Vincristin-Teva (Vincristine-Teva)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceVincristineVincristine
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    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    In 1 ml contains:

    active substance: vincristine sulfate (in terms of anhydrous substance) 1.0 mg;

    Excipients: Mannitol, sodium hydroxide, sulfuric acid, water for injection.

    Description:Transparent solution from colorless to slightly yellow in color.
    Pharmacotherapeutic group:Antitumor agent - alkaloid
    ATX: & nbsp

    L.01.C.A.02   Vincristine

    Pharmacodynamics:

    Vincristine is an alkaloid vinca pink (Catharanthus roseus), which binds to the protein-tubulin leads to a violation of the microtubule apparatus of the cells and to the rupture of the mitotic spindle. Suppresses mitosis in metaphase. Vincristine selectively blocks the DNA repair mechanism in tumor cells, and also blocks the synthesis of RNA by blocking the action of DNA-dependent synthetase RNA.

    Pharmacokinetics:

    After intravenous administration vincristine quickly removed from the blood.After 15-30 minutes more than 90% of the drug is distributed from blood serum into tissues and other blood components. In the equilibrium state, the volume of distribution is 8.4 ± 3.2 l / kg.

    20 minutes after intravenous administration of more than 50% vincristine is associated with blood components, mainly with platelets, which contain tubulin in high concentrations.

    After intravenous jet administration vincristine penetrates the blood-brain barrier only in small amounts, but it can have adverse effects on the central nervous system.

    Vincristine is metabolized mainly in the liver, possibly by the microsomal enzyme system of cytochrome P450 (isoform CYP3A).

    The excretion of vincristine from blood plasma after rapid intravenous administration is best described by a three-phase model. The initial, middle and final half-lives are 5 minutes, 2.3 hours and 85 hours (interval 19-155 hours), respectively.

    Due to low plasma clearance to prevent cumulative toxicity, the interval between treatment cycles should be at least 1 week.

    Vincristine is excreted mainly by the liver, about 80% of the administered dose is excreted with feces and 10-20% in urine.

    Patients with hepatic impairment

    In patients with impaired hepatic function, a metabolic disorder may occur and, as a result, a decrease in vincristine excretion, which increases the risk of toxicity in these patients. If necessary, reduce the dose.

    Children

    Children have significant individual differences in pharmacokinetic parameters, such as clearance, volume of distribution and half-life, in addition, these parameters differ depending on age. Plasma clearance in children is usually higher than in adults and infants, but there is no clear data on the decrease in clearance in children with increasing age.

    Indications:

    Acute leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, Ewing's sarcoma, neuroblastoma, Wilms tumor, rhabdomyosarcoma, multiple myeloma, Kaposi's sarcoma, uterine choriocarcinoma, small cell lung cancer.

    Contraindications:

    - Hypersensitivity to vincristine or any other component of the drug;

    - neuromuscular disorders (in particular the demyelinating form of the Charcot-Marie-Toot syndrome);

    - severe violations of liver function;

    - threatening intestinal obstruction, especially in children;

    - simultaneous radiotherapy with involvement of the liver region;

    - pregnancy and the period of breastfeeding.

    Carefully:

    With a decrease in liver function, the presence of constipation, oppression of bone marrow hematopoiesis, in the presence of a history of neuropathy, acute infectious diseases, with previous chemotherapy or radiotherapy, in elderly patients.

    Dosing and Administration:

    Vincristine is administered strictly intravenously (avoid extravasation) at intervals of 1 week. The duration of the injection should be approximately 1 minute.

    Intrathecal use of the drug is prohibited!

    The dose should be determined individually, depending on the treatment regimen used and the clinical condition of the patient.

    Adults: usually 1.0-1.4 mg / m2 body surface, a single dose should not exceed 2 mg / m2. The maximum total dose is 10-12 mg / m2.

    For children: 1.5-2.0 mg / m2 surface of the body. For children with a body weight of ≤ 10 kg, the initial dose should be 0.05 mg / kg per week.

    The course of therapy is usually 4-6 weeks.

    With a decrease in liver function (concentration of direct bilirubin in the serum ≥ 3 mg / dl), the dose of vincristine should be reduced by 50%.

    When there are signs of severe damage to the nervous system, especially with the development of paresis, treatment with vincristine should not be done. After the disappearance of the neurological symptoms with the withdrawal of the drug, therapy can be resumed at a dose of 50% of the initial.

    In applications in elderly patients correction of the dose is not required.

    Side effects:

    The incidence of side effects is given in accordance with the following gradation: very often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100), rarely (≥ 1 / 10000, <1/1000), very rarely (<1/10000).

    From the nervous system: often - peripheral sensorimotor neuropathy (paresthesia, loss of deep tendon reflexes, sagging of the feet, muscle weakness, ataxia, paralysis), neuralgia (including pains in the jaws, throat, parotid glands, back, bones, muscles and male sex glands) violation of the functions of the cranial nerves (hoarseness of voice, paresis of vocal cords, ptosis, neuropathy of the optic nerve and other neuropathies), transient cortical blindness, nystagmus, diplopia, atrophy of the optic nerve. Sometimes - convulsions with increased blood pressure, headache, dizziness, depression, agitation, increased drowsiness, confusion, psychosis, hallucinations, sleep disturbance, hearing loss.

    Neurotoxicity is a dose limiting factor.

    From the gastrointestinal tract: often - constipation, pain in the abdominal cavity; sometimes - anorexia, weight loss, nausea, vomiting, diarrhea, paralytic intestinal obstruction (especially often in children); rarely - stomatitis, necrosis of the small intestine and / or perforation.

    From the hepatobiliary system: primary thrombosis of hepatic veins (especially in children).

    From the urinary system: sometimes - polyuria, dysuria, urinary retention, due to atony of the bladder, hyperuricemia, urate nephropathy; rarely - the syndrome of inadequate secretion of antidiuretic hormone (hyponatremia in combination with a high level of sodium excretion in the urine without signs of impaired renal and adrenal function, hypotension, dehydration, azotemia or edema).

    From the cardiovascular system: sometimes - ischemic heart disease, myocardial infarction (in patients who previously received radiotherapy in the mediastinum, when combined therapy, including vincristine); rarely - increase or decrease in blood pressure.

    From the immune system: often acute respiratory failure and bronchospasm, sometimes expressed and life-threatening (observed with vincristine with mitomycin C); rarely - anaphylactic shock, skin rash and swelling.

    From the skin and skin appendages: very often - alopecia.

    From the side of the reproductive system: very often - azoospermia, amenorrhea.

    On the part of the hematopoiesis system: often - transient thrombocytosis; sometimes - marked depression of bone marrow function, anemia, leukopenia and thrombocytopenia. Usually vincristine does not have a significant effect on hematopoiesis.

    Local Reactions: often - irritation at the injection site; sometimes - if the product gets under the skin inflammation of subcutaneous fat, phlebitis, pain, necrosis of surrounding tissues.

    Other: myalgia, arthralgia, fever.

    Overdose:

    In case of an accidental overdose, vincristine should be expected to increase in side effects.

    The specific antidote is not known.

    Treatment should be symptomatic and should include restriction of fluid intake, the appointment of diuretics (for the prevention of ADH secretion syndrome),the use of phenobarbital (to prevent seizures), the use of enemas and laxatives (prevention of intestinal obstruction). It is also necessary to monitor the activity of the cardiovascular system and carry out hematological control.

    Hemodialysis is ineffective.

    In addition to the above, can be appointed calcium folinate in a dose of 100 mg intravenously every 3 hours for 24 hours and then every 6 hours for at least 48 hours.

    Interaction:

    Metabolism of vinca alkaloids is realized by cytochrome isoenzyme P-450 - CYP3A4. In connection with this, with simultaneous administration of inhibitors CYP3A4, such as ritonavir, nelfinavir, ketoconazole, itraconazole, erythromycin, fluoxetine and nefazodone, an increase in vincristine concentration in the blood plasma can be observed.

    With the combined administration of itraconazole and vincristine, neuromuscular disorders developed more rapidly and / or were more pronounced, which, apparently, is due to the inhibition of vincristine metabolism.

    Simultaneous administration of phenytoin in combination with antitumor treatment, including vincristine, led to a decrease in the content of phenytoin in the blood and, accordingly, to a decrease in its anticonvulsant effect.

    The simultaneous use of vincristine with other mielodepressive drugs and prednisolone may increase oppression of bone marrow hematopoiesis.

    When used simultaneously with neurotoxic drugs (isoniazid, itraconazole, nifedipine) and ototoxic drugs, there is an increase in side effects from the nervous system and the hearing system, respectively.

    Vincristine reduces the effectiveness of digoxin and ciprofloxacin.

    Verapamil increases the toxicity of vincristine.

    With simultaneous application vincristine weakens the effect of anti-gouty drugs.

    When used simultaneously with uricosuric agents, the risk of nephropathy increases.

    When administered in combination with mitomycin C vincristine can cause severe bronchospasm.

    If it is necessary to use the drug in combination with L-asparhinase vincristine should be administered 12 to 24 hours before application. L-asparhinase. Assigning asparaginase before the administration of vincristine can disrupt its hepatic clearance.

    In connection with the possible inhibition of immune system function, caused by treatment with vincristine, the formation of antibodies in response to the vaccine can be reduced. With simultaneous administration with live viral vaccines, it is possible to intensify the process of replication of the vaccine virus, increase its side / adverse effects and / or reduce the production of antibodies in the patient's body in response to the introduction of the vaccine.

    Radiation therapy can lead to increased peripheral neurotoxicity vincristine.

    Do not mix vincristine with other drugs in one syringe.

    Special instructions:

    Treatment with vincristine should be carried out under the strict supervision of a physician with experience in cytotoxic therapy.

    The drug should be administered only intravenously. Intrathecal injection of vincristine leads to the development of lethal neurotoxicity.

    During treatment should be carried out regular hematological control. In case of detection of leukopenia with the introduction of repeated doses, special care should be taken.

    When the activity of hepatic enzymes is increased, the dose of vincristine should be reduced.

    Periodically, the concentration of sodium ions in serum should be determined. For the correction of hyponatremia, the administration of appropriate solutions is recommended.

    Special control is given to patients who have a history of neuropathy.

    When symptoms of neurotoxicity appear, treatment with vincristine should be discontinued.

    To support regular bowel work, it is recommended that you follow an appropriate diet, take laxatives or use enemas.

    In the case of extravasation, vincristine should be discontinued immediately. The remaining dose of the drug should be injected into another vein. The place of extravasation can be chopped with hyaluronidase solution.

    Caution should be given vincristine elderly patients, as neurotoxicity in them can be more pronounced.

    Any complaint of pain in the eyes or a decrease in vision requires a careful ophthalmological examination.

    To prevent the development of urate nephropathy, regular monitoring of serum uric acid levels is required. With an increase in the level of uric acid, alkalinization of urine and the administration of uricosynthesis inhibitors are recommended.

    Women and men during treatment with vincristine and at least 3 months afterwards should use reliable methods of contraception.

    With caution appoint vincristine patients with ischemic heart disease.

    The diluted solution is chemically and physically stable for 48 hours at 2-8 ° C. From the point of view of microbiological purity, the diluted solution should be used immediately, it is allowed to store dilute solution in the refrigerator (2-8 ° C) for no more than 24 hours.

    When working with vincristine solution, you should follow the rules for handling cytotoxic drugs. Avoid contact with solution! If the solution comes into contact with the skin, mucous membranes or eyes, rinse thoroughly with plenty of water. Contact vincristine in the eyes can lead to severe irritation and ulcerative lesions of the cornea.

    Effect on the ability to drive transp. cf. and fur:

    Some of the side effects of vincristine, in particular neurotoxicity, can adversely affect the ability to drive or perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Solution for intravenous administration, 1 mg / ml.

    Packaging:

    1 mg / 1 ml, 2 mg / 2 ml and 5 mg / 5 ml in vials of colorless glass with a plug of bromobutyl rubber, an aluminum cap provided with a protective cap made of colored polypropylene.

    1 a vial covered with a transparent film of PVC / polyethylene, together with instructions for use in a cardboard bundle.

    Storage conditions:

    At a temperature of 2 to 8 ° C in a dark place. Do not freeze.

    Keep out of the reach of children.

    Shelf life:

    2 of the year.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015355 / 01
    Date of registration:18.09.2008
    Expiration Date:Unlimited
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp16.02.2017
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