Bevacizumab
Bevacizumab: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Bevacizumab
ATX code: L01XC07
Active ingredient: bevacizumab (bevacizumab)
Manufacturer: Biocad (Russia)
Description and photo update: 2018-21-11
Bevacizumab is an anti-tumor drug.
Release form and composition
The dosage form of Bevacizumab is a concentrate for the preparation of a solution for infusion: light brown or colorless, opalescent or transparent (0.5; 4 or 16 ml each in glass vials / vials; in a cardboard box 1 glass bottle / bottle, in a blister strip packaging or without it).
Composition of 1 ml of concentrate:
- active substance: bevacizumab - 25 mg;
- auxiliary components: polysorbate 20 - 0.4 mg; α, α-trehalose dihydrate - 60 mg; sodium hydrogen phosphate - 1.2 mg; sodium dihydrogen phosphate monohydrate - 5.8 mg; water for injection - up to 1 ml.
Pharmacological properties
Pharmacodynamics
Bevacizumab is an anticancer drug. Its active ingredient, bevacizumab, is a recombinant humanized monoclonal antibodies that selectively bind, thereby neutralizing the biological activity of human vascular endothelial growth factor (VEGF).
Bevacizumab contains human scaffold regions with complementary determined regions of humanized mouse antibodies that bind to VEGF. Bevacizumab is produced by recombinant DNA technology in Chinese hamster ovary cells. It is composed of 214 amino acids and has a molecular weight of approximately 149,000 daltons.
Inhibits the binding of VEGF on the surface of endothelial cells with its receptors, Flt-1 and KDR. Neutralization of VEGF bioactivity reduces tumor vascularization, thus inhibiting its growth.
Pharmacokinetics
Pharmacokinetic parameters of bevacizumab (based on the results of clinical studies) are linear dose-dependent, in the dose range of 1-10 mg / kg.
Evaluation of the metabolism of the substance in experimental studies in rabbits after a single intravenous administration of bevacizumab showed that its metabolic profile is similar to that expected for a native IgG molecule, which does not bind VEGF.
The clearance of the substance is 0.207 and 0.262 liters per day for women and men, respectively.
Indications for use
- locally recurrent / metastatic breast cancer: as the first line of therapy concurrently with paclitaxel;
- metastatic colorectal cancer: along with chemotherapy based on fluoropyrimidine derivatives;
- advanced and / or metastatic renal cell carcinoma: as the first line of therapy simultaneously with interferon alpha-2a;
- common inoperable, metastatic, or recurrent non-squamous cell non-small cell lung cancer: as a first line of therapy as an adjunct to chemotherapy (platinum drugs);
- epithelial cancer of the fallopian tube, ovary, primary cancer of the peritoneum: in advanced (according to the FIGO classification - III B, III C and IV stages) epithelial cancer of the ovary, fallopian tube and primary cancer of the peritoneum - as the first line of therapy simultaneously with carboplatin and paclitaxel; with recurrent epithelial cancer of the ovary, fallopian tube and primary cancer of the peritoneum, sensitive to the action of platinum drugs, in patients who had not previously received Bevacizumab or other VEGF inhibitors - simultaneously with gemcitabine and carboplatin; with recurrent, platinum-resistant epithelial cancer of the ovary, fallopian tube and primary cancer of the peritoneum in patients who previously received up to two chemotherapy regimens - simultaneously with paclitaxel, or topotecan, or pegylated liposomal doxorubicin;
- glioblastoma (according to the WHO classification - grade IV glioma): for newly diagnosed glioblastoma - simultaneously with radiation therapy and temozolomide; in case of relapse / progression of the disease - as monotherapy or simultaneously with irinotecan.
Contraindications
Absolute:
- hepatic / renal failure;
- metastatic lesion of the central nervous system;
- age up to 18 years;
- pregnancy and the period of breastfeeding;
- individual intolerance to the components of the drug, as well as drugs based on Chinese hamster ovary cells or other recombinant human or close to human antibodies.
Relative (Bevacizumab is prescribed under medical supervision):
- burdened history of arterial thromboembolism;
- congenital hemorrhagic diathesis and acquired coagulopathy;
- anticoagulant therapy in the treatment of thromboembolism before the start of Bevacizumab;
- arterial hypertension;
- clinically significant cardiovascular diseases (ischemic heart disease or chronic heart failure in history);
- venous thromboembolism;
- bleeding / hemoptysis;
- period of wound healing;
- posterior reversible encephalopathy syndrome;
- burdened history of gastrointestinal perforation;
- diabetes;
- proteinuria;
- neutropenia;
- age over 65.
Instructions for use of Bevacizumab: method and dosage
The dosage regimen of Bevacizumab is determined individually.
Side effects
- cardiovascular system: bleeding, deep vein thrombosis, heart failure, arterial hypertension, supraventricular tachycardia, arterial thromboembolism;
- respiratory system: perforation of the nasal septum, pulmonary embolism, shortness of breath, rhinitis, epistaxis, hypoxia, dyspnea;
- digestive system: stomatitis, obstruction of the small intestine, nausea, diarrhea, gastrointestinal disorders, abdominal pain, perforation of the gastrointestinal tract, constipation, rectal bleeding;
- nervous system: reversible posterior leukoencephalopathy syndrome, headache, lethargy, taste disturbances, ischemic stroke, peripheral sensory neuropathy, syncope, drowsiness, hypertensive encephalopathy (possibly fatal);
- hematopoietic system: febrile neutropenia, neutropenia, leukopenia, anemia;
- blood coagulation system: development of arterial thromboembolism, bleeding (including pulmonary hemoptysis / bleeding);
- urinary system: urinary tract infections, proteinuria;
- dermatological reactions: dry skin, exfoliative dermatitis, palmar-plantar erythrodysesthesia syndrome, skin discoloration;
- metabolism: anorexia, dehydration;
- the body as a whole: often - fever, pain, asthenia / fatigue, abscesses, sepsis, infections;
- others: myasthenia gravis, visual disturbances.
Overdose
There is no data.
special instructions
The use of the drug should be carried out only under the supervision of a physician who has experience in anticancer therapy.
Bevacizumab may interfere with wound healing. Treatment should not be started earlier than 28 days after surgery, or until the surgical wounds have healed completely. If complications develop during treatment that are associated with wound healing, Bevacizumab should be temporarily canceled until complete healing. Therapy is also interrupted in cases of elective surgery.
Bevacizumab can only be used after pre-compensated hypertension and under blood pressure control.
With arterial hypertension, it is recommended to temporarily interrupt therapy until adequate blood pressure control is achieved. Normalization of indicators is achieved with the help of angiotensin-converting enzyme inhibitors, calcium channel blockers and diuretics. If blood pressure has not returned to normal, or if a hypertensive crisis or hypertensive encephalopathy occurs, Bevacizumab is discontinued.
An increased risk of developing proteinuria is noted with a burdened history of arterial hypertension.
If bleeding of grade III or IV occurs, Bevacizumab is discontinued.
Patients with acquired coagulopathy, congenital hemorrhagic diathesis or after receiving a full dose of anticoagulants for thromboembolism require caution when prescribing the drug.
Patients with non-small cell lung cancer have an increased risk of serious and in some cases fatal pulmonary hemorrhage / hemoptysis with Bevacizumab.
Bevacizumab should not be used with a history of bleeding / hemoptysis (more than 2.5 ml of blood). Taking anticoagulants, anti-inflammatory / antirheumatic drugs, previous radiation therapy, central tumor location, atherosclerosis, cavity formation before / during treatment are all possible risk factors for pulmonary hemorrhage / hemoptysis. Reliable connection of these symptoms with the development of bleeding has been proven only for squamous cell lung cancer.
In colorectal cancer, bleeding in the gastrointestinal tract associated with the tumor, including rectal bleeding and melena, is possible.
The development of mucocutaneous bleeding was observed in 20–40% of cases. In most cases, nosebleeds were observed that did not exceed the first degree of severity, lasting less than 5 minutes. Less commonly, vaginal bleeding or bleeding from the gums was observed.
When combined with chemotherapy, the incidence of arterial thromboembolism, including stroke, transient ischemic attack, and myocardial infarction, was higher than with chemotherapy alone. Age over 65 or a history of arterial thromboembolism is associated with an increased likelihood of developing arterial thromboembolism. The use of Bevacizumab in such patients requires special care.
If arterial / venous thromboembolism occurs, the drug should be discontinued.
In the event of a reversible late leukoencephalopathy, symptomatic therapy should be prescribed. Careful blood pressure monitoring and discontinuation of Bevacizumab are required. The safety of repeated use of the drug in these patients has not been established.
Congestive heart failure most commonly occurs in patients with metastatic breast cancer who have received anthracyclines / chest radiation therapy in history, as well as other risk factors for congestive heart failure, such as coronary artery disease or concomitant drug therapy with cardiotoxicity. This applies to both asymptomatic decreases in left ventricular ejection fraction and congestive heart failure requiring hospitalization or therapy. Caution should be exercised when prescribing Bevacizumab to patients with clinically significant cardiovascular disease or a history of congestive heart failure.
Most often, fistulas of the gastrointestinal tract developed in metastatic colorectal cancer, less often in patients with other tumor localizations. In rare cases, fistula formations of other localizations (urogenital, bronchopleural, biliary) are recorded. Fistula formation is more often observed in the first six months of Bevacizumab use, but they can also occur both after 7 days and 1 year or later after the start of treatment. With the development of a tracheoesophageal fistula or fistula of any localization of the IV degree of severity, Bevacizumab is canceled. If an internal fistula occurs that does not penetrate into the gastrointestinal tract, the doctor decides on the cancellation of therapy on an individual basis.
When Bevacizumab is used in combination with chemotherapy drugs that have myelotoxicity, there is an increase in the incidence of febrile neutropenia, severe neutropenia, or infections with severe neutropenia (possibly fatal).
In patients over 65 years of age, the use of Bevacizumab is accompanied by an increase in the risk of arterial thromboembolism (including stroke, myocardial infarction, transient ischemic attack), grade III – IV leukopenia and thrombocytopenia, as well as neutropenia (all severity), nausea, diarrhea, asthenia, headache.
Application during pregnancy and lactation
According to the instructions, Bevacizumab is not used during pregnancy / lactation.
Pediatric use
Bevacizumab therapy is contraindicated in patients under 18 years of age.
With impaired renal function
Bevacizumab is not prescribed for renal impairment.
For violations of liver function
Bevacizumab is not prescribed for hepatic impairment.
Use in the elderly
For elderly patients, the drug is prescribed with caution.
Drug interactions
With the combined use of bevacizumab with sunitinib (50 mg daily) in patients with metastatic renal cell carcinoma, cases of microangiopathic hemolytic anemia have been reported (belongs to the subgroup of hemolytic anemias, can manifest such symptoms as fragmentation of erythrocytes, thrombocytopenia and anemia). In some cases, neurological disorders, arterial hypertension (including hypertensive crisis), and increased creatinine levels are also noted. Symptoms are reversible (go away on their own after canceling both drugs).
Analogs
Analogues of Bevacizumab are: Avastin, Avegra BIOCAD.
Terms and conditions of storage
Store in a place protected from light at a temperature of 2-8 ° C. Do not freeze. Keep out of the reach of children.
Expiration date - 1 year.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Bevacizumab
Reviews of Bevacizumab are few, since in most cases the drug is used in combination with other drugs.
Price for Bevacizumab in pharmacies
The approximate price for Bevacizumab is: for 1 bottle of 4 ml - 8000 rubles; for 1 bottle of 16 ml - 30,000-30,067 rubles.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
