Indications

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 2.4% 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
  • 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. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%
  • 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
  • Non-GI fistula formation (≤0.3%)
  • Arterial thromboembolic events (grade ≥3, 2.4%)
  • Proteinuria including nephrotic syndrome (<1%)
• Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included
  • Hypertension (grade 3–4, 5%–18%)
  • Reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%)
• 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

• Most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate 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 8.4% 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
• In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)
• 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%)
• In first-line MCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)
• In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%)

Please see full Prescribing Information, including Boxed WARNINGS, for additional important safety information.