Jobevne
bevacizumab-nwgd · Injection · Intravascular
Uses
Jobevne 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 fluoropyrimidine-irinotecan-or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen. ( 1.1 ) Limitations of Use : Jobevne is not indicated for adjuvant treatment of colon cancer. ( 1.1 )
• Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment. ( 1.2 )
• Recurrent glioblastoma in adults. ( 1.3 )
• Metastatic renal cell carcinoma in combination with interferon alfa. ( 1.4 )
• Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan. ( 1.5 )
• Epithelial ovarian, fallopian tube, or primary peritoneal cancer: o in combination with carboplatin and paclitaxel, followed by Jobevne as a single agent, for stage III or IV disease following initial surgical resection ( 1.6 ) o in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens ( 1.6 ) o in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by Jobevne as a single agent, for platinum-sensitive recurrent disease ( 1.6 ) 1.1 Metastatic Colorectal Cancer Jobevne, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first-or second-line treatment of patients with metastatic colorectal cancer (mCRC). Jobevne, in combination with fluoropyrimidine-irinotecan-or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product-containing regimen. Limitations of Use Jobevne is not indicated for adjuvant treatment of colon cancer [see Clinical Studies (14.2) ]. 1.2 First-Line Non-Squamous Non–Small Cell Lung Cancer Jobevne, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer (NSCLC). 1.3 Recurrent Glioblastoma Jobevne is indicated for the treatment of recurrent glioblastoma (GBM) in adults. 1.4 Metastatic Renal Cell Carcinoma Jobevne, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma (mRCC). 1.5 Persistent, Recurrent, or Metastatic Cervical Cancer Jobevne, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer. 1.6 Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Jobevne, in combination with carboplatin and paclitaxel, followed by Jobevne as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection. Jobevne, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens. Jobevne, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Jobevne as a single agent, is indicated for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Dosage and administration
Withhold for at least 28 days prior to elective surgery. Do not administer Jobevne for 28 days following major surgery and until adequate wound healing. ( 2.1 ) Metastatic colorectal cancer ( 2.2 )
• 5 mg/kg every 2 weeks with bolus-IFL
• 10 mg/kg every 2 weeks with FOLFOX4
• 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy after progression on a first-line bevacizumab product-containing regimen First-line non−squamous non−small cell lung cancer ( 2.3 )
• 15 mg/kg every 3 weeks with carboplatin and paclitaxel Recurrent glioblastoma ( 2.4 )
• 10 mg/kg every 2 weeks Metastatic renal cell carcinoma ( 2.5 )
• 10 mg/kg every 2 weeks with interferon alfa Persistent, recurrent, or metastatic cervical cancer ( 2.6 )
• 15 mg/kg every 3 weeks with paclitaxel and cisplatin, or paclitaxel and topotecan Stage III or IV epithelial ovarian, fallopian tube or primary peritoneal cancer following initial surgical resection ( 2.7 )
• 15 mg/kg every 3 weeks with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 weeks as a single agent, for a total of up to 22 cycles Platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer ( 2.7 )
• 10 mg/kg every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or topotecan given every week
• 15 mg/kg every 3 weeks with topotecan given every 3 weeks Platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer ( 2.7 )
• 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. See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions ( 2.8 , 2.9 ) 2.1 Important Administration Information Withhold for at least 28 days prior to elective surgery. Do not administer Jobevne until at least 28 days following major surgery and until adequate wound healing. 2.2 Metastatic Colorectal Cancer The recommended dosage when Jobevne 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 2 weeks or 7.5 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. 2.3 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. 2.4 Recurrent Glioblastoma The recommended dosage is 10 mg/kg intravenously every 2 weeks. 2.5 Metastatic Renal Cell Carcinoma The recommended dosage is 10 mg/kg intravenously every 2 weeks in combination with interferon alfa. 2.6 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. 2.7 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 Jobevne 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). 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 Jobevne 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 Jobevne 15 mg/kg every 3 weeks as a single agent until disease progression. 2.8 Dosage Modifications for Adverse Reactions Table 1 describes dosage modifications for specific adverse reactions . No dose reductions for Jobevne are recommended. Table 1: Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Gastrointestinal Perforations and Fistulae [see Warnings and Precautions (5.1) ].
• Gastrointestinal perforation, any grade
• Tracheoesophageal fistula, any grade
• Fistula, Grade 4
• Fistula formation involving any internal organ Discontinue Jobevne Wound Healing Complications [see Warnings and Precautions (5.2) ].
• Any Withhold Jobevne until adequate wound healing. The safety of resumption of bevacizumab products after resolution of wound healing complications has not been established
• Necrotizing fasciitis Discontinue Jobevne Hemorrhage [see Warnings and Precautions (5.3) ].
• Grade 3 or 4 Discontinue Jobevne
• Recent history of hemoptysis of 1/2 teaspoon (2.5 mL) or more Withhold Jobevne Thromboembolic Events [see Warnings and Precautions (5.4 , 5.5) ].
• Arterial thromboembolism, severe Discontinue Jobevne
• Venous thromboembolism, Grade 4 Discontinue Jobevne Hypertension [see Warnings and Precautions (5.6) ].
Dosage forms and strengths
Injection: 100 mg/4 mL (25 mg/mL) or 400 mg/16 mL (25 mg/mL) clear to slightly opalescent, colorless to pale brown solution in a single-dose vial. Injection: 100 mg/4 mL (25 mg/mL) or 400 mg/16 mL (25 mg/mL) in a single-dose vial ( 3 )
Contraindications
None. None ( 4 )
Warnings and precautions
• Gastrointestinal Perforations and Fistula : Discontinue for gastrointestinal perforations, tracheoesophageal fistula, Grade 4 fistula, or fistula formation involving any organ ( 5.1 )
• Surgery and Wound Healing Complications : In patients who experience wound healing complications during Jobevne treatment, withhold Jobevne until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer Jobevne 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 complications of necrotizing fasciitis ( 5.2 )
• Hemorrhage : Severe or fatal hemorrhages have occurred. Do not administer for recent hemoptysis. Discontinue for Grade 3-4 hemorrhage ( 5.3 )
• Arterial Thromboembolic Events (ATE) : Discontinue for severe ATE. ( 5.4 )
• Venous Thromboembolic Events (VTE) : Discontinue for Grade 4 VTE. ( 5.5 )
• Hypertension : Monitor blood pressure and treat hypertension. Withhold until medically controlled; resume once controlled. Discontinue for hypertensive crisis or hypertensive encephalopathy. ( 5.6 )
• Posterior Reversible Encephalopathy Syndrome (PRES) : Discontinue. ( 5.7 )
• Renal Injury and Proteinuria : Monitor urine protein. Discontinue for nephrotic syndrome. Withhold until less than 2 grams of protein in urine. ( 5.8 )
• Infusion-Related Reactions : Decrease rate for infusion-related reactions. Discontinue for severe infusion-related reactions and administer medical therapy. ( 5.9 )
• Embryo-Fetal Toxicity : May cause fetal harm. Advise females of potential risk to fetus and need for use of effective contraception. ( 5.10 , 8.1 , 8.3 )
• Ovarian Failure : Advise females of the potential risk. ( 5.11 , 8.3 )
• Congestive Heart Failure (CHF) : Discontinue Jobevne in patients who develop CHF. ( 5.12 ) 5.1 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. The incidence ranged from 0.3% 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. The majority of perforations occurred within 50 days of the first dose [see Adverse Reactions (6.1) ] . 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. The incidence ranged from < 1% to 1.8% 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 Jobevne 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 . 5.2 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. In a controlled clinical study in patients with relapsed or recurrent GBM, the incidence of wound healing events was 5% in patients who received bevacizumab and 0.7% in patients who did not receive bevacizumab [see Adverse Reactions (6.1) ]. In patients who experience wound healing complications during Jobevne treatment, withhold Jobevne 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. The safety of resumption of bevacizumab products after resolution of wound healing complications has not been established [see Dosage and Administration (2.8) ] . Necrotizing fasciitis including fatal cases, has been reported in patients receiving bevacizumab, usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Discontinue Jobevne in patients who develop necrotizing fasciitis . 5.3 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. Across clinical studies, the incidence of Grades 3-5 hemorrhagic events ranged from 0.4% to 7% in patients receiving bevacizumab [see Adverse Reactions (6.1) ]. 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 Jobevne to patients with recent history of hemoptysis of 1/2 teaspoon or more of red blood. Discontinue in patients who develop a Grades 3-4 hemorrhage.
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling:
• Gastrointestinal Perforations and Fistulae [see Warnings and Precautions (5.1) ] .
• Surgery and Wound Healing Complications [see Warnings and Precautions (5.2) ].
• Hemorrhage [see Warnings and Precautions (5.3) ].
• Arterial Thromboembolic Events [see Warnings and Precautions (5.4) ].
• Venous Thromboembolic Events [see Warnings and Precautions (5.5) ].
• Hypertension [see Warnings and Precautions (5.6) ].
• Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.7) ].
• Renal Injury and Proteinuria [see Warnings and Precautions (5.8) ].
• Infusion-Related Reactions [see Warnings and Precautions (5.9) ].
• Ovarian Failure [see Warnings and Precautions (5.11) ].
• Congestive Heart Failure [see Warnings and Precautions (5.12) ]. 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biocon Biologics at 1-833-986-1468 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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), and epithelial ovarian, fallopian tube, or primary peritoneal cancer (MO22224 AVF4095, GOG-0213, and GOG-0218) or another cancers 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) ]. Metastatic Colorectal Cancer In Combination with bolus-IFL The safety of bevacizumab was evaluated in 392 patients who received at least one dose of bevacizumab in a double-blind, active-controlled study (AVF2107g), which compared bevacizumab (5 mg/kg every 2 weeks) with bolus-IFL to placebo with bolus-IFL in patients with mCRC [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. All Grades 3−4 adverse reactions and selected Grades 1−2 adverse reactions (i.e., hypertension, proteinuria, thromboembolic events) were collected in the entire study population. Adverse reactions are presented in Table 2. 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. First-Line Non-Squamous Non-Small Cell Lung Cancer The safety of bevacizumab was evaluated as first-line treatment in 422 patients with unresectable NSCLC who received at least one dose of bevacizumab in an active-controlled, open-label, multicenter trial (E4599) [see Clinical Studies (14.3) ] . 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.
Drug interactions
Effects of Jobevne on Other Drugs No clinically meaningful effect on the pharmacokinetics of irinotecan or its active metabolite SN38, interferon alfa, carboplatin or paclitaxel was observed when bevacizumab was administered in combination with these drugs; however, 3 of the 8 patients receiving bevacizumab with paclitaxel and carboplatin had lower paclitaxel exposure after four cycles of treatment (at Day 63) than those at Day 0, while patients receiving paclitaxel and carboplatin alone had a greater paclitaxel exposure at Day 63 than at Day 0.
Use in specific populations
Lactation: Advise not to breastfeed. ( 8.2 ) *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of JOBEVNE has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. 8.1 Pregnancy Risk Summary Based on findings from animal studies and their mechanism of action [see Clinical Pharmacology (12.1) ], bevacizumab products may cause fetal harm in pregnant women. Limited postmarketing reports describe cases of fetal malformations with use of bevacizumab products in pregnancy; however, these reports are insufficient to determine drug-associated risks. In animal reproduction studies, intravenous administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses approximately 1 to 10 times the clinical dose of 10 mg/kg produced fetal resorptions, decreased maternal and fetal weight gain and multiple congenital malformations including corneal opacities and abnormal ossification of the skull and skeleton including limb and phalangeal defects (see Data ) . 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. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Pregnant rabbits dosed with 10 mg/kg to 100 mg/kg bevacizumab (approximately 1 to 10 times the clinical dose of 10 mg/kg) every three days during the period of organogenesis (gestation day 6−18) exhibited decreases in maternal and fetal body weights and increased number of fetal resorptions. There were dose-related increases in the number of litters containing fetuses with any type of malformation (42% for the 0 mg/kg dose, 76% for the 30 mg/kg dose, and 95% for the 100 mg/kg dose) or fetal alterations (9% for the 0 mg/kg dose, 15% for the 30 mg/kg dose, and 61% for the 100 mg/kg dose). Skeletal deformities were observed at all dose levels, with some abnormalities including meningocele observed only at the 100 mg/kg dose level. Teratogenic effects included: reduced or irregular ossification in the skull, jaw, spine, ribs, tibia and bones of the paws; fontanel, rib and hindlimb deformities; corneal opacity; and absent hindlimb phalanges. 8.2 Lactation Risk Summary No data are available regarding the presence of bevacizumab products in human milk, the effects on the breast fed infant, or the effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with Jobevne and for 6 months after the last dose. 8.3 Females and Males of Reproductive Potential Contraception Females Bevacizumab products may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with Jobevne and for 6 months after the last dose. Infertility Females Bevacizumab products increase the risk of ovarian failure and may impair fertility. Inform females of reproductive potential of the risk of ovarian failure prior to the first-dose of Jobevne. Long-term effects of bevacizumab products on fertility are not known. In a clinical study of 179 premenopausal women randomized to receive chemotherapy with or without bevacizumab, the incidence of ovarian failure was higher in patients who received bevacizumab with chemotherapy (34%) compared to patients who received chemotherapy alone (2%). After discontinuing bevacizumab with chemotherapy, recovery of ovarian function occurred in 22% of these patients [see Warnings and Precautions (5.11) , Adverse Reactions (6.1) ] . 8.4 Pediatric Use The safety and effectiveness of Jobevne in pediatric patients have not been established. In published literature reports, cases of non-mandibular osteonecrosis have been observed in patients under the age of 18 years who received bevacizumab. Bevacizumab products are not approved for use in patients under the age of 18 years. Antitumor activity was not observed among eight pediatric patients with relapsed GBM who received bevacizumab and irinotecan. Addition of bevacizumab to standard of care did not result in improved event-free survival in pediatric patients enrolled in two randomized clinical studies, one in high grade glioma (n = 121) and one in metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma (n = 154). Based on the population pharmacokinetics analysis of data from 152 pediatric and young adult patients with cancer (7 months to 21 years of age), bevacizumab clearance normalized by body weight in pediatrics was comparable to that in adults. Juvenile Animal Toxicity Data Juvenile cynomolgus monkeys with open growth plates exhibited physeal dysplasia following 4 to 26 weeks exposure at 0.4 to 20 times the recommended human dose (based on mg/kg and exposure). The incidence and severity of physeal dysplasia were dose-related and were partially reversible upon cessation of treatment. 8.5 Geriatric Use In an exploratory pooled analysis of 1745 patients from five randomized, controlled studies, 35% of patients were ≥ 65 years old.
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and their mechanism of action [see Clinical Pharmacology (12.1) ], bevacizumab products may cause fetal harm in pregnant women. Limited postmarketing reports describe cases of fetal malformations with use of bevacizumab products in pregnancy; however, these reports are insufficient to determine drug-associated risks. In animal reproduction studies, intravenous administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses approximately 1 to 10 times the clinical dose of 10 mg/kg produced fetal resorptions, decreased maternal and fetal weight gain and multiple congenital malformations including corneal opacities and abnormal ossification of the skull and skeleton including limb and phalangeal defects (see Data ) . 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. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Pregnant rabbits dosed with 10 mg/kg to 100 mg/kg bevacizumab (approximately 1 to 10 times the clinical dose of 10 mg/kg) every three days during the period of organogenesis (gestation day 6−18) exhibited decreases in maternal and fetal body weights and increased number of fetal resorptions. There were dose-related increases in the number of litters containing fetuses with any type of malformation (42% for the 0 mg/kg dose, 76% for the 30 mg/kg dose, and 95% for the 100 mg/kg dose) or fetal alterations (9% for the 0 mg/kg dose, 15% for the 30 mg/kg dose, and 61% for the 100 mg/kg dose). Skeletal deformities were observed at all dose levels, with some abnormalities including meningocele observed only at the 100 mg/kg dose level. Teratogenic effects included: reduced or irregular ossification in the skull, jaw, spine, ribs, tibia and bones of the paws; fontanel, rib and hindlimb deformities; corneal opacity; and absent hindlimb phalanges.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Jobevne in pediatric patients have not been established. In published literature reports, cases of non-mandibular osteonecrosis have been observed in patients under the age of 18 years who received bevacizumab. Bevacizumab products are not approved for use in patients under the age of 18 years. Antitumor activity was not observed among eight pediatric patients with relapsed GBM who received bevacizumab and irinotecan. Addition of bevacizumab to standard of care did not result in improved event-free survival in pediatric patients enrolled in two randomized clinical studies, one in high grade glioma (n = 121) and one in metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma (n = 154). Based on the population pharmacokinetics analysis of data from 152 pediatric and young adult patients with cancer (7 months to 21 years of age), bevacizumab clearance normalized by body weight in pediatrics was comparable to that in adults. Juvenile Animal Toxicity Data Juvenile cynomolgus monkeys with open growth plates exhibited physeal dysplasia following 4 to 26 weeks exposure at 0.4 to 20 times the recommended human dose (based on mg/kg and exposure). The incidence and severity of physeal dysplasia were dose-related and were partially reversible upon cessation of treatment.
Geriatric use
8.5 Geriatric Use In an exploratory pooled analysis of 1745 patients from five randomized, controlled studies, 35% of patients were ≥ 65 years old. The overall incidence of ATE was increased in all patients receiving bevacizumab with chemotherapy as compared to those receiving chemotherapy alone, regardless of age; however, the increase in the incidence of ATE was greater in patients ≥ 65 years (8% vs. 3%) as compared to patients < 65 years (2% vs. 1%) [see Warnings and Precautions (5.4) ].
Description
Bevacizumab-nwgd is a vascular endothelial growth factor inhibitor. Bevacizumab-nwgd is a recombinant humanized monoclonal IgG1 antibody that contains human framework regions and murine complementarity-determining regions. Bevacizumab-nwgd has an approximate molecular weight of 149 kDa. Bevacizumab-nwgd is produced in a mammalian cell (Chinese Hamster Ovary) expression system. Jobevne (bevacizumab-nwgd) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale brown solution in a single-dose vial for intravenous use. Jobevne contains bevacizumab-nwgd at a concentration of 25 mg/mL in either a 100 mg/4 mL or 400 mg/16 mL single-dose vial. Each mL of solution contains 25 mg bevacizumab-nwgd, dibasic sodium phosphate (1.2 mg), monobasic sodium phosphate (4.5 mg), polysorbate 20 (0.4 mg), trehalose (54.3 mg) and Water for Injection, USP. Sodium hydroxide and phosphoric acid may be used to adjust pH to 6.2 during manufacturing.
Mechanism of action
12.1 Mechanism of Action Bevacizumab products bind VEGF and prevent the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression.
How supplied
Jobevne (bevacizumab-nwgd) injection is a clear to slightly opalescent, colorless to pale brown, sterile solution for intravenous infusion supplied as single-dose vials in the following strengths:
• 100 mg/4 mL (25 mg/mL): carton of one vial (NDC 83257-009-11 ).
• 400 mg/16 mL (25 mg/mL): carton of one vial (NDC 83257-010-11 ). Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton until time of use to protect from light. Do not freeze or shake the vial or carton.
Patient information
Gastrointestinal Perforations and Fistulae : Bevacizumab products may increase the risk of developing gastrointestinal perforations and fistulae. Advise patients to immediately contact their health care provider for high fever, rigors, persistent or severe abdominal pain, severe constipation, or vomiting [see Warnings and Precautions (5.1) ]. Surgery and Wound Healing Complications : Bevacizumab products can increase the risk of wound healing complications. Instruct patients not to undergo surgery without first discussing this potential risk with their health care provider [see Warnings and Precautions (5.2) ] . Hemorrhage : Bevacizumab products can increase the risk of hemorrhage. Advise patients to immediately contact their health care provider for signs and symptoms of serious or unusual bleeding including coughing or spitting blood [see Warnings and Precautions (5.3) ] . Arterial and Venous Thromboembolic Events : Bevacizumab products increase the risk of arterial and venous thromboembolic events. Advise patients to immediately contact their health care provider for signs and symptoms of arterial or venous thromboembolism [see Warnings and Precautions (5.4 , 5.5) ] . Hypertension : Bevacizumab products can increase blood pressure. Advise patients that they will undergo routine blood pressure monitoring and to contact their health care provider if they experience changes in blood pressure [see Warnings and Precautions (5.6) ] . Posterior Reversible Leukoencephalopathy Syndrome : Posterior reversible encephalopathy syndrome (PRES) has been associated with bevacizumab products treatment. Advise patients to immediately contact their health care provider for new onset or worsening neurological function [see Warnings and Precautions (5.7) ] . Renal Injury and Proteinuria : Bevacizumab products increase the risk of proteinuria and renal injury, including nephrotic syndrome. Advise patients that treatment with Jobevne requires regular monitoring of renal function and to contact their health care provider for proteinuria or signs and symptoms of nephrotic syndrome [see Warnings and Precautions (5.8) ] . Infusion-Related Reactions : Bevacizumab products can cause infusion-related reactions. Advise patients to contact their health care provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.9) ]. Congestive Heart Failure : Bevacizumab products can increase the risk of developing congestive heart failure. Advise patients to contact their health care provider immediately for signs and symptoms of CHF [see Warnings and Precautions (5.12) ]. Embryo-Fetal Toxicity : Advise female patients that bevacizumab products may cause fetal harm and to inform their health care provider with a known or suspected pregnancy [see Warnings and Precautions (5.10) , Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with Jobevne and for 6 months after the last dose [see Use in Specific Populations (8.3) ]. Ovarian Failure : Bevacizumab products may lead to ovarian failure. Advise patients of potential options for preservation of ova prior to starting treatment [see Warnings and Precautions (5.11) ]. Lactation : Advise women not to breastfeed during treatment with Jobevne and for 6 months after the last dose [see Use in Specific Populations (8.2) ] . The brands listed are trademarks of their respective owners. JOBEVNE™ is a trademark of Biocon Biologics UK PLC.; a Biocon Biologics Company. Copyright © 2025 Biocon Biologics Inc. All rights reserved. Manufactured by: Biocon Biologics Inc. 685 Route 202/206, Suite 204, Bridgewater, NJ 08807, U.S.A. U.S. Licence No. 2324 Product of India Revised: 03/2026 KR/DRUGS/KTK/28D/07/2006
Label text from the FDA structured product label by Biocon Biologics Inc. (revised Mar 11, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Bevacizumab in 2 products
Jobevne NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 83257-009 | Bevacizumab 25 mg/mL Injection | Biocon Biologics Inc. | BLA |
| 83257-010 | Bevacizumab 25 mg/mL Injection | Biocon Biologics Inc. | BLA |
Frequently asked questions
What is Jobevne used for?
Jobevne 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 fluoropyrimidine-irinotecan-or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients…
What are the side effects of Jobevne?
The following clinically significant adverse reactions are described elsewhere in the labeling: • Gastrointestinal Perforations and Fistulae [see Warnings and Precautions (5.1) ] . • Surgery and Wound Healing Complications [see Warnings and Precautions (5.2) ]. • Hemorrhage [see Warnings and Precautions (5.3) ]. • Arterial Thromboembolic Events [see Warnings and Precautions (5.4) ]. • Venous… See the full label for the complete list.
Who makes Jobevne?
Jobevne is listed by 1 labeler in the FDA NDC directory, including Biocon Biologics Inc..