Bevacizumab

Usage

Bevacizumab is a recombinant humanized monoclonal antibody that acts as a vascular endothelial growth factor (VEGF) inhibitor. It is prescribed for various cancers, including metastatic colorectal cancer, non-squamous non-small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, persistent, recurrent, or metastatic cervical cancer, and recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Bevacizumab is also used off-label for some eye diseases.

Alternate Names

Bevacizumab is also known by the brand names Avastin, Mvasi, Zirabev, Alymsys, Avzivi, and Vegzelma.

How It Works

Pharmacodynamics: Bevacizumab binds to VEGF, preventing its interaction with receptors on endothelial cells. This inhibits angiogenesis, the formation of new blood vessels, which is essential for tumor growth and metastasis.

Pharmacokinetics: Bevacizumab is administered intravenously. Its volume of distribution is relatively small, typically between 2.66 and 3.25 L. It is not extensively metabolized in the liver or excreted by the kidneys. Elimination occurs primarily through other pathways, likely involving receptor-mediated endocytosis and degradation within cells. Its terminal half-life is relatively long, around 19 to 20 days. Interpatient variability in clearance can be up to 44%, and factors like body weight and markers of disease severity can influence clearance. Males tend to have a larger volume of distribution and higher clearance compared to females, even after adjusting for body weight.

Mode of action: Bevacizumab acts by binding to and inhibiting VEGF, a key signaling protein involved in angiogenesis. This inhibits the activation of VEGFR2, the primary receptor for VEGF on endothelial cells. By blocking this pathway, bevacizumab reduces the formation of new blood vessels that supply tumors with oxygen and nutrients, ultimately hindering tumor growth and spread.

Receptor binding, enzyme inhibition, or neurotransmitter modulation: Bevacizumab primarily acts through receptor binding, specifically targeting VEGF. This binding inhibits VEGF signaling, ultimately leading to suppression of angiogenesis. It doesn’t primarily function through enzyme inhibition or neurotransmitter modulation.

Elimination pathways: The exact elimination pathways for bevacizumab are not fully elucidated. However, it is not primarily eliminated via renal or hepatic routes. Elimination likely occurs through other pathways, such as receptor-mediated endocytosis and subsequent degradation within cells.

Dosage

Standard Dosage

Adults:

Dosages vary depending on the condition being treated. Common dosages include:

• 5 mg/kg every 2 weeks
• 7.5 mg/kg every 3 weeks
• 10 mg/kg every 2 weeks
• 15 mg/kg every 3 weeks

The initial infusion is often given over 90 minutes. If tolerated, subsequent infusions can be administered over 60 or 30 minutes.

Children:

The safety and efficacy of bevacizumab in pediatric patients have not been fully established. Unlicensed use in children sometimes occurs with dosages based on body weight (e.g., 5-10 mg/kg every 2-3 weeks) but should be approached with caution.

Special Cases:

• Elderly Patients: No specific dose adjustments are typically required, but careful monitoring for adverse events is recommended.
• Patients with Renal Impairment: No dose adjustments are usually necessary, as renal excretion is not a major elimination pathway.
• Patients with Hepatic Dysfunction: No dose adjustments are usually necessary, as hepatic metabolism is not a major elimination pathway.
• Patients with Comorbid Conditions: Dosage adjustments may be required based on the specific comorbid condition and its impact on drug tolerance.

Clinical Use Cases

Dosage and administration guidelines for specific clinical use cases are typically determined by established protocols and treatment guidelines. Bevacizumab is not typically used in the context of intubation, surgical procedures (should be avoided 28 days before/after major surgery), mechanical ventilation, emergency situations like status epilepticus or cardiac arrest. Its use in the ICU setting is context-specific and depends on the underlying cancer being treated.

Dosage Adjustments

Dosage adjustments are not usually recommended for specific adverse events. Treatment might be interrupted or stopped if serious toxicity occurs. Dose modifications are considered for patients with severe adverse events or other factors affecting drug tolerance.

Side Effects

Common Side Effects

High blood pressure, proteinuria, fatigue, diarrhea, nausea, abdominal pain, headache, epistaxis, stomatitis, and taste changes.

Rare but Serious Side Effects

Gastrointestinal perforation, hemorrhage (including severe bleeding), arterial thromboembolic events (stroke, myocardial infarction), hypertension (including hypertensive crisis), posterior reversible encephalopathy syndrome (PRES), nephrotic syndrome, congestive heart failure, impaired wound healing, and severe infusion-related reactions.

Long-Term Effects

Ovarian failure (in premenopausal women), osteonecrosis of the jaw, and potentially increased risk of future malignancies.

Adverse Drug Reactions (ADR)

Severe hypersensitivity reactions, including anaphylaxis, severe infusion-related reactions, and gastrointestinal perforation require immediate medical attention.

Contraindications

Hypersensitivity to bevacizumab or any of its components, pregnancy, active bleeding or high risk of bleeding, untreated central nervous system metastases, and recent major surgery.

Drug Interactions

Bevacizumab has potential interactions with several medications. Some of the most notable interactions include:

• Chemotherapy agents: Increased risk of adverse effects, such as myelosuppression, stomatitis, and hand-foot syndrome.
• Immunosuppressants: Increased risk of infection.
• Antihypertensives: Additive effects on blood pressure lowering.
• CYP450 interactions: Bevacizumab is not significantly metabolized by CYP450 enzymes, so clinically significant interactions are less likely.

Bevacizumab should not be administered with dextrose solutions due to the risk of precipitation. Concomitant use with live vaccines should be avoided.

Pregnancy and Breastfeeding

Bevacizumab is contraindicated during pregnancy due to its potential to cause fetal harm, including malformations and embryofetal toxicity. It is recommended to avoid breastfeeding during treatment and for 6 months after the last dose, as it may be excreted in breast milk. Effective contraception is essential for women of childbearing potential during treatment and for at least 6 months after the last dose.

Drug Profile Summary

• Mechanism of Action: VEGF inhibitor, inhibits angiogenesis.
• Side Effects: High blood pressure, proteinuria, fatigue, gastrointestinal perforation (rare).
• Contraindications: Pregnancy, active bleeding.
• Drug Interactions: Chemotherapy agents, immunosuppressants.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Varies based on indication; common ranges: 5-15 mg/kg every 2-3 weeks.
• Monitoring Parameters: Blood pressure, urine protein, complete blood counts, signs of bleeding or infection.

Popular Combinations

Bevacizumab is often used in combination with various chemotherapy regimens depending on the specific cancer. Consult relevant treatment guidelines for specific combinations and indications.

Precautions

• Screen for allergies, bleeding disorders, and cardiovascular disease.
• Monitor blood pressure and urine protein regularly.
• Caution is advised in patients with a history of thromboembolic events, impaired wound healing, or gastrointestinal conditions.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Bevacizumab?

A: The dosage varies depending on the indication. It is typically administered as 5 mg/kg every two weeks, 7.5 mg/kg every 3 weeks, 10 mg/kg every two weeks or 15 mg/kg every three weeks intravenously.

Q2: How is Bevacizumab administered?

A: Intravenous infusion.

Q3: What are the common side effects of Bevacizumab?

A: High blood pressure, proteinuria, fatigue, and gastrointestinal issues like diarrhea.

Q4: Can pregnant women take Bevacizumab?

A: No, Bevacizumab is contraindicated in pregnancy.

Q5: How long does Bevacizumab stay in the body?

A: Bevacizumab has a long half-life, approximately 19-20 days.

Q6: What are the serious side effects of Bevacizumab that require urgent medical attention?

A: Gastrointestinal perforation, severe bleeding, arterial thromboembolic events (stroke, heart attack), and severe infusion reactions.

Q7: Does Bevacizumab interact with other medications?

A: Yes, it can interact with chemotherapy agents, immunosuppressants, and some antihypertensives.

Q8: Can Bevacizumab affect fertility?

A: Yes, it can cause ovarian failure in premenopausal women, potentially affecting fertility. This may be reversible in some cases after treatment discontinuation.

Q9: What monitoring parameters should be considered for patients on Bevacizumab?

A: Blood pressure, urine protein levels, complete blood count, and monitoring for signs of bleeding or infection.

Q10: What precautions should be taken before administering Bevacizumab?

A: Screen patients for allergies, bleeding disorders, cardiovascular issues, and recent major surgeries. Patients with uncontrolled hypertension or a history of thromboembolic events should be monitored closely.