Bevixa 400 IV Infusion

Bevixa 400 IV Infusion is used for: Colorectal cancer, Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, Renal cancers, Epithelial ovarian, fallopian tube, or primary peritoneal cancer, Breast cancers, Persistent, recurrent, or metastatic cervical cancer, Glioblastoma multiforme of the brain, Exudative ARMD, Hepatocellular Carcinoma

General: Bevacizumab should be prepared by a healthcare professional using aseptic technique. The initial Bevacizumab dose should be delivered over 90 min as an IV infusion. If the 1st infusion is well tolerated, the 2nd infusion may be administered over 60 min. If the 60-min infusion is well tolerated, all subsequent infusions may be administered over 30 min. Withhold for at least 28 days prior to elective surgery. Do not administer Avastin for 28 days following major surgery and until adequate wound healing. Metastatic colorectal cancer • 5 mg/kg every 2 weeks with bolus-IFL • 10 mg/kg every 2 weeks with Oxaliplatin plus leucovorin and 5-fluorouracil • 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 • 15 mg/kg every 3 weeks with carboplatin and paclitaxel Recurrent glioblastoma • 10 mg/kg every 2 weeks Metastatic renal cell carcinoma • 10 mg/kg every 2 weeks with interferon alfa Persistent, recurrent, or metastatic cervical cancer • 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 • 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 • 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 • 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 Hepatocellular Carcinoma • 15 mg/kg after administration of 1,200 mg of atezolizumab every 3 weeks

IV Preparation Aseptically withdraw necessary amount & dilute in a total volume of 100 mL NS Diluted solutions for infusion may be stored at 2-8°C for 8 hr IV Administration Do not administer as IV push or bolus; administer only as an IV infusion Do not initiate until at least 28 days following major surgery; wait until the surgical incision has fully healed Deliver first infusion over 90 min IV; if well-tolerated, second infusion may be administered over 60 min & each subsequent infusion, over 30 min if 60 min infusion tolerated

Hypersensitivity to any component Recent hemoptysis

Gastrointestinal Perforations and Fistula: Discontinue for gastrointestinal perforations, tracheoesophageal fistula, grade 4 fistula, or fistula formation involving any organ. Surgery and Wound Healing Complications: In patients who experience wound healing complications during Avastin treatment, withhold Bevacizumab until adequate wound healing. Withhold for at least 28 days prior to elective surgery. Do not administer Bevacizumab for at least 28 days following a major surgery, and until adequate wound healing. The safety of resumption of Bevacizumab after the resolution of wound healing complications has not been established. Discontinue for wound healing complication of necrotizing fasciitis. Hemorrhage: Severe or fatal hemorrhages have occurred. Do not administer for recent hemoptysis. Discontinue for Grade 3-4 hemorrhage. Arterial Thromboembolic Events (ATE): Discontinue for severe ATE. Venous Thromboembolic Events (VTE): Discontinue for Grade 4 VTE. Hypertension: Monitor blood pressure and treat hypertension. Withhold if not medically controlled; resume once controlled. Discontinue for hypertensive crisis or hypertensive encephalopathy. Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue. Renal Injury and Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome. Withhold until less than 2 grams of protein in urine. Infusion-Related Reactions: Decrease rate for infusion-related reactions. Discontinue for severe infusion-related reactions and administer medical therapy. Embryo-Fetal Toxicity: May cause fetal harm. Advise females of potential risk to the fetus and the need for the use of effective contraception. Ovarian Failure: Advise females of the potential risk. Congestive Heart Failure (CHF): Discontinue Avastin in patients who develop CHF. MONITORING PARAMETERS Monitor for necrotizing fasciitis (usually secondary to wound healing complications, gastro-intestinal perforation or fistula formation)—discontinue and initiate treatment promptly. Monitor for congestive heart failure. Monitor blood pressure and treat hypertension. Monitor for posterior reversible encephalopathy syndrome (presenting as seizures, headache, altered mental status, visual disturbance or cortical blindness, with or without hypertension). Consider dental check-ups before initiating treatment (risk of osteonecrosis of the jaw).

Pregnancy Based on findings from animal studies and its mechanism of action, drug may cause fetal harm in pregnant women Limited postmarketing reports describe cases of fetal malformations with bevacizumab use in pregnancy; however, these reports are insufficient to determine drug associated risks Animal data In animal reproduction studies, IV administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses ~1-10 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 Animal models link angiogenesis and VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development Contraception Advise pregnant women of the potential risk to a fetus Advise female patients of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of bevacizumab Infertility Inform females of reproductive potential of the risk of ovarian failure prior to starting; long term effects of bevacizumab exposure on fertility are unknown Lactation No data available on the presence of bevacizumab 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 and for 6 months after last dose

Irinotecan/5–fluorouracil/leucovorin The incidence of epistaxis and grade 1 or 2 hemorrhage (including GI hemorrhage, minor gum bleeding, vaginal hemorrhage) was greater in patients receiving bevacizumab plus irinotecan/5-fluorouracil/leucovorin compared with patients receiving irinotecan/5-fluorouracil/leucovorin plus placebo. Closely monitor the patient during coadministration. Live vaccines The administration of live vaccines to patients receiving bevacizumab may result in a reduced immune response. Avoid coadministration. Paclitaxel Decreased paclitaxel exposure was seen when paclitaxel/carboplatin was given in combination with bevacizumab. Closely monitor the patient during coadministration. Sunitinib Coadministration of bevacizumab and sunitinib has been reported to cause unexpected severe toxicity (eg, microangiopathic hemolytic anemia). Coadministration of sunitinib and bevacizumab is not recommended. Contraindicated (0) Serious (10) axicabtagene ciloleucel brexucabtagene autoleucel ciltacabtagene autoleucel etrasimod idecabtagene vicleucel lisocabtagene maraleucel palifermin ropeginterferon alfa 2b sunitinib tisagenlecleucel

Side effects of Bevacizumab : >10% (Epithelial ovarian, fallopian tube or primary peritoneal cancer) Treatment following resection Fatigue (72-80%) Nausea (53-58%) Arthralgia (33-41%) Diarrhea (38-40%) Headache (26-34%) Hypertension (24-32%) Epistaxis (30-31%) Dyspnea (26-28%) Stomatitis (19-25%) Pain in extremity (19-25%) Muscular weakness (13-15%) Dysarthria (10-12%) Platinum-resistant Neutropenia, Grade 2-4 (31%) Hypertension, Grade 2-4 (19%) Peripheral sensory neuropathy, Grade 2-4 (18%) Mucosal inflammation, Grade 2-4 (13%) Proteinuria, Grade 2-4 (12%) Infection, Grade 2-4 (11%) Palmar-plantar erythrodysesthesia, Grade 2-4 (11%) Platinum-sensitive Fatigue (82%) Nausea (72%) Thrombocytopenia (58%) Epistaxis (55%) Headache (49%) Hypertension (42%) Diarrhea (38-39%) Decreased appetite (35%) Abdominal pain, stomatitis, vomiting (33%) Hyperglycemia (31%) Dyspnea (30%) Arthralgia (28%) Hypomagnesemia (27%) Cough (26%) Insomnia, back pain (21%) >10% (Metastatic Renal Cell Carcinoma) Decreased appetite (36%) Fatigue (33%) Hypertension (28%) Epistaxis (27%) Headache (24%) Diarrhea (21%) Decreased weight (20%) Proteinuria (20%) Myalgia (19%) Back pain (12%) >10% (Metastatic Colorectal Cancer) Leukopenia (37%) Diarrhea (34%) Neutropenia (21%) Hypertension (12%) >10% (HCC) Increased AST (86%) Increased alkaline phosphatase (70%) Decreased platelet (68%) Decreased lymphocytes (62%) Increased ALT (62%) Decreased albumin (60%) Decreased hemoglobin (58%) Decreased sodium (54%) Increased glucose (48%) Decreased leukocytes (32%) Decreased calcium (30%) Hypertension (30%) Decreased phosphorus (26%) Fatigue/asthenia (26%) Decreased neutrophil (23%) Increased potassium (23%) Hypomagnesia (22%) Proteinuria (20%) Pruritus (19%) Diarrhea (19%) Decreased appetite (18%) Pyrexia (18%) Increased AST, Grade 3-4 (16%) Hypertension, Grade 3-4 (15%) Constipation (13%) Decreased lymphocytes, Grade 3-4 (13%) Decreased sodium, Grade 3-4 (13%) Abdominal pain (12%) Nausea (12%) Rash (12%) Cough (12%) Infusion-related reactions (11%) 1-10% (Epithelial ovarian, fallopian tube or primary peritoneal cancer) Treatment following resection Nasal mucosal disorder (7-10%) Platinum resistant Epistaxis (5%) Platinum-sensitive Rhinorrhea (10%) Hyperkalemia (9%) Hemorrhoids (8%) Sinus congestion (8%) Gingival bleeding (7%) 1-10% (Metastatic Colorectal Cancer) Asthenia (10%) Deep vein thrombosis (9%) Abdominal pain (8%) Pain (8%) Constipation (4%) Intra-abdominal thrombosis (3%) Syncope (3%) 1-10% (Metastatic Renal Cell Carcinoma) Dysphonia (5%) 1-10% (HCC) Increased glucose, Grade 3-4 (9%) Increased ALT, Grade 3-4 (8%) Increased bilirubin, Grade 3-4 (8%) Decreased phosphorus, Grade 3-4 (4.7%) Increased alkaline phosphatase, Grade 3-4 (4%) Increased leukocytes, Grade 3-4 (3.4%) Decreased hemoglobin, Grade 3-4 (3.1%) Proteinuria, Grade 3-4 (3%) Infusion-related reactions, Grade 3-4 (2.4%) Decreased neutrophils (2.3%) Fatigue/asthenia, Grade 3-4 (2%) Increased potassium, Grade 3-4 (1.9%) Diarrhea, Grade 3-4 (1.8%) Decreased albumin, Grade 3-4 (1.5%) Decreased appetite, Grade 3-4 (1.2%) <1% (HCC) Decreased calcium, Grade 3-4 (0.3%)

Bevacizumab binds to VEGF, the key driver of vasculogenesis and angiogenesis, and thereby inhibits the binding of VEGF to its receptors, Flt-1 (VEGFR-1) and KDR (VEGFR-2), on the surface of endothelial cells. Neutralising the biological activity of VEGF reduces the vascularisation of tumours, normalises remaining tumour vasculature and inhibits the formation of new tumour vasculature thereby inhibiting tumour growth.

Bevixa 400 400mg in 16 ml IV Infusion manufactured by Incepta Pharmaceuticals Ltd.. Its generic name is Bevacizumab. Bevixa 400 is availble in Bangladesh. Farmaco BD drug index information on Bevixa 400 IV Infusion is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.