bevacizumab

Trade Name:

Avastin®

Mvasi®; Zirabev®; Bambevi®; Abevmy®; Aybintio®; Vegzelma™

Other Names:

Avastin®; Mvasi®; Zirabev®; Bambevi®, Abevmy®, Aybintio®, Vegzelma™

Appearance:

Clear, colourless solution mixed into larger bags of fluids

Monograph Name:

bevacizumab

Monograph Body:

Drug Monograph

A - Drug Name

bevacizumab

COMMON TRADE NAME(S): Avastin®; Mvasi®; Zirabev®; Bambevi®; Abevmy®; Aybintio®; Vegzelma™

Different bevacizumab products are not interchangeable.
For additional information on biosimilars, refer to:
- Position Statements for the Clinical Operational Implementation of Oncology Biosimilars from the pan-Canadian Clinical Operations Working Group
- Clinician Fact Sheet

B - Mechanism of Action and Pharmacokinetics

Human vascular endothelial growth factor (VEGF) binding to its receptor initiates angiogenesis (endothelial proliferation and the formation of new blood vessels). Bevacizumab is a recombinant humanized monoclonal antibody that prevents binding of VEGF to its receptors on the surface of endothelial cells and inhibits the biologic activity of VEGF.

Distribution

Pharmacokinetics of bevacizumab are linear at doses ranging from 1 to 10 mg/kg. The predicted time to reach steady state is 100 days. Male subjects had a higher volume of distribution (+ 22%) than females.

Cross blood brain barrier?

No information found (unlikely)

PPB

No information found

Metabolism

Bevacizumab is metabolized and eliminated via the reticuloendothelial system.

Active metabolites

Inactive metabolites

Elimination

Males and patients with low albumin or high alkaline phosphatase have higher clearance (+20-26%).

Half-life

19-20 days

C - Indications and Status

Health Canada Approvals:

Colorectal cancer
Non-small cell lung cancer (NSCLC)
Ovarian, fallopian tube, or primary peritoneal cancer
Glioblastoma

Refer to the product monograph for a full list and details of approved indications.

Other Uses:

Cervical cancer
Mesothelioma
Hepatocellular carcinoma

D - Adverse Effects

Emetogenic Potential:

Minimal

Extravasation Potential: None

Adverse effects noted below are based on bevacizumab monotherapy from the phase II study, compared to combination with irinotecan in patients with glioblastoma. Severe or life-threatening events are also listed from pooled analyses of multiple indications or post-marketing data.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arrhythmia (<10%)	E
	Arterial thromboembolism (6%)	E
	Artery aneurysm (rare)	E D L
	Artery dissection (rare)	E D L
	Cardiotoxicity (13%) (2% severe)	I E
	Hypertension (44%) (up to 18% severe)	I E
	Pulmonary hypertension (rare)	E D L
	Venous thromboembolism (≤17%) (8% severe)	E
Dermatological	Other - Necrotizing fasciitis (rare)	E
	Rash (13%) (may be severe)	E
Gastrointestinal	Abdominal pain (4%)	E
	Anorexia (13%)	E
	Constipation (14%)	E
	Diarrhea (21%)	I E
	GI obstruction (<10%)	E
	GI perforation (3%) (or GI ulceration)	E
	Nausea, vomiting (16%)	I E
	Other (7%) - Pharyngolaryngeal pain	E
General	Delayed wound healing (4%) /dehiscence	E
	Fatigue (45%)	E
	Fistula (GI - 2%; tracheo-esophageal, biliary, urogenital; rare), organ perforation (nasal; rare)	E D L
Hematological	Hemorrhage (≤50%) (includes epistaxis; < 10% severe)	E
	Myelosuppression ± infection (7%) (may be severe)	E
	Thrombotic microangiopathy (rare)	E
Hypersensitivity	Hypersensitivity (≤5%)	I E
Infection	Infection (12%)	E
Musculoskeletal	Musculoskeletal pain (14%)	E
	Osteonecrosis of jaw and other (rare)	E
Nervous System	Dizziness (7%)	E
	Headache (37%)	E
	Insomnia (14%)	E D
	Posterior reversible encephalopathy syndrome (PRES) (rare)	E D L
	Somnolence (<10%)	E
Renal	Proteinuria (38%) (severe 10%)	E D
Respiratory	Cough, dyspnea (14%)	E D
	Dysphonia (≤10%)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for bevacizumab include bleeding, fatigue, hypertension, proteinuria, headache, diarrhea, venous thromboembolism, nausea, vomiting and constipation.

The most serious adverse effects include gastrointestinal perforation, fistulas, hemorrhage, thromboembolism, severe hypertension (including PRES), cardiac and renal effects.

Bevacizumab may exacerbate common toxicities of chemotherapy (hand foot syndrome, neurotoxicity, thrombocytopenia) when given in combination.

Hypertension is commonly observed, likely dose-dependent and should be managed with antihypertensives. Avoid diuretics in patients receiving cisplatin chemotherapy. The risk may be greater in platinum-sensitive, recurrent ovarian cancer patients. Pre-existing hypertension should be adequately controlled before starting bevacizumab treatment.

Patients with a history of hypertension may be at increased risk for the development of proteinuria. This is likely dose-related and may not completely resolve after discontinuing bevacizumab. Monitoring of proteinuria by dipstick urinalysis is recommended prior to starting and during bevacizumab therapy (see Monitoring section). Grade 4 proteinuria was seen in up to 1.4% of patients and was sometimes fatal.

Infusion and hypersensitivity reactions (including hypertension, respiratory and neurologic symptoms and hypertensive crisis) have been reported and appear to be more common when given in combination with chemotherapy.

Posterior reversible encephalopathy syndrome (PRES) is rare and may occur from 16 hours to 1 year after the start of bevacizumab. Patients present with seizures, headache, altered mental status, visual disturbance or cortical blindness, with or without associated hypertension. It is reversible if treated promptly after diagnosis with brain imaging, particularly MRI. Treatment of specific symptoms, including control of hypertension is recommended along with discontinuation of bevacizumab.

An increased risk of arterial thromboembolic events, including cerebrovascular accident, transient ischemic attack and myocardial infarction have been reported, especially in older patients, those with diabetes or prior events. Venous thromboembolism is also a risk, especially in patients with a prior history and patients with glioblastoma or cervical cancer (increased risk reported in clinical trials).

Congestive heart failure has been reported especially in metastatic breast cancer patients as well as patients with risk factors such as prior anthracyclines, radiation treatment, prior cardiovascular disease and in patients with lymphoma treated with R-CHOP. Bevacizumab is not indicated for use in the treatment of metastatic breast cancer.

Gastrointestinal perforation (including gallbladder) has been reported in all tumour types, although it is more common in colorectal and cervical cancer. An increased risk (nearly double) of intestinal perforation has been reported in colorectal cancer patients who have colorectal stents. The use of bevacizumab in these patients should be considered with caution (Health Canada review, Feb 2017).

Fistulas have been reported in all sites, including nasal septal perforation, and more common in colorectal cancer, especially with prior surgery or radiation in the area. Most fistulas were reported within the first 6 months of treatment, but may occur more than a year from treatment initiation. An increased risk (up to 8%) of gastrointestinal-vaginal fistulae was reported in patients with cervical cancer especially those patients who had received pelvic radiation. Use of bevacizumab in cervical cancer is off-label and has not been approved by Health Canada.

Hemorrhagic events may be life-threatening and include tumour-associated hemorrhage in all tumour types as well as CNS bleeding (especially in malignant glioma). The risk of hemoptysis is increased in patients with squamous NSCLC. There does not appear to be an increased risk in patients who are anticoagulated for venous thromboembolism.

Bevacizumab may adversely affect wound healing and should not be initiated for at least 28 days following major surgery (and held for 28 days prior to surgery, if elective) or until the surgical wound is fully healed.

Necrotizing fasciitis has been reported rarely, often secondary to wound healing complications, gastrointestinal perforation or fistulas. All patients were receiving additional chemotherapies other than bevacizumab; however, some patients did not have any other risk factors.

There is an increased risk of myelosuppression when used in combination with chemotherapy, and of thrombocytopenia when used in combination with gemcitabine/platinum-based treatment, especially in older patients.

Osteonecrosis of the jaw (ONJ) has been reported with prior or concomitant IV bisphosphonate treatment, radiation to the jaw, invasive dental procedures or glucocorticoid treatment.

Increased ovarian failure has been reported and appears to be reversible.

Intraocular inflammation or hemorrhage, retinal detachment or tear, increased need for cataract surgery, arterial thromboembolism and hypertension have been reported at increased rates with intraocular use, which is not approved in Canada and for which bevacizumab is not formulated.

Anti-bevacizumab and neutralizing antibodies have been observed rarely (<1%). The clinical significance of these is unknown.

E - Dosing

Refer to protocol by which patient is being treated.

Different bevacizumab products are not interchangeable.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Bevacizumab should not be initiated in patients with recurrent hemoptysis, uncontrolled hypertension or wounds that require healing.

Prior to treatment, a dental evaluation should be performed and major dental procedures completed.

Routine primary prophylaxis for infusion reactions is not recommended; the use of secondary prophylaxis pre-medications should be based on clinical judgement.

Bevacizumab should not be initiated for at least 28 days following major surgery or until wound healing has occurred; hold for 28 days prior to major elective surgery

Adults:

Combination therapy

Various dosing and schedules are used depending on the indication or chemotherapy regimen; the dosages listed below do not represent a comprehensive list. Refer to the related regimen monographs for details.

Colorectal Cancer:
Intravenous: 5 mg/kg Every 2 weeks (refer to FOLFIRI+BEVA or mFOLFOX6+BEVA)
Intravenous: 7.5 mg/kg Every 3 weeks* (refer to XELOX+BEVA or CAPE+BEVA)

Glioblastoma (in combination with lomustine):
Intravenous: 10 mg/kg Every 2 weeks

NSCLC:
Intravenous: 15 mg/kg Every 3 weeks

Recurrent epithelial ovarian, fallopian tube and primary peritoneal cancer in platinum-resistant or platinum-sensitive patients, in combination with

q3w topotecan (platinum-resistant) or
carboplatin and gemcitabine (platinum-sensitive)

Intravenous: 15 mg/kg Every 3 weeks

Recurrent epithelial ovarian, fallopian tube and primary peritoneal cancer in platinum-resistant patients, in combination with

weekly topotecan, or
weekly paclitaxel, or
pegylated liposomal doxorubicin

Intravenous: 10 mg/kg Every 2 weeks

High Risk epithelial ovarian, fallopian tube and primary peritoneal cancer (in combination with carboplatin and paclitaxel*):
Intravenous: 7.5 mg/kg Every 3 weeks

*based on NDFP, not Health Canada

Dosage with Toxicity:

Dose reductions are not recommended. Bevacizumab should be held or discontinued based on toxicity.

Bevacizumab action	Toxicity
Bevacizumab action	Any grade	Grade 3	Grade 4
Hold:	Uncontrolled hypertension
	Delayed wound healing
	Proteinuria ≥ 2g/ 24 hours*
	Surgery**
Discontinue:		Hypertension, not controlled with medical management	Hypertension
	Wound dehiscence, poor healing requiring medical intervention; necrotizing fasciitis
	Nephrotic syndrome; non-recovery of proteinuria ≥ 2g/24 hours
	Tracheo-esophageal fistula, other non-GI fistulae		Any internal fistula
	GI perforation or fistula
	PRES, hypertensive encephalopathy
	Arterial thromboembolism	Pulmonary embolism	Venous thromboembolism (including pulmonary embolism)
	Symptomatic cardiac failure
	Recurrent hemoptysis > 2.5 mL	Bleeding (any)	Bleeding (any)
	Intracranial bleeding
* may restart when < 2g/24hrs ** for 28 days PRIOR (if surgery elective) and AFTER major surgery, or until wound healed

Management of Infusion-related reactions:

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

Grade

Management

Re-challenge

1 or 2

Stop or slow the infusion rate.
Manage the symptoms.

Restart:

Once symptoms resolve, the infusion can be restarted at a slower rate, unless a serious reaction occurred.

No specific recommendations can be made at this time

3 or 4

Stop treatment.
Aggressively manage symptoms.

Discontinue permanently (do not rechallenge)

Dosage with Hepatic Impairment:

Has not been studied. Not a major route of bevacizumab metabolism or excretion.

Dosage with Renal Impairment:

Has not been studied. Not a major route of bevacizumab metabolism or excretion.

Dosage in the elderly:

Use with caution; patients > 65 years old have an increased risk of arterial thrombotic events as well as myelosuppression, fatigue, proteinuria, hypertension, dizziness, dysphonia, anorexia and GI effects (except gastrointestinal perforation).

Dosage based on gender:

Women have increased risk of severe hypertension, fatigue and abdominal pain, and lower bevacizumab clearance than men; however, no dose adjustment is required.

Children:

The safety and efficacy of bevacizumab in patients less than 18 years of age have not been established. The addition of bevacizumab to standard of care did not show clinical benefit in this population in some phase II clinical trials. Osteonecrosis has been observed in clinical trials.

F - Administration Guidelines

Different bevacizumab products are not interchangeable.

DO NOT ADMINISTER AS AN IV PUSH OR BOLUS.
Bevacizumab infusions should NOT be administered or mixed with dextrose or glucose solutions due to potential for drug degradation.
Mix in 100 mL bag NS. (Final concentration should be 1.4 -16.5 mg/mL).
Compatible with PVC or polyolefin bags.
Do not shake. Should not be mixed or diluted with other drugs.
Infuse over 90 minutes as loading dose, if well tolerated next infusion can be given over 60 minutes; if well tolerated, can thereafter be given over 30 minutes as maintenance dose.
Bevacizumab rapid infusion (over 10 minutes) has safely been administered with no significant increase in infusion reactions (for 5mg/kg and 7.5mg/kg doses)¹.
Refrigerate unopened vials and protect from light; do not freeze.

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

_{¹Mahfood et al. 2012, Reidy et. al 2007}

G - Special Precautions

Contraindications:

Patients with known hypersensitivity to bevacizumab or its components
Patients with known hypersensitivity to Chinese hamster ovary cell product or to other recombinant human or humanized antibodies
Patients with untreated CNS metastases

Other Warnings/Precautions:

Elderly patients
Patients with a history of arterial thromboembolism or significant cardiovascular disease or cardiac failure
Patients with coagulopathies (congenital, acquired or therapeutic)
Patients with recurrent hemoptysis (>2.5ml), serious hemorrhage, or with squamous NSCLC
Patients with colorectal cancer and colorectal stents; increased risk of GI perforation has been reported; use with caution.
Hypertension should be controlled prior to starting treatment
Use caution if given with bisphosphonates or other anti-angiogenic agents, given increased risk of ONJ
Do not use with diuretics in patients who are receiving platinum-based chemotherapy
The safety and efficacy of concurrent radiotherapy and bevacizumab has not been established
Bevacizumab IV solution is not formulated for, and has not been authorized for intravitreal use

Other Drug Properties:

Carcinogenicity: Unknown
Carcinogenicity and mutagenicity have not been studied.

Pregnancy and Lactation:

Embryotoxicity: Yes
Fetotoxicity: Yes
Teratogenicity: Yes
Pregnancy:
Bevacizumab is not recommended for use in pregnancy. Cases of fetal abnormalities have been reported. Adequate contraception (including at least 2 contraceptive methods) should be used by patients and their partners during treatment, and for at least 6 months after the last dose.
Excretion into breast milk: Probable
Breastfeeding is not recommended during treatment and for at least 6 months following the last dose.
Fertility effects: Yes
Bevacizumab may cause ovarian failure. Prior to starting treatment, discuss fertility preservation with patients who can become pregnant.

H - Interactions

No formal drug interaction studies have been performed.

Combinations with EGFR monoclonal antibodies (e.g. cetuximab) and bevacizumab have not been studied and should not be administered for metastatic colorectal cancer.

The safety and efficacy of concurrent radiotherapy has not been established.

AGENT	EFFECT	MECHANISM	MANAGEMENT
Anthracycline, thoracic radiation	↑ cardiotoxicity	Unknown	Caution
Irinotecan	Potential ↑ toxicity of Irinotecan	↑ SN38 (irinotecan metabolite) concentrations	Caution
sunitinib	Microangiopathic hemolytic anemia reported when used in combination	Unknown	Avoid this combination
Bisphosphonates, anti-angiogenic drugs	↑ risk of ONJ	Additive	Caution
Platinum or taxane-based chemotherapy	Increased risk of myelosuppression +/- infection, bleeding	Additive	Caution and closely monitor CBC

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline and at each visit
Urine dipstick, a 24 hour urine collection is recommended for patients with a 2+ or greater urine dipstick	Baseline and at each visit
Blood pressure	Baseline and every 2-3 weeks during therapy; more frequently in patients who develop hypertension
Dental evaluation	Baseline
Clinical assessment of hypersensitivity, perforation, fistula, GI symptoms, ONJ, hemorrhage, infection, myelosuppression, thromboembolism, delayed wound healing, hypertension, neurologic and cardiac effects	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
Liver and renal function tests	Baseline and at each visit
Cardiac function tests (Echo, RNA and/or MUGA scans) especially in patients who are close to the lifetime cumulative dose of anthracyclines/anthracenediones	Baseline and as clinically indicated
INR for patients receiving warfarin	Baseline and as clinically indicated

J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

Bevacizumab (Biosimilar) - Metastatic (Stage IVB), Persistent, or Recurrent Carcinoma of the Cervix
Bevacizumab (Biosimilar) with Paclitaxel and Carboplatin - Front-line Treatment (Previously Untreated) Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Bevacizumab (Biosimilar) for Platinum-Resistant Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Bevacizumab (Biosimilar) - Metastatic Colorectal, Small Bowel, or Appendiceal Cancer
Atezolizumab with Bevacizumab (Biosimilar) - Previously Untreated Unresectable or Metastatic Hepatocellular Carcinoma
Bevacizumab (Biosimilar) - In Combination with Lomustine for Recurrent Glioblastoma
Bevacizumab (Biosimilar) - In Combination with Trifluridine and Tipiracil for Previously Treated Metastatic Colorectal Cancer

K - References

Colorectal stents and bevacizumab: increased risk of intestinal perforation. Review. Health Canada Product InfoWatch. February 2017.

Dhillon, S. Bevacizumab combination therapy for the first-line treatment of advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Drugs 2012; 72(7): 917-30.

Gressett SM, Shah SR. Intricacies of bevacizumab-induced toxicities and their management. Ann Pharmacother. 2009 Mar;43(3):490-501.

Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42.

Mahfoud T, Tanz R, Mesmoudi M, et al. Bevacizumab 5 or 7.5 mg/kg in metastatic colorectal cancer can be infused safely over 10 minutes. J Gastrointest Cancer. 2012 Jun;43(2):244-8.

Perren TJ, Swart AM, Pfisterer J, et al; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96.

Product Monograph: Avastin® (bevacizumab). Roche Canada. February 2017.

Product Monograph: Avastin® (bevacizumab). Roche Canada. August 4, 2023.

Reidy DL, Chung KY, Timoney JP, et al. Bevacizumab 5 mg/kg can be infused safely over 10 minutes. Journal of Clinical Oncology 2007; 25: 2691-5.

November 2024 Updated NDFP forms

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

bevacizumab (patient)

Info Sheet Introduction:

For treating certain types of colorectal, lung, brain, ovarian, cervical, kidney and other cancers. It may be used alone or with other chemotherapy drugs, depending on the type of cancer.
Bevacizumab is available as a biosimilar medication. See our biosimilar pamphlet for more information.

Info Sheet Date: Tuesday, July 23, 2024 Info Sheet body:

bevacizumab

Pronunciation:

be-vuh-SIZ-uh-mab

Other Name(s):

Avastin®; Mvasi®; Zirabev®; Bambevi®, Abevmy®, Aybintio®, Vegzelma™

Appearance:

Clear, colourless solution mixed into larger bags of fluids

This handout gives general information about this cancer medication.

You will learn:

who to contact for help
what the medication is
how it is given
what to expect while on medication

This handout was created by Ontario Health (Cancer Care Ontario) together with patients and their caregivers who have also gone through cancer treatment. It is meant to help support you through your cancer treatment and answer some of your questions.

This information does not replace the advice of your health care team. Always talk to your health care team about your treatment.

Who do I contact if I have questions or need help?

My cancer health care provider is: _____________________________________________

During the day I should contact: _______________________________________________

Evenings, weekends and holidays: _____________________________________________

This page gives general information about this cancer medication.

You will learn:

who to contact for help
what the medication is
how it is given
what to expect while on this medication

This information was created by Ontario Health (Cancer Care Ontario) together with patients and their caregivers who have also gone through cancer treatment. It is meant to help support you through your cancer treatment and answer some of your questions.

This information does not replace the advice of your health care team. Always talk to your health care team about your treatment.

What is this treatment for?

For treating certain types of colorectal, lung, brain, ovarian, cervical, kidney and other cancers. It may be used alone or with other chemotherapy drugs, depending on the type of cancer.
Bevacizumab is available as a biosimilar medication. See our biosimilar pamphlet for more information.

What should I do before I start this treatment?

Tell your health care team if you have or had significant medical condition(s), especially if you have / had:
- high blood pressure
- surgery in the last 28 days (or will be having surgery or dental procedures)
- heart problems (including heart attack or stroke)
- kidney problems
- coughed up blood or had other bleeding
- any allergies

Remember To:

Tell your health care team about all of the other medications you are taking.
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.

You will have a blood test to check for hepatitis B before starting treatment. See the Hepatitis B and Cancer Medications pamphlet for more information.

How is this treatment given?

This drug is given through an IV (injected into a vein). Talk to your health care team about your treatment schedule.
Bevacizumab will be given over a longer period of time for the first cycle. If you have no problems with this infusion, it will be given over a shorter time for the following cycles.
If you missed your treatment appointment, talk to your health care team to find out what to do.

Other important things for you to know about this treatment

While taking bevacizumab, wounds may take longer to heal than normal or may not fully heal. Tell your health care team if you plan to have any surgery (including dental surgery). Your health care team may ask you to stop bevacizumab treatment for 28 days or more before any scheduled surgery.

DO this while on treatment

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.

DO NOT do this while on treatment

Stop Icon

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

DO this while on treatment

Check Mark Icon

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures.

DO NOT do this while on treatment

Stop Icon

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

Will this treatment interact with other medications or natural health products?

Yes, this medication can interact with other medications, vitamins, foods and natural health products. Interactions can make this medication not work as well or cause severe side effects.

Tell your health care team about all of your:

prescription and over-the-counter (non-prescription) medications
natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements

Check with your health care team before starting or stopping any of them.

Talk to your health care team BEFORE taking or using these :

Anti-inflammatory medications such as ibuprofen (Advil^® or Motrin^®), naproxen (Aleve^®) or Aspirin^®.
Over-the-counter products such as dimenhydrinate (Gravol^®)
Natural health products such as St. John’s Wort
Supplements such as vitamin C
Grapefruit juice
Alcoholic drinks
Tobacco
All other drugs, such as marijuana or cannabis (medical or recreational)

What to do if you feel unwell, have pain, a headache or a fever

Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol^®) or ibuprofen (Advil^®)).
- Fever can be a sign of infection that may need treatment right away.
- If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.

How to check for fever:

Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).

You have a fever if your temperature taken in your mouth (oral temperature) is:
- 38.3°C (100.9°F) or higher at any time
OR
- 38.0°C (100.4°F) or higher for at least one hour.

If you do have a fever :

Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
Ask your health care team for the Fever pamphlet for more information.

If you do not have a fever but have mild symptoms such as headache or mild pain:

Ask your health care team about the right medication for you. Acetaminophen (Tylenol^®) is a safe choice for most people.

Talk to your health care team before you start taking ibuprofen (Advil^®, Motrin^®), naproxen (Aleve^®) or ASA (Aspirin^®), as they may increase your chance of bleeding or interact with your cancer treatment.

Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.

How will this treatment affect sex, pregnancy and breastfeeding?

Talk to your health care team about:

How this treatment may affect your sexual health.
How this treatment may affect your ability to have a baby, if this applies to you.

This treatment may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.

If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time until at least 6 months after your last treatment dose. Talk to your health care team about which birth control options are best for you.
Do not breastfeed while on this treatment, and for at least 6 months after the last dose.

What are the side effects of this treatment?

The following table lists side effects that you may have when getting bevacizumab. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.

Read over the side effect table so that you know what to look for and when to get help. Keep this paper during your treatment so that you can refer to it if you need to.

Common Side Effects (25 to 49 out of 100 people)
Side effects and what to do	When to contact health care team
Unusual bleeding or bruising (May be severe) What to look for? Watch for signs of bleeding: bleeding from your gums unusual or heavy nosebleeds bruising easily or more than normal black coloured stools (poo) or blood in your stools (poo) coughing up red or brown coloured mucus dizziness, constant headache or changes in your vision heavy vaginal bleeding What to do? Check with your healthcare team before you go to the dentist or if you have a surgery planned. Take care of your mouth and use a soft toothbrush. Try to prevent cuts and bruises. Ask your health care team what activities are safe for you. If you have signs of bleeding: If you have a small bleed, clean the area with soap and water or a saline (saltwater) rinse. Apply pressure for at least 10 minutes. If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away.	Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe, you MUST get emergency medical help right away.
Fatigue What to look for? Feeling of tiredness or low energy that lasts a long time and does not go away with rest or sleep. What to do? Be active. Aim to get 30 minutes of moderate exercise (you are able to talk comfortably while exercising) on most days. Check with your health care team before starting any new exercise. Pace yourself, do not rush. Put off less important activities. Rest when you need to. Ask family or friends to help you with things like housework, shopping, and child or pet care. Eat well and drink at least 6 to 8 glasses of water or other liquids every day (unless your health care team has told you to drink more or less). Avoid driving or using machinery if you are feeling tired. Ask your health care team for the Fatigue pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
High blood pressure (May be severe) What to look for? There are usually no signs of high blood pressure. Rarely, you may have headaches, shortness of breath or nosebleeds. What to do? Check your blood pressure regularly. Your doctor may prescribe medication to treat high blood pressure. If you have a severe headache get emergency help right away as it may be a sign your blood pressure is too high.	Talk to your health care team if it does not improve or if it is severe.
Proteins in Urine (May be severe) Your health care team may do urine tests to check for proteins in your pee. What to look for? Swelling in your face, legs, or belly. Recent weight gain that is not normal for you. Foamy, frothy, or bubbly-looking pee. What to do? Talk to your health care team if it does not improve or if it is severe.	Talk to your health care team if it does not improve or if it is severe.
Headache, mild joint, muscle pain or cramps What to look for? Headache, new pain in your muscles or joints, muscle cramps, or feeling achy. What to do? Take pain medication (acetaminophen or opioids such as codeine, morphine, hydromorphone, oxycodone) as prescribed. Read the above section: "What should I do if I feel unwell, have pain, a headache or a fever?" before taking acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or Aspirin. These medications may hide an infection that needs treatment or they may increase your risk of bleeding. Rest often and try light exercise (such as walking) as it may help. Ask your health care team for the Pain pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.

Less Common Side Effects (10 to 24 out of 100 people)
Side effects and what to do	When to contact health care team
Diarrhea What to look for? Loose, watery, unformed stool (poo) that may happen days to weeks after you get your treatment. What to do? If you have diarrhea: Take anti-diarrhea medication if your health care team prescribed it or told you to take it. Do not eat foods or drinks with artificial sweetener (like chewing gum or ‘diet’ drinks), coffee and alcohol, until your diarrhea has stopped. Eat many small meals and snacks instead of 2 or 3 large meals. Drink at least 6 to 8 cups of liquids each day, unless your health care team has told you to drink more or less. Talk to your health care team if you can’t drink 6 to 8 cups of liquids each day when you have diarrhea. You may need to drink special liquids with salt and sugar, called Oral Rehydration Therapy. Talk to your health care team if your diarrhea does not improve after 24 hours of taking diarrhea medication or if you have diarrhea more than 7 times in one day. Ask your health care team for the Diarrhea pamphlet for more information.	Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day).
Blood clots What to look for? Blood clots can cause pain, swelling and hardening of the vein in the body part that has the clot. If the clot is severe it can block a big artery or vein. A blood clot in your lungs can cause: coughing, problems breathing, pain in your chest or coughing up blood. A blood clot in you brain (stroke) can cause: trouble seeing, speaking, or using your arms and legs. A blood clot in your heart (heart attack) can cause: chest pain, shortness of breath and pain in your belly or arms. What to do? Get emergency medical help right away.	Get emergency medical help right away.
Nausea and vomiting (Generally mild) What to look for? Nausea is feeling like you need to throw up. You may also feel light-headed. You may feel nausea within hours to days after your treatment. What to do? To help prevent nausea: It is easier to prevent nausea than to treat it once it happens. Drink clear liquids and have small meals. Get fresh air and rest. Do not eat spicy, fried foods or foods with a strong smell. Limit caffeine (like coffee, tea) and avoid alcohol. If you have nausea or vomiting: Take your rescue (as needed) anti-nausea medication(s) as prescribed. Talk to your health care team if: nausea lasts more than 48 hours vomiting lasts more than 24 hours or if it is severe Ask your health care team for the Nausea & Vomiting pamphlet for more information.	Talk to your health care team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if severe.
Constipation What to look for? Having bowel movements (going poo) less often than normal. Small hard stools (poo) that look like pellets. The need to push hard and strain to have any stool (poo) come out. Stomach ache or cramps. A bloated belly, feeling of fullness, or discomfort. Leaking of watery stools (poo). Lots of gas or burping. Nausea or vomiting. What to do? To help prevent constipation: Try to eat more fiber rich foods like fruits with skin, leafy greens and whole grains. Drink at least 6 to 8 cups of liquids each day unless your health care team has told you to drink more or less. Be Active. Exercise can help to keep you regular. If you take opioid pain medication, ask your health care team if eating more fibre is right for you. To help treat constipation: If you have not had a bowel movement in 2 to 3 days you may need to take a laxative (medication to help you poo) to help you have regular bowel movements. Ask your health care team what to do. Ask your health care team for the Constipation Pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Cough and feeling short of breath What to look for? You may have a cough and feel short of breath. Symptoms that commonly occur with a cough are: Wheezing or a whistling breathing Runny nose Sore throat Heartburn Weight loss Fever and chills Rarely this may be severe with chest pain, trouble breathing or coughing up blood. What to do? Check your temperature to see if you have a fever. Read the above section "What should I do if I feel unwell, have pain, a headache or a fever?". If you have a fever, try to talk to your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away. If you have a severe cough with chest pain, trouble breathing or you are coughing up blood, get medical help right away.	Talk to your health care team. If you are not able to talk to your health care team for advice, and you have a fever or severe symptoms, you MUST get emergency medical help right away.
Trouble Sleeping Your medications may cause trouble sleeping. It may get better once your body gets used to the medication or when your treatment ends. What to look for? You may find it hard to fall asleep or stay asleep. How well you sleep may change over your treatment. For example, you may have several nights of poor sleep followed by a night of better sleep. You may wake up too early or not feel well-rested after a night's sleep. You may feel tired or sleepy during the day. What to do? Talk to your health care team if it does not improve or if it is severe.	Talk to your health care team if it does not improve or if it is severe.
Low appetite What to look for? Loss of interest in food or not feeling hungry. Weight loss. What to do? Try to eat your favourite foods. Eat small meals throughout the day. You may need to take meal supplements to help keep your weight up. Talk to your health care team if you have no appetite. Ask your health care team for the Loss of Appetite pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Heart problems What to look for? You may have an irregular heartbeat, shortness of breath, chest pain or fainting spells. Swelling in your legs, ankles and belly. Sharp pain in the centre or left side of the chest (often worsens when taking a deep breath). Extreme tiredness that prevents you from exercising or doing normal activities. What to do? Get emergency medical help right away.	Get emergency medical help right away.
Rash; dry, itchy skin What to look for? You may have cracked, rough, flaking or peeling areas of the skin. Your skin may look red and feel warm, like a sunburn. Your skin may itch, burn, sting or feel very tender when touched. What to do? To prevent and treat dry skin: Use fragrance-free skin moisturizer. Protect your skin from the sun and the cold. Use sunscreen with UVA and UVB protection and a SPF of at least 30. Avoid perfumed products and lotions that contain alcohol. Drink 6 to 8 cups of non-alcoholic, non-caffeinated liquids each day, unless your health care team has told you to drink more or less. Rash may be severe in some rare cases and cause your skin to blister or peel. If this happens, get emergency medical help right away.	Talk to your health care team if it does not improve or if it is severe.
Fever, chills, infection What to look for? If you feel hot or unwell (for example if you have chills or a new cough), you must check your temperature to see if you have a fever. Do not take medications that treat a fever before you take your temperature (for example, Tylenol®, acetaminophen, Advil® or ibuprofen). Do not eat or drink anything hot or cold right before taking your temperature. You have a fever if your temperature taken in your mouth (oral temperature) is: 38.3°C (100.9°F) or higher at any time OR 38.0°C (100.4°F) or higher for at least one hour. What to do? Wash your hands often to prevent infection. Check with your doctor before getting any vaccines, surgeries, medical procedures or visiting your dentist. Keep a digital thermometer at home so you can easily check for a fever. If you have a fever: If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you must get emergency medical help right away.	If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you MUST get emergency medical help right away.
Hoarseness (raspy voice) What to look for? Your voice may sound breathy, raspy or strained. You may hear changes in loudness or how high or low your voice is. What to do? Talk to your health care team if it does not improve or if it is severe.	Talk to your health care team if it does not improve or if it is severe.

Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:

Red dots on skin, pale skin and/or severe tiredness, passing little or no pee or dark-coloured pee
Flushing, swollen lips, face or tongue, wheezing and/or throat tightness, usually during or shortly after the drug is given
Severe belly pain, bloating or feeling of fullness and severe constipation or sudden, severe pain in belly or stomach area
Teeth, mouth or jaw pain and swelling, poor healing of mouth sores, unusual discharge from gums, loosening of teeth and the feeling of numbness or heaviness in the jaw
Severe headache, fainting, seizures, confusion and vision loss
Wounds that take longer to heal or not fully heal
Sudden severe pain in your chest, upper back, that moves up your neck or down your back, when you didn’t hurt yourself
High fever and red, very painful swelling of the skin, which may feel hot or turn purplish

For more information on how to manage your symptoms ask your health care provider, or visit: https://www.cancercareontario.ca/symptoms.

Notes

July 2024 Updated/Revised information sheet

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

bevacizumab patient.pdf Info Sheet (French):

bvacizumab pour le patient.pdf Monograph:

bevacizumab.pdf Funding Program: New Drug Funding Program Funding Instance:

Bevacizumab (Biosimilar) - Metastatic (Stage IVB), Persistent, or Recurrent Carcinoma of the Cervix
Bevacizumab (Biosimilar) with Paclitaxel and Carboplatin - Front-line Treatment (Previously Untreated) Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Bevacizumab (Biosimilar) for Platinum-Resistant Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Bevacizumab (Biosimilar) - Metastatic Colorectal, Small Bowel, or Appendiceal Cancer
Atezolizumab with Bevacizumab (Biosimilar) - Previously Untreated Unresectable or Metastatic Hepatocellular Carcinoma
Bevacizumab (Biosimilar) - In Combination with Lomustine for Recurrent Glioblastoma
Bevacizumab (Biosimilar) - In Combination with Trifluridine and Tipiracil for Previously Treated Metastatic Colorectal Cancer

Phonetic Spelling:

be-vuh-SIZ-uh-mab

Eligibility Form:

Bevacizumab (Biosimilar) for Platinum-Resistant Recurrent Ovarian Fallopian Tube or Primary Peritoneal Cancer

Bevacizumab (Biosimilar) - Metastatic (Stage IVB) Persistent or Recurrent Carcinoma of the Cervix

Bevacizumab (Biosimilar) with Paclitaxel and Carboplatin - Front-line Treatment (Previously Untreated) Ovarian, Fallopian Tube,

Bevacizumab (Biosimilar) - In Combination with Lomustine for Recurrent Glioblastoma

Bevacizumab (Biosimilar) - Metastatic Colorectal Small Bowel or Appendiceal Cancer

Bevacizumab (Biosimilar) - In Combination with Trifluridine and Tipiracil for Previously Treated Metastatic Colorectal Cancer Cancer Type: Central Nervous System Gastrointestinal Colorectal Hepatobiliary / Liver / Bile Duct Small bowel and appendix Gynecologic Cervix Ovary Lung Mesothelioma (Pleural) Non-Small Cell Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Monday, November 4, 2024 Universal Date: 2024-11-04 00:00:00 AddThis: Title URL: bevacizumab Drug Display Status: Active Revision Summary:

Drug Monograph: Updated NDFP forms