Vincristine - instructions for use, dose, side effects, contraindications

It binds to tubulin, inhibits the formation of the mitotic spindle and stops the mitotic division of cells at the metaphase stage. In high doses, it also inhibits the synthesis of nucleic acids and protein.

Pharmacokinetics:

After intravenous The introduction is quickly distributed into tissues (90% of the substance within 15-30 minutes after administration). Do not go through blood-brain barrier. Binding to plasma proteins is 75-90%. Metabolised in the liver. The kinetics of excretion is three-phase. The half-life of alpha is 5 minutes, the half-life of beta is 2.3 hours, the half-life of gamma is 85 hours on average (in the range of 19-155 hours). It is excreted with bile (80%) and urine (10-20%).

Indications:

Acute leukemia, lymphogranulomatosis, non-Hodgkin's lymphoma, myeloma,rhabdomyosarcoma, Ewing's sarcoma, sarcoma of bones and soft tissues, osteogenic sarcoma, neuroblastoma, Kaposi's sarcoma, uterine sarcoma, breast cancer, small cell lung cancer, melanoma, epithelioma, renal pelvis and ureter cancer, bladder cancer, Wilms tumor, cervical cancer , germinogenous testicular and ovarian tumor, uterine choriocarcinoma, ependymoma, meningioma, pleurisy of tumor etiology, malignant tumors of genital organs in girls. Idiopathic thrombocytopenic purpura (with resistance to glucocorticosteroids and ineffectiveness of splenectomy).

ICD-10

II.C73-C75.C74 Malignant neoplasm of adrenal gland

II.C69-C72.C71 Malignant neoplasm of brain

II.C64-C68.C67 Malignant neoplasm of bladder

II.C64-C68.C64 Malignant neoplasm of kidney, except for renal pelvis

II.C60-C63.C62 Malignant neoplasm of testis

II.C51-C58.C54 Malignant neoplasm of uterine body

II.C51-C58.C53 Malignant neoplasm of cervix

II.C50.C50 Malignant neoplasm of breast

II.C40-C41.C40 Malignant neoplasm of bones and articular cartilages of extremities

II.C30-C39.C34 Malignant neoplasm of bronchi and lungs

II.C81-C96.C92.0 Acute myeloid leukemia

II.C81-C96.C91.0 Acute lymphoblastic leukemia

III.D65-D69.D69.3 Idiopathic thrombocytopenic purpura

II.C81-C96.C81 Hodgkin's disease [lymphogranulomatosis]

Contraindications:

Diseases of the central and peripheral nervous system, severe leukopenia, pregnancy.

Carefully:

With caution appoint the drug while using drugs that inhibit the isoenzyme CYP3A.

Care should be taken when using vincristine for gout (including a history) and nephrolithiasis, as well as in patients who have previously received cytotoxic or radiation therapy.

Pregnancy and lactation:

Action category for the fetus by Food and Drug Administration (US Food and Drug Administration) - D.

Vincristine is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Dosing and Administration:

Intravenously, spray or drip, once a week. The dosage regimen is set individually. A single dose for adults is 1-1.4 mg / m² (a maximum of 2 mg / m²), exchange rate - 10-12 mg / m². For violations of liver function, smaller doses are used.

Children are prescribed depending on body weight, once a week for 4-6 weeks.

Intrapleural 1 mg.

Side effects:

On the part of the hematopoiesis system: leukopenia, anemia, thrombocytopenia.

From the central nervous system and the peripheral nervous system: neuropathy, neuritis of peripheral nerves, headache, convulsions, ataxia, depression, diplopia, ptosis, hallucinations, sleep disorders.

From the urinary system: polyuria, dysuria, atony of the bladder, edema, acute urinary nephropathy.

From the digestive system: vomiting, diarrhea, stomatitis, constipation, anorexia, paralytic ileus (especially often in children).

Other: alopecia (passing after the withdrawal of treatment), arterial hypotension, swelling.

Overdose:

Symptoms: increased severity of side effects.

Treatment: prevention of syndrome of secretion disorders antidiuretic hormone (restriction of fluid intake, the appointment of a diuretic), the administration of phenobarbital (to prevent seizures) and other means of symptomatic therapy, washing the intestines (prevention of obstruction), if necessary, the appointment of calcium folinate (intravenously in a dose of 100 mg every 3 hours for 24 hours, then every 6 hours for at least 2 days), monitoring of cardiovascular function, hematological control. The specific antidote is unknown. Hemodialysis is ineffective.

Interaction:

With simultaneous application vincristine enhances the neurotoxic effects of other drugs.

With simultaneous application vincristine weakens the effect of anti-gouty drugs. With simultaneous use with uricosuric drugs, the risk of developing nephropathy increases.

The introduction of vincristine prior to the use of bleomycin increases the antitumor effect of therapy.

Simultaneous use with mitomycin C can cause respiratory depression, bronchospasm, especially in predisposed patients.

With the simultaneous use of vincristine and itraconazole, an earlier and more severe development of the neurotoxic effect is possible.

Special instructions:

Do not recommend applying vincristine in patients with chicken pox (including recently transferred or after contact with the diseased), with herpes zoster, other acute infectious diseases.

The frequency of side effects of vincristine is related to the total dose and duration of therapy.

With the simultaneous carrying out of radiotherapy on the area of the spinal cord, it is possible to enhance the neurotoxic effect of vincristine.

The risk of neurotoxic effects is higher in elderly patients and in persons with history of neurological diseases. With the development of peripheral neuritis should stop the injection of vincristine.

During the treatment it is necessary to control the picture of peripheral blood, the activity of hepatic transaminases and lactate dehydrogenase, the concentration of uric acid and bilirubin in the blood plasma.

During the period of treatment, vaccination of patients and their families is not recommended.

AT experimental research the carcinogenic and mutagenic effect of vincristine is established.

Instructions

Vincristine (Vincristinum)