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Related Experiment Videos

Pharmacokinetic interaction between nortriptyline and terbinafine.

P-Hugo M Van Der Kuy1, Harrie A Van Den Heuvel, Rob W Kempen

  • 1Department of Clinical Pharmacy and Toxicology, Academic Hospital Maastricht, Netherlands. hkuy@kfls.azm.nl

The Annals of Pharmacotherapy
|October 26, 2002
PubMed
Summary
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Terbinafine inhibits the metabolism of nortriptyline by blocking the CYP2D6 enzyme. This drug interaction can lead to nortriptyline intoxication, even in individuals without genetic variations in CYP2D6.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Clinical Toxicology

Background:

  • Nortriptyline is an antidepressant metabolized primarily by the cytochrome P450 2D6 (CYP2D6) enzyme.
  • Terbinafine is an antifungal medication known to inhibit certain CYP450 enzymes.

Observation:

  • A case of nortriptyline intoxication was observed in a patient undergoing treatment with terbinafine for major depressive disorder.
  • This represents the second reported instance of this significant drug interaction.

Findings:

  • Rechallenge confirmed the interaction, with elevated serum concentrations of nortriptyline and its hydroxy metabolites.
  • Genotyping indicated that the interaction is likely due to terbinafine's competitive inhibition of CYP2D6-mediated nortriptyline hydroxylation.
  • The interaction is not limited to individuals with CYP2D6 genetic variations.

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Implications:

  • Clinicians should be aware of the potential for nortriptyline toxicity when co-prescribed with terbinafine.
  • Monitoring of nortriptyline levels may be warranted in patients receiving both medications.
  • This interaction highlights the importance of considering drug metabolism pathways in clinical practice.