Abstract
Case 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. Conclusion 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.
This is a preview of subscription content, log in via an institution to check access.
References
Ehret GB, Desmeules JA, Broers B. Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned from pharmacology. Expert Opin Drug Saf. 2007;6:289–303.
Totah RA, Sheffels P, Roberts T, Whittington D, Thummel K, Kharasch ED. Role of CYP2B6 in stereoselective human methadone metabolism. Anesthesiology. 2008;108:363–74.
Levêque D, Nivoix Y, Jehl F, Herbrecht R. Clinical pharmacokinetics of voriconazole. Int J Antimicrob Agents. 2006;27:274–84.
Jeong S, Nguyen PD, Desta Z. Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes; major effects of CYPs 2B6, 2C9, 2C19, and 3A4. Antimicrob Agents Chemother. 2009;53:541–51.
Äbelö A, Andersson TB, Antonsson M, Naudot AK, Skanberg I, Weidolf L. Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos. 2000;28:966–72.
Li XQ, Andersson TB, Ahlström M, Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lanzoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004;32:821–7.
Liu P, Foster G, LaBadie R, Somoza E, Sharma A. Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy. Antimicrob Agents Chemother. 2007;51:110–8.
Wood N, Tan K, Purkins L, Layton G, Hamlin J, Kleinermans D, Nichols D. Effect of omeprazole on the steady-state pharmacokinetics of voriconazole. Br J Clin Pharmacol. 2003;56 Suppl 1:56–61.
Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008;46:201–11.
Falagas ME, Rafailidis PI, Rosmarakis ES. Arrhythmias associated with fluoroquinolone therapy. Int J Antimicrob Agents. 2007;29:374–9.
Funding
None.
Conflicts of interest
D Levêque, J Scholler, Y Nivoix declare no conflicts of interest; R Herbrecht has served as consultant for Astellas, Basilea, Gilead, Merck Sharp & Dohme, Pfizer, and Schering-Plough.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Scholler, J., Nivoix, Y., Herbrecht, R. et al. Ventricular bigeminy associated with voriconazole, methadone and esomeprazole. Int J Clin Pharm 33, 905–908 (2011). https://doi.org/10.1007/s11096-011-9581-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11096-011-9581-3