2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Information
Do not administer ZIRABEV until at least 28 days following surgery and the wound is fully healed.
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.
2.7 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)].||Discontinue ZIRABEV|
|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)].||Any||Discontinue ZIRABEV|
2.8 Preparation and Administration
- Use appropriate aseptic technique.
- Visually inspect vial for particulate matter and discoloration prior to preparation and 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.