Indication

Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

Boxed WARNINGS

• Gastrointestinal (GI) perforation
  • Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to controls
  • The incidences of GI perforation ranged from 0.3% to 3.2% 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
  • Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined
  • Discontinue Avastin at least 28 days prior to elective surgery and in patients with wound healing complications requiring medical intervention
• Hemorrhage
  • bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 0.4% to 6.9%
  • Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood)
  • Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention)

Additional serious adverse events

• Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included
  • GI fistulae (up to 2%)
  • Non-GI fistulae (≤1.8%)
  • Arterial thromboembolic events (grade ≥3, 2.6%)
  • Proteinuria (nephrotic syndrome, <1%)
• Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included
  • GI-vaginal fistulae occurred in 8.2% of patients in a cervical cancer trial
  • Hypertension (grade 3–4, 5%–18%)
  • Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
• Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients
• Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin

Most common adverse events

• Across indications, the most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were
  • Epistaxis
  • Proteinuria
  • Lacrimation disorder
  • Headache
  • Taste alteration
  • Back pain
  • Hypertension
  • Dry skin
  • Exfoliative dermatitis
  • Rhinitis
  • Rectal hemorrhage
• Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

Pregnancy warning

• Avastin may impair fertility
• Based on animal data, Avastin may cause fetal harm
• Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin
• For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother

Indication-specific adverse events

• In NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in Avastin-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thrombus/embolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)

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, for additional important safety information.