AVZIVI

14.1 Metastatic Colorectal Cancer Study AVF2107g The safety and efficacy of bevacizumab was evaluated in a double-blind, active-controlled study [AVF2107g (NCT00109070)] in 923 patients with previously untreated mCRC who were randomized (1:1:1) to placebo with bolus-IFL (irinotecan 125 mg/m 2 , fluorouracil 500 mg/m 2 , and leucovorin 20 mg/m 2 given once weekly for 4 weeks every 6 weeks), bevacizumab (5 mg/kg every 2 weeks) with bolus-IFL, or bevacizumab (5 mg/kg every 2 weeks) with fluorouracil and leucovorin. Enrollment to the bevacizumab with fluorouracil and leucovorin arm was discontinue...

The following clinically significant adverse reactions are described elsewhere in the labeling: Gastrointestinal Perforations and Fistulae [see Warnings and Precautions ( 5.1 )] . Surgery and Wound Healing Complications [see Warnings and Precautions ( 5.2 )]. Hemorrhage [see Warnings and Precautions ( 5.3 )]. Arterial Thromboembolic Events [see Warnings and Precautions ( 5.4 )]. Venous Thromboembolic Events [see Warnings and Precautions ( 5.5 )]. Hypertension [see Warnings and Precautions ( 5.6 ...

None. None. ( 4 )

• Gastrointestinal Perforations and Fistula : Discontinue for gastrointestinal perforations, tracheoesophageal fistula, grade 4 fistula, or fistula formation involving any organ. ( 5.1 )
• Surgery and Wound Healing Complications : In patients who experience wound healing complications during Avzivi treatment, withhold Avzivi until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer Avzivi for at least 28 days following a major surgery, and until ade...

7 DRUG INTERACTIONS Effects of Avzivi on Other Drugs No clinically meaningful effect on the pharmacokinetics of irinotecan or its active metabolite SN38, interferon alfa, carboplatin or paclitaxel was observed when bevacizumab was administered in combination with these drugs; however, 3 of the 8 patients receiving bevacizumab with paclitaxel and carboplatin had lower paclitaxel exposure after four...