Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 1A2 and/or 3A4 may increase the plasma concentrations of levobupivacaine, which is primarily metabolized by these isoenzymes. Although no clinical studies have been conducted, the possibility of prolonged and/or increased pharmacologic effects of levobupivacaine should be considered.

MANAGEMENT: Caution may be advisable if levobupivacaine is administered to patients receiving inhibitors of CYP450 1A2 (e.g., quinolones, deferasirox, mexiletine, propafenone, ticlopidine, zileuton) or CYP450 3A4 (e.g., azole antifungals, macrolide antibiotics, protease inhibitors, kinase inhibitors, aprepitant, conivaptan, cyclosporine, delavirdine, diltiazem, nefazodone, verapamil). Particular caution and dosage adjustment of levobupivacaine may be warranted during concomitant use of both a CYP450 1A2 inhibitor and a CYP450 3A4 inhibitor, or a drug that inhibits both isoenzymes (e.g., fluvoxamine). Patients should be monitored for early signs and symptoms of central nervous system toxicity such as dizziness, drowsiness, lightheadedness, anxiety, restlessness, incoherent speech, tremors, twitching, numbness and tingling of the mouth and lips, metallic taste, tinnitus, and blurred vision, as well as more serious reactions including convulsions, hypotension, arrhythmias, and cardiorespiratory depression.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.