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Abraxane (Paclitaxel) - Indications and Dosage

 
 



INDICATIONS AND USAGE

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.

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.

Adenocarcinoma of the Pancreas

ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

DOSAGE AND ADMINISTRATION

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.

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 ].

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].

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 metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment.

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
MBC = Metastatic Breast Cancer; 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 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.
SGOT (AST) Levels Bilirubin Levels ABRAXANE Dosea
MBC NSCLC c Pancreatic c
Adenocarcinoma
Mild < 10 x ULN AND > ULN to ≤ 1.5 x ULN 260 mg/m2 100 mg/m2 125 mg/m2
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

Dose Reduction/Discontinuation Recommendations

Metastatic Breast Cancer
Patients 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 ].

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),Warnings and Precautions and Adverse Reactions].
  • 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 and Adverse Reactions].
Table 2: Permanent Dose Reductions for Hematologic and Neurologic Adverse Drug Reactions in NSCLC
Adverse Drug 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)
                                                      OR
Delay of next cycle by more than 7 days for ANC less than 1500/mm3
                                                      OR
ANC 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 Pancreas
Dose level reductions for patients with adenocarcinoma of the pancreas, as referenced in Tables 4 and 5, are provided in Table 3.

Table 3: Dose Level Reductions for Patients with Adenocarcinoma of the Pancreas
  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.

Table 4: Dose Recommendation and Modifications for Neutropenia and/or Thrombocytopenia at the Start of a Cycle or within a Cycle for Patients with Adenocarcinoma of the Pancreas
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 drug reactions in patients with adenocarcinoma of the pancreas are provided in Table 5.

Table 5: Dose Modifications for Other Adverse Drug Reactions in Patients with Adenocarcinoma of the Pancreas
Adverse Drug 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

Preparation and Administration Precautions

ABRAXANE is a cytotoxic drug and, as with other potentially toxic paclitaxel compounds, caution should be exercised in handling ABRAXANE. The use of gloves is recommended. If ABRAXANE (lyophilized cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure to paclitaxel, events may include tingling, burning and redness. If ABRAXANE contacts mucous membranes, the membranes should be flushed thoroughly with water.

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces the likelihood of infusion-related reactions [see Adverse Reactions ].

Premedication to prevent hypersensitivity reactions is generally not needed prior to the administration of ABRAXANE. Premedication may be needed in patients who have had prior hypersensitivity reactions to ABRAXANE. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be re-challenged with this drug [see Warnings and Precautions].

Preparation for Intravenous Administration

ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION.

  1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP.
  2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a minimum of 1 minute, using the
    sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL.
  3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this
    will result in foaming.
  4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of
    the lyophilized cake/powder.
  5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder
    occurs. Avoid generation of foam.
  6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides.

Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.

Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing volume (mL) = Total dose (mg)/5 (mg/mL).

The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. Discard any unused portion.

Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile intravenous bag [plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type intravenous bag]. The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of an in-line filter is not recommended.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Stability

Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20°C to 25°C (68°F to 77°F) in the original package. Neither freezing nor refrigeration adversely affects the stability of the product.

Stability of Reconstituted Suspension in the Vial
Reconstituted ABRAXANE in the vial should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 24 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion.

Stability of Reconstituted Suspension in the Infusion Bag
The suspension for infusion when prepared as recommended in an infusion bag should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) and protected from bright light for a maximum of 24 hours.

The total combined refrigerated storage time of reconstituted ABRAXANE in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25°C) and lighting conditions for a maximum of 4 hours.

Discard any unused portion.

DOSAGE FORMS AND STRENGTHS

For injectable suspension: lyophilized powder containing 100 mg of paclitaxel formulated as albumin-bound particles in single-use vial for reconstitution.

HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Product No.: 103450
NDC No.: 68817-134-50        100 mg of paclitaxel in a single-use vial, individually packaged in a carton.

Storage

Store the vials in original cartons at 20°C to 25°C (68°F to 77°F). Retain in the original package to protect from bright light.

Handling and Disposal

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published [see References]. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

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