Levobupivacaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics since the toxic effects of these drugs could be additive. CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. Thus, agents likely to be concomitantly administered with levobupivacaine that are metabolized by this isoenzyme family may potentially interact with levobupivacaine. It is likely that the metabolism of levobupivacaine may be affected by the known CYP3A4 inducers (such as phenytoin, phenobarbital, rifampin); CYP3A4 inhibitors (azole antimycotics, e.g., ketoconazole; certain protease inhibitors, e.g., ritonavir; macrolide antibiotics, e.g., erythromycin; and calcium channel antagonists, e.g. verapamil), CYP1A2 inducers (omeprazole) and CYP1A2 inhibitors (furafylline and clarithromycin). Dosage adjustments may be warranted when levobupivacaine hydrochloride monohydrate is concurrently administered with CYP3A4 inhibitors and CYP1A2 inhibitors, as systemic levobupivacaine levels may rise resulting in toxicity.
Levobupivacaine should be used with caution in patients receiving antiarrythmic agents with local anesthetic activity, e.g., mexiletine, or class III antiarrythmic agents since their use may be additive.