Fluconazole may increase the levels and AUC of
methadone by about 30%; a single case reports opioid
toxicity. Ketoconazole and
voriconazole appear to interact with
methadone to a greater extent (methadone levels raised by 50% or more).
Patients given these
azoles with
methadone should be monitored for signs of opioid
toxicity and a
methadone dose alteration should be considered. However, note that the interaction with
fluconazole is considered unlikely to be of general
clinical significance.