Drug Interaction Report

Rifampin or other rifamycins may decrease the plasma concentrations of ropivacaine. The mechanism is rifamycin induction of CYP450 1A2 and 3A4, the isoenzymes responsible for the metabolic clearance of ropivacaine. In 18 healthy volunteers, rifampin (600 mg once a day for 5 days) increased the mean area under the plasma concentration-time curve of a single 0.6 mg/kg IV dose of ropivacaine by 52% and 38% in nonsmokers and smokers, respectively, compared to placebo. In nonsmokers, rifampin increased the clearance of ropivacaine by 93% and shortened its half-life by 25%. In smokers, rifampin increased the clearance of ropivacaine by 47% and shortened its half-life by 20%. The reduced effect of rifampin seen in smokers may be due to induction of ropivacaine metabolism via CYP450 1A2 caused by smoking. In clinical practice, the interaction should have minimal impact on the quality and duration of local anesthesia produced by ropivacaine, since induction of CYP enzymes is not likely to affect local anesthetic before it enters the systemic blood circulation.