bevacizumab

High Alert

Alymsys, Avastin, Avzivi, Mvasi, Vegzelma, and Zirabev

Treatment of the following conditions:
- First- or second-line treatment of metastatic colorectal cancer (in combination with IV 5-fluorouracil-based chemotherapy);
- Second-line treatment of 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 nonsquamous 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);
- 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).

Avastin, Mvasi, Vegzelma, and Zirabev

Treatment of the following conditions:
- Platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine);
- 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 in patients who have not previously received systemic therapy (in combination with atezolizumab).

Action ⬆ ⬇

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

Therapeutic effects:

Decreased metastatic disease progression and microvascular growth.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

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

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	14 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Recent hemoptysis or other serious recent bleeding episode;
First 28 days after major surgery;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Cardiovascular disease;
Diabetes (↑ risk of arterial thromboembolic events);
Previous use of anthracyclines (↑ risk of HF);
Esophageal varices (in patients with hepatocellular carcinoma);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children; cases of nonmandibular osteonecrosis reported;
Geri: risk of serious adverse reactions including arterial thromboembolic events in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: HF, hypertension, hypotension

Derm: impaired wound healing, NECROTIZING FASCIITIS, WOUND DEHISCENCE

EENT: nasal septum perforation

GI: GI PERFORATION

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

Hemat: BLEEDING, THROMBOEMBOLIC EVENTS

Neuro: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Resp: HEMOPTYSIS

Misc: INFUSION REACTIONS

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 ): Alymsys, Avastin, Avzivi, Mvasi, Vegzelma, or Zirabev: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 ): Alymsys, Avastin, Avzivi, Mvasi, Vegzelma, or Zirabev: 15 mg/kg every 3 wk.

Glioblastoma or Renal Cell Carcinoma

IV (Adults ): Alymsys, Avastin, Avzivi, Mvasi, Vegzelma, or Zirabev: 10 mg/kg every 2 wk.

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

IV (Adults ): Alymsys, Avastin, Avzivi, Mvasi, Vegzelma, or Zirabev: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 ): Avastin, Mvasi, Vegzelma, or Zirabev: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 ): Avastin, Mvasi, Vegzelma, or Zirabev: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 ): Avastin: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 ≥½ 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–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.

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 4 hr (Alymsys), 8 hr (Avastin, Mvasi, Zirabev), 24 hr (Vegzelma), or at room temperature up to 4 hr (Vegzelma).
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.
Y-Site Incompatibility: Do not administer with other solutions or medications.

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, 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: May cause fetal harm. 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇