ALYMSYS

2 DOSAGE AND ADMINISTRATION Withhold for at least 28 days prior to elective surgery. Do not administer Alymsys for 28 days following major surgery and until adequate wound healing. (2.1) Metastatic colorectal cancer (2.2) 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 (2.3) 15 mg/kg every 3 weeks with carboplatin and paclitaxel Recurrent glioblastoma (2.4) 10 mg/kg every 2 weeks Metastatic renal cell carcinoma (2.5) 10 mg/kg every 2 weeks with interferon alfa Persistent, recurrent, or metastatic cervical cancer (2.6) 15 mg/kg every 3 weeks with paclitaxel and cisplatin, or paclitaxel and topotecan Platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (2.7) 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 Administer as an intravenous infusion (2.9) 2.1 Important Administration Information Withhold for at least 28 days prior to elective surgery. Do not administer Alymsys until at least 28 days following major surgery and until adequate wound healing. 2.2 Metastatic Colorectal Cancer The recommended dosage when Alymsys 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 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). 2.8 Dosage Modifications for Adverse Reactions Table 1 describes dosage modifications for specific adverse reactions. No dose reductions for Alymsys are recommended. Table 1: Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Gastrointestinal Perforations and Fistulae [see Warnings and Precautions (5.1)] . Gastrointestinal perforation, any grade Tracheoesophageal fistula, any grade Fistula, Grade 4 Fistula formation involving any internal organ Discontinue Alymsys Wound Healing Complications [see Warnings and Precautions (5.2)] . Any Withhold Alymsys until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complications has not been established. Necrotizing fasciitis Discontinue Alymsys Hemorrhage [see Warnings and Precautions (5.3)] . Grade 3 or 4 Discontinue Alymsys Recent history of hemoptysis of 1/2 teaspoon (2.5 mL) or more Withhold Alymsys Thromboembolic Events [see Warnings and Precautions (5.4, 5.5)] . Arterial thromboembolism, severe Discontinue Alymsys Venous thromboembolism, Grade 4 Discontinue Alymsys Hypertension [see Warnings and Precautions (5.6)] . Hypertensive crisis Hypertensive encephalopathy Discontinue Alymsys Hypertension, severe Withhold Alymsys if not controlled with medical management; resume once controlled Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.7)] . Any Discontinue Alymsys Renal Injury and Proteinuria [see Warnings and Precautions (5.8)] . Nephrotic syndrome Discontinue Alymsys Proteinuria greater than or equal to 2 grams per 24 hours in absence of nephrotic syndrome Withhold Alymsys until proteinuria less than 2 grams per 24 hours Infusion-Related Reactions [see Warnings and Precautions (5.9)] . Severe Discontinue Alymsys Clinically significant Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve Mild, clinically insignificant Decrease infusion rate Congestive Heart Failure [see Warnings and Precautions (5.12)] . Any Discontinue Alymsys 2.9 Preparation and Administration Preparation 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 Alymsys 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 Alymsys solution at 2°C to 8°C (36°F to 46°F) for up to 12 hours. No incompatibilities between Alymsys 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.

See official label

1 INDICATIONS AND USAGE Alymsys is a vascular endothelial growth factor inhibitor indicated for the treatment of: Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment.