ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension)(十七)
ABRAXANE did not include sufficient number of patients with pancreatic cancer who were 75 years and older to determine whether they respond differently from younger patients.
8.6 Patients with Hepatic Impairment
The exposure to paclitaxel may be higher in patients with hepatic impairment than in patients with normal hepatic function. Reduce ABRAXANE starting dose in patients with moderate to severe hepatic impairment. Do not administer ABRAXANE to patients with total bilirubin > 5 x ULN or AST > 10 x ULN [see Dosage and Administration (2.4), Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)]. Do not administer to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment see Dosage and Administration (2.4)].
8.7 Patients with Renal Impairment
Adjustment of the starting ABRAXANE dose is not required for patients with mild to moderate renal impairment (estimated creatinine clearance ≥30 to <90 mL/min) [see Clinical Pharmacology (12.3)]. There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min).
10 OVERDOSAGE
There is no known antidote for ABRAXANE overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, sensory neurotoxicity, and mucositis.
11 DESCRIPTION
ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is paclitaxel formulated as albumin-bound nanoparticles with a mean particle size of approximately 130 nanometers. Paclitaxel exists in the particles in a non-crystalline, amorphous state. ABRAXANE is supplied as a white to yellow, sterile, lyophilized powder for reconstitution with 20 mL of 0.9% Sodium Chloride Injection, USP prior to intravenous infusion. Each single-use vial contains 100 mg of paclitaxel (bound to human albumin) and approximately 900 mg of human albumin (containing sodium caprylate and sodium acetyltryptophanate). Each milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel formulated as albumin-bound particles. ABRAXANE is free of solvents.
The active agent in ABRAXANE is paclitaxel, a microtubule inhibitor. The chemical name for paclitaxel is 5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine.
Paclitaxel has the following structural formula:
Paclitaxel is a white to off-white crystalline powder with the empirical formula C47H51NO14 and a molecular weight of 853.91. It is highly lipophilic, insoluble in water, and melts at approximately 216°C to 217°C.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
ABRAXANE is a microtubule inhibitor that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
12.3 Pharmacokinetics
Absorption
The pharmacokinetics of total paclitaxel following 30 and 180-minute infusions of ABRAXA |
