Two antihistaminics terfenadine and astemizole were withdrawn from the market following the occurrence of cardiac arrhythmias when they were present in high levels in the blood. These effects were explained by the fact :
Astemizole and terfenadine are metabolized by microsomal enzymes. Erythromycin inhibits these enzymes and raises the plasma concentration of these drugs. At high levels, these agents block cardiac K+ channels leading to arrhythmias.
Use of these drugs by addicts
Genetic predisposition to metabolize succinylcholine slowly
Concurrent treatment with phenobarbital
Treatment of these patients with erythromycin, a macrolide antibiotic