ABRAXANE
ABRAXANE- paclitaxel injection, powder, lyophilized, for suspension
Abraxis BioScience, LLC
ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)
WARNING: SEVERE MYELOSUPPRESSION
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- Do not administer ABRAXANE therapy to patients with baseline neutrophil counts of less than 1,500 cells/mm3 [see Contraindications (4)].
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- Monitor for neutropenia, which may be severe and result in infection or sepsis [see Warnings and Precautions (5.1, 5.3)].
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- Perform frequent complete blood cell counts on all patients receiving ABRAXANE [see Warnings and Precautions (5.1, 5.3)].
1 INDICATIONS AND USAGE
1.1 Metastatic Breast Cancer
ABRAXANE is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
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.
1.3 Adenocarcinoma of the Pancreas
ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.
2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions
DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS. ABRAXANE has different dosage and administration instructions from other paclitaxel products.
Closely monitor the infusion site for extravasation or drug infiltration during administration. Limiting the infusion of ABRAXANE to 30 minutes may reduce the risk of infusion-related reactions [see Adverse Reactions (6.2)].
Consider premedication in patients who have had prior hypersensitivity reactions to ABRAXANE. Do not re-challenge patients who experience a severe hypersensitivity reaction to ABRAXANE [see Contraindications (4) and Warnings and Precautions (5.5)].
2.2 Recommended Dosage for Metastatic Breast Cancer
After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.
2.3 Recommended Dosage for 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 Recommended Dosage for Adenocarcinoma of the Pancreas
The recommended dose of ABRAXANE is 125 mg/m2 administered as an intravenous infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer gemcitabine immediately after ABRAXANE on Days 1, 8, and 15 of each 28-day cycle [see Clinical Studies (14.3)].
2.5 Dosage Modifications for Hepatic Impairment
For patients with moderate or severe hepatic impairment, reduce the starting dose of ABRAXANE as shown in Table 1.
AST = Aspartate Aminotransferase; MBC = Metastatic Breast Cancer; NSCLC = Non-Small Cell Lung Cancer; ULN = Upper limit of normal.a Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance.b A dose increase to 260 mg/m2 for patients with metastatic breast cancer or 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 pancreatic or lung cancer. | ||||||
AST Levels | Bilirubin Levels | ABRAXANE Dosea | ||||
MBC | NSCLC c | Adenocarcinoma of Pancreasc | ||||
Moderate | < 10 x ULN | AND | > 1.5 to ≤ 3 x ULN | 200 mg/m2 b | 80 mg/m2 b | not recommended |
Severe | < 10 x ULN | AND | > 3 to ≤ 5 x ULN | 200 mg/m2 b | 80 mg/m2 b | not recommended |
> 10 x ULN | OR | > 5 x ULN | not recommended | not recommended | not recommended |
2.6 Dosage Modifications for Adverse Reactions
Metastatic Breast CancerPatients who experience severe neutropenia (neutrophils less than 500 cells/mm3 for a week or longer) or severe sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m2 for subsequent courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m2. For Grade 3 sensory neuropathy hold treatment until resolution to Grade 1 or 2, followed by a dose reduction for all subsequent courses of ABRAXANE [see Contraindications (4), Warnings and Precautions (5.1, 5.2) and Adverse Reactions (6.1)].
Non-Small Cell Lung Cancer
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- 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), Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
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- 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.
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- 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 (6.1)].
Adverse Reaction | Occurrence | Weekly ABRAXANE Dose (mg/m2) | Every 3-Week Carboplatin Dose (AUC mg•min/mL) |
Neutropenic Fever (ANC less than 500/mm3 with fever >38°C) ORDelay of next cycle by more than 7 days for ANC less than 1500/mm3 ORANC less than 500/mm3 for more than 7 days | First | 75 | 4.5 |
Second | 50 | 3 | |
Third | Discontinue Treatment | ||
Platelet count less than 50,000/mm3 | First | 75 | 4.5 |
Second | Discontinue Treatment | ||
Severe sensory Neuropathy – Grade 3 or 4 | First | 75 | 4.5 |
Second | 50 | 3 | |
Third | Discontinue Treatment |
Adenocarcinoma of the PancreasDose level reductions for patients with adenocarcinoma of the pancreas, as referenced in Tables 4 and 5, are provided in Table 3.
Dose Level | ABRAXANE (mg/m2) | Gemcitabine (mg/m2) |
Full dose | 125 | 1000 |
1st dose reduction | 100 | 800 |
2nd dose reduction | 75 | 600 |
If additional dose reduction required | Discontinue | Discontinue |
Recommended dose modifications for neutropenia and thrombocytopenia for patients with adenocarcinoma of the pancreas are provided in Table 4.
ANC = Absolute Neutrophil Count | ||||
Cycle Day | ANC (cells/mm3) | Platelet count (cells/mm3) | ABRAXANE / Gemcitabine | |
Day 1 | < 1500 | OR | < 100,000 | Delay doses until recovery |
Day 8 | 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 1 dose level |
| < 500 | OR | < 50,000 | Withhold doses |
Day 15: If Day 8 doses were reduced or given without modification: | ||||
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 1 dose level from Day 8 |
| < 500 | OR | < 50,000 | Withhold doses |
Day 15: If Day 8 doses were withheld: | ||||
| ≥ 1000 | OR | ≥ 75,000 | Reduce 1 dose level from Day 1 |
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 2 dose levels from Day 1 |
| < 500 | OR | < 50,000 | Withhold doses |
Recommended dose modifications for other adverse reactions in patients with adenocarcinoma of the pancreas are provided in Table 5.
Adverse Reaction | ABRAXANE | Gemcitabine |
Febrile Neutropenia: Grade 3 or 4 | Withhold until fever resolves and ANC ≥ 1500; resume at next lower dose level | |
Peripheral Neuropathy: Grade 3 or 4 | Withhold until improves to ≤ Grade 1; resume at next lower dose level | No dose reduction |
Cutaneous Toxicity: Grade 2 or 3 | Reduce to next lower dose level; discontinue treatment if toxicity persists | |
Gastrointestinal Toxicity: Grade 3 mucositis or diarrhea | Withhold until improves to ≤ Grade 1; resume at next lower dose level |
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