Drug Interactions between bupivacaine liposome and ropivacaine / sufentanil

ADJUST DOSING INTERVAL: Administration of bupivacaine liposome suspension together with other local anesthetics, either simultaneously in the same syringe or sequentially to the same site, may impact the pharmacokinetic and/or physicochemical properties of bupivacaine liposome. In vitro and animal studies have shown that local anesthetics such as lidocaine, mepivacaine, and ropivacaine can cause substantial displacement and rapid release of free bupivacaine from liposomes, which may affect the safety and efficacy of the medication.

MONITOR CLOSELY: Additive toxicities may occur when bupivacaine liposome suspension is coadministered with other local anesthetics. The potential for increased risk of systemic toxicities such as methemoglobinemia and central nervous system and cardiovascular adverse reactions should be recognized.

MANAGEMENT: Bupivacaine liposome suspension should not be admixed with other, non-bupivacaine based local anesthetics. It may be admixed with bupivacaine hydrochloride as long as the ratio of the milligram dose of bupivacaine HCl to bupivacaine liposome does not exceed 1:2. Additional use of local anesthetics should generally be avoided within 96 hours following administration of bupivacaine liposome suspension. According to the manufacturer, bupivacaine liposome may be locally administered after at least 20 minutes following the local administration of lidocaine. However, there are no data to support administration of other local, non-bupivacaine based anesthetics prior to administration of bupivacaine liposome. Because the toxic effects of these medications are additive, caution and close observation for development of methemoglobinemia as well as central nervous system and cardiovascular adverse reactions are advised during concomitant use. Early warning signs of central nervous system toxicity may include restlessness, anxiety, incoherent speech, dizziness, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, blurred vision, tremors, twitching, depression, and drowsiness. Cardiovascular toxicity include atrioventricular block, ventricular arrhythmias, cardiac arrest, and decreased cardiac output and arterial blood pressure due to depressed cardiac conductivity, excitability, and myocardial contractility. Patients should have cardiovascular and respiratory vital signs and state of consciousness constantly monitored while under treatment.