Avastin® (Bevacizumab)

Bevacizumab - Avastin®

Usual Diluents

Dilution Data

Preparation for Administration
Use appropriate aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Withdraw necessary amount of Avastin and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Discard any unused portion left in a vial, as the product contains no preservatives.

DO NOT ADMINISTER OR MIX WITH DEXTROSE SOLUTION.

Administration
Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion.
Do not initiate Avastin until at least 28 days following major surgery. Administer Avastin after the surgical incision has fully healed.
First infusion: Administer infusion over 90 minutes.
Subsequent infusions: Administer second infusion over 60 minutes if first infusion is tolerated; administer all subsequent infusions over 30 minutes if infusion over 60 minutes is tolerated.

Storage:
Diluted Avastin solutions may be stored at 2–8°C (36–46°F) for up to 8 hours. Store in the original carton until time of use. No incompatibilities between Avastin and polyvinylchloride or polyolefin bags have been observed

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use AVASTIN safely and effectively. See full prescribing information for AVASTIN.

RECENT MAJOR CHANGES
Indications and Usage, Glioblastoma 5/2009
Indications and Usage, Renal Cell Carcinoma 7/2009
Dosage and Administration, Glioblastoma 5/2009
Dosage and Administration, Renal Cell Carcinoma 7/2009
Warnings and Precautions, Hemorrhage 5/2009
Warnings and Precautions, Proteinuria 7/2009

DOSAGE AND ADMINISTRATION
Do not administer as an IV push or bolus.
Do not initiate Avastin for 28 days following major surgery and until surgical wound is fully healed.

Metastatic colorectal cancer:
5 mg/kg IV every 2 weeks with bolus-IFL
10 mg/kg IV every 2 weeks with FOLFOX4

Non-squamous, non-small cell lung cancer:
15 mg/kg IV every 3 weeks with carboplatin/paclitaxel

Metastatic breast cancer:
10 mg/kg IV every 2 weeks with paclitaxel

Glioblastoma:
10 mg/kg IV every 2 weeks

Metastatic renal cell carcinoma (mRCC):
10 mg/kg IV every 2 weeks with interferon alfa

1. INDICATIONS AND USAGE

1.1 Metastatic Colorectal Cancer (mCRC)
Avastin is indicated for the first - or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy.

1.2 Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer in combination with carboplatin and paclitaxel.

1.3 Metastatic Breast Cancer (MBC)
Avastin is indicated for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer in combination with paclitaxel.

The effectiveness of Avastin in MBC is based on an improvement in progression free survival. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin. [ See PACKAGE INSERT FOR Clinical Studies (14.3). ]

Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease.

1.4 Glioblastoma
Avastin is indicated for the treatment of glioblastoma with progressive disease following prior therapy as a single agent.

The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin. [ See PACKAGE INSERT FOR Clinical Studies (14.4). ]

1.5 Metastatic Renal Cell Carcinoma (mRCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

2.  DOSAGE AND ADMINISTRATION

2.1 Administration
Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion.

Do not initiate Avastin until at least 28 days following major surgery. Administer Avastin after the surgical incision has fully healed.
First infusion: Administer infusion over 90 minutes.
Subsequent infusions: Administer second infusion over 60 minutes if first infusion is tolerated; administer all subsequent infusions over 30 minutes if infusion over 60 minutes is tolerated.

2.2 Recommended Doses and Schedules
Patients should continue treatment until disease progression or unacceptable toxicity.

Metastatic Colorectal Cancer (mCRC)
The recommended doses are 5 mg/kg or 10 mg/kg every 2 weeks when used in combination with intravenous 5-FU-based chemotherapy.

Administer 5 mg/kg when used in combination with bolus-IFL.
Administer 10 mg/kg when used in combination with FOLFOX4.
Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

The recommended dose is 15 mg/kg every 3 weeks in combination with carboplatin and paclitaxel.

Metastatic Breast Cancer (MBC)
The recommended dose is 10 mg/kg every 2 weeks in combination with paclitaxel.

Glioblastoma
The recommended dose is 10 mg/kg every 2 weeks.

Metastatic Renal Cell Carcinoma (mRCC)
The recommended dose is 10 mg/kg every 2 weeks in combination with interferon alfa.

2.3 Preparation for Administration
Use appropriate aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Withdraw necessary amount of Avastin and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Discard any unused portion left in a vial, as the product contains no preservatives.

DO NOT ADMINISTER OR MIX WITH DEXTROSE SOLUTION.

2.4 Dose Modifications
There are no recommended dose reductions.

Discontinue Avastin for: Gastrointestinal perforations (gastrointestinal perforations, fistula formation in the gastrointestinal tract, intra-abdominal abscess), fistula formation involving an internal organ [ See PACKAGE INSERT - Boxed Warning , Warnings and Precautions (5.1, 5.4). ] Wound dehiscence and wound healing complications requiring medical intervention [ See PACKAGE INSERT -Warnings and Precautions ] Serious hemorrhage (i.e., requiring medical intervention) [ See PACKAGE INSERT -Boxed Warning,  Warnings and Precautions. ] Severe arterial thromboembolic events [ See PACKAGE INSERT -Warnings and Precautions. ] Hypertensive crisis or hypertensive encephalopathy [ See PACKAGE INSERT -Warnings and Precautions. ] Reversible posterior leukoencephalopathy syndrome (RPLS) [ See PACKAGE INSERT -Warnings and Precautions. ] Nephrotic syndrome [ See PACKAGE INSERT -Warnings and Precautions. ] Temporarily suspend Avastin for: At least 4 weeks prior to elective surgery [ See PACKAGE INSERT -Warnings and Precautions. ] Severe hypertension not controlled with medical management [ See PACKAGE INSERT -Warnings and Precautions. ] Moderate to severe proteinuria pending further evaluation [ See PACKAGE INSERT - Warnings and Precautions. ] Severe infusion reactions [ See PACKAGE INSERT -Warnings and Precautions. ]

3. DOSAGE FORMS AND STRENGTHS
100 mg per 4 mL single-use vial
400 mg per 16 mL single-use vial

4. CONTRAINDICATIONS
None.

HOW SUPPLIED/STORAGE AND HANDLING
Avastin vials [100 mg (NDC-50242-060-01) and 400 mg (NDC 50242-061-01)] are stable at 2–8°C (36–42°F). Avastin vials should be protected from light. Do not freeze or shake.

Storage:
Diluted Avastin solutions may be stored at 2–8°C (36–46°F) for up to 8 hours. Store in the original carton until time of use. No incompatibilities between Avastin and polyvinylchloride or polyolefin bags have been observed

©2009 Genentech, Inc.