Important Safety Information

Boxed WARNINGS

• Gastrointestinal (GI) perforation
  • Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to patients treated with chemotherapy
  • The incidence of GI perforation ranged from 0.3% to 3% across clinical studies
  • Discontinue Avastin in patients with GI perforation
• Surgery and wound healing complications
  • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients
  • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed 
  • Discontinue in patients with wound healing complications requiring medical intervention
• Hemorrhage
  • Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. In clinical studies, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 0.4% to 7% 
  • Do not administer Avastin to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 tsp of red blood) 
  • Discontinue Avastin in patients who develop grade 3-4 hemorrhage

Additional serious adverse events

• Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
  • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer) 
  • Arterial thromboembolic events (grade ≥3, 5%, highest in patients with GBM)
  • Renal injury and proteinuria 
    • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
    • Nephrotic syndrome (<1%)
• Additional serious adverse events with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
  • Venous thromboembolism (grade ≥3, 11% seen in GOG-0240)
  • Hypertension (grade 3–4, 5%–18%)
  • Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
  • Congestive heart failure (CHF) (1%)

• Infusion reactions with the first dose of Avastin occurred in <3% of patients, and severe reactions occurred in 0.2% of patients
• Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction 
• Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with Avastin

Pregnancy warning

• Based on the mechanism of action and animal studies, Avastin may cause fetal harm
• Advise female patients that Avastin may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy 
• Advise females of reproductive potential to use effective contraception during treatment with Avastin and for 6 months after the last dose of Avastin
• Advise nursing women that breastfeeding is not recommended during treatment with Avastin and for 6 months following their last dose of treatment
• Avastin may impair fertility

Most common adverse events

• Across studies, the most common adverse reactions observed in Avastin patients at a rate >10% were:
  • Epistaxis
  • Headache
    
  • Hypertension
    
  • Rhinitis
    
  • Proteinuria
  • Taste alteration
    
  • Dry skin
    
  • Rectal hemorrhage
    
  • Lacrimation disorder
  • Back pain
  • Exfoliative dermatitis

Across all studies, Avastin was discontinued in 8% to 22% of patients because of adverse reactions.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

You may also report side effects to Genentech at (888) 835-2555.

Please see full Prescribing Information, including Boxed WARNINGS, at www.avastin.com for additional important safety information