2 DOSAGE AND ADMINISTRATION
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.
2.5 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.
2.8 Dosage Modifications for Adverse Reactions
Table 1 describes dosage modifications for specific adverse reactions. No dose reductions for ZIRABEV are recommended.
|Adverse Reaction||Severity||Dosage Modification|
|Gastrointestinal Perforations and Fistulae [see Warnings and Precautions (5.1)].||Discontinue ZIRABEV|
|Wound Healing Complications [see Warnings and Precautions (5.2)].||Withhold ZIRABEV until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complications has not been established.|
|Hemorrhage [see Warnings and Precautions (5.3)].||Discontinue ZIRABEV|
|Thromboembolic Events [see Warnings and Precautions (5.4, 5.5)].||Discontinue ZIRABEV|
|Hypertension [see Warnings and Precautions (5.6)].||Discontinue ZIRABEV|
|Withhold ZIRABEV if not controlled with medical management; resume once controlled|
|Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.7)].||Discontinue ZIRABEV|
|Renal Injury and Proteinuria [see Warnings and Precautions (5.8)].||Discontinue ZIRABEV|
|Withhold ZIRABEV until proteinuria less than 2 grams per 24 hours|
|Infusion-Related Reactions [see Warnings and Precautions (5.9)].||Discontinue ZIRABEV|
|Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve|
|Decrease infusion rate|
|Congestive Heart Failure [see Warnings and Precautions (5.12)].||Discontinue ZIRABEV|
2.9 Preparation and Administration
- Use appropriate aseptic technique.
- 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.
- Store diluted ZIRABEV solution at 2°C to 8°C (36°F to 46°F) for up to 8 hours.
- No incompatibilities between ZIRABEV and polyvinylchloride or polyolefin bags have been observed.
- 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.