Arrhythmias astemizole causing

Macrolide antibiotics are contraindicated in patients with known hypersensitivity or intolerance to any macrolide. Because clarithromycin can have adverse effects on embryo-fetal development in animals, this drug should be avoided in pregnant women unless no other therapy is appropriate. Concurrent administration of the macrolides and astemizole or terfenadine can cause elected antihistamine levels, resulting in life-threatening cardiac arrhythmias, and should be avoided. 

Reports of cardiac arrhythmias caused by unusually high blood levels of two antihistamines, terfenadine and astemizole, led to their removal from the market. These effects were best explained by... 

Astemizole and terfenadine should generally not be used with other drugs that can also prolong the QT interval. The manufacturer of mizolastine issues the same advice. One early study found that hydroxyzine caused ECG abnormalities in high doses. The authors suggested that its use with other drugs that can cause cardiac abnormalities might increase the likelihood of arrhythmias and sudden death, but there is no published evidence of this. 

Erythromycin causes terfenadine and astemizole to accumulate in a few individuals, which can prolong the QT interval and lead to life-threatening torsade de pointes arrhythmias. Cases of torsade de pointes have been reported for astemizole with erythromycin, and terfenadine with erythromycin or troleandomycin. Other macrolides are believed to interact similarly, with the exception of azithromycin and possibly dirithromycin. 

Some macrolides (particularly erythromycin and clarithromycin) appear to reduce the metabolism of terfenadine and astemizole by inhibition of the cytochrome P450 isoenzyme CYP3A. High serum levels of astemizole and terfenadine cause a prolongation of the QT interval and 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... 

Quinine causes a marked but transient increase in plasma astemizole levels, and to avoid the possible risk of cardiac arrhythmias the manufacturers contraindicate this combination. Three case reports confirm that this is a clinically important interaction. 

First-generation antihistamines provide symptomatic relief from allergies and the common cold to patients. However, their therapeutic potential is hampered by the sedation caused by their effects on histamine receptors in the brain (1-3). Second-generation antihistamine (astemizole, as an example) block peripheral HI receptors were introduced to provide comparable therapeutic benefit without the CNS side effects under manufactures recommended doses (1-4). It was reported that astemizole was found to cause arrhythmias when drug exposures became... 

Absolute aprepitant is contraindicated in patients who are hypersensitive to any component of the product. Aprepitant is a weak-to-moderate (dose-dependent) cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Aprepitant should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Dose-dependent inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening ventricular arrhythmias. 

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