AVASTIN- bevacizumab injection, solution
Genentech, Inc.

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.

​ Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

​ Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer. [See Clinical Studies (14.2).]

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 Glioblastoma

Avastin is indicated for the treatment of glioblastoma with progressive disease in adult patients 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 Clinical Studies (14.4).]

1.4 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.
• ​ Administer 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks when used in combination with a fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy regimen in patients who have progressed on a first-line Avastin-containing regimen.

Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

The recommended dose is 15 mg/kg every 3 weeks in combination with carboplatin and 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 Boxed Warning, Warnings and Precautions (5.1, 5.4).]
• Wound dehiscence and wound healing complications requiring medical intervention [See Warnings and Precautions (5.2).]
• Serious hemorrhage (i.e., requiring medical intervention) [See Boxed Warning, Warnings and Precautions (5.3).]
• Severe arterial thromboembolic events [See Warnings and Precautions (5.5).]
• Hypertensive crisis or hypertensive encephalopathy [See Warnings and Precautions (5.6).]
• Reversible posterior leukoencephalopathy syndrome (RPLS) [See Warnings and Precautions (5.7).]
• Nephrotic syndrome [See Warnings and Precautions (5.8).]

Temporarily suspend Avastin for:

• At least 4 weeks prior to elective surgery [See Warnings and Precautions (5.2).]
• Severe hypertension not controlled with medical management [See Warnings and Precautions (5.6).]
• Moderate to severe proteinuria pending further evaluation [See Warnings and Precautions (5.8).]
• Severe infusion reactions [See Warnings and Precautions (5.9).]

3 DOSAGE FORMS AND STRENGTHS

100 mg per 4 mL single-use vial

400 mg per 16 mL single-use vial

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Gastrointestinal Perforations

Serious and sometimes fatal gastrointestinal perforation occurs at a higher incidence in Avastin treated patients compared to controls. The incidence of gastrointestinal perforation ranged from 0.3 to 2.4% across clinical studies. [See Adverse Reactions (6.1).]

The typical presentation may include abdominal pain, nausea, emesis, constipation, and fever. Perforation can be complicated by intra-abdominal abscess and fistula formation. The majority of cases occurred within the first 50 days of initiation of Avastin.

Discontinue Avastin in patients with gastrointestinal perforation. [See Boxed Warning, Dosage and Administration (2.4).]