Vincristin-Richter - instructions for use, doses, side effects, contraindications

Active substanceVincristineVincristine

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Vero Vincristine

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Vincristin Richter

lyophilizate in / in

GEDEON RICHTER, OJSC Hungary

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RNTS named after N.N. Blokhin RAMS Russia

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solution in / in

Teva Pharmaceutical Enterprises Co., Ltd. Israel

Dosage form: & nbsplyophilizate for the preparation of a solution for intravenous administration

Composition:

1 bottle with lyophilizate contains:

active substance: vincristine sulfate 1 mg;

Excipients: lactose.

Composition of solvent: sodium chloride, benzyl alcohol, water for injection.

Description:

Lyophilizate: white or yellowish-white lyophilizate.

Solvent: clear, colorless solution.

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:

Vincristine undergoes metabolism in the liver and is excreted mainly with bile (70-80%).From 10 to 20% of the drug is excreted by the kidneys. Vincristine accumulates in the pancreas, in the spleen, in the kidneys, in the lungs and in the liver. To isolate vincristine in humans, a three-phase curve with half-life periods is typical: 4-5 minutes, 2-3 hours and 19-155 hours.

About 90% of the drug binds to blood plasma proteins. The drug penetrates poorly through the blood-brain barrier.

Pharmacokinetic parameters have significant individual variability.

Indications:

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

Contraindications:

- Hypersensitivity to vincristine or any other constituent substance of the drug;

- neurodystrophic diseases (in particular, the demyelinated form of the Charcot-Marie-Toot syndrome);

- simultaneous radiation therapy involving the liver region;

- pregnancy and the period of breastfeeding.

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

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. 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 ≥ 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 serum ≥ 3 mg / 100 ml), the dose of vincristine should be reduced by 50%.

The dry contents of the vial must be dissolved with the help of an applied solvent (the final solution contains 0.1 mg vincristine in one milliliter). This solution can then be diluted with 0.9% sodium chloride solution and administered as an intravenous injection or simultaneously with an intravenous infusion of 0.9% sodium chloride, through the infusion set, for 1 minute.

Side effects:

Side effects are usually reversible and are dose-dependent.

Children are usually better tolerated vincristine, than adults.

In elderly patients there is an increased tendency to neurotoxicity.

From the side of the central nervous system and the peripheral nervous system: convulsions with increased blood pressure, parasthesia, neuralgia, neuropathy, pain in the jaws, pharynx and in the parotid glands, lowering of muscle strength, loss of deep tendon reflexes, gait disturbance, ataxia, headache, dizziness, depression, hallucinations, sleep disorders, diplopia_,ptosis, nystagmus, transient blindness and optic atrophy, hearing loss.

Neurotoxicity is a dose limiting factor.

From the gastrointestinal tract: constipation, abdominal pain, nausea, vomiting, stomatitis, diarrhea, paralytic intestinal obstruction (especially common in children), small intestine necrosis and / or perforation, anorexia.

From the urinary system: polyuria, dysuria, urinary retention due to atony of the bladder, edema, nephropathy due to hyperuricemia.

From the cardiovascular system: increase or decrease in blood pressure. In patients with previously irradiated mediastinum with the use of polychemotherapy with the inclusion of vincristine, the occurrence of angina and myocardial infarction is possible.

From the respiratory system: acute dyspnoea and severe bronchospasm were observed with vincristine and mitomycin C.

From the endocrine system: there is rarely a syndrome caused by a violation of the secretion of antidiuretic hormone (ADH), in which a large amount of sodium is released in the urine, leading to hyponatremia. In this case, there are no signs of damage to the kidneys and adrenal glands, arterial hypotension, dehydration, azotemia and edema.

On the part of the hematopoiesis system: vincristine does not have a significant effect on hematopoiesis. However, mild leukopenia, thrombocytopenia and anemia can occur.

Local Reactions: when the product gets under the skin, inflammation of the subcutaneous fat, phlebitis, necrosis of surrounding tissues may develop.

Other: alopecia, allergic reactions (rash, swelling, anaphylaxis), weight loss, myalgia, arthralgia, fever, amenorrhea, azoospermia.

Overdose:

In case of an accidental overdose, one should expect an increase in Vincristine 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.

The implementation of hemodialysis is ineffective.

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

Interaction:

Vincristine can not be used with inhibitor drugs CYP3A4, the enzyme of the liver (a decrease in the metabolism of vincristine and an increase in its toxicity).

Potential inducers CYP3A4 reduce the effectiveness of vincristine.

Vincristine can reduce the anticonvulsant effect of phenytoin.

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 decreases 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.

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

Do not mix vincristine with other drugs in one syringe.

Dilute vincristine can only 0.9% solution of sodium chloride.

Special instructions:

Treatment with vincristine should be carried out under the supervision of a specialist,who has experience in carrying out antitumor chemotherapy.

Intrathecal injection of vincristine can lead to death.

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.

With an increase in the level of uric acid, alkalinization of urine and the administration of uricosynthesis inhibitors are recommended.

When the level of hepatic samples 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 movements, it is recommended to 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.

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

Avoid contact with vincristine solution in the eyes. If this happens, immediately be abundant and rinse the eyes thoroughly with plenty of liquid.

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:Lyophilizate for the preparation of a solution for intravenous administration, 1 mg.

Packaging:

Lyophilizate - 1 mg in a bottle of brown glass.

Solvent - 10 ml in a colorless glass ampoule with a point for the break in blue.

1 bottle and 1 ampoule in a plastic pallet; on 10 plastic pallets with instructions for medical use in a cardboard bundle.

Storage conditions:

At a temperature of 2-8 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014883 / 01

Date of registration:29.02.2008 / 11.06.2008

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp16.02.2017

Illustrated instructions

Instructions

Vincristin Richter (Vincristine-Richter)