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Open Access Case report

Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity

Yassine Bouatou12*, Caroline Flora Samer13, Kuntheavy Roseline Ing Lorenzini1, Youssef Daali13, Samira Daou4, Marc Fathi5, Michela Rebsamen5, Jules Desmeules13, Alexandra Calmy4 and Monica Escher1

Author Affiliations

1 Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland

2 Division of Nephrology, Geneva University Hospitals, Geneva, Switzerland

3 Swiss Centre for Applied Human Toxicology (SCAHT), Geneva, Switzerland

4 Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland

5 Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland

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AIDS Research and Therapy 2014, 11:25  doi:10.1186/1742-6405-11-25

Published: 4 August 2014

Abstract

Background

Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.

Case presentation

A 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. Voriconazole trough concentrations (C0) were within target range while the patient was under esomeprazole, a CYP2C19 inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping showed a variant allele associated with increased enzyme activity. The patient was switched to ranitidine because of the introduction of atazanavir. CYP3A4 inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed restoring voriconazole C0 back to target range.

Conclusion

The integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole.

Keywords:
Drug interaction; Pharmacogenetics; Individualization; Therapeutic drug monitoring; CYP; antifungal