- R.F.W. Moulds, Andrew Dawson
- Aust Prescr 1995;18:18
- 1 January 1995
- DOI: 10.18773/austprescr.1995.027
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.
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.
Department of Clinical Pharmacology and Therapeutics, Royal Melbourne Hospital, Melbourne
Director, Clinical Toxicology and Pharmacology, Mater Misericordiae Hospital, Newcastle, N.S.W.