Loading…
MVASI is a brand name for Bevacizumab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE MVASI is a vascular endothelial growth factor inhibitor indicated for the treatment of: Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment. ( 1.1 ) Metastatic colorectal cancer, in combination with…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Withhold for at least 28 days prior to elective surgery. Do not administer MVASI for 28 days following major surgery and until adequate wound healing. 7 ) 15 mg/kg every 3 weeks with carboplatin and paclitaxel for 6-8 cycles, followed by 15 mg/kg every 3 weeks as a single agent 15 mg/kg every 3 weeks with carboplatin and gemcitabine for 6-10 cycles, followed by 15 mg/kg every 3 weeks as a single agent Administer as an intravenous infusion after dilution.
1 Important Administration Information Withhold for at least 28 days prior to elective surgery. Do not administer MVASI until at least 28 days following major surgery and until adequate wound healing. 2 Metastatic Colorectal Cancer The recommended dosage when MVASI is administered in combination with intravenous fluorouracil-based chemotherapy is: 5 mg/kg intravenously every 2 weeks in combination with bolus-IFL.
10 mg/kg intravenously every 2 weeks in combination with FOLFOX4. 5 mg/kg intravenously every 3 weeks in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy in patients who have progressed on a first-line bevacizumab product-containing regimen.
3 First-Line Non-Squamous Non-Small Cell Lung Cancer The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel. 4 Recurrent Glioblastoma The recommended dosage is 10 mg/kg intravenously every 2 weeks.
5 Metastatic Renal Cell Carcinoma The recommended dosage is 10 mg/kg intravenously every 2 weeks in combination with interferon-alfa. 6 Persistent, Recurrent, or Metastatic Cervical Cancer The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with paclitaxel and cisplatin, or in combination with paclitaxel and topotecan.
7 Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Stage III or IV Disease Following Initial Surgical Resection The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by MVASI 15 mg/kg every 3 weeks as a single agent for a total of up to 22 cycles or until disease progression, whichever occurs earlier.
Recurrent Disease Platinum Resistant The recommended dosage is 10 mg/kg intravenously every 2 weeks in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan (every week). The recommended dosage is 15 mg/kg intravenously every 3 weeks in combination with topotecan (every 3 weeks).
1) ] . 2) ] . 3) ] . 4) ] . 5) ] . 6) ] . 7) ] . 8) ] . 9) ] . 11) ] . 12) ] . Most common adverse reactions incidence (incidence > 10%) are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.
gov/medwatch. 1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
The safety data in Warnings and Precautions and described below reflect exposure to bevacizumab in 4463 patients including those with mCRC (AVF2107g, E3200), non-squamous NSCLC (E4599), GBM (EORTC 26101), mRCC (BO17705), cervical cancer (GOG-0240), epithelial ovarian, fallopian tube, or primary peritoneal cancer (MO22224, AVF4095, GOG-0213, and GOG-0218), or another cancer, at the recommended dose and schedule for a median of 6 to 23 doses.
The most common adverse reactions observed in patients receiving bevacizumab as a single agent or in combination with other anti-cancer therapies at a rate > 10% were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.
Across clinical studies, bevacizumab was discontinued in 8% to 22% of patients because of adverse reactions [see Clinical Studies (14) ] . 1) ] . Patients were randomized (1:1:1) to placebo with bolus-IFL, bevacizumab with bolus-IFL, or bevacizumab with fluorouracil and leucovorin.
The demographics of the safety population were similar to the demographics of the efficacy population. , hypertension, proteinuria, thromboembolic events) were collected in the entire study population. Adverse reactions are presented in Table 2.
5 WARNINGS AND PRECAUTIONS Gastrointestinal Perforations and Fistula : Discontinue for gastrointestinal perforations, tracheoesophageal fistula, Grade 4 fistula, or fistula formation involving any organ. 1 ) Surgery and Wound Healing Complications : In patients who experience wound healing complications during MVASI treatment, withhold MVASI until adequate wound healing.
Withhold for at least 28 days prior to elective surgery. Do not administer MVASI for at least 28 days following a major surgery, and until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complication has not been established.
Discontinue for wound healing complication of necrotizing fasciitis. 2 ) Hemorrhage : Severe or fatal hemorrhages have occurred. Do not administer for recent hemoptysis. Discontinue for Grade 3-4 hemorrhage. 3 ) Arterial Thromboembolic Events (ATE) : Discontinue for severe ATE.
4 ) Venous Thromboembolic Events (VTE) : Discontinue for Grade 4 VTE. 5 ) Hypertension : Monitor blood pressure and treat hypertension. Withhold if not medically controlled; resume once controlled. Discontinue for hypertensive crisis or hypertensive encephalopathy.
6 ) Posterior Reversible Encephalopathy Syndrome (PRES) : Discontinue. 7 ) Renal Injury and Proteinuria : Monitor urine protein. Discontinue for nephrotic syndrome. Withhold until less than 2 grams of protein in urine. 8 ) Infusion-Related Reactions : Decrease rate for infusion-related reactions.
Discontinue for severe infusion-related reactions and administer medical therapy. 9 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of potential risk to fetus and need for use of effective contraception. 3 ) Ovarian Failure : Advise females of the potential risk.
3 ) Congestive Heart Failure (CHF) : Discontinue MVASI in patients who develop CHF. 1 Gastrointestinal Perforations and Fistulae Serious, and sometimes fatal, gastrointestinal perforation occurred at a higher incidence in patients receiving bevacizumab products compared to patients receiving chemotherapy.
4 CONTRAINDICATIONS None. None ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in United States of America? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Platinum Sensitive The recommended dosage is 15 mg/kg intravenously every 3 weeks, in combination with carboplatin and paclitaxel for 6 to 8 cycles, followed by MVASI 15 mg/kg every 3 weeks as a single agent until disease progression.
The recommended dosage is 15 mg/kg intravenously every 3 weeks, in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by MVASI 15 mg/kg every 3 weeks as a single agent until disease progression. 8 Dosage Modifications for Adverse Reactions Table 1 describes dosage modifications for specific adverse reactions.
No dose reductions for MVASI are recommended. 2) ] Any Withhold MVASI until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complications has not been established. 9 Preparation and Administration Preparation Use appropriate aseptic technique.
Use sterile needle and syringe to prepare MVASI. Visually inspect vial for particulate matter and discoloration prior to preparation for administration. Discard vial if solution is cloudy, discolored or contains particulate matter. 9% Sodium Chloride Injection, USP.
DO NOT ADMINISTER OR MIX WITH DEXTROSE SOLUTION. Discard any unused portion left in a vial, as the product contains no preservatives. Diluted MVASI solution may be stored at 2°C to 8°C (36°F to 46°F) for up to 8 hours, if not used immediately.
No incompatibilities between MVASI and polyvinylchloride or polyolefin bags have been observed. Administration Administer as an intravenous infusion.
First infusion:
Administer infusion over 90 minutes.
Subsequent infusions:
Administer second infusion over 60 minutes if first infusion is tolerated. Administer all subsequent infusions over 30 minutes if second infusion over 60 minutes is tolerated.
Table 2:
Grades 3-4 Adverse Reactions Occurring at Higher Incidence (≥ 2%) in Patients Receiving Bevacizumab vs. Placebo in Study AVF2107g Adverse Reaction NCI-CTC version 3. Bevacizumab with IFL (N = 392) Placebo with IFL (N = 396) Hematology Leukopenia 37% 31% Neutropenia 21% 14% Gastrointestinal Diarrhea 34% 25% Abdominal pain 8% 5% Constipation 4% 2% Vascular Hypertension 12% 2% Deep vein thrombosis 9% 5% Intra-abdominal Thrombosis 3% 1% Syncope 3% 1% General Asthenia 10% 7% Pain 8% 5% In Combination with FOLFOX4 The safety of bevacizumab was evaluated in 521 patients in an open-label, active-controlled study (E3200) in patients who were previously treated with irinotecan and fluorouracil for initial therapy for mCRC.
Patients were randomized (1:1:1) to FOLFOX4, bevacizumab (10 mg/kg every 2 weeks prior to FOLFOX4 on Day 1) with FOLFOX4, or bevacizumab alone (10 mg/kg every 2 weeks). Bevacizumab was continued until disease progression or unacceptable toxicity.
The demographics of the safety population were similar to the demographics of the efficacy population. Selected Grades 3–5 non-hematologic and Grades 4–5 hematologic occurring at a higher incidence (≥ 2%) in patients receiving bevacizumab with FOLFOX4 compared to FOLFOX4 alone were fatigue (19% vs.
13%), diarrhea (18% vs. 13%), sensory neuropathy (17% vs. 9%), nausea (12% vs. 5%), vomiting (11% vs. 4%), dehydration (10% vs. 5%), hypertension (9% vs. 2%), abdominal pain (8% vs. 5%), hemorrhage (5% vs. 1%), other neurological (5% vs. 3%), ileus (4% vs.
1%) and headache (3% vs. 0%). These data are likely to under-estimate the true adverse reaction rates due to the reporting mechanisms. 3) ] . Chemotherapy-naïve patients with locally advanced, metastatic or recurrent non–squamous NSCLC were randomized (1:1) to receive six 21-day cycles of paclitaxel and carboplatin with or without bevacizumab (15 mg/kg every 3 weeks).
After completion or upon discontinuation of chemotherapy, patients randomized to receive bevacizumab continued to receive bevacizumab alone until disease progression or until unacceptable toxicity. The trial excluded patients with predominant squamous histology (mixed cell type tumors only), CNS metastasis, gross hemoptysis (1/2 teaspoon or more of red blood), unstable angina, or receiving therapeutic anticoagulation.
The demographics of the safety population were similar to the demographics of the efficacy population. Only Grades 3-5 non-hematologic and Grades 4-5 hematologic adverse reactions were collected. Grades 3-5 non-hematologic and Grades 4-5 hematologic adverse reactions occurring at a higher incidence (≥ 2%) in patients receiving bevacizumab with paclitaxel and carboplatin compared with patients receiving chemotherapy alone were neutropenia (27% vs.
17%), fatigue (16% vs. 13%), hypertension (8% vs. 7%), infection without neutropenia (7% vs. 3%), venous thromboembolism (5% vs. 3%), febrile neutropenia (5% vs. 2%), pneumonitis/pulmonary infiltrates (5% vs. 3%), infection with Grade 3 or 4 neutropenia (4% vs.
2%), hyponatremia (4% vs. 1%), headache (3% vs. 1%) and proteinuria (3% vs. 0%). 4) ] . Patients were randomized (2:1) to receive bevacizumab (10 mg/kg every 2 weeks) with lomustine or lomustine alone until disease progression or unacceptable toxicity.
The demographics of the safety population were similar to the demographics of the efficacy population. In the bevacizumab with lomustine arm, 22% of patients discontinued treatment due to adverse reactions compared with 10% of patients in the lomustine arm.
In patients receiving bevacizumab with lomustine, the adverse reaction profile was similar to that observed in other approved indications. Metastatic Renal Cell Carcinoma The safety of bevacizumab was evaluated in 337 patients who received at least one dose of bevacizumab in a multicenter, double-blind study (BO17705) in patients with mRCC.
5) ] . Patients were treated until disease progression or unacceptable toxicity. The demographics of the safety population were similar to the demographics of the efficacy population. Grades 3-5 adverse reactions occurring at a higher incidence (> 2%) were fatigue (13% vs.
8%), asthenia (10% vs. 7%), proteinuria (7% vs. 0%), hypertension (6% vs. 1%; including hypertension and hypertensive crisis), and hemorrhage (3% vs. 3%; including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma).
Adverse reactions are presented in Table 3.
Table 3:
Grades 1-5 Adverse Reactions Occurring at Higher Incidence (≥ 5%) of Patients Receiving Bevacizumab vs. Placebo with Interferon-Alfa in Study BO17705 Adverse Reaction NCI-CTC version 3. Bevacizumab with Interferon-Alfa (N = 337) Placebo with Interferon-Alfa (N = 304) Metabolism and nutrition Decreased appetite 36% 31% Weight loss 20% 15% General Fatigue 33% 27% Vascular Hypertension 28% 9% Respiratory, thoracic and mediastinal Epistaxis 27% 4% Dysphonia 5% 0% Nervous system Headache 24% 16% Gastrointestinal Diarrhea 21% 16% Renal and urinary Proteinuria 20% 3% Musculoskeletal and connective tissue Myalgia 19% 14% Back pain 12% 6% The following adverse reactions were reported at a 5-fold greater incidence in patients receiving bevacizumab with interferon-alfa compared to patients receiving placebo with interferon-alfa and not represented in Table 3: gingival bleeding (13 patients vs.
1 patient); rhinitis (9 vs. 0); blurred vision (8 vs. 0); gingivitis (8 vs. 1); gastroesophageal reflux disease (8 vs. 1); tinnitus (7 vs. 1); tooth abscess (7 vs. 0); mouth ulceration (6 vs. 0); acne (5 vs. 0); deafness (5 vs. 0); gastritis (5 vs.
0); gingival pain (5 vs. 0) and pulmonary embolism (5 vs. 1). 6) ] . Patients were randomized (1:1:1:1) to receive paclitaxel and cisplatin with or without bevacizumab (15 mg/kg every 3 weeks), or paclitaxel and topotecan with or without bevacizumab (15 mg/kg every 3 weeks).
The demographics of the safety population were similar to the demographics of the efficacy population. Grades 3–4 adverse reactions occurring at a higher incidence (≥ 2%) in 218 patients receiving bevacizumab with chemotherapy compared to 222 patients receiving chemotherapy alone were abdominal pain (12% vs.
10%), hypertension (11% vs. 5%), thrombosis (8% vs. 3%), diarrhea (6% vs. 3%), anal fistula (4% vs. 0%), proctalgia (3% vs. 0%), urinary tract infection (8% vs. 6%), cellulitis (3% vs. 5%), fatigue (14% vs. 10%), hypokalemia (7% vs. 4%), hyponatremia (4% vs.
1%), dehydration (4% vs. 5%), neutropenia (8% vs. 4%), lymphopenia (6% vs. 3%), back pain (6% vs. 3%), and pelvic pain (6% vs. 1%). Adverse reactions are presented in Table 4.
Table 4:
Grades 1-4 Adverse Reactions Occurring at Higher Incidence (≥ 5%) in Patients Receiving Bevacizumab with Chemotherapy vs. Chemotherapy Alone in Study GOG-0240 Adverse Reaction NCI-CTC version 3. 7) ] . Patients were randomized (1:1:1) to carboplatin and paclitaxel without bevacizumab (CPP), carboplatin and paclitaxel with bevacizumab for up to six cycles (CPB15), or carboplatin and paclitaxel with bevacizumab for six cycles followed by bevacizumab as a single agent for up to 16 additional doses (CPB15+).
Bevacizumab was given at 15 mg/kg every three weeks. On this trial, 1215 patients received at least one dose of bevacizumab. The demographics of the safety population were similar to the demographics of the efficacy population. Grades 3-4 adverse reactions occurring at a higher incidence (≥2%) in either of the bevacizumab arms versus the control arm were fatigue (CPB15+ - 9%, CPB15 - 6%, CPP - 6%), hypertension (CPB15+ - 10%, CPB15 - 6%, CPP - 2%), thrombocytopenia (CPB15+ - 21%, CPB15 - 20%, CPP - 15%) and leukopenia (CPB15+ - 51%, CPB15 - 53%, CPP - 50%).
Adverse reactions are presented in Table 5.
Table 5:
Grades 1-5 Adverse Reactions Occurring at Higher Incidence (≥ 5%) in Patients Receiving Bevacizumab with Chemotherapy vs. 8) ] . Patients were randomized to receive bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks. Patients had received no more than 2 prior chemotherapy regimens.
The trial excluded patients with evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction. Patients were treated until disease progression or unacceptable toxicity.
Forty percent of patients on the chemotherapy alone arm received bevacizumab alone upon progression. The demographics of the safety population were similar to the demographics of the efficacy population. 7% vs. 5% vs. 7%). Adverse reactions are presented in Table 6.
Table 6:
Grades 2–4 Adverse Reactions Occurring at Higher Incidence ( ≥ 5%) in Patients Receiving Bevacizumab with Chemotherapy vs. 9) ] . Patients were randomized (1:1) to receive bevacizumab (15 mg/kg) or placebo every 3 weeks with carboplatin and gemcitabine for 6 to 10 cycles followed by bevacizumab or placebo alone until disease progression or unacceptable toxicity.
The demographics of the safety population were similar to the demographics of the efficacy population. Grades 3-4 adverse reactions occurring at a higher incidence (≥ 2%) in patients receiving bevacizumab with chemotherapy compared to placebo with chemotherapy were: thrombocytopenia (40% vs.
34%), nausea (4% vs. 3%), fatigue (6% vs. 4%), headache (4% vs. 9%), proteinuria (10% vs. 4%), dyspnea (4% vs. 7%), epistaxis (5% vs. 4%), and hypertension (17% vs. 9%). Adverse reactions are presented in Table 7.
Table 7:
Grades 1–5 Adverse Reactions Occurring at a Higher Incidence (≥ 5%) in Patients Receiving Bevacizumab with Chemotherapy vs. 9) ] . Patients were randomized (1:1) to receive carboplatin and paclitaxel for 6 to 8 cycles or bevacizumab (15 mg/kg every 3 weeks) with carboplatin and paclitaxel for 6 to 8 cycles followed by bevacizumab as a single agent until disease progression or unacceptable toxicity.
The demographics of the safety population were similar to the demographics of the efficacy population. Grades 3-4 adverse reactions occurring at a higher incidence (≥ 2%) in patients receiving bevacizumab with chemotherapy compared to chemotherapy alone were: hypertension (11% vs.
6%), fatigue (8% vs. 3%), febrile neutropenia (6% vs. 3%), proteinuria (8% vs. 0%), abdominal pain (6% vs. 9%), hyponatremia (4% vs. 9%), headache (3% vs. 9%), and pain in extremity (3% vs. 0%). Adverse reactions are presented in Table 8.
Table 8:
Grades 1–5 Adverse Reactions Occurring at Higher Incidence (≥ 5%) in Patients Receiving Bevacizumab with Chemotherapy vs. 2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and the specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other bevacizumab products may be misleading. 6% (14/2233) of patients tested positive for treatment-emergent anti-bevacizumab antibodies as detected by an electrochemiluminescent (ECL) based assay.
Among these 14 patients, three tested positive for neutralizing antibodies against bevacizumab using an enzyme-linked immunosorbent assay (ELISA). The clinical significance of these anti-bevacizumab antibodies is not known. 3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of bevacizumab products.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
General:
Polyserositis Cardiovascular: Pulmonary hypertension, Mesenteric venous occlusion Gastrointestinal: Gastrointestinal ulcer, Intestinal necrosis, Anastomotic ulceration Hemic and lymphatic: Pancytopenia Hepatobiliary disorders: Gallbladder perforation Musculoskeletal and Connective Tissue Disorders: Osteonecrosis of the jaw Renal: Renal thrombotic microangiopathy (manifested as severe proteinuria) Respiratory: Nasal septum perforation Vascular: Arterial (including aortic) aneurysms, dissections, and rupture
3% to 3% across clinical studies, with the highest incidence in patients with a history of prior pelvic radiation. Perforation can be complicated by intra-abdominal abscess, fistula formation, and the need for diverting ostomies. 1) ] .
Serious fistulae (including, tracheoesophageal, bronchopleural, biliary, vaginal, renal and bladder sites) occurred at a higher incidence in patients receiving bevacizumab products compared to patients receiving chemotherapy. 8% across clinical studies, with the highest incidence in patients with cervical cancer.
The majority of fistulae occurred within 6 months of the first dose. Patients who develop a gastrointestinal vaginal fistula may also have a bowel obstruction and require surgical intervention, as well as a diverting ostomy. Avoid MVASI in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
Discontinue in patients who develop gastrointestinal perforation, tracheoesophageal fistula or any Grade 4 fistula. Discontinue in patients with fistula formation involving any internal organ. 2 Surgery and Wound Healing Complications In a controlled clinical study in which bevacizumab was not administered within 28 days of major surgical procedures, the incidence of wound healing complications, including serious and fatal complications, was 15% in patients with mCRC who underwent surgery while receiving bevacizumab and 4% in patients who did not receive bevacizumab.
1) ] . In patients who experience wound healing complications during MVASI treatment, withhold MVASI until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer for at least 28 days following major surgery and until adequate wound healing.
7) ] . Necrotizing fasciitis including fatal cases, has been reported in patients receiving bevacizumab, usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Discontinue MVASI in patients who develop necrotizing fasciitis.
3 Hemorrhage Bevacizumab products can result in two distinct patterns of bleeding: minor hemorrhage, which is most commonly Grade 1 epistaxis, and serious hemorrhage, which in some cases has been fatal. Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, hematemesis, CNS hemorrhage, epistaxis, and vaginal bleeding occurred up to 5-fold more frequently in patients receiving bevacizumab compared to patients receiving chemotherapy alone.
1) ] . Serious or fatal pulmonary hemorrhage occurred in 31% of patients with squamous NSCLC and 4% of patients with non-squamous NSCLC receiving bevacizumab with chemotherapy compared to none of the patients receiving chemotherapy alone.
Do not administer MVASI to patients with recent history of hemoptysis of 1/2 teaspoon or more of red blood. Discontinue in patients who develop a Grade 3-4 hemorrhage. 4 Arterial Thromboembolic Events Serious, sometimes fatal, arterial thromboembolic events (ATE) including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina occurred at a higher incidence in patients receiving bevacizumab compared to patients receiving chemotherapy.
Across clinical studies, the incidence of Grades 3-5 ATE was 5% in patients receiving bevacizumab with chemotherapy compared to ≤ 2% in patients receiving chemotherapy alone; the highest incidence occurred in patients with GBM. 5) ] .
Discontinue in patients who develop a severe ATE. The safety of reinitiating bevacizumab products after an ATE is resolved is not known. 1) ] . In Study GOG-0240, Grades 3-4 VTE occurred in 11% of patients receiving bevacizumab with chemotherapy compared with 5% of patients receiving chemotherapy alone.
In EORTC 26101, the incidence of Grades 3-4 VTE was 5% in patients receiving bevacizumab with chemotherapy compared to 2% in patients receiving chemotherapy alone. Discontinue MVASI in patients with a Grade 4 VTE, including pulmonary embolism.
6 Hypertension Severe hypertension occurred at a higher incidence in patients receiving bevacizumab products as compared to patients receiving chemotherapy alone. Across clinical studies the incidence of Grades 3-4 hypertension ranged from 5% to 18%.
Monitor blood pressure every two to three weeks during treatment with MVASI. Treat with appropriate anti-hypertensive therapy and monitor blood pressure regularly. Continue to monitor blood pressure at regular intervals in patients with MVASI-induced or -exacerbated hypertension after discontinuing MVASI.
Withhold MVASI in patients with severe hypertension that is not controlled with medical management; resume once controlled with medical management. Discontinue in patients who develop hypertensive crisis or hypertensive encephalopathy.
5% of patients across clinical studies. The onset of symptoms occurred from 16 hours to 1 year after the first dose. PRES is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances.
Mild to severe hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of PRES. Discontinue MVASI in patients who develop PRES. Symptoms usually resolve or improve within days after discontinuing bevacizumab products, although some patients have experienced ongoing neurologic sequelae.
The safety of reinitiating bevacizumab products in patients who developed PRES is not known. 8 Renal Injury and Proteinuria The incidence and severity of proteinuria was higher in patients receiving bevacizumab as compared to patients receiving chemotherapy.
7% to 7% in clinical studies. The overall incidence of proteinuria (all grades) was only adequately assessed in Study BO17705, in which the incidence was 20%. 6 months (15 days to 37 months) after initiating bevacizumab. 3). 1) ] . In an exploratory, pooled analysis of patients from seven randomized clinical studies, 5% of patients receiving bevacizumab with chemotherapy experienced Grades 2-4 (defined as urine dipstick 2+ or greater or > 1 gram of protein per 24 hours or nephrotic syndrome) proteinuria.
Grades 2-4 proteinuria resolved in 74% of patients. Bevacizumab was reinitiated in 42% of patients. Of the 113 patients who reinitiated bevacizumab, 48% experienced a second episode of Grades 2-4 proteinuria. Nephrotic syndrome occurred in < 1% of patients receiving bevacizumab across clinical studies, in some instances with fatal outcome .
In a published case series, kidney biopsy of 6 patients with proteinuria showed findings consistent with thrombotic microangiopathy. 9 times baseline levels) in patients who received bevacizumab. Serum creatinine levels did not return to baseline in approximately one-third of patients who received bevacizumab.
Monitor proteinuria by dipstick urine analysis for the development or worsening of proteinuria with serial urinalyses during MVASI therapy. Patients with a 2+ or greater urine dipstick reading should undergo further assessment with a 24-hour urine collection.
Withhold for proteinuria greater than or equal to 2 grams per 24 hours and resume when less than 2 grams per 24 hours. Discontinue in patients who develop nephrotic syndrome. 57)]. 9 Infusion-Related Reactions Infusion-related reactions reported across clinical studies and postmarketing experience include hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, Grade 3 hypersensitivity, anaphylactoid/anaphylactic reactions, chest pain, headaches, rigors, and diaphoresis.
4% of patients. Decrease the rate of infusion for mild, clinically insignificant infusion-related reactions. Interrupt the infusion in patients with clinically significant infusion-related reactions and consider resuming at a slower rate following resolution.
, epinephrine, corticosteroids, intravenous antihistamines, bronchodilators and/or oxygen). 10 Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal studies, bevacizumab products may cause fetal harm when administered to pregnant women.
Congenital malformations were observed with the administration of bevacizumab to pregnant rabbits during organogenesis every 3 days at a dose as low as a clinical dose of 10 mg/kg. Furthermore, animal models link angiogenesis and VEGF and VEGFR2 to critical aspects of female reproduction, embryo-fetal development, and postnatal development.
Advise pregnant women of the potential risk to a fetus. 3) ] . 11 Ovarian Failure The incidence of ovarian failure was 34% vs. 2% in premenopausal women receiving bevacizumab with chemotherapy as compared to those receiving chemotherapy alone for adjuvant treatment of a solid tumor.
After discontinuing bevacizumab, recovery of ovarian function at all time points during the post-treatment period was demonstrated in 22% of women receiving bevacizumab. Recovery of ovarian function is defined as resumption of menses, a positive serum β-HCG pregnancy test, or an FSH level < 30 mIU/mL during the post-treatment period.
Long-term effects of bevacizumab products on fertility are unknown. 3) ] . 12 Congestive Heart Failure MVASI is not indicated for use with anthracycline-based chemotherapy. 6% of patients receiving chemotherapy alone. 6% for patients receiving chemotherapy alone.
In previously untreated patients with a hematological malignancy, the incidence of CHF and decline in left-ventricular ejection fraction (LVEF) were increased in patients receiving bevacizumab with anthracycline-based chemotherapy compared to patients receiving placebo with the same chemotherapy regimen.
The proportion of patients with a decline in LVEF from baseline of ≥ 20% or a decline from baseline of 10% to < 50%, was 10% in patients receiving bevacizumab with chemotherapy compared to 5% in patients receiving chemotherapy alone.
Time to onset of left-ventricular dysfunction or CHF was 1 to 6 months after the first dose in at least 85% of the patients and was resolved in 62% of the patients who developed CHF in the bevacizumab arm compared to 82% in the placebo arm.
Discontinue MVASI in patients who develop CHF.