Universal reference book for medicines
Product name: AVASTIN ® (AVASTIN ® )

Active substance: bevacizumab

Type: Antitumor drug.
Monoclonal antibodies
Manufacturer: F.Hoffmann-La Roche (Switzerland) manufactured by Genentech (USA)
Composition, form of production and packaging
Concentrate for the preparation of solution for infusion
, clear or opalescent liquid, colorless or light brown in color.

1 f.
(4 ml)
bevacizumab 100 mg

Excipients:?,? - trehalose dihydrate - 240 mg, sodium dihydrogen phosphate monohydrate - 23.2 mg, sodium hydrophosphate anhydrous - 4.8 mg, polysorbate 20 - 1.6 mg, water d / and - up to 4 ml.

4 ml - bottles of glass (1) - packs of cardboard.

Concentrate for the preparation of solution for infusion , clear or opalescent liquid, colorless or light brown in color.

1 f.
(16 ml)
bevacizumab 400 mg

Excipients:?,? - trehalose dihydrate - 960 mg, sodium dihydrogen phosphate monohydrate - 92.8 mg, sodium hydrophosphate anhydrous - 19.2 mg, polysorbate 20 - 6.4 mg, water d / and - 16 ml.

16 ml - bottles of glass (1) - packs of cardboard.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

Antitumor drug.
Avastin ® (bevacizumab) is a humanized recombinant hyperchimeric monoclonal antibody that selectively binds to the biologically active vascular endothelial growth factor (VEGF) and neutralizes it. Avastin ® inhibits the binding of vascular endothelial growth factor to its type 1 and 2 receptors (Flt-1, KDR) on the surface of endothelial cells, which leads to a reduction in vascularization and inhibition of tumor growth.
Bevacizumab contains fully human framework regions with complementarity determining regions of the hyperchimeric mouse antibody that bind to VEGF.
Bevacizumab is produced by recombinant DNA technology in a system for expression represented by Chinese hamster ovary cells. Bevacizumab consists of 214 amino acids and has a molecular weight of about 149,000 daltons.
The introduction of bevacizumab leads to suppression of metastatic progression of the disease and a decrease in microvascular permeability in various human tumors, including colon, breast, pancreas and prostate cancer.

Preclinical safety data

The carcinogenic and mutagenic potential of Avastin ® has not been studied.

When Avastin ® was administered to animals, embryotoxic and teratogenic effects were observed.

In actively growing animals with open growth zones, Avastin ® was associated with dysplasia of the cartilaginous plate.

PHARMACOKINETICS

The pharmacokinetics of the Avastin ® preparation was studied after iv administration at various doses (0.1-10 mg / kg every week, 3-20 mg / kg every 2 or 3 weeks, 5 mg / kg every 2 weeks or 15 mg / kg every 3 weeks ) in patients with various solid tumors.

The pharmacokinetics of bevacizumab, like other antibodies, is described by a two-compartment model.

Distribution of Avastin ® is characterized by low clearance, low volume of distribution in the central chamber (V c ) and a long half-life (T 1/2 ), which allows to maintain the necessary therapeutic concentration of the drug in the plasma when administered once every 2-3 weeks.

The clearance of bevacizumab does not depend on the age of the patient.
Bevacizumab clearance is 30% higher in patients with low albumin levels and 7% higher in patients with a large tumor mass compared to patients with average albumin and tumor mass.
Distribution

V c is 2.73 L and 3.28 L in women and men, respectively, which corresponds to the distribution of IgG and other monoclonal antibodies.
The volume of distribution in the peripheral chamber (V p ) is 1.69 L and 2.35 L in women and men, respectively, with the appointment of bevacizumab with other antitumor drugs. After correcting the dose, taking into account the body weight in men, V with 20% more than women.
Metabolism

After a single intravenous administration of 125 I-bevacizumab, its metabolic characteristics are similar to those of a natural IgG molecule that does not bind to VEGF.Metabolism and excretion of bevacizumab corresponds to the metabolism and excretion of endogenous IgG, i.e.
mainly carried out by proteolytic catabolism in all cells of the body, including endothelial cells, and not through the kidneys and liver. Binding of IgG to neonatal receptors to the crystallizing fragment of IgG (FcRn receptors) protects it from cellular metabolism and provides a long T 1/2 .
Excretion

The pharmacokinetics of bevacizumab in a dose range of 1.5 to 10 mg / kg per week is linear.

The clearance of bevacizumab is 0.188 l / day for women and 0.220 l / day for men.
After correcting the dose, taking into account the body weight in men, the clearance of bevacizumab 17% more than women. According to the two-chamber model, T 1/2 for women is 18 days, for men - 20 days.
Pharmacokinetics in specific patient groups

Patients of advanced age (over 65 years)

There was no significant difference in the pharmacokinetics of bevacizumab, depending on age.

Children and teens

There are limited data on the pharmacokinetics of bevacizumab in children and adolescents.
The available data indicate that there is no difference between V d and the clearance of bevacizumab in children, adolescents and adult patients with solid tumors.
Patients with renal or hepatic insufficiency

The safety and efficacy of bevacizumab in patients with renal or hepatic insufficiency has not been studied,
Kidney and liver are not the main organs of metabolism and excretion of bevacizumab.
INDICATIONS

Metastatic colorectal cancer:

- in combination with chemotherapy based on fluoropyrimidine derivatives.

Locally recurrent or metastatic breast cancer:

- as the first line of therapy in combination with paclitaxel.

Common inoperable, metastatic or recurrent non-cell lung non-small cell lung cancer:

- as a first-line therapy in addition to chemotherapy based on platinum drugs.

Common and / or metastatic renal cell carcinoma:

- as the first line of therapy in combination with interferon alpha-2a.

Glioblastoma (grade IV glioma according to WHO classification):

- in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma;

- in monotherapy or in combination with irinotecan in patients with recurrent glioblastoma or disease progression.

Epithelial cancer of the ovary, uterine tube and primary cancer of the peritoneum:

- as the first line of therapy in combination with carboplatin and paclitaxel in the spread (IIIB, IIIC and IV stage according to FIGO classification) of epithelial ovarian cancer, fallopian tube and primary peritoneal cancer;

- in combination with carboplatin and gemcitabine with relapsing platinum-sensitive epithelial ovarian cancer, fallopian tube and primary peritoneal cancer in patients who have not previously been treated with bevacizumab or other VEGF inhibitors;

- in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin in relapsing, platinum-resistant epithelial ovarian cancer, fallopian tube, and primary peritoneal cancer in patients who received no more than two regimens of chemotherapy.

DOSING MODE

Avastin ® is administered only in / in the drip;
inject the drug intravenously!
Avastin ® is not intended for intravitreal administration.

Avastin ® is pharmaceutically incompatible with dextrose solutions.

The required amount of Avastin ® is diluted to the required volume with 0.9% sodium chloride solution in compliance with aseptic rules.
The concentration of bevacizumab in the prepared solution should be in the range of 1.4-16.5 mg / ml.
The initial dose of the drug is given IV infusion for 90 minutes.
If the first infusion is well tolerated, then the second infusion can be performed within 60 minutes. If the infusion is well tolerated within 60 minutes, all subsequent infusions can be carried out within 30 minutes.
It is not recommended to reduce the dose of bevacizumab because of undesirable phenomena.
If necessary, Avastin® should be completely or temporarily discontinued.
Standard dosing regimen

Metastatic colorectal cancer

As the first line of therapy: 5 mg / kg every 2 weeks or 7.5 mg / kg once every 3 weeks as an IV infusion, long-term.

It is recommended that Avastin ® treatment be given before signs of disease progression or to unacceptable toxicity.

As a second line of therapy: patients who previously received Avastin ® therapy after the first progression of the disease may continue Avastin ® treatment if the chemotherapy regimen is changed:

- with the progression of the disease after first-line therapy, including Avastin®: 5 mg / kg once every 2 weeks or 7.5 mg / kg once every 3 weeks as an IV infusion, long-term;

- with progression of the disease after first-line therapy, not including Avastin ® : 10 mg / kg once every 2 weeks or 15 mg / kg 1 every 3 weeks as an IV infusion, long-term.

Locally recurrent or metastatic breast cancer

The drug is prescribed in a dose of 10 mg / kg once every 2 weeks as an IV infusion, long-term.

If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.

Common inoperable, metastatic or recurrent non-cell lung non-small cell lung cancer

Avastin ® is prescribed in addition to platinum-based chemotherapy (the maximum duration of chemotherapy is 6 cycles), then Avastin ® is continued as monotherapy.
If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.
Recommended doses:

- 7.5 mg / kg once every 3 weeks as an intravenous infusion in addition to cisplatin-based chemotherapy;

- 15 mg / kg once every 3 weeks as an intravenous infusion in addition to carboplatin-based chemotherapy.

Common and / or metastatic renal cell carcinoma

The drug is prescribed in a dose of 10 mg / kg once every 2 weeks as an IV infusion, long-term.

If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.

Glioblastoma (glioma IV degree of malignancy according to WHO classification)

For the first time diagnosed, 10 mg / kg once every 2 weeks as an IV infusion in combination with radiotherapy and temozolomide for 6 weeks.
After a 4-week break, Avastin® is resumed at a dose of 10 mg / kg every 2 weeks in combination with temozolomide. Temozolomide appointed 4 - week cycles, duration of therapy with temozolomide - up to 6 cycles. Further, Avastin is continued as monotherapy at a dose of 15 mg / kg once every 3 weeks. If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.
In case of recurrent disease: 10 mg / kg once every 2 weeks as an IV infusion, prolonged.
If there is evidence of progression of the disease or unacceptable toxicity, Avastin® should be discontinued.
Epithelial cancer of the ovary, uterine tube and primary cancer of the peritoneum

As the first line of therapy: 15 mg / kg once every 3 weeks as an IV infusion in addition to carboplatin and paclitaxel (the maximum duration of chemotherapy is 6 cycles), then Avastin® continues as a monotherapy.
The total duration of therapy with Avastin ® is 15 months. If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.
With a recurrent disease:

- sensitive to platinum preparations - 15 mg / kg once every 3 weeks as an IV infusion in combination with carboplatin and gemcitabine (6-10 cycles), then the Avastin® treatment continues as monotherapy.
If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.
- resistant to platinum preparations - 10 mg / kg once every 2 weeks as an intravenous infusion in combination with one of the following drugs: paclitaxel, topotecan (with weekly topotecan administration, ie, 1, 8 and 15- th days every 4 weeks) or pegylated liposomal doxorubicin

or

15 mg / kg once every 3 weeks as an IV infusion in combination with topotecan, applied daily for 5 consecutive days every 3 weeks.

If signs of disease progression or unacceptable toxicity appear, Avastin® therapy should be discontinued.

Dosage regimen for specific patient groups

In elderly patients (over 65 years of age), dose adjustment is not required.

The safety and efficacy of bevacizumab in patients with renal insufficiency has not been studied.

The safety and efficacy of bevacizumab in patients with hepatic insufficiency has not been studied.

The safety and efficacy of bevacizumab in children and adolescents have not been established.

Instructions for use, handling and destruction of the drug

Before use, the solution should be inspected for mechanical inclusions and discoloration.

Avastin ® does not contain an antimicrobial preservative, so it is necessary to ensure the sterility of the prepared solution and use it immediately.
If the preparation is not used immediately, the time and storage conditions of the prepared solution are the responsibility of the user.
Store the prepared solution for a maximum of 24 hours at a temperature of + 2 ° to + 8 ° C if dilution is carried out in controlled and validated aseptic conditions.

The chemical and physical stability of the prepared solution (in a 0.9% solution of sodium chloride) is maintained for 48 hours at a temperature of + 2 ° to + 30 ° C.
The unused drug remaining in the vial is destroyed. it does not contain preservatives.
SIDE EFFECT

The most serious adverse reactions: gastrointestinal perforation, hemorrhage, including pulmonary hemorrhage / hemoptysis (more common in patients with non-small cell lung cancer), arterial thromboembolism.

In patients receiving Avastin ® , the most frequently observed: increased blood pressure, weakness or asthenia, diarrhea and abdominal pain.

The increase in blood pressure and the development of proteinuria probably have a dose-dependent character.

Below are the adverse reactions of all severity grades according to the classification of the National Cancer Institute (NCI-CTC) that occurred in patients treated with Avastin® in combination with various chemotherapeutic regimens for all indications.
To describe the frequency of adverse reactions, the following criteria are used: very often (? 10%), often (? 1% - <10%), infrequently (? 0.1% - <1%), rarely (? 0.01% - <0.1%), very rarely (<0.01%).
Undesirable reactions are assigned to a specific category according to the highest frequency of occurrence.
Within the same frequency category, unwanted reactions are presented in order of severity. Some of these unwanted reactions are often observed with chemotherapy (for example, palmar-plantar syndrome with capecitabine therapy and peripheral sensory neuropathy with paclitaxel or oxaliplatin); However, we can not rule out the weight gain during Avastin® therapy. When Avastin ® is used in combination with pegylated liposomal doxorubicin, an increased risk of developing the palmar-plantar syndrome is possible.
From the hemopoietic system: very often - febrile neutropenia, leukopenia, neutropenia, thrombocytopenia;
often anemia.
From the side of the nervous system: very often - peripheral sensory neuropathy, dysgeusia, headache, dysarthria;
often - stroke, syncope, drowsiness.
From the side of the organ of vision: very often - visual impairment, increased lachrymation.

From the cardiovascular system: very often - increased blood pressure;
often - chronic heart failure, supraventricular tachycardia, arterial thromboembolism, deep vein thrombosis, bleeding (including pulmonary, intracranial, mucosa and skin, GI and tumors).
From the respiratory system : very often - shortness of breath, nosebleeds, rhinitis;
often - thromboembolism of the pulmonary artery (PE), hypoxia.
From the digestive system: very often - anorexia, diarrhea, nausea, vomiting, constipation, stomatitis, rectal bleeding;
often - perforation of the digestive tract, intestinal obstruction (including obturation), abdominal pain, gastrointestinal disorders.
On the part of the reproductive system: very often - failure of the function of the ovaries (amenorrhea lasting 3 months or more (concentration of FSH-30 mIU / ml with a negative pregnancy test with determination of human beta-chorionic gonadotropin in serum)).

From the skin and subcutaneous tissues: very often - exfoliative dermatitis, dry skin, discoloration of the skin;
often - palmar-plantar syndrome.
From the musculoskeletal system: very often - arthralgia;
often - muscle weakness, myalgia.
From the urinary system: very often - proteinuria; often - urinary tract infection.
Local reactions: often - pain, including at the site of injection.
Other: often - fatigue, increased fatigue, pyrexia, inflammation of the mucous membranes of various localization; often - lethargy, confusion, sepsis, abscess, accession secondary infections, dehydration.
From the laboratory parameters: hyperglycemia, hypokalemia, hyponatremia, increased prothrombin time, increased MHO.
Post-marketing surveillance
of the nervous system:rarely - rear reversible encephalopathy syndrome; very rarely - hypertensive encephalopathy.
Cardio-vascular system: the frequency of occurrence is unknown - renal thrombotic microangiopathy, clinically manifested by proteinuria.
On the part of the respiratory system: often - dysphonia; the frequency of occurrence is unknown - perforation of the nasal septum, pulmonary hypertension.
On the part of the digestive tract: frequency of occurrence is unknown - gastrointestinal ulcer.
Of the liver and biliary tract: frequency of unknown - perforation of the gall bladder.
Allergic and infusion reactions:frequency of unknown - hypersensitivity reactions, infusion reactions with the following possible simultaneous manifestations: dyspnoea / difficulty breathing, flushing / redness / rash, decrease or increase in blood pressure, reduction in oxygen saturation, chest pain, vomiting, and nausea / vomiting.
From the musculoskeletal system: osteonecrosis of the jaw (mainly in patients receiving concomitant therapy with bisphosphonates or receiving bisphosphonate therapy earlier).
Other: rarely - necrotizing fasciitis usually on the background of impaired wound healing, perforation of the gastrointestinal tract or fistula.
CONTRAINDICATIONS

- increased sensitivity to bevacizumab or any other component of the preparation, formulations based on Chinese hamster ovary cells or other recombinant human or approximate to human antibodies;
- renal and hepatic insufficiency (efficacy and safety have not been established);
- Pregnancy;

- lactation;
- Children up to age 18 years (effectiveness and safety have been established).
With caution should be prescribed to patients with arterial thromboembolism; diabetes; Patients over the age of 65 years; hemorrhagic diathesis in congenital or acquired coagulopathy; taking anticoagulants for the treatment of thromboembolism before therapy drug Avastin ® ; clinically significant cardiovascular disease (ischemic heart disease, or chronic heart failure history); hypertension; venous thromboembolism; wound healing; bleeding / hemoptysis; Gastrointestinal perforation in history; syndrome rear reversible encephalopathy; neutropenia; proteinuria.
PREGNANCY AND LACTATION

The drug is contraindicated during pregnancy and lactation.
Men and women of childbearing age during treatment with Avastin ® and for at least 6 months after completion of treatment necessary to use reliable contraception.
Avastin ® may interfere with fertility in women. The majority of patients recovered fertility after discontinuation of therapy with Avastin ® . Long-term effects of therapy with Avastin ® fertility unknown.
Breastfeeding is not recommended during treatment with Avastin ® and at least for 6 months after the end of therapy with Avastin® .
APPLICATION FOR FUNCTIONS OF THE LIVER

The drug is contraindicated in patients with renal insufficiency (efficacy and safety have not been established).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

The drug is contraindicated in hepatic insufficiency (efficacy and safety have not been established).
APPLICATION FOR CHILDREN

Contraindicated: children's age (efficacy and safety have not been established).
APPLICATION IN ELDERLY PATIENTS

Be wary appoint elderly patients (over 65 years) .
SPECIAL INSTRUCTIONS

The patient's medical records should indicate the trade name of the drug (Avastin ® ). Replacement of the drug to any other biological medicinal product requires agreement with the attending physician. The information provided in this specification refers only to the drug Avastin ® .
Treatment with Avastin ® only under medical supervision can be carried out, having experience of anticancer therapy.
Patients receiving Avastin ® , there is an increased risk of perforation of the gastrointestinal tract and gallbladder . Experienced severe GI perforation cases, including and fatal (at 0.2-1% of all patients receiving the drug Avastin ®). The clinical picture is characterized by perforations on the digestive tract, and severity varied depending on the sign of free gas at the abdomen radiography, which disappeared without any treatment, to the perforations with abdominal abscess and fatal. In some cases, there has been initial intraperitoneal inflammation of the gastric ulcer, tumor necrosis, diverticulitis or colitis associated with chemotherapy. The connection between inflammation and the development of intraperitoneal perforation and gastrointestinal therapy Avastin ® has not been established. With the development of gastrointestinal perforation treatment with Avastin ® should be discontinued.
When therapy with Avastin ® are registered serious cases the formation of fistulas, Including cases with fatal outcome. Gastrointestinal fistulas occur most often in patients with metastatic colorectal cancer and ovarian cancer (up to 2% of patients), more rarely in other tumor localizations. Infrequently (? 0.1- <1%) were recorded cases of fistula formation at other sites (bronchopleural, urogenital, biliary). Fistulas often occurs in the first 6 months of therapy with Avastin ® , but can occur both at 1 week and at 1 year and later after the start of therapy.
In the event of tracheo-esophageal fistula or fistula any location 4 severity therapy Avastin ® should be canceled. There are limited data on the continued use of Avastin®patients with fistulas of other locations. In the event of internal fistula does not penetrate into the digestive tract, it should consider the abolition of Avastin ® .
Patients receiving Avastin ® , increased risk of bleeding , particularly bleeding from the tumor. Avastin ® should be canceled in the event of bleeding 3 or 4 severity classification NCI-CTC. The total incidence of 3-5 severity of bleeding when used Avastin ® for all indications of 0.4-6.5%. Most often observed bleeding from a tumor or minor bleeding from the skin and mucosal (e.g., nasal bleeding).
Most often observed nosebleeds 1 severity classification NCI-CTC, which lasted less than 5 minutes, resolved without medical intervention and without requiring changes dosing regimen Avastin ® . The frequency of small bleeding from mucous membranes and skin depends on the dose. Less commonly, there is a slight bleeding of the gums, or vaginal bleeding.
Heavy or massive pulmonary hemorrhage / hemoptysis were observed mainly in the non-small cell lung cancer. Admission antirheumatic / anti-inflammatory drugs, anticoagulants, prior radiotherapy, atherosclerosis, central tumor location, the formation of a cavity before or during treatment are possible risk factors for pulmonary hemorrhage / hemoptysis, and only for squamous cell carcinoma of the lung proved statistically significant association with the development of bleeding.
Patients who had recent bleeding / hemoptysis (over 2.5 ml of blood) should not receive the drug Avastin ® .
In patients with colorectal cancer are possible gastrointestinal bleeding associated with the tumor, including rectal bleeding and melena.
Rarely observed bleeding, including intracranial hemorrhage in patients with metastatic disease of the CNS or with glioblastoma.
It is necessary to monitor symptoms of intracranial hemorrhage, in the case of their occurrence cancel therapy with Avastin ® .
In patients with congenital bleeding diathesis, acquired coagulopathy or receiving full dose of anticoagulants on the thromboembolism before prescribing Avastin ® should be careful because of the lack of information on the safety profile of the drug in these patients. There was no increase incidence of bleeding of grade 3 or higher severity in patients receiving the drug Avastin ® and warfarin.
Reported individual cases, as well as a series of cases of serious adverse events associated with the organ of vision (including infectious endophthalmitis, and other inflammatory diseases) after intravitreal unregistered Avastin ® . Some of these events have led to the loss of visual acuity of varying severity, including persistent blindness. Avastin ® is not designed for intravitreal administration.
Patients treated with Avastin ® , was observed increased incidence of hypertensionall degrees of severity (to 42.1%). For all indications frequency hypertension 3-4 severity of NCI-CTC classification was 0.4% -17.9%; 4 severity (hypertonic crisis) occurred in 1% of patients.
Clinical safety data suggest that the incidence of high BP is likely to depend on the dose of bevacizumab.
Avastin ® can only be assigned to patients with hypertension pre-compensated with a further control of blood pressure. Information on the effect of Avastin ®in patients with uncontrolled hypertension at the time of initiation of therapy available. In patients with hypertension requiring drug therapy, it is recommended to temporarily discontinue therapy with Avastin ® to achieve normalization of blood pressure.
In most cases, normalization of blood pressure is achieved using standard antihypertensive agents (ACE inhibitor, diuretics and calcium channel blockers slow) selected individually for each patient. Cancel therapy Avastin ® or hospitalization is required infrequently.
Very rare cases of hypertensive encephalopathy have been observed, some with a fatal outcome. The risk of hypertension associated with treatment Avastin ®It does not correlate with the initial characteristics of the patient, concurrent disease or concomitant therapy.
Therapy Avastin ® should be stopped when there is no normalization of blood pressure, the development of hypertensive crisis or hypertensive encephalopathy.
When therapy with Avastin ® registered isolated cases syndrome rear reversible encephalopathy,manifested seizures, headache, mental disorders, visual impairment, lesion of the visual centers of the cerebral cortex, with or without hypertension and other symptoms. Diagnosis can be confirmed by brain imaging techniques (preferably with MRI). In the case of posterior reversible encephalopathy syndrome should appoint a symptomatic therapy, carefully monitor blood pressure and stop the drug Avastin ® . Typically, the resolution or improvement of symptoms occurs within a few days, but some patients experienced neurological complications. Safety reappointment Avastin ® in these patients has not been established.
When therapy with Avastin ®in combination with chemotherapy frequency arterial thromboembolism , including stroke, transient ischemic attack, myocardial infarction and other phenomena of arterial thromboembolism was higher than the appointment chemotherapy alone. The overall incidence of cases of arterial thromboembolic events was 3.8%. When an arterial thromboembolism therapy Avastin ® should be discontinued. Arterial thromboembolism or age greater than 65 years is associated with an increased risk of arterial thromboembolic events during treatment with Avastin ® . When treating such patients need to exercise caution.
During treatment with Avastin ® have an increased risk of developingvenous thromboembolism (pulmonary embolism, deep vein thrombosis, thrombophlebitis). The overall incidence of venous thromboembolism (deep vein thrombosis and pulmonary embolism) ranges from 2.8% to 17.3%.
Therapy Avastin ® should be stopped in case of life-threatening events (Grade 4 severe) venous thromboembolism, including pulmonary embolism, and in the severity of venous thromboembolism? 3 should be carefully monitoring the patient's condition.
Chronic heart failure (CHF), occurred when using the drug Avastin ® for all indications, but mainly in metastatic breast cancer. Observed both asymptomatic decrease in left ventricular ejection fraction and heart failure, which required treatment or hospitalization.
CHF Grade 3 or higher was observed in 3.5% of patients treated with Avastin ® . In patients receiving the drug Avastin ® combined with drugs anthracyclines, CHF 3 frequency and severity above does not differ from the data available in the therapy of metastatic breast cancer. The majority of patients had improvement of symptoms and / or left ventricular ejection fraction with appropriate treatment.
Data on the risk of CHF in patients with heart failure class II-IV of NYHA classification in the history of no.
In most cases, heart failure occurred in patients with metastatic breast cancer receiving anthracycline therapy, radiation therapy to the chest area with a history or other risk factors for heart failure development.
Caution must be exercised when administering the drug Avastin ® in patients with clinically significant cardiovascular disease in history, such as coronary heart disease or heart failure.
Patients who did not receive therapy with anthracyclines earlier, when using the drug Avastin ® and preparations anthracyclines no increase in frequency of any severity of CHF in comparison with monotherapy with anthracyclines. 3 CHF severity and occurred more frequently mentioned in the therapy group Avastin ®in combination with chemotherapy compared to chemotherapy alone, and another which corresponds to the data obtained in patients with metastatic breast cancer and not receiving concomitant therapy with anthracyclines.
Patients with diffuse large-cell lymphoma with bevacizumab and a cumulative doxorubicin dose of 300 mg / m 2 showed an increase in new cases of CHF. When comparing the therapy with rituximab / cyclophosphamide / doxorubicin / vincristine / prednisone (R-CHOP) + bevacizumab and R-CHOP number of new cases was not different, but was higher than observed previously in the treatment of doxorubicin. CHF rate was higher in the group R-CHOP + bevacizumab.
Avastin ®may adversely affect the wound healing. Bevacizumab treatment should be started at least 28 days after major surgery or complete healing of surgical wounds. With the development in the treatment of complications associated with wound healing, drug Avastin ® necessary to temporarily lift the complete healing of the wound.Introduction Avastin ® also need to temporarily stop in the case of elective surgery.
There have been rare cases of necrotising fasciitis (in

Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y
Rambler's Top100
Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!