Itraconazole Bupivacaine

The interaction of itraconazole 200 mg orally od for 4 days with a single intravenous dose of racemic bupivacaine (0.3 mg /kg given over 60 minutes) has been examined in a placebo-controlled crossover study in 10 healthy volunteers (65). Itraconazole reduced the clearance of i -bupivacaine by 21% and that of 5-bupivacaine by 25%, but had no other significant effects on the pharmacokinetics of the enantiomers. Reduction of bupivacaine clearance by itraconazole is likely to increase steady-state concentrations of bupivacaine enantiomers by 20-25%, and this should be taken into account in the concomitant use of itraconazole and bupivacaine. 

A drug interaction has been identified between the antimycotic agent itraconazole and bupivacaine enantiomers. Coadministration of itraconazole orally with intravenous bupivacaine caused the clearance of both bupivacaine enantiomers to decrease by 25% [214]. This interaction is of concern for the drug, since the R enantiomer has been linked with the development of cardiac arrhythmias. 

Itraconazole may reduce the clearance of bupivacaine, and itraconazole, ketoconazole or clarithromycin may slightly decrease ropivacaine clearance, but the clinical importance of these interactions appears to be limited. 

In a double-blind, placebo-controlled, crossover study in 7 healthy subjects pretreatment with itraconazole 200 mg once daily for 4 days reduced the clearance of bupivacaine (0.3 mg/kg given intravenously over 60 minutes) by 20 to 25%. The increase in plasma concentrations of bupivacaine should be taken into account when itraconazole is used concurrently, although the interaction is probably of limited clinical significance. ... 

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