Drug interactions

Erythromycin and terfenadine should not be used together

Terfenadine is becoming widely used, both in Australia and other countries, as it probably causes less sedation than the older antihistamines. In general, it is a safe drug, but in overdose it has been reported to cause the rare cardiac arrhythmia of 'torsades de pointes'. This arrhythmia is a particular type of ventricular tachycardia which is potentially very serious.

Terfenadine is really a prodrug, being very rapidly converted to an active metabolite. High plasma concentrations of the active metabolite are thought to be responsible for the development of the arrhythmia in overdose.

Erythromycin inhibits the breakdown of the active metabolite of terfenadine. If terfenadine is taken chronically in the presence of erythromycin, much higher plasma concentrations of the active metabolite will occur. In some patients, the concentrations become high enough to predispose to torsades de pointes.

There have been case reports of torsades de pointes occurring in patients taking both terfenadine and erythromycin, so these commonly prescribed drugs should not be used together.

Fluoxetine is a serotonin uptake inhibitor used in the treatment of depression. Prescribers should be aware that fluoxetine significantly inhibits the hepatic metabolism of virtually all the tricyclic antidepressants, phenothiazines and haloperidol. The interaction is significant and may lead to an increase in the serum levels of other psychotropics of up to 400%. This drug interaction has been manifested by increased anticholinergic symptoms, cardiac toxicity and seizures.

Importantly, these interactions have been noted to occur after the cessation of fluoxetine therapy. This has been explained by the long half life of fluoxetine (2-3 days) and its active metabolite norfluoxetine (7-9 days). On this basis, prescribers should be aware that such an interaction may occur up to 4 weeks after cessation of fluoxetine.