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Inherited long QT syndrome revealed by antifungals drug-drug interaction

C Eiden1, H Peyrière, R Tichit

  • 1Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France.

Journal of Clinical Pharmacy and Therapeutics
|May 11, 2007
PubMed

Insights

A young patient on antifungal medication experienced a life-threatening heart condition due to drug interactions and genetic factors. This case highlights the importance of monitoring QT interval and considering genetic predispositions during antifungal therapy.

Area of Science:

  • Pharmacology
  • Cardiology
  • Genetics

Background:

  • A 14-year-old girl with acute myeloid leukemia and mucormycosis infection was treated with voriconazole and caspofungin.
  • Voriconazole was switched to posaconazole due to disease progression.

Observation:

  • The patient developed QT interval prolongation and torsades de pointes, leading to reversible cardiac arrest.
  • Voriconazole plasma levels were high (7 mg/L) 15 hours post-administration.
  • Genetic testing indicated the patient was an extensive metabolizer for CYP2C9 and CYP2C19.

Findings:

  • Antifungal agents, particularly voriconazole, in conjunction with other pro-arrhythmogenic drugs and risk factors, precipitated torsades de pointes.
  • The event revealed an underlying inherited long QT syndrome.

Implications:

  • This case underscores the critical need for vigilant cardiac monitoring (QT interval) in patients receiving azole antifungals, especially those with risk factors.
  • Pharmacogenetic considerations (CYP2C9, CYP2C19 metabolism) are crucial for optimizing antifungal therapy and preventing adverse cardiac events.
  • Early identification and management of drug-induced QT prolongation and underlying inherited conditions are vital for patient safety.

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