions do not result in clinically relevant cardiac toxicity. In fact, studies have shown that desloratadine at nine times the recommended dose, fexofenadine in overdose, and mizolastine at four times the recommended dose do not affect the QT interval. However, some questions remain about loratadine and ebastine. Additionally, some studies have reported that ketoconazole alone is associated with a small increase in QT interval, and at least one case of torsade de pointes has been reported for ketoconazole alone. Therefore the cardiac effects of ketoconazole may be additive with those of the antihistamines, and this may be important for ebastine and loratadine. 

Erythromycin and propably clarithromycin inhibit this metabolism, and the increased terfenadine serum concentration can result in cardiac arrhythmias (e.g., torsades de pointes). Early evidence suggests that astemizole can produce the same result if combined with erythromycin. Erythromycin also inhibits the metabolism of loratadine however, loratadine does not appear to be cardiotoxic. 

Du Busks LM Second-generation antihistamines the risk of ventricular amhythmlas. Clin Ther 1999 21 281-295. [PMID 10211532] (The newer agents loratadine, cetlrizlne, azelastine, and fexofenadine are not associated with torsade de pointes or other ventricular arrhythmias.) HIgh-dose loratadine exposure In a six-year-old child. Vet Hum Tox/co/2001 43(3) 163-164. [PMID 11383659] (A 300-mg overdose caused only minor elevation of blood pressure and heart rate.)... 

Loratadine, a second-generation antihistamine, is well tolerated, nonsedating, and has not been associated with cardiac arrhythmias. 

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