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Distribution, Metabolism, and Excretion

Once bupivacaine is released from the liposome, its distribution, metabolism, and excretion are expected to follow the same kinetics as bupivacaine HCl.25 The rate of systemic absorption of bupivacaine is dependent upon the total dose of drug administered, the route of administration, and the vascularity of the administration site. To some extent, local anesthetics such as bupivacaine are distributed to all body tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and brain.

Elimination of bupivacaine depends largely on the reversible binding to plasma proteins and red blood cells in the systemic circulation to transport bupivacaine to the liver, where it is metabolized; bupivacaine has a high protein-binding capacity of 95%. The kidney is the main excretory organ for bupivacaine and its metabolites. Patients with hepatic disease, especially those with severe hepatic disease, may be more susceptible to the potential toxicities of the aminoamide local anesthetics such as bupivacaine.25 NOCITA® (bupivacaine liposome injectable suspension) is intended for single-dose administration; therefore, accumulation of bupivacaine or its metabolites is not expected even in patients with impaired hepatic or renal function.

NOCITA is a suspension of multivesicular liposomes containing bupivacaine in 0.9% sodium chloride solution along with a small amount (< 8%) of free (unencapsulated) bupivacaine. Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug’s functional properties relative to those of the unencapsulated or non–lipid-associated drug. In addition, different liposomal or lipid-complexed products with a common active ingredient may vary in the chemical composition and physical form of the lipid component. Such differences may affect functional properties of these drug products. Do not mix NOCITA with other local anesthetics or other drugs prior to administration.

25. Marcaine™ [package insert]. Lake Forest, IL: Hospira, Inc.; 2014.