Avastin® (bevacizumab)

• Full Prescribing Information including boxed WARNINGS
• Healthcare Provider Letters

  9 letters

  Intraocular Inflammatory Reactions - Dec 2008 Warning for Counterfeit Product Labeled as Avastin in the United States Feb 2012 Important Drug Warning: Necrotizing Fasciitis - Apr 2013 Important New Safety Information in Women Receiving AVASTIN - Oct 2011 Microangiopathic Hemolytic Anemia (MAHA) - July 2008 Cases of RPLS in Patients Receiving AVASTIN - Sept 2006 Tracheoesophageal (TE) Fistula - April 2007 VEGF antibodies for the treatment of retinopathy of prematurity - Aug 2006 Important Change to Avastin® label for treatment of metastatic breast cancer - Nov 2011

Alert

• Important information regarding counterfeit drug labeled as Altuzan (bevacizumab) Learn more
• FDA Alerts Health Care Professionals of Infection Risk from Repackaged Avastin Intravitreal Injections Learn more

Indication

(RCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

(NSCLC)
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.

(CRC)
Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy. Avastin, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Important Safety Information and 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 (i.e., 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, 2.6%)
  — Proteinuria (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 patient
•  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 — 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.

Second-line Metastatic Colorectal Cancer in Patients who Have Progressed on an Avastin Containing Regimen in First-line mCRC
In this second-line trial, no new safety signals were observed when Avastin was administered in second-line mCRC patients who progressed on an Avastin containing regimen in first-line mCRC. The safety data was consistent with the known safety profile established in first- and second-line mCRC.

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.

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.