Terfenadine interaction with macrolides

Accumulation of the parent drug and resultant QT prolongation may occur following a overdose, a drug interaction that limits metabolism of terfenadine (e.g., concomitant administration with erythromycin or other macrolide antibiotic or with the azole derivatives ketoconazole or itraconazole), or significant hepatic dysfunction that limits metabolism of terfenadine. Patients with preexisting cardiac disease or those with electrolyte abnormalities are also at increased risk for cardiac toxicity. 

One of the important limitations to the widespread use of the macrolides has been the propensity to interact with other commonly administered medications. Serious, sometimes life-threatening, consequences have resulted from the administration of macrolides to patients receiving routine medications including theophylline, carbamazepine, terfenadine, and other frequently prescribed medications [4-6]. Most of these interactions involve inhibition of drug metabolism via cytochrome P-450 microsomal enzyme. However, not all macrolides have been associated with such drug interactions. 

The interactions of terfenadine with erythromycin, clarithromycin, and troieandomycin and astemizole with erythromycin are established, clinically important and potentially hazardous. From the reports above it does seem that only a very few individuals develop a clinically important adverse interaction with these macrolides, but identifying them in advance is not often practical or possible. Because of the unpredictability and potential severity of this interaction, the FDA, the CSM" in the UK and the manufacturers of terfenadine and astemizole now contraindicate macrolides in anyone taking terfenadine or astemizole. The only exception to this is azithromycin with astemizole. The manufacturer of terfenadine extends this contraindication to the concurrent use of topical macrolides. ... 

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. 

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