What are the contraindications for Bevacizumab (Avastin) therapy?

Contraindications of Bevacizumab

Bevacizumab has no absolute contraindications listed in FDA labeling, but carries serious warnings for specific clinical scenarios that functionally preclude its use in certain high-risk situations. 1

Key Clinical Scenarios Requiring Bevacizumab Avoidance or Discontinuation

Perioperative Period

• Stop bevacizumab at least 6 weeks (2 half-lives) before any elective surgery to minimize wound healing complications 2
• Delay reinitiation for at least 6-8 weeks postoperatively to allow adequate wound healing 2
• The risk of wound healing complications increases significantly when major surgery occurs while receiving bevacizumab (13% vs 3.4% with chemotherapy alone) 2
• When bevacizumab is stopped ≥6 weeks before surgery, wound complication rates are acceptably low (1.3% vs 0.5%) 2

Active or Recent Gastrointestinal Perforation

• Discontinue bevacizumab permanently if gastrointestinal perforation occurs 1
• Gastrointestinal perforation is a rare but potentially fatal complication (7.1% of treatment-related deaths) 2
• Extensive prior intra-abdominal surgery (peritoneal stripping, peritoneal debulking) represents a major risk factor for perforation and warrants extreme caution 2
• Patients with advanced ovarian cancer who underwent peritoneal debulking had unacceptably high perforation rates with bevacizumab 2

Life-Threatening Hemorrhage

• Discontinue bevacizumab for serious or life-threatening hemorrhage, including hemoptysis, gastrointestinal bleeding, CNS hemorrhage, or hematemesis 1
• Hemorrhage accounts for 23.5% of bevacizumab-related treatment deaths 2
• Patients with untreated CNS metastases or recent hemoptysis (≥2.5 mL of red blood) were excluded from major trials 1

Arterial Thromboembolic Events

• Discontinue bevacizumab permanently for arterial thromboembolic events including stroke, myocardial infarction, or transient ischemic attacks 1
• Risk is particularly elevated in patients ≥65 years of age 2
• The overall incidence of arterial thromboembolic events is significantly increased with bevacizumab 2

Severe Hypertensive Crisis or Hypertensive Encephalopathy

• Discontinue bevacizumab for hypertensive crisis or hypertensive encephalopathy 1
• Hypertension is the most common adverse event with bevacizumab (Grade 3-4 hypertension: 12% vs 2% with chemotherapy alone) 1, 3
• Blood pressure requires routine monitoring throughout therapy 1

Posterior Reversible Encephalopathy Syndrome (PRES)

• Discontinue bevacizumab if PRES develops (presents with headache, seizure, lethargy, confusion, blindness, or altered mental function) 1

Nephrotic Syndrome

• Discontinue bevacizumab for nephrotic syndrome 1
• Monitor for proteinuria regularly; discontinue for nephrotic syndrome or persistent proteinuria >2+ 3

Congestive Heart Failure

• Discontinue bevacizumab in patients who develop CHF 1
• Bevacizumab is not indicated for use with anthracycline-based chemotherapy due to increased CHF risk (4% vs 0.6%) 1

Necrotizing Fasciitis

• Discontinue bevacizumab if necrotizing fasciitis develops, which is sometimes fatal and usually secondary to wound healing complications, GI perforation, or fistula formation 2
• This carries an FDA safety label warning despite being listed as rare 4

Special Populations Requiring Extreme Caution

Pregnancy

• Bevacizumab can cause fetal harm and should be avoided in pregnancy 1
• Females of reproductive potential must use effective contraception during treatment and for 6 months after the last dose 1

Perioperative Stage IV Colorectal Cancer

• NCCN guidelines do not recommend bevacizumab in the perioperative stage IV setting for resectable metastases 2
• This recommendation stems from lack of efficacy data in the adjuvant setting for stage II-III colon cancer 2

Common Pitfalls to Avoid

• Do not assume the presence of an intact primary tumor increases perforation risk—data show peritoneal debulking surgery is the actual risk factor, not the primary tumor itself 2
• Do not restart bevacizumab too early postoperatively—waiting only 4 weeks is insufficient; 6-8 weeks minimum is required 2
• Do not overlook the increased treatment-related mortality (RR 1.33; 95% CI 1.02-1.73) when adding bevacizumab to chemotherapy 2
• Monitor blood pressure at every visit—hypertension is by far the most common adverse event and requires proactive management 3