Avastin dosing and administration

Avastin dosing in approved indications

  • In clinical trials in non-small cell lung cancer (NSCLC) and first- and second-line metastatic colorectal cancer (MCRC), Avastin has been approved at the following doses

Avastin dosing in approved indications

  • †15 mg/kg dose evaluated first-line in combination with PC.
  • ‡ 5 mg/kg dose evaluated first-line in combination with IFL.
  • §10 mg/kg dose evaluated second-line in combination with FOLFOX4.

Treatment discontinuation and suspension1

  • Permanently discontinue Avastin in patients with gastrointestinal (GI) perforation (GI perforation, fistula formation in the GI tract, intra-abdominal abscess), wound dehiscence requiring medical intervention, serious bleeding, fistula formation involving an internal organ, severe arterial thromboembolic event, nephrotic syndrome, hypertensive crisis, or hypertensive encephalopathy

  • In patients developing reversible posterior leukoencephalopathy syndrome, discontinue Avastin and initiate treatment of hypertension if present. Symptoms usually resolve or improve within days, although some patients have experienced ongoing neurologic sequelae

  • Temporary suspension is recommended in patients with evidence of moderate to severe proteinuria, in patients with severe hypertension that is not controlled with medical management, and for at least several weeks prior to elective surgery. Avastin should not be resumed until the surgical incision is fully healed

  • Patients who become pregnant while on Avastin therapy should be counseled regarding possible risk to the fetus and/or loss of pregnancy

    • The approximate half-life of Avastin is 20 days (range 11–50 days)

Duration of Avastin treatment

  • In NSCLC and MCRC, the clinical benefit of Avastin plus chemotherapy was observed when Avastin was given until disease progression

Avastin duration per Phase III trial protocols

Avastin duration per Phase III trial protocols

  • ¶ In NSCLC, Avastin is indicated in combination with PC.
  • # In MCRC, Avastin is indicated in combination with IV 5-FU–containing chemotherapy.
  • ** In NSCLC, Avastin plus PC was given for up to 6 cycles, after which Avastin was continued alone.
Per pivotal study protocols across indications, Avastin administration was1-6

  • Not modified due to chemotherapy-related toxicity

  • Not stopped when tumor response or stable disease was achieved

  • Not impacted by chemotherapy dose modifications, delays, or discontinuations (planned or unplanned)

  • Avastin should be suspended at least several weeks prior to elective surgery and should not be resumed until the surgical incision is fully healed

    • The calculated half-life of Avastin (~20 days) should be considered when determining the interval between suspension and subsequent surgery

Important treatment considerations—Women of childbearing potential

Prior to initiation of therapy, advise patients of the potential risk of Avastin to the developing fetus. Counsel patients who become pregnant about the possible risks of both continued treatment (including hazard to the fetus and/or loss of pregnancy) and prolonged exposure following discontinuation, keeping in mind the approximate half-life of Avastin (20 days; range 11-50 days).

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

Preparation for administration1

  • Avastin should be diluted for infusion using aseptic technique

  • Withdraw the necessary amount of Avastin to obtain the required dose and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP

  • Discard any unused portion left in a vial, as the product contains no preservatives. Inspect visually for particulate matter and discoloration prior to administration

  • Diluted Avastin solutions for infusion may be stored at 2°C-8°C (36°F-46°F) for up to 8 hours

  • Avastin infusions should not be administered or mixed with dextrose solutions

Administration1

  • DO NOT ADMINISTER AS AN IV PUSH OR BOLUS

Infusion times

Infusion times

  • In clinical trials, infusion reactions with the first dose of Avastin were uncommon (<3%) and severe reactions occurred in 0.2% of patients. Adequate information on rechallenge is not available. Avastin infusion should be interrupted in all patients with severe infusion reactions and appropriate medical therapy administered

Boxed WARNINGS and Additional Important Safety Information

Gastrointestinal (GI) perforation: Avastin administration can result in the development of GI perforation, in some cases resulting in fatality. GI perforation, sometimes associated with intra-abdominal abscess, occurred throughout treatment with Avastin. Permanently discontinue Avastin therapy in patients with GI perforation.

Wound healing complication: Avastin administration can result in the development of wound dehiscence, in some instances resulting in fatality. Permanently discontinue Avastin therapy in patients with wound dehiscence requiring medical intervention. The appropriate interval between termination of Avastin and subsequent elective surgery has not been determined.

Hemorrhage: Severe, and in some cases fatal, pulmonary hemorrhage can occur in patients with NSCLC treated with chemotherapy and Avastin. Do not administer Avastin to patients with recent hemoptysis (≥1/2 tsp of red blood). Permanently discontinue Avastin in patients with serious hemorrhage and initiate aggressive medical management.

Additional serious adverse events included non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure.

The most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events that may have occurred in Avastin indications (first-line NSCLC, first- and second-line MCRC) included neutropenia, fatigue, hypertension, infection, hemorrhage, asthenia, abdominal pain, pain, deep vein thrombosis, intra-abdominal thrombosis, syncope, diarrhea, constipation, leukopenia, nausea, vomiting, dehydration, ileus, neuropathy–sensory, neurologic–other, and headache.

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

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References
  1. Avastin Prescribing Information. Genentech, Inc. March 2008.
  2. Miller K, Wang M, Gralow J, et al. N Engl J Med. 2007;357:2666-2676.
  3. Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550.
  4. Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.
  5. Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544.
  6. Data on file. Genentech, Inc.