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 may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.