title: Ventricular bigeminy associated with voriconazole, methadone and esomeprazole.
abstract: METHODS
  We report a case of ventricular bigeminy with concomitant administration of methadone, voriconazole and esomeprazole in a Caucasian woman aged 26 with acute lymphoblastic leukaemia. Plasma concentrations of voriconazole and methadone were high, 12.4 mg/l (therapeutic range: 1-4 mg/l) and 1.6 mg/l (therapeutic range: 0.2-0.4 mg/l), respectively. In the absence of esomeprazole, no more episode of cardiac arrhythmia occurred and 7 days after, methadone plasma concentration fell at 0.57 ml/l while voriconazole concentration was at 5.5 mg/l. We speculate that a pharmacokinetic interaction between methadone and voriconazole was amplified by the addition of esomeprazole. This led to the large increase of the plasma concentration of methadone and was potentially responsible for its cardiac toxicity.
  
  
  CONCLUSIONS
  Physicians should be aware of the potential interaction between voriconazole, esomeprazole and methadone leading to arrhythmia. The inhibitory potential of voriconazole is possibly increased by esomeprazole.
authors: Pharmacy, Hôpital Hautepierre, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67000, Strasbourg, France.
authors: Julie
authors: J
authors: Scholler
authors: Yasmine
authors: Y
authors: Nivoix
authors: Raoul
authors: R
authors: Herbrecht
authors: Véronique
authors: V
authors: Kemmel
authors: Dominique
authors: D
authors: Levêque
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D004347:Drug Interactions; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008691:Methadone / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018754:Ventricular Dysfunction / Q000139:chemically induced / Q000503:physiopathology; D065819:Voriconazole
chemical_list: D000701:Analgesics, Opioid; D000935:Antifungal Agents; D054328:Proton Pump Inhibitors; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole; D064098:Esomeprazole; D008691:Methadone