Bevacizumab-bvzrdosage

Withhold for at least 28 days prior to elective surgery. Do not administer ZIRABEV for 28 days following major surgery and until adequate wound healing. Metastatic colorectal cancer.

5 mg/kg every 2 weeks with bolus-IFL.

10 mg/kg every 2 weeks with FOLFOX4.

5 mg/ kg every 2 weeks or 7.5 mg/kg every 3 weeks with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin based chemotherapy after progression on a first-line bevacizumab product containing regimen. First-line non−squamous non−small cell lung cancer.

15 mg/kg every 3 weeks with carboplatin and paclitaxel. Recurrent glioblastoma.

10 mg/kg every 2 weeks. Metastatic renal cell carcinoma.

10 mg/kg every 2 weeks with interferon alfa. Persistent, recurrent, or metastatic cervical cancer.

15 mg/kg every 3 weeks with paclitaxel and cisplatin or paclitaxel and topotecan. Stage III or IV epithelial ovarian, fallopian tube or primary peritoneal cancer following initial surgical resection.

15 mg/kg every 3 weeks with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 weeks as a single agent, for a total of up to 22 cycles. Platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer.

10 mg/kg every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or topotecan given every week.

15 mg/kg every 3 weeks with topotecan given every 3 weeks Platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

15 mg/kg every 3 weeks with carboplatin and paclitaxel for 6–8 cycles, followed by 15 mg/kg every 3 weeks as a single agent.

15 mg/kg every 3 weeks with carboplatin and gemcitabine for 6–10 cycles, followed by 15 mg/kg every 3 weeks as a single agent. Administer as an intravenous infusion after dilution. See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions.

2.1 Important

Administration Information Withhold for at least 28 days prior to elective surgery. Do not administer ZIRABEV until at least 28 days following major surgery and until adequate wound healing.

2.2 Metastatic

Colorectal Cancer The recommended dosage when ZIRABEV is administered in combination with intravenous fluorouracil-based chemotherapy is:

5 mg/kg intravenously every 2 weeks in combination with bolus-IFL.

10 mg/kg intravenously every 2 weeks in combination with FOLFOX4.

5 mg/kg intravenously every 2 weeks or 7.5 mg/kg intravenously every 3 weeks in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy in patients who have progressed on a first-line bevacizumab product-containing regimen.

2.3 First-Line

Non-Squamous Non-Small Cell Lung Cancer The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel.

2.4 Recurrent

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

2.5 Metastatic

Renal Cell Carcinoma The recommended dosage is 10 mg/kg intravenously every 2 weeks in combination with interferon alfa.

2.6 Persistent,

Recurrent, or Metastatic Cervical Cancer The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with paclitaxel and cisplatin or in combination with paclitaxel and topotecan.

2.7 Epithelial

Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Stage III or IV Disease Following Initial Surgical Resection The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by ZIRABEV 15 mg/kg every 3 weeks as a single agent for a total of up to 22 cycles or until disease progression, whichever occurs earlier. Recurrent Disease Platinum Resistant The recommended dosage is 10 mg/kg intravenously every 2 weeks in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan (every week). The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with topotecan (every 3 weeks). Platinum Sensitive The recommended dosage is 15 mg/kg intravenously every 3 weeks, in combination with carboplatin and paclitaxel for 6 to 8 cycles, followed by ZIRABEV 15 mg/kg every 3 weeks as a single agent until disease progression. The recommended dosage is 15 mg/kg intravenously every 3 weeks, in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by ZIRABEV 15 mg/kg every 3 weeks as a single agent until disease progression.

2.8 Dosage Modifications for

Adverse Reactions Table 1 describes dosage modifications for specific adverse reactions. No dose reductions for ZIRABEV are recommended. Table 1: Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Gastrointestinal Perforations and Fistulae.

Gastrointestinal perforation, any grade

Tracheoesophageal fistula, any grade

Fistula, Grade 4

Fistula formation involving any internal organ Discontinue ZIRABEV Wound Healing Complications.

Any Withhold ZIRABEV until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complications has not been established.

Necrotizing fasciitis Discontinue ZIRABEV Hemorrhage.

Grade 3 or 4 Discontinue ZIRABEV

Recent history of hemoptysis of 1/2 teaspoon (2.5 mL) or more Withhold ZIRABEV Thromboembolic Events.

Arterial thromboembolism, severe Discontinue ZIRABEV

Venous thromboembolism, Grade 4 Discontinue ZIRABEV Hypertension.

Hypertensive crisis

Hypertensive encephalopathy Discontinue ZIRABEV

Hypertension, severe Withhold ZIRABEV if not controlled with medical management; resume once controlled Posterior Reversible Encephalopathy Syndrome (PRES).

Any Discontinue ZIRABEV Renal Injury and Proteinuria.

Nephrotic syndrome Discontinue ZIRABEV

Proteinuria greater than or equal to 2 grams per 24 hours in absence of nephrotic syndrome Withhold ZIRABEV until proteinuria less than 2 grams per 24 hours Infusion-Related Reactions.

Severe Discontinue ZIRABEV

Clinically significant Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve

Mild, clinically insignificant Decrease infusion rate Congestive Heart Failure.

Any Discontinue ZIRABEV

2.9 Preparation and

Administration Preparation

Use appropriate aseptic technique.

Use sterile needle and syringe to prepare ZIRABEV.

Visually inspect vial for particulate matter and discoloration prior to preparation for administration. Discard vial if solution is cloudy, discolored, or contains particulate matter.

Withdraw necessary amount of ZIRABEV and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. DO NOT ADMINISTER OR MIX WITH DEXTROSE SOLUTION.

Discard any unused portion left in a vial, as the product contains no preservatives.

Diluted ZIRABEV solution may be stored at 2°C to 8°C (36°F to 46°F) for up to 16 days, if not used immediately.

No incompatibilities between ZIRABEV and polyvinylchloride or polyolefin bags have been observed. Administration

Administer as an intravenous infusion.

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 second infusion over 60 minutes is tolerated.