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Interaction of terbinafine (anti-fungal agent) with perhexiline: a case report

Abdul Rauf Sheikh1, Ian Westley2, Benedetta Sallustio3

  • 1The Discipline of Medicine, The Queen Elizabeth Hospital, The University of Adelaide, Adelaide, South Australia; Cardiology Unit, The Queen Elizabeth Hospital, Central Adelaide Local Health Network.

Heart, Lung & Circulation
|December 31, 2013
PubMed

Insights

The anti-anginal drug perhexiline can reach toxic levels when taken with terbinafine, a CYP2D6 inhibitor. This interaction highlights the importance of monitoring perhexiline levels during co-administration with CYP2D6 inhibiting medications.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Clinical Toxicology

Background:

  • Perhexiline is an anti-anginal medication used for chronic refractory angina.
  • Its use is limited by complex pharmacokinetics, particularly its metabolism.
  • Perhexiline is primarily metabolized by cytochrome P450 2D6 (CYP2D6).

Observation:

  • Cytochrome P450 2D6 (CYP2D6) inhibitors can impede perhexiline metabolism.
  • This inhibition can lead to increased plasma perhexiline concentrations and potential toxicity.
  • A case study revealed elevated perhexiline levels after initiating terbinafine hydrochloride.

Findings:

  • Terbinafine hydrochloride is identified as a moderate inhibitor of CYP2D6.
  • The introduction of terbinafine led to a significant rise in a patient's perhexiline plasma concentration.
  • Perhexiline levels reached a toxic threshold due to this drug interaction.

Implications:

  • Clinicians should exercise caution when prescribing CYP2D6 inhibitors with perhexiline.
  • Therapeutic drug monitoring of perhexiline is crucial when co-administering with CYP2D6 inhibitors.
  • Understanding drug-drug interactions involving CYP2D6 is vital for patient safety and effective angina treatment.
Keywords:
Cytochrome P450 2D6 (CYP2D6)PerhexilineSelective serotonin re-uptake inhibitors (SSRIs)Terbinafine

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