Drug Interactions between bupivacaine liposome and bupivacaine / sufentanil

ADJUST DOSING INTERVAL: Administration of bupivacaine liposome suspension together with other bupivacaine (hydrochloride) formulations, either simultaneously in the same syringe or sequentially to the same site, may impact the pharmacokinetic and/or physicochemical properties of bupivacaine liposome in a concentration-dependent manner. Specifically, when the milligram dose of bupivacaine HCl exceeds 50% of the bupivacaine liposome dose, substantial displacement and rapid release of free bupivacaine from liposomes may occur, 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, including bupivacaine HCl. Moreover, injection of multiple doses of bupivacaine or other amide-containing anesthetics may cause significant increases in plasma concentrations with each repeated dose due to slow accumulation of the drug or its metabolites, or to slow metabolic degradation. Tolerance to elevated concentrations will vary with patient status, but the potential for increased risk of systemic toxicities such as methemoglobinemia and central nervous system and cardiovascular adverse reactions should be recognized.

MANAGEMENT: Additional use of local anesthetics, including bupivacaine HCl, should generally be avoided within 96 hours following administration of bupivacaine liposome suspension. If necessary, bupivacaine HCl and bupivacaine liposome may be administered simultaneously in the same syringe, or bupivacaine HCl may be injected immediately before bupivacaine liposome, as long as the ratio of the milligram dose of bupivacaine HCl to bupivacaine liposome does not exceed 1:2. Some authorities recommend that the total amount of co-administered bupivacaine HCl and bupivacaine liposomal should not exceed 400 mg equivalents of bupivacaine HCl (UK). However, 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. 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.

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