Label Changes for:
Changes have been made to the ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Clinical Trial Experience
- A retrospective analysis across clinical trials where 5805 patients had received Avastin and chemotherapy and 3713 had received chemotherapy alone has shown higher rates of elevated serum creatinine levels (ranging between 1.5 – 1.9 times baseline levels) in patients who had received Avastin. Creatinine levels did not return to baseline in approximately one-third of patients who received Avastin
WARNINGS AND PRECAUTIONS
Embryo-fetal Toxicity section added
- Avastin may cause fetal harm based on the drug’s mechanism of action and findings from animal studies. Congenital malformations were observed with the administration of bevacizumab to pregnant rabbits during organogenesis every 3 days at a dose as low as a clinical dose of 10 mg/kg. Furthermore, animal models link angiogenesis and VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryo-fetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with and for 6 months after the last dose of Avastin. [See Use in Specific Populations (8.1, 8.3), Clinical Pharmacology (12.1).]
USE IN SPECIFIC POPULATIONS
- Section updated; animal data section added
- Females and Males of Reproductive Potential section added
Clinical Trial Experience
- *revised to provide the incidence information regarding post-treatment vascular events.*
- As with all therapeutic proteins, there is a potential for an immune response to Avastin. In clinical trials of adjuvant colon carcinoma, 14 of 2233 evaluable patients (0.63%) tested positive for treatment-emergent anti-bevacizumab antibodies detected by an electrochemiluminescent (ECL) based assay. Among these 14 patients, three tested positive for neutralizing antibodies against bevacizumab using an enzyme-linked immunosorbent assay (ELISA). The clinical significance of these anti-product antibody responses to bevacizumab is unknown.
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
- congestive heart failure
6.3 Postmarketing Experience
- hepatobiliary disorders, gallbladder perforation
- include additional information regarding ocular and systemic adverse events following unapproved intravitreal use for treatment of various ocular disorders.