ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension)(八)
t with appropriate dose reduction if recommended [see Dosage and Administration (2.5)].
5.2 Nervous System
Sensory neuropathy is dose- and schedule-dependent [see Adverse Reactions (6.1, 6.2, 6.3)]. The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification. If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to Grade 1 or 2 for metastatic breast cancer or until resolution to ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE [see Dosage and Administration (2.5)].
5.3 Sepsis
Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine. Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis. If a patient becomes febrile (regardless of ANC) initiate treatment with broad spectrum antibiotics. For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥ 1500, then resume treatment at reduced dose levels [see Dosage and Administration (2.5)].
5.4 Pneumonitis
Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine. Monitor patients for signs and symptoms of pneumonitis and interrupt ABRAXANE and gemcitabine during eva luation of suspected pneumonitis. After ruling out infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue treatment with ABRAXANE and gemcitabine.
5.5 Hypersensitivity
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be re-challenged with this drug.
5.6 Hepatic Impairment
Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution. Patients with hepatic impairment may be at increased risk of toxicity, particularly from myelosuppression; such patients should be closely monitored for development of profound myelosuppression. ABRAXANE is not recommended in patients who have total bilirubin >5 x ULN or AST >10 x ULN. In addition, ABRAXANE is not recommended in patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and AST ≤10 x ULN). The starting dose should be reduced for patients with moderate or severe hepatic impairment [see Dosage and Administration (2.4), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
5.7 Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries a remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
5.8 Use in Pregnancy
ABRAXANE can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy at doses lower than the maximum recommended human dose, based on body surface area, caused embryo-fetal toxicities, including intrauterine mortality, increased r |
