Specific complications of vincristine therapy include: The drug 'Vincristine' - instructions for use, description and reviews
Price from: 102 rub.
Vincristine is an alkaloid cytotoxic agent that is obtained from the periwinkle Vinca rosea L. It is included in the list of Vital and essential medicines. It is used to treat various types leukemias and solid tumors. Vincristine can also be used for non-oncological diseases.
- Active substance: vincristine sulfate.
- Pharmacotherapeutic group: Antineoplastic agent. Alkaloid plant origin.
- ATS code: L01C A02.
- Release form: lyophilisate for solution for injection.
- Storage conditions: Store vials at 2-8°C.
- Terms of sale: on prescription.
Indications for use
Vincristine is prescribed for:
- (for example, in combination therapy acute lymphoblastic leukemia in children);
As directed, Vincristine may be used in chemotherapy to treat:
- , ureter, ;
- Williams tumors;
- neuroblastomas;
- ependymomas;
- malignant tumors on the genitals in girls;
- idiopathic thrombocytopenic purpura, resistant to glucocorticosteroids, as well as in cases where splenectomy did not work.
Contraindications
Vincristine is not prescribed to patients with:
- high sensitivity to vinca alkaloids;
- acute infectious diseases of fungal, viral or bacterial origin;
- heavy suppression bone marrow;
- neurodystrophic pathologies.
Also, the drug should not be prescribed to patients who receive radiation to the liver area.
With extreme caution, Vincristine is used if the patient has obstructive jaundice, hyperbilirubinemia, suppression of bone marrow hematopoiesis after radiotherapy, against the background of hyperuricemia and liver failure.
Taking Vincristine during pregnancy and lactation
The drug can penetrate into breast milk. Do not breastfeed while undergoing therapy!
There is positive evidence that vincristine is teratogenic, so it should only be used during pregnancy if emergency situations when there is a danger to the life of the mother and there is no safer drug.
pharmachologic effect
After entering the bloodstream, Vincristine binds to the protein tubulin, affecting the synthesis of DNA and RNA of tumor cells. The drug disrupts the formation of mitotic spindles, which stop the replication of cells during metaphase - a special phase in the life of cells.
Vincristine also interferes with nucleic acid and protein synthesis.
Pharmacokinetics
After intravenous administration vincristine is rapidly distributed throughout body tissues. Up to 90% of the drug binds to blood proteins. His active substance has the ability to accumulate in the tissues of the liver, lungs, spleen, pancreas, kidneys. Vincristine does not penetrate the meninges.
The elimination half-life of Vincristine is three-phase and is 5 minutes, 2.3 hours and 85 hours, respectively. Metabolism is hepatic. Clearance is 146 ml / min. Excretion occurs mainly with faeces (80%) and 20% with urine.
Instructions for use Vincristine
A solution of vincristine must be prepared immediately before administration. The dry contents of the vial are dissolved with a solvent, which is often included in the kit. This may be sodium chloride solution or water for injection. Typically, Vincristine is given once a week as an intravenous injection or as a short 15-minute infusion. The treatment regimen is prescribed strictly individually.
The average weekly dose of vincristine according to the instructions is 0.4-1.4 mg / m2 (for adults). Children are prescribed 1.5-2 mg / m2 of the body. On average, the duration of therapy is at least 1-1.5 months, after which a break is taken. If the concentration of bilirubin in the blood changes, the dose of vincristine should be reduced by 50%.
In some cases, the drug is injected into the cavity between the membranes of the lungs - 1 mg of the drug dissolved in physiological saline 10 ml. Intrathecal administration of vincristine is not carried out, as there is a possibility of death.
Important: If vincristine enters the surrounding area from a vein, it can cause serious damage to the skin and tissues. Tell your nurse right away if you have pain or redness at the injection site.
Side effects
The most common side effects of Vincristine are listed below. They may be temporary, and some may be permanent. This is:
- insomnia;
- headache;
- dizziness;
- muscle weakness;
- hair loss;
- numbness in the limbs;
- violation of motor functions;
- constipation;
- fever;
- weight loss;
- decrease in the number of leukocytes in the blood.
In addition, the drug is neurotoxic, that is, it has a negative effect on the nervous system. central system. This should be taken into account when treating the elderly and those who have previously suffered neurological diseases.
Tell your doctor right away if you have any serious side effects, including: vision/hearing changes, mental/mood changes (eg, depression, hallucinations, confusion), severe fatigue, seizures, chest pain.
Rarely, taking Vincristine can provoke:
- profuse urination;
- inflammation of the oral mucosa;
- dysuria;
- loss of appetite;
- vomiting, nausea;
- hypotension;
- bronchospasm.
Dark urine, persistent nausea, vomiting, abdominal pain, yellowing of the eyes and skin can all be signs of liver dysfunction!
In some patients, vincristine can have toxic effects on the lungs. This is more often observed with combined chemotherapy with Mitomycin-C. Contact immediately medical care if you experience shortness of breath or cough.
serious allergic reaction this drug is rare. However, be sure to contact your doctor if you notice any of the following symptoms: rash, itching, swelling (especially of the face, tongue, throat).
The frequency and severity of side effects are largely related to the duration of treatment and the dose of the drug received.
Overdose
With an overdose, the aforementioned side effects are aggravated. In severe cases, liver failure, cirrhosis and coma may develop. Treatment of overdose with Vincristine is symptomatic. Hemodialysis in such cases is ineffective.
special instructions
The drug should be administered under the supervision of an experienced physician in a facility equipped to diagnose and treat possible complications.
The product has a strong irritant property, so avoid contact with skin and eyes.
Unless your doctor tells you otherwise, drink plenty of fluids while using Vincristine. This helps reduce some of the side effects on the kidneys. Since patients often develop constipation during treatment, it is advisable to take laxatives or perform cleansing enemas.
This medicine may make you more likely to get an infection, so wash your hands well to prevent the spread of bacteria and avoid contact with people who are sick.
Do not drive or do anything that requires attention as vincristine causes dizziness. Limit your consumption of alcoholic beverages.
Women and men who have been treated with Vincristine should use reliable contraceptives for 3-6 months after the last dose.
Interaction
Concomitant use of certain drugs may affect pharmachologic effect Vincristine or increase the risk of serious side effects. Do not start any medication without your doctor's permission.
Here are some drugs that can interact with Vincristine:
- Digoxin;
- Phenytoin;
- platinum compounds;
- drugs that can cause difficulty urinating (for example, belladonna alkaloids);
- Atropine and other anticholinergic drugs;
- Dicyclomine;
- Oxybutynin.
There are also drugs that can affect the removal of vincristine from the body, such as azole antifungals(such as Itraconazole), macrolide antibiotics (Erythromycin), rifamycins (Rifabutin), anticonvulsants (Carbamazepine), and others.
Vincristine sulfate is not used simultaneously with Furosemide solution, Cefepime, Sodium bicarbonate.
Vincristine is compatible with drugs:,.
Composition and form of release
1 ml solution for injection contains vincristine sulfate 1 mg; in bottles of 1, 2, 3 and 5 ml, in a carton box 10 bottles.
Characteristic
pharmachologic effect
pharmachologic effect– antitumor.Binds to tubulin and prevents the formation of the mitotic spindle - stops mitotic division cells at the metaphase stage.
Pharmacokinetics
After intravenous administration, more than 90% binds to tissues. Doesn't penetrate well cerebrospinal fluid. It is metabolized in the liver. Excreted with feces (80%) and urine. The kinetics of excretion is three-phase, T 1/2 - 19-155 hours.
Indications for Vincristine
Acute leukemia, lymphogranulomatosis, non-Hodgkin's lymphoma, rhabdomyosarcoma, neuroblastoma, Wilms tumor, osteosarcoma, Ewing's sarcoma, bone and soft tissue sarcoma, breast and uterine cancer, small cell carcinoma lung, gynecological tumors in children.
Contraindications
Diseases of the nervous system; pregnancy, breastfeeding.
Side effects
Convulsions with increased blood pressure, paresthesia, intestinal paresis, vomiting, weight loss, polyuria, dysuria, impaired secretion of ADH, shortness of breath, bronchospasm, fever, headache, cranial nerve damage, ataxia, alopecia, amenorrhea, azoospermia.
Interaction
Reduces the elimination of L-asparaginase.
Dosage and administration
In / in, with an interval between two injections of at least 1 week. The average dose for a child is 2 mg / m 2, for an adult - 1.4 mg / m 2 (but not more than 2 mg / m 2 per injection). In hepatic insufficiency, the dose should not exceed 1 mg / m 2. The solution can be injected directly into a vein or into a rubber tube during another perfusion already in progress. The duration of the injection should be approximately 1 minute.
Overdose
Treatment: is reduced to the prevention of the syndrome of impaired secretion of ADH (restriction of fluid intake, the appointment of a diuretic acting at the level of the loop of Henle and distal tubules); the introduction of phenobarbital (to prevent seizures), other symptomatic agents; bowel lavage (prevention of the development of its obstruction).
Precautionary measures
Introduced strictly in / in (cannot be injected into the spinal canal due to the risk of death, avoid getting the drug into the eyes). Alkalinization of urine and content control are recommended. uric acid(may cause kidney damage due to uric acid formed during the massive decay of the tumor). It should not be combined with other agents that have a neurotoxic effect. Do not prescribe during radiation therapy.
Storage conditions for Vincristine
In a place protected from light, at a temperature of 4 ° C.Keep out of the reach of children.
Shelf life of Vincristine
1.5 years.Do not use after the expiry date stated on the packaging.
Synonyms of nosological groups
| Category ICD-10 | Synonyms of diseases according to ICD-10 |
|---|---|
| C40-C41 Malignant neoplasms of bones and articular cartilage | malignant neoplasm bones |
| Tumors of bones and articular cartilage | |
| Osteogenic sarcoma | |
| osteosarcoma | |
| Osteogenic cancer | |
| Reticulosarcoma of the bone | |
| C43 malignant melanoma skin | Disseminated malignant melanoma |
| malignant melanoma | |
| Localized malignant melanoma | |
| Localized form of malignant melanoma | |
| Melanoma | |
| Melanoma after surgical resection | |
| Metastatic form of malignant melanoma | |
| Metastatic melanoma | |
| Disseminated metastatic malignant melanoma | |
| C50 Malignant neoplasms of the mammary gland | Hormone-dependent form of recurrent breast cancer in menopausal women |
| Hormone dependent breast cancer | |
| Disseminated breast carcinoma | |
| Disseminated breast cancer | |
| Disseminated breast cancer with HER2 overexpression | |
| Malignant tumor of the breast | |
| Malignant neoplasm of the breast | |
| breast carcinoma | |
| Contralateral breast cancer | |
| Locally advanced or metastatic breast cancer | |
| Locally advanced breast cancer | |
| Locally recurrent breast cancer | |
| Metastatic breast carcinoma | |
| Metastases of breast tumors | |
| Metastatic breast carcinoma | |
| Inoperable breast carcinoma | |
| inoperable breast cancer | |
| Tumors of the mammary glands | |
| Breast cancer in women with metastases | |
| Breast cancer in men with metastases | |
| breast cancer | |
| Cancer mammary glands in men | |
| Mammary cancer | |
| Breast cancer with distant metastases | |
| Postmenopausal breast cancer | |
| Breast cancer hormone dependent | |
| Breast cancer with local metastases | |
| Breast cancer with metastases | |
| Breast cancer with regional metastases | |
| Breast cancer with metastases | |
| Cancer of the nipple and areola of the breast | |
| Common hormone-dependent forms of breast cancer | |
| Advanced breast cancer | |
| Recurrent breast cancer | |
| Recurrence of breast tumors | |
| breast cancer | |
| Estrogen-dependent breast cancer | |
| Estrogen dependent breast cancer | |
| C51-C58 Malignant neoplasms of female genital organs | Tumors of the female genital organs |
| C53 Malignant neoplasm of cervix | Intraepithelial tumor of the cervix |
| cervical carcinoma | |
| Cervical cancer | |
| C71 Malignant neoplasm of brain | Adenoma of the pineal body |
| Anaplastic astrocytoma | |
| Astrocytoma | |
| glioblastoma | |
| Glioma sarcomatous | |
| Granuloblastoma | |
| Malignant glioma | |
| Malignant brain tumor | |
| Metastatic brain tumors | |
| Metastases to the brain | |
| Neurilemmoma | |
| Neuroblastoma | |
| Neuroglioma embryonic | |
| Neurospongioblastoma | |
| Neurospongioma | |
| Oligodendroglioma | |
| Oligodendrocytoma | |
| Tumors of the cerebral hemispheres | |
| brain tumors | |
| brain tumors | |
| A brain tumor | |
| Brain tumor | |
| Primary malignant brain tumor | |
| Primary brain tumor | |
| Pinealoma | |
| brain cancer | |
| Spheroblastoma | |
| Fibroblastoma perineural | |
| Chemodectoma | |
| Choroidpapilloma | |
| Choroidepithelioma | |
| Schwannoglioma | |
| Schwannoma | |
| ependymoma | |
| C81 Hodgkin's disease [lymphogranulomatosis] | Hodgkin's disease |
| Generalized form of Hodgkin's disease | |
| Lymphogranulomatosis | |
| Hodgkin's lymphoma | |
| Lymphoproliferative diseases | |
| Paltauf-Sternberg disease | |
| Pel-Ebstein fever | |
| Reticulosis fibromyeloid | |
| Hodgkin's malignant lymphoma | |
| Hodgkin's lymphoma | |
| C83.3 Large cell (diffuse) non-Hodgkin's lymphoma | Histiocytic lymphoma |
| Lymphoma histiocytic | |
| Reticulocellular sarcoma | |
| Reticulosarcoma | |
| Reticulosarcoma with lesions of peripheral lymph nodes | |
| Reticulosarcomas | |
| C84.0 Mycosis fungoides | Mycosis fungiformis |
| Fungoid granuloma | |
| C85 Other and unspecified types of non-Hodgkin's lymphoma | Malignant lymphoma |
| Lymphoma lymphocytic | |
| Lymphoma non-Hodgkin's | |
| Mixed type lymphoma | |
| Lymphomas from cells of the mantle zone | |
| Lymphocytic lymphoma | |
| C95 Leukemia, unspecified cell type | Leukemia undifferentiated |
| Leukemia non-lymphocytic | |
| undifferentiated leukemia | |
| Non-lymphocytic leukemia | |
| Acute leukemia in adults | |
| Acute non-lymphocytic leukemia | |
| D69.3 Idiopathic thrombocytopenic purpura | Autoimmune thrombocytopenic purpura during pregnancy |
| Werlhof disease | |
| Idiopathic autoimmune thrombocytopenia | |
| Adult idiopathic thrombocytopenic purpura | |
| Idiopathic thrombocytopenic purpura in adults | |
| Immune idiopathic thrombocytopenic purpura | |
| Immune thrombocytopenia | |
| Bleeding in patients with thrombocytopenic purpura | |
| Posttransfusion purpura | |
| Evans syndrome | |
| Thrombocytopenic purpura | |
| Thrombocytopenia of immune origin | |
| Chronic idiopathic thrombocytopenic purpura | |
| Essential thrombocytopenia |
Formula: C46H56N4O10, chemical name: 22-oxovinkleukoblastin (as sulfate 1:1).
Pharmacological group: antitumor agents / antitumor agents of plant origin.
Pharmachologic effect: antitumor, cytostatic.
Pharmacological properties
Vincristine is an anticancer cytostatic chemotherapeutic drug of plant origin. Vincristine is an alkaloid found in the plant Periwinkle Rose or Catharanthus rosea (Vinca rosea L. or Catharanthus roseus). Vincristine lyophilized is a slightly yellowish powder. white color. Vincristine sulfate is almost insoluble in ether, slightly soluble in ethanol, soluble in methanol, chloroform (1 to 30), freely soluble in water (1 to 2). Vincristine binds to tubulin protein molecules, which leads to disruption of the microtubular apparatus of cells, rupture of the mitotic spindle, and stops mitosis at the metaphase stage. At high doses, vincristine inhibits protein synthesis and nucleic acids. Vincristine also has an immunosuppressive effect, can change the metabolism of amino acids, glutathione, cyclic adenosine monophosphate, the activity of calmodulin-dependent calcium-transport adenosine triphosphatase, cellular respiration, lipid and nucleic acid biosynthesis.
Vincristine is rapidly distributed in body tissues after intravenous administration (90% of the substance within 15-30 minutes after administration). Vincristine is 75-90% bound to serum proteins, shaped elements vincristine binds to blood by 15%. Vincristine does not cross the blood-brain barrier well. The initial, average, final elimination half-lives of vincristine are 5 minutes, 2.3 hours, 85 hours, respectively. The terminal half-life of vincristine can range from 19 to 155 hours. Vincristine is metabolized in the liver and is mainly excreted in the bile. Vincristine is metabolized with the participation of isoenzymes of the cytochrome P450 system of the CYP3A subfamily and is a substrate for glycoprotein-P. 70 - 80% of vincristine is excreted as metabolites and unchanged through the intestines, from 10 to 20% of vincristine is excreted by the kidneys. The pharmacokinetic parameters of vincristine have significant individual variability. Due to the low plasma clearance of vincristine, to prevent its cumulative toxicity, the interval between cycles of therapy should be at least one week. In patients with disorders functional state liver may disrupt the metabolism of vincristine and reduce its excretion, which increases the risk of toxicity. If necessary, in patients with impaired liver function, the dose of vincristine is reduced. In children, there were significant individual differences in the parameters of the pharmacokinetics of vincristine: volume of distribution, clearance, half-life (also, these parameters of the pharmacokinetics of vincristine differ depending on age). Plasma clearance of vincristine in children is usually higher than in infants and adults, but there is no clear evidence of a decrease in clearance in children with increasing age.
Indications
Leukemia; acute leukemia; acute lymphoblastic leukemia in children (for combined treatment); non-Hodgkin's lymphomas; non-Hodgkin's malignant lymphomas; lymphogranulomatosis; Hodgkin's disease; multiple myeloma; myeloma; fungoid granuloma; fungal mycosis; rhabdomyosarcoma; Ewing's sarcoma; osteogenic sarcoma; sarcomas of bones and soft tissues; uterine sarcoma; Kaposi's sarcoma; neuroblastoma; Wilms tumor; epithelioma; melanoma; small cell lung cancer; cancer of the renal pelvis and ureters; mammary cancer; cancer Bladder; cervical cancer; choriocarcinoma of the uterus; chorionepithelioma of the uterus; germ cell tumor of the testis and ovaries; malignant tumors of the genital organs in girls; meningioma; ependymoma; pleurisy of tumor etiology; idiopathic thrombocytopenic purpura (resistant to glucocorticosteroid drugs and with ineffective splenectomy).
Method of application of vincristine and doses
Vincristine is administered intravenously (stream or drip), intrapleurally. When vincristine is administered, extravasation should be avoided. Vincristine is administered one week apart. The duration of the injection should be at least one minute. Intrathecal administration of vincristine is prohibited.
The dose of vincristine is set individually depending on the therapy regimen used and clinical condition patient.
Adults usually enter 1 - 1.4 mg / m2 of body surface, a single dose of vincristine should not exceed 2 mg. The maximum exchange rate of vincristine is 10-12 mg/m2. Children are injected with 1.5 - 2.0 mg/m2 of body surface. For children weighing 10 kg or less, the initial dose of vincristine should be 0.05 mg/kg per week. Usually the course of treatment is 4 - 6 weeks.
In case of violation of the functional state of the liver (with a concentration of bilirubin in the blood plasma of 3 mg / 100 ml (51 μmol / l)) or more, the dose of vincristine should be reduced by 50%.
When signs and symptoms develop severe injury nervous system, especially with the appearance of paresis, vincristine therapy must be discontinued. After the disappearance neurological symptoms when vincristine is discontinued, treatment may be resumed at a dose that should be 50% of the initial dose.
When using vincristine in elderly patients, dose adjustment is not required.
It is not recommended to prescribe vincristine during radiation therapy or use medicines that affect the hematopoietic organs (mutual enhancement of myelotoxic action is possible), except special programs chemotherapy with individual dose selection.
The use of vincristine should be carried out under the strict supervision of a physician who has experience in the treatment of cytotoxic drugs.
Intrathecal administration of vincristine is prohibited. Intrathecal administration of vincristine can lead to fatal neurotoxicity. Unacceptable intramuscular injection vincristine due to the possibility of tissue necrosis.
With an increase in the activity of liver transaminases, the dose of vincristine must be reduced.
During the use of vincristine, it is necessary to regularly monitor hematological parameters. If leukopenia is detected, it is advisable to take a break in treatment and prescribe antibiotics; in the future, with the introduction of repeated doses of vincristine, special care must be taken.
In the process of treatment, it is necessary to control the picture of peripheral blood, the activity of hepatic transaminases and lactate dehydrogenase, the concentration of bilirubin and uric acid in the blood serum.
Vincristine does not usually have a significant effect negative impact for hematopoiesis.
During the use of vincristine, it is periodically necessary to determine the level of sodium in the blood plasma. To correct hyponatremia, appropriate solutions should be administered.
During the use of vincristine, patients who have a history of neuropathy are subject to special control. With the development of symptoms of neurotoxicity, vincristine therapy should be discontinued. Neurotoxicity with the use of vincristine is a factor that limits the dose of the drug in reuse. Caution should be exercised when prescribing vincristine to elderly patients because their neurotoxicity may be more pronounced. The risk of developing neurotoxic effects of vincristine is higher in elderly patients and patients with a history of neurological diseases. When carried out jointly radiation treatment per area spinal cord may increase the neurotoxic effects of vincristine.
An appropriate diet, enemas, or laxative medications are recommended to support regular bowel movements during treatment with vincristine.
In case of extravasation, the administration of vincristine should be stopped immediately, the remainder of the drug should be injected into another vein. The sensation of local discomfort can be reduced by topical administration of hyaluronidase and the use of cold compresses or moderate heat.
If any complaints of decreased vision or eye pain appear during the use of vincristine, a thorough ophthalmological examination is necessary.
Vincristine should be used with caution in patients with ischemic heart disease.
Caution must be exercised when using vincristine for gout (including history) and nephrolithiasis, in patients who have previously received cytotoxic or radiation treatment.
Vincristine can increase the level of uric acid in the blood serum, therefore, in the treatment of gout and hyperuricemia, dose adjustment of anti-gout drugs may be necessary. To prevent the development of urate nephropathy during the use of vincristine, it is necessary to regularly monitor the plasma concentration of uric acid and ensure adequate diuresis. With an increase in the content of uric acid, alkalinization of urine and the appointment of inhibitors of uricosynthesis (for example, allopurinol) are recommended.
Women and men during therapy with vincristine and for at least three months after its termination, it is necessary to use reliable methods of contraception.
AT experimental studies embryotoxic, teratogenic, mutagenic and carcinogenic effects of vincristine have been established.
With caution, vincristine is prescribed in conjunction with drugs that inhibit the cytochrome P450 CYP3A isoenzyme.
The use of vincristine in patients with herpes zoster is not recommended. chicken pox(including chicken pox, recently transferred, or after contact with sick chicken pox), other acute infectious diseases.
During the period of treatment with vincristine, vaccination of patients and their families is not recommended.
Side effects vincristine are dose-dependent and may disappear completely when the drug is discontinued. Frequency adverse reactions vincristine is related to the total dose of the drug and the duration of treatment.
When working with a solution of vincristine, it is necessary to follow the rules for handling cytotoxic drugs. Contact with vincristine solution and contact with eyes should be avoided. If vincristine solution gets into the eyes, skin and mucous membranes, rinse them thoroughly with plenty of water. Contact with vincristine in the eyes can cause severe irritation and ulceration of the cornea.
Given that the use of vincristine may develop neurotoxicity and other symptoms that have a negative effect on nervous system, sense organs and general state, during therapy, you should refrain from engaging in potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions (including control vehicles, mechanisms).
Contraindications for use
Hypersensitivity (including to auxiliary components medicinal product); severe violations of the functional state of the liver; threatening intestinal obstruction, especially in children; neurodystrophic diseases (for example, the demyelinating form of Charcot-Marie-Tooth syndrome); diseases of the central and peripheral nervous system; infectious diseases; severe leukopenia; joint radiation therapy involving the liver area; intrathecal administration (possibly death); lactation period; pregnancy.
Application restrictions
Inhibition of bone marrow hematopoiesis; bone marrow hypoplasia; the presence of neuropathy in history; decreased liver function; mechanical jaundice; hyperbilirubinemia; constipation; infectious diseases; prior radiotherapy; previous radiation therapy of the hepatobiliary region and the spinal cord region; previous chemotherapy; elderly age.
Use during pregnancy and lactation
The use of vincristine is contraindicated in pregnancy and lactation. Women and men during therapy with vincristine and for at least three months after its termination, it is necessary to use reliable methods of contraception. In experimental studies, the embryotoxic and teratogenic effects of vincristine have been established. During therapy with vincristine, breastfeeding should be discontinued.
Side effects of vincristine
Nervous system, psyche and sense organs: peripheral sensory neuropathy (loss of sensation, paresthesia, loss of deep tendon reflexes, muscle weakness, sagging feet, paralysis, ataxia), impaired function of the cranial nerves (especially the VIII pair) (paresis vocal cords, ptosis, hoarseness, neuropathy optic nerve and other neuropathies), neuralgia (including pain in the pharynx, muscles, jaws, parotid glands, bones, back, male gonads), neuritis peripheral nerves, loss of sensation, decreased muscle strength, neuropathy, paresthesia, headache, dizziness, convulsions, decreased deep tendon reflexes, isolated paresis, muscle paralysis, convulsions with elevation blood pressure, depression, increased drowsiness, agitation, confusion, hallucinations, psychosis, sleep disturbance, impaired motor function, ataxia, transient cortical blindness, transient blindness, diplopia, nystagmus, ptosis, optic nerve atrophy, hearing loss.
Cardiovascular system, blood (hemostasis, hematopoiesis) and lymphatic system:
coronary heart disease, increased blood pressure, edema, lowering blood pressure, blood pressure lability, angina pectoris, myocardial infarction (in patients who previously received radiation therapy in the mediastinal region, when using combined chemotherapy with the inclusion of vincristine), anemia, thrombocytopenia, leukopenia, transient thrombocytosis.
Digestive system: pain in abdominal cavity, abdominal pain, constipation, anorexia, nausea, weight loss, vomiting, paralytic ileus (especially in children), paralytic ileus (especially often in children), organ smooth muscle spasm gastrointestinal tract, diarrhea, wall necrosis small intestine, perforation of the wall of the small intestine, stomatitis, primary thrombosis of the hepatic veins (especially in children).
Respiratory system: shortness of breath, bronchospasm, acute respiratory failure(including expressed and life threatening(especially noted when using vincristine in conjunction with mitomycin)).
Musculoskeletal system: arthralgia, myalgia.
Urogenital system: polyuria, bladder atony, urinary retention due to bladder atony, dysuria, urate nephropathy, edema, acute uric acid nephropathy, hyperuricemia, azoospermia, amenorrhea.
Endocrine system: syndrome of inappropriate secretion of antidiuretic hormone (hyponatremia in combination with high level excretion of sodium in the urine without signs of violations of the functional state of the kidneys and adrenal glands, azotemia, dehydration, hypotension, edema).
skin, subcutaneous tissue and mucous membranes: alopecia.
The immune system: skin rash, anaphylactic shock, anaphylaxis, angioedema.
Others: fever, feeling hot, hyponatremia.
Local reactions: irritation at the injection site; if vincristine gets under the skin, pain, phlebitis, cellulitis, inflammation of the subcutaneous fat, necrosis of surrounding tissues can develop.
Interaction of vincristine with other substances
Vinca alkaloids, including vincristine, are metabolized with the participation of the isoenzyme of the cytochrome P450 system CYP3A4 and are substrates for glycoprotein-P. Therefore, the combined use of vincristine and inhibitors of the isoenzyme system of the cytochrome P450 CYP3A4 system and glycoprotein-P (for example, nelfinavir, ritonavir, itraconazole, ketoconazole, erythromycin, nefazodone, fluoxetine, nifedipine, cyclosporine) may increase the plasma concentration of vincristine. The co-administration of itraconazole and vincristine was associated with more pronounced and/or faster neuromuscular adverse reactions, most likely due to a slower metabolism of vincristine. Vincristine is prescribed with caution in conjunction with drugs that inhibit the cytochrome P450 CYP3A isoenzyme.
With the combined use of vincristine and phenytoin, it is possible to reduce the concentration of phenytoin in the blood serum and, accordingly, reduce its anticonvulsant effect.
With the combined use of vincristine and myelodepressants, prednisolone, the inhibition of bone marrow hematopoiesis increases.
With the combined use of vincristine and neurotoxic drugs (eg, asparaginase, isoniazid, cyclosporine), prolonged and severe peripheral neuropathy may develop. Therefore, drugs with a known neurotoxic effect should be administered with caution in conjunction with vincristine under constant neurological monitoring.
When used together, vincristine enhances the neurotoxic effects of other drugs.
With the combined use of vincristine and digoxin, ciprofloxacin reduces the effectiveness of the latter.
With the combined use of vincristine and verapamil, the toxicity of vincristine increases.
With the joint use of vincristine and anti-gout drugs, the effect of the latter is weakened.
The combined use of vincristine and uricosuric drugs increases the risk of nephropathy, which is associated with advanced education uric acid. The most preferred drug for the prevention or elimination of hyperuricemia associated with vincristine treatment is allopurinol.
With the combined use of vincristine and mitomycin, the likelihood of developing bronchospasm and respiratory depression increases, especially in predisposed patients.
When combined with vincristine and bleomycin, depending on the dose, vincristine can cause Raynaud's syndrome. The introduction of vincristine prior to the use of bleomycin increases the antitumor effect of the treatment.
With the combined use of vincristine and cyclosporine, tacrolimus, severe immunosuppression may develop with the risk of lymphoproliferation.
If necessary, the combined use of vincristine and asparaginase, vincristine can be administered only 12 to 24 hours before the administration of asparaginase. The use of asparaginase prior to the use of vincristine may interfere with its excretion from the liver.
With the combined use of vincristine and colony-stimulating factors (GM-CSF, G-CSF), the development of atypical neuropathies with a burning or tingling sensation in the distal extremities was more often reported.
Glucocorticosteroids, estrogens, androgens, progestins, when used together with vincristine, enhance its effect.
Due to the possible inhibition of the function immune system, which is caused by the use of vincristine, the formation of antibodies in response to the vaccine may be reduced. At joint application Vincristine and live virus vaccines may intensify the replication process of the vaccine virus, enhance its adverse and adverse reactions, reduce the formation of antibodies in the patient's body in response to the vaccine. Patients with leukemia in remission should not be given live viral vaccine for at least three months after the last course of chemotherapy.
The pharmacodynamic interaction of vincristine with other cytostatics may potentiate the therapeutic and toxic effect. The combined use of vincristine and other drugs that suppress bone marrow function, such as doxorubicin (especially in combination with prednisone), may potentiate the depressive effect of vincristine on the bone marrow.
Radiation therapy may increase the peripheral neurotoxicity of vincristine.
Vincristine is pharmaceutically incompatible with furosemide solution (a precipitate forms upon mixing).
Vincristine should not be mixed in the same syringe with other drugs.
Overdose
With an overdose of vincristine, an increase in its adverse reactions should be expected. Treatment of vincristine overdose should be symptomatic and supportive and should include fluid restriction, diuretic medications (to prevent inappropriate antidiuretic hormone secretion syndrome), enemas and laxatives (to prevent intestinal obstruction), the use of phenobarbital (for the prevention of seizures). It is also necessary to control activities of cardio-vascular system and hematological parameters. In addition, calcium folinate 100 mg intravenously can be given every three hours during the day and then every six hours for at least two days. There is currently no specific antidote for vincristine. Hemodialysis with an overdose of vincristine is not effective.
Trade names of drugs with the active ingredient vincristine
Vero-Vincristine
Vincristine
Vincristine liquid-Richter
Vincristine-RONC®
Wincristine-Richter
Vincristine-Teva
Vincristine sulfate
Oncocristin
Pharmachologic effect:
Vincristine - antitumor agent.
Indications for use
AT complex therapy acute leukemia (malignant tumor blood arising from blast cells / bone marrow cells, from which leukocytes, lymphocytes, erythrocytes, etc. are formed / and characterized by the appearance of these immature cells in the bloodstream); with lymphosarcoma (malignant tumor arising from immature lymphoid cells); Ewing's sarcoma (malignant bone tumor).Mode of application
Vincristine administered intravenously at weekly intervals. The dosage of the drug should be selected strictly individually. Assign adults 0.4-1.4 mg / m2 of body surface per week, children - 2 mg / m2 of body surface per week. Intrapleurally (into the cavity between the pulmonary membranes), 1 mg of the drug, previously dissolved in 10 ml of physiological, is injected.Avoid getting the drug into the eyes and surrounding tissues due to strong irritant, upon contact with the skin causes necrosis (death of tissues).
Side effects
Hair loss, constipation, insomnia, paresthesia (numbness in the limbs), ataxia (impaired movement), muscle weakness, weight loss, fever, leukopenia (low white blood cell count), less often - polyuria (excessive urination), dysuria (urinary disorders), ulcerative stomatitis (inflammation of the oral mucosa), nausea, vomiting, loss of appetite. Neurotoxicity (damaging effect on the central nervous system) of the solution. Elderly patients and people with a history of neuralgic diseases (previously) may be more sensitive to neurotoxic effects (damaging effects on the central nervous system) vincristina. With simultaneous use with other neurotoxic drugs, during radiation therapy to the spinal cord area, it is possible to increase the neurotoxic effect of vincristine.The frequency of side effects of the drug is related to the total dose and duration of therapy.
Contraindications
Solution vincristina sulfate is incompatible in one volume with a solution of furosemide (due to the formation of a precipitate).Release form
In ampoules of 0.5 mg with the application of a solvent in a package of 10 pieces.Storage conditions
In a cool, dark place.Synonyms
Onkovin.Main settings
| Name: | VINCRISTIN |
| ATX code: | L01CA02 - |
1 ml of solution contains:
active substance:
vincristine sulfate - 1.0 mg;Excipients: mannitol - 100.0 mg, methyl parahydroxybenzoate - 1.8 mg, propyl parahydroxybenzoate - 0.2 mg, sodium hydroxide - up to pH 4.5, sulfuric acid - up to pH 4.5, water for injection - up to 1 ml.
Description: Clear, colorless to light yellow solution. Pharmacotherapeutic group:Antitumor agent - alkaloid ATX:L.01.C.A.02 Vincristine
Pharmacodynamics:Vincristine is a vinca alkaloid catharanthus roseus), a cytostatic chemotherapeutic agent.
Use with caution in patients with ischemic disease hearts. Women and men must use reliable methods of contraception during treatment with vincristine and for at least 3 months thereafter.
Side effects are dose-dependent and may disappear completely upon discontinuation.
Intramuscular administration is unacceptable due to the possibility of tissue necrosis.
When working with a solution of vincristine, the rules for handling cytotoxic drugs should be observed. Avoid contact with the solution! If the solution comes into contact with the skin, mucous membranes or eyes, rinse thoroughly with plenty of water. Contact with vincristine in the eyes can lead to severe irritation and ulceration of the cornea.
Influence on the ability to drive transport. cf. and fur.:Given that the use of vincristine may develop neurotoxicity and other symptoms that affect the general condition, during the period of treatment it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Release form / dosage:Solution for intravenous administration, 1 mg/ml.
Package:1 ml, 2 ml or 5 ml in a light-protective glass vial of hydrolytic class I, corked with a stopper and bromobutyl rubber for running in with an aluminum cap or an aluminum cap with a plastic insert.
1 bottle with instructions for use in a cardboard box.
Storage conditions:In a place protected from light, at a temperature of 2 to 8 ° C.
Keep out of the reach of children.
Shelf life:2 years.
Do not use the drug after the expiration date indicated on the package.
Conditions for dispensing from pharmacies: On prescription Registration number: LP-003309 Date of registration: 13.11.2015 / 11.07.2016 Expiration date: 13.11.2020 Registration certificate holder:National Research Center of Oncology named after N.N. N.N. Blokhin of the Ministry of Health of Russia, FBSU Russia Manufacturer: Information update date: 16.02.2017 Illustrated Instructions