Loading…
AYBINTIO is a brand name for Bevacizumab, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Indications have been granted on the basis of similarity between AYBINTIO and the reference biologic drug AVASTIN. AYBINTIO (bevacizumab) is indicated for: • Metastatic Colorectal Cancer (mCRC) AYBINTIO in combination with fluoropyrimidine-based chemotherapy is indicated for first-line treatment of patients with…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations It is recommended that AYBINTIO treatment be continued until progression of the underlying disease. There are no recommended dose reductions. Discontinue AYBINTIO for: • Gastrointestinal perforations (gastrointestinal perforations, fistula formation in the gastrointestinal tract, intra-abdominal abscess); • Internal fistula not arising in the GI tract, tracheoesophageal (TE) fistula or any Grade 4 fistula; AYBINTIO (bevacizumab) Page 7 of 91 • Wound dehiscence and wound healing complications requiring medical intervention; • Necrotizing fasciitis; • Serious hemorrhage or recent hemoptysis; • Severe arterial thromboembolic events; • Life-threatening (Grade 4) VTEs, including pulmonary embolism; • Severe hypertension not controlled with medical management; • Hypertensive crisis or hypertensive encephalopathy; • Posterior Reversible Encephalopathy Syndrome (PRES); • Nephrotic syndrome.
Temporarily suspend AYBINTIO for: • At least 4 weeks prior to elective surgery; • Moderate to severe proteinuria pending further evaluation; • Severe infusion reactions. 2 Recommended Dose and Dosage Adjustment Health Canada has not authorized an indication for pediatric use (see WARNINGS AND PRECAUTIONS, Special Populations, Pediatrics).
Metastatic Colorectal Cancer The recommended dose of AYBINTIO is 5 mg/kg of body weight given once every 14 days as an intravenous infusion. Locally Advanced, Metastatic or Recurrent Non-Small Cell Lung Cancer (NSCLC) The recommended dose of AYBINTIO, is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion in addition to carboplatin + paclitaxel chemotherapy regimen.
In clinical trials, bevacizumab was administered in addition to carboplatin/paclitaxel chemotherapy for up to 6 cycles of treatment followed by bevacizumab as a single agent until disease progression. Platinum-Sensitive Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer The recommended dose of AYBINTIO is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.
AYBINTIO is administered in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles followed by continued use of AYBINTIO as single agent until disease progression. Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer The recommended dose of AYBINTIO is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion when administered in combination with one of the following agents – paclitaxel, topotecan (given weekly) or pegylated liposomal doxorubicin (see CLINICAL TRIALS AYBINTIO (bevacizumab) Page 8 of 91 – REFERENCE BIOLOGIC DRUG, Study MO22224 (AURELIA) for chemotherapy regimens).
The adverse drug reaction profiles reported in clinical studies that compared AYBINTIO to the reference biologic drug were comparable. The description of adverse reactions in this section is based on clinical experience with the reference biologic drug.
1 Adverse Reaction Overview Clinical trials have been conducted in patients with various malignancies treated with bevacizumab, predominantly in combination with chemotherapy. The safety profile from a clinical trial population of approximately 5000 patients is presented in this section.
The most serious adverse drug reactions were: • Gastrointestinal Perforations (see WARNINGS AND PRECAUTIONS) • Hemorrhage including pulmonary hemorrhage/hemoptysis, which is more common in NSCLC patients (see WARNINGS AND PRECAUTIONS) • Arterial Thromboembolism (see WARNINGS AND PRECAUTIONS) • Non-gastrointestinal Fistula • Hypertensive Crises AYBINTIO (bevacizumab) Page 19 of 91 • Posterior Reversible Encephalopathy Syndrome (PRES) • Neutropenia and Infections • Nephrotic Syndrome • Congestive Heart Failure Please refer to Further Information on Selected, Serious Adverse Drug Reactions for clinical trial frequency analysis of each serious adverse drug reaction listed above.
Analyses of the clinical safety data suggest that the occurrence of hypertension and proteinuria with bevacizumab therapy are likely to be dose-dependent. The most frequently observed adverse drug reactions across all clinical trials in patients receiving bevacizumab were fatigue or asthenia, diarrhea, hypertension, and abdominal pain , all with a frequency of very common (≥ 10%).
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Please see 3 Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information. General All patients discontinuing treatment with AYBINTIO should be monitored according to medical practice. In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Unauthorized Intravitreal Use:
Eye Disorders Individual cases and clusters of serious ocular adverse events affecting multiple patients have been reported from unauthorized intravitreal use of bevacizumab following variable and non- validated methods in compounding, storage, and handling of bevacizumab vials authorized for intravenous administration in cancer patients.
These events included infectious endophthalmitis (some cases leading to permanent blindness, one case reported extraocular extension of For management of a suspected drug overdose, contact your regional Poison Control Centre. Route of Administration Dosage Form/ Strength/Composition Non-medicinal Ingredients Intravenous 100 mg and 400 mg vials (25 mg/mL solution f or injection) Acetic acid, polysorbate 20, sodium acetate trihydrate, trehalose dihydrate, water f or injection AYBINTIO (bevacizumab) Page 10 of 91 infection resulting in meningoencephalitis), intraocular inflammation1 (such as sterile endophthalmitis, uveitis, and vitritis) (some cases leading to permanent blindness), retinal detachment, retinal pigment epithelial tear, intraocular pressure increased, intraocular hemorrhage (such as vitreous hemorrhage or retinal hemorrhage), conjunctival hemorrhage.
64 events per 100 patients per year). 51 events per 100 patients per year). 0%). The most frequent serious systemic adverse events reported directly to the sponsor include myocardial infarction, cerebrovascular accident, and hypertension.
Bevacizumab is contraindicated in patients with known hypersensitivity to: • This drug or to any ingredient in the formulation, including any non -medicinal ingredient, or component of the container. (for a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING), • Chinese hamster ovary cell products or other recombinant human or humanised antibodies .
Bevacizumab is contraindicated in patients with untreated Central Nervous System (CNS) metastases (see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Bevacizumab in Canada.
Know a brand we are missing in Canada? 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.
Alternatively, the recommended dose of AYBINTIO is 15 mg/kg every 3 weeks when administered in combination with topotecan given on days 1-5, every 3 weeks (see CLINICAL TRIALS – REFERENCE BIOLOGIC DRUG, Study MO22224 (AURELIA) for chemotherapy regimen).
Malignant Glioma (WHO Grade IV) – Glioblastoma The recommended dose of AYBINTIO is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion in combination with lomustine every 6 weeks until disease progression. An oral dose of 90 mg/m2 (maximum dose 160 mg) of lomustine is recommended for the first cycle; in the absence of Grade > 1 hematological toxicity during the first cycle, it can be escalated to 110 mg/m2 (maximum dose 200 mg) from the second cycle onwards (see also CLINICAL TRIALS – REFERENCE BIOLOGIC DRUG).
4 Administration Do not administer as an intravenous push or bolus. The initial AYBINTIO dose should be delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes.
If the 60-minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes. AYBINTIO INFUSIONS SHOULD NOT BE ADMINISTERED OR MIXED WITH DEXTROSE OR GLUCOSE SOLUTIONS. A concentration-dependent degradation profile of bevacizumab was observed when diluted with dextrose solutions (5%).
No incompatibilities between bevacizumab and polyvinyl chloride or polyolefin bags have been observed. AYBINTIO should be prepared by a healthcare professional using aseptic technique. Use sterile needle and syringe to prepare AYBINTIO.
9% sodium chloride solution. 5 mg/ml. Discard any unused portion left in a vial, as the product contains no preservatives. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
AYBINTIO is not formulated for intravitreal use (see WARNINGS AND PRECAUTIONS, General). 5 Missed Dose For a missed dose of AYBINTIO, the physician will decide when the patient should receive the next dose. AYBINTIO (bevacizumab) Page 9 of 91
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Table 2 lists adverse drug reactions associated with the use of bevacizumab in combination with different chemotherapy regimens in multiple indications.
These reactions had occurred either with at least a 2% difference compared to the control arm (NCI-CTC Grade 3-5 reactions) or with at least a 10% difference compared to the control arm (NCI-CTC Grade 1-5 reactions), in at least one of the major clinical trials.
The adverse drug reactions listed in the table fall into the following categories:
Very Common (≥ 10%) and Common (≥ 1% - < 10%). Adverse drug reactions are added to the appropriate category in the table below according to the highest incidence seen in any of the major clinical trials. Within each frequency grouping adverse drug reactions are presented in order of decreasing seriousness.
Some of the adverse reactions are reactions commonly seen with chemotherapy; however, bevacizumab may exacerbate these reactions when combined with chemotherapeutic agents. Examples include palmar -plantar erythrodysaesthesia syndrome with capecitabine or pegylated liposomal doxorubicin and peripheral sensory neuropathy with paclitaxel or oxaliplatin and nail disorders or alopecia with paclitaxel.
Table 2 Very Common and Common Adverse Drug Reactions System Organ Class (SOC) NCI-CTC Grade 3-5 Reactions (≥ 2 % difference between the study arms in at least one clinical trial) All Grade Reactions (≥ 10 % difference between the study arms in at least one clinical trial) Very common (≥ 10%) Common (≥ 1% - < 10%) Very Common (≥ 10%) Infections and infestations Sepsis Abscess Cellulitis Inf ection AYBINTIO (bevacizumab) Page 20 of 91 System Organ Class (SOC) NCI-CTC Grade 3-5 Reactions (≥ 2 % difference between the study arms in at least one clinical trial) All Grade Reactions (≥ 10 % difference between the study arms in at least one clinical trial) Blood and the lymphatic systems disorders Febrile neutropenia Leukopenia Neutropenia Thrombocytopenia Anemia Lymphopenia Immune system disorders Hypersensitivity, anaphylaxis, inf usion- related reactions Metabolism and nutrition disorders Dehydration Hyponatremia Anorexia Hypomagnesemia Hyponatremia Nervous system disorders Peripheral sensory neuropathy Cerebrovascular accident Syncope Somnolence Headache Dysgeusia Headache Eye disorders Eye disorder Lacrimation increased Cardiac disorders Cardiac f ailure congestive Supraventricular tachycardia Vascular disorders Hypertension Thromboembolism (arterial) Deep vein thrombosis Hemorrhage Hypertension Respiratory, thoracic and mediastinal disorders Pulmonary embolism Dyspnea Hypoxia Epistaxis Dyspnea Epistaxis Rhinitis Cough Gastroin testin al disorders Diarrhea Nausea Vomiting Abdominal pain Intestinal Perforation Ileus Intestinal obstruction Recto-vaginal f istulae* Gastrointestinal disorder Stomatitis Proctalgia Constipation Stomatitis Rectal hemorrhage Endocrine disorders Ovarian f ailure** Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome Exf oliative dermatitis Dry skin Skin discoloration Musculoskeletal, connective tissue and bone disorders Muscular weakness Myalgia Back pain Arthralgia Renal and urinary disorders Proteinuria Urinary Tract Inf ection Proteinuria General disorders and administration site conditions Asthenia Fatigue Pain Lethargy Mucosal Inf lammation Pyrexia Asthenia Pain Mucosal inf lammation Reproductive System and Breast Pelvic pain Investigations Weight decreased AYBINTIO (bevacizumab) Page 21 of 91 * Recto-vaginal fistulae are the most common fistulae in the GI-vaginal fistula category.
**Based on a substudy from AVF3077s (NSABP C-08) with 295 patients Metastatic Colorectal Cancer (mCRC) (Studies AVF 2107g, AVF 0780g, and AVF 2192g) Data presented in Table 3 are based on the experience with the recommended dose of bevacizumab in 788 patients treated with irinotecan/5-fluorouracil/leucovorin (IFL) in Study AVF2107g.
Table 3 NCI-CTC […]
Carcinogenesis and Mutagenesis Studies have not been performed to evaluate the carcinogenic and mutagenic potential of bevacizumab. Cardiovascular Hypertension An increased incidence of hypertension was observed in patients treated with bevacizumab.
Clinical safety data from a single phase III study suggests that the risk of hypertension may be greater in platinum-sensitive recurrent ovarian cancer patients treated with bevacizumab (see ADVERSE REACTIONS). Clinical safety data suggest that the incidence of hypertension is likely to be dose -dependent.
Pre-existing hypertension should be adequately controlled before starting AYBINTIO treatment. There is no information on the effect of bevacizumab in patients with uncontrolled hypertension 1 Gower et al. Adverse Event Rates Following Intravitreal Injection of AVASTIN or LUCENTIS for Treating Age - Related Macular Degeneration ARVO 2011, Poster 6644, Data on File 2 Ibid 3 Ibid 4 Curtis LH, et al.
Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age- related macular degeneration. Arch Ophthalmol. 2010;128(10):1273-1279 5 Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) Research Group, Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration.
1056/NEJMoa1102673 AYBINTIO (bevacizumab) Page 11 of 91 at the time of initiating bevacizumab therapy. g. 2-3 weeks) during AYBINTIO therapy in order to detect potentially serious complications of therapy, including hypertensive encephalopathy and Posterior Reversible Encephalopathy Syndrome (PRES) (see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS).
In most cases hypertension was controlled adequately using standard antihypertensive treatment appropriate for the individual situation of the affected patient. The use of diuretics to manage hypertension is not advised in patients who receive a cisplatin -based chemotherapy regimen.
AYBINTIO treatment should be permanently discontinued if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, or, if the patient develops hypertensive crisis or hypertensive encephalopathy (see ADVERSE REACTIONS).
Thromboembolism (see ADVERSE REACTIONS) Arterial Thromboembolism In clinical trials, the incidence of Arterial Thromboembolic Events (ATEs) including cerebrovascular accident, transient ischemic attack and myocardial infarction was higher in patients receiving bevacizumab in combination with […]