bevacizumab

General

Pronunciation:
be-va-siz-uh-mab


Trade Name(s)

  • Avastin
  • Mvasi
  • Zirabev

Ther. Class.
antineoplastics

Pharm. Class.
monoclonal antibodies

Indications

  • Avastin, Mvasi, and Zirabev:

    Treatment of the following conditions:

    • Metastatic colorectal cancer (in combination with IV 5–fluorouracil-based chemotherapy as first-line or second-line therapy).
    • Metastatic colorectal cancer in patients who have progressed on a first-line regimen containing bevacizumab (in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy),
    • First-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (in combination with carboplatin and paclitaxel),
    • Recurrent glioblastoma (as monotherapy),
    • Metastatic renal cell carcinoma (in combination with interferon alfa),
    • Persistent, recurrent, or metastatic cervical cancer (in combination with paclitaxel and cisplatin or paclitaxel and topotecan),
  • Avastin and Zirabev only:

    Treatment of the following conditions:

    • Platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have received ≤2 previous chemotherapy regimens (in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan),
    • Platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (in combination with carboplatin and paclitaxel or carboplatin and gemcitabine followed by bevacizumab as a single agent),
    • Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection (in combination with carboplatin and paclitaxel followed by bevacizumab as a single agent).
  • Avastin only: Unresectable or metastatic hepatocellular carcinoma (HCC) in patients who have not previously received systemic therapy (in combination with atezolizumab).

Action

A monoclonal antibody that binds to vascular endothelial growth factor (VEGF), preventing its attachment to binding sites on vascular endothelium, thereby inhibiting growth of new blood vessels (angiogenesis).

Therapeutic Effect(s):

Decreased metastatic disease progression and microvascular growth.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 20 days (range 11–50 days).

TIME/ACTION PROFILE

ROUTEONSETPEAKDURATION
IVrapidend of infusion14 days

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Recent hemoptysis or other serious recent bleeding episode;
  • First 28 days after major surgery;
  • OB:  Pregnancy (can cause fetal harm);
  • Lactation: Discontinue nursing during treatment and, due to long half-life, for several wk following treatment.

Use Cautiously in:

  • Cardiovascular disease;
  • Diabetes (↑ risk of arterial thromboembolic events);
  • Previous use of anthracyclines (↑ risk of HF);
  • Esophageal varices (in patients with HCC)
  • Rep:   Women of reproductive potential;
  • Pedi:  Safety not established (cases of non-mandibular osteonecrosis reported);
  • Geri:  ↑ risk of serious adverse reactions including arterial thromboembolic events.

Adverse Reactions/Side Effects

CV: HF, THROMBOEMBOLIC EVENTS, hypertension, hypotension

Derm: NECROTIZING FASCIITIS

GI: GI PERFORATION

GU: ↑ serum creatinine, nephrotic syndrome, ovarian failure, proteinuria

Hemat: BLEEDING

Neuro: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Resp: HEMOPTYSIS, non-gastrointestinal fistulas, nasal septum perforation

Misc: WOUND DEHISCENCE, impaired wound healing, infusion reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • ↑ blood levels of SN 38 (the active metabolite of  irinotecan ); significance is not known.
  • ↑ risk of microangiopathic hemolytic anemia when used with  sunitinib ; concurrent use should be avoided.

Route/Dosage

Colorectal Cancer

IV (Adults): 5 mg/kg every 14 days when given with bolus-IFL chemotherapy regimen  or  10 mg/kg every 14 days when given with FOLFOX4 chemotherapy regimen  or 5 mg/kg every 14 days or 7.5 mg/kg every 21 days when given with a fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy regimen.

Lung Cancer or Cervical Cancer

IV (Adults): 15 mg/kg every 3 wk.

Glioblastoma or Renal Cell Carcinoma

IV (Adults): 10 mg/kg every 2 wk.

Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

IV (Adults): 10 mg/kg every 2 wk when given with paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly)  or  15 mg/kg every 3 wk when given with topotecan (every 3 wk).

Platinum-Sensitive Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

IV (Adults): 15 mg/kg every 3 wk when given with carboplatin and paclitaxel for 6–8 cycles, followed by 15 mg/kg every 3 wk as a single agent  or  15 mg/kg every 3 wk when given with carboplatin and gemcitabine for 6–10 cycles, followed by 15 mg/kg every 3 wk as a single agent.

Stage III or IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Following Surgical Resection

IV (Adults): 15 mg/kg every 3 wk when given with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 wk as a single agent for a total up to 22 cycles or until disease progression, whichever occurs earlier

Hepatocellular Carcinoma

IV (Adults): 15 mg/kg every 3 wk (administer after atezolizumab on same day) until disease progression or unacceptable toxicity.

Availability

Solution for injection: 25 mg/mL

Assessment

  • Assess for signs of GI perforation (abdominal pain associated with constipation, fever, nausea, and vomiting), fistula formation, and wound dehiscence during therapy; discontinue therapy if this occurs.
  • Assess for signs of hemorrhage (epistaxis, hemoptysis, bleeding) and thromboembolic events (stroke, MI, deep vein thrombosis, pulmonary embolus) during therapy. If Grade 3 or 4 hemorrhage, severe arterial thromboembolism, or Grade 4 venous thromboembolism occurs, discontinue therapy. Hold bevacizumab for patients with recent history of hemoptysis of ≥1/2 teaspoon (2.5 mL) of red blood.
  • Monitor BP every 2–3 wk during therapy. Temporarily suspend therapy during severe hypertension not controlled with medical management; permanently discontinue if hypertensive crisis or encephalopathy occurs.
  • Assess for infusion reactions (stridor, wheezing, hypertension, oxygen desaturation, chest pain, headache, rigors, diaphoresis) during therapy. May require epinephrine, corticosteroids, IV antihistamines, bronchodilators and/or oxygen. If clinically significant reaction occurs, hold therapy until resolved and resume at decreased rate. Stop therapy if severe reaction occurs.
  • Assess for signs of HF (dyspnea, peripheral edema, rales/crackles, jugular venous distension) during therapy. Discontinue therapy if symptoms occur.
  • Monitor for signs of PRES (headache, seizure, lethargy, confusion, blindness). Hypertension may or may not be present. May occur within 16 hr to 1 yr of initiation of therapy. Treat hypertension if present and discontinue bevacizumab therapy. Symptoms usually resolve within days.
  • Monitor wound healing.  If wound healing complications occur,  hold bevacizumab until adequate wound healing.  If necrotizing fasciitis occurs,  discontinue therapy.

Lab Test Considerations:

Monitor serial urinalysis for proteinuria during therapy. Patients with a 2+ or greater urine dipstick require further testing with a 24-hr urine collection. Hold therapy for ≥2 grams of proteinuria/24 hr and resume when proteinuria is <2 g/24 hr. Discontinue therapy in patients with nephrotic syndrome.

  • May cause leukopenia, thrombocytopenia, hypokalemia, and hyperbilirubinemia.
  • May cause ↑ serum creatinine.

Potential Diagnoses

Implementation

  • Avoid administration for at least 28 days before elective surgery and at least 28 days following major surgery; surgical incision should be fully healed due to potential for impaired wound healing.

IV Administration

  • Intermittent Infusion:   Diluent:  Dilute prescribed dose in 100 mL of 0.9% NaCl. Do not shake. Discard unused portions. Solution is colorless to pale yellow; do not administer solution that is discolored or contains particulate matter. Stable if refrigerated for up to 8 hr.
  • Rate: Administer initial dose over 90 min. If well tolerated, second infusion may be administered over 60 min. If well tolerated, all subsequent infusions may be administered over 30 min. Do not administer as an IV push or bolus.
  • Additive Incompatibility: Do not mix or administer with dextrose solutions.

Patient/Family Teaching

  • Inform patient of purpose of medication.
  • Advise patient of the need for monitoring BP periodically during therapy; notify health care professional if BP is elevated.
  • Advise patient to report any signs of bleeding, unusual bleeding, high fever, rigors, sudden onset of worsening neurological function, or persistent or severe abdominal pain, severe constipation, or vomiting immediately to health care professional.
  • Inform patient of increased risk of wound healing complications and arterial thromboembolic events.
  • Rep:  Bevacizumab is teratogenic. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for 6 mo after last dose. Inform female patient of reproductive potential of risk of ovarian failure that may lead to sterility following therapy.

Evaluation/Desired Outcomes

Decreased metastatic disease progression and microvascular growth.

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