ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles
for injectable suspension) (albumin-bound)
The following is a Brief Summary; refer to full Prescribing Information for
complete product information.
1 INDICATIONS AND USAGE
1.2 Non-Small Cell Lung Cancer
ABRAXANE is indicated for the first-line treatment of locally advanced or
metastatic non-small cell lung cancer, in combination with carboplatin, in
patients who are not candidates for curative surgery or radiation therapy.
2 DOSAGE AND ADMINISTRATION
2. 2 Non-Small Cell Lung Cancer
The recommended dose of ABRAXANE is 100 mg/m2 administered as an
intravenous infusion over 30 minutes on Days 1, 8, and 15 of each 21-day
cycle. Administer carboplatin on Day 1 of each 21 day cycle immediately
after ABRAXANE [see Clinical Studies( 14. 2)].
2. 4 Dosage in Patients with Hepatic Impairment
For patients with mild hepatic impairment (total bilirubin greater than ULN
and less than or equal to 1.5 x ULN and aspartate aminotransferase [AST]
less than or equal to 10 x ULN), no dose adjustments are required,
regardless of indication.
Do not administer ABRAXANE to patients with total bilirubin greater than
5 x ULN or AST greater than 10 x ULN regardless of indication as these
patients have not been studied.
Recommendations for dosage adjustment for the first course of therapy
are shown in Table 1.
Table 1: Recommendations for Starting Dose
in Patients with Hepatic Impairment
SGOT (AST) Bilirubin ABRAXANE Dosea
Levels Levels NSCLC c
Mild < 10 x ULN AND > ULN to ≤ 1.5 x ULN 100 mg/m2
Moderate < 10 x ULN AND > 1.5 to ≤ 3 x ULN 80 mg/m2 b
Severe < 10 x ULN AND > 3 to ≤ 5 x ULN 80 mg/m2 b
> 10 x ULN OR > 5 x ULN not recommended
NSCLC = Non-Small Cell Lung Cancer.
a Dosage recommendations are for the first course of therapy. The need for
further dose adjustments in subsequent courses should be based on
b A dose increase to 100 mg/m2 for patients with non-small cell lung cancer in
subsequent courses should be considered if the patient tolerates the reduced
dose for two cycles.
c Patients with bilirubin levels above the upper limit of normal were excluded
from clinical trials for lung cancer.
2. 5 Dose Reduction/Discontinuation Recommendations
Non-Small Cell Lung Cancer
• Do not administer ABRAXANE on Day 1 of a cycle until absolute
neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is
at least 100,000 cells/mm3 [see Contraindications ( 4), Warningsand
Precautions ( 5.1) and Adverse Reactions ( 6. 2)].
• In patients who develop severe neutropenia or thrombocytopenia
withhold treatment until counts recover to an absolute neutrophil count
of at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3
on Day 1 or to an absolute neutrophil count of at least 500 cells/mm3
and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the
cycle. Upon resumption of dosing, permanently reduce ABRAXANE and
carboplatin doses as outlined in Table 2.
• Withhold ABRAXANE for Grade 3-4 peripheral neuropathy. Resume
ABRAXANE and carboplatin at reduced doses (see Table 2) when
peripheral neuropathy improves to Grade 1 or completely resolves [see
Warnings and Precautions ( 5. 2) and Adverse Reactions ( 6. 2)].
Table 2: Permanent Dose Reductions for Hematologic and
Neurologic Adverse Drug Reactions in NSCLC
Weekly Every 3-Week
Adverse Drug Occurrence ABRAXANE Dose Carboplatin Dose
Reaction (mg/m2) (AUC mg•min/mL)
(ANC less than 500/mm3 First 75 4. 5
with fever > 38°C)
Delay of next cycle by Second 50 3 more than 7 days for
ANC less than 1500/mm3
ANC less than 500/mm3 Third Discontinue Treatment
for more than 7 days
Platelet count less than First 75 4. 5
50,000/mm3 Second Discontinue Treatment
Severesensory First 75 4. 5
Neuropathy – Second 50 3
Grade 3 or 4 Third Discontinue Treatment
• ABRAXANE should not be used in patients who have baseline neutrophil
counts of < 1,500 cells/mm3.
• Patients who experience a severe hypersensitivity reaction to ABRAXANE
should not be rechallenged with the drug.
5 WARNINGS AND PRECAUTIONS
5.1 Hematologic Effects
Bone marrow suppression (primarily neutropenia) is dose-dependent
and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4
neutropenia occurred in 47% of patients with non-small cell lung cancer
Monitor for myelotoxicity by performing complete blood cell counts
frequently, including prior to dosing on Days 1, 8, and 15. Do not
administer ABRAXANE to patients with baseline absolute neutrophil counts
(ANC) of less than 1,500 cells/mm3. In the case of severe neutropenia
(<500 cells/mm3 for seven days or more) during a course of ABRAXANE
therapy, reduce the dose of ABRAXANE in subsequent courses in patients.
In patients with NSCLC, resume treatment if recommended (see Dosage
and Administration, Table 2) at permanently reduced doses for both
weekly ABRAXANE and every-3-week carboplatin after ANC recovers to
at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3
on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at
least 50,000 cells/mm3 on Days 8 or 15 of the cycle [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 followed by a dose reduction for all subsequent
courses of ABRAXANE [see Dosageand Administration( 2. 5)].
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 rechallenged with
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. The starting dose should be reduced for patients with
moderate or severe hepatic impairment [see Dosageand 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
• Do not administer ABRAXANE therapy to patients who have baseline
neutrophil counts of less than 1,500 cells/mm3. In order to monitor the
occurrence of bone marrow suppression, primarily neutropenia, which
may be severe and result in infection, it is recommended that frequent
peripheral blood cell counts be performed on all patients receiving
ABRAXANE [see Contraindications ( 4), Warnings and Precautions ( 5.1)
and Adverse Reactions ( 6.1, 6. 2, 6. 3)].
• Note: An albumin form of paclitaxel may substantially affect a drug’s
functional properties relative to those of drug in solution. DO NOT
SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.