Vincristine-Teva
Vincristin-Teva: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. For violations of liver function
- 11. Use in the elderly
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Vincristine-Teva
ATX code: L01CA02
Active ingredient: vincristine (Vincristine)
Manufacturer: Farmahemi B. V. (Pharmachemie BV) (Netherlands)
Description and photo update: 2019-11-07
Vincristine-Teva is a herbal antineoplastic agent.
Release form and composition
Dosage form - solution for intravenous administration: transparent, from slightly yellow to colorless (in a cardboard box 1 bottle of 1, 2 or 5 ml and instructions for use of Vincristine-Teva).
Composition of 1 ml solution:
- active substance: vincristine sulfate - 1 mg (in terms of anhydrous substance);
- auxiliary components: mannitol, sulfuric acid, sodium hydroxide, water for injection.
Pharmacological properties
Pharmacodynamics
Vincristine - the active substance of the drug is the alkaloid of pink vinca (Catharanthus roseus), which binds to the protein tubulin and leads to disruption of the microtubular apparatus of cells and rupture of the mitotic spindle. The substance suppresses mitosis in metaphase. Vincristine in tumor cells selectively blocks the DNA repair mechanism, and also blocks RNA biosynthesis by blocking the effect of DNA-dependent RNA synthetase.
Pharmacokinetics
After intravenous administration, vincristine is rapidly cleared from the blood. More than 90% of the dose in 15-30 minutes comes from blood serum to tissues and other blood components. V d (volume of distribution) at equilibrium is 8.4 ± 3.2 l / kg.
More than 50% of the drug in 20 minutes after administration is associated with blood components, mainly platelets, which contain high concentrations of tubulin.
After intravenous jet injection, a small amount of vincristine penetrates the blood-brain barrier, while the development of adverse events from the central nervous system is possible.
Vincristine is metabolized mainly in the liver, presumably by the microsomal enzyme system of cytochrome P 450 (isoform CYP3A).
After rapid intravenous administration, vincristine is eliminated from the blood plasma in three phases. T 1/2 (half-life) of the initial, middle and final phases is 0.08; 2,3 and 85 hours (interval 19-155 hours), respectively.
To prevent cumulative toxicity due to low plasma clearance of the substance, the interval between therapy cycles should be at least 7 days.
Vincristine is excreted mainly by the liver, approximately 80% of the dose is excreted in the feces, and 10–20% in the urine.
Against the background of hepatic dysfunction, metabolism can be impaired, which in turn can lead to a decrease in the excretion of vincristine and, as a consequence, an increase in the risk of toxicity. Due to the fact that in patients with impaired liver function, the likelihood of toxicity increases, a decrease in the dose of Vincristine-Teva is required.
In children, there is significant individual variability in pharmacokinetic parameters, including clearance, T 1/2 and V d. The values of these indicators also differ depending on age. In children, in comparison with adults and infants, plasma clearance is usually higher, but there is no clear evidence of a decrease in clearance in children with increasing age.
Indications for use
- small cell lung cancer;
- Ewing's sarcoma;
- Hodgkin's disease;
- Wilms tumor;
- Kaposi's sarcoma;
- multiple myeloma;
- acute leukemia;
- choriocarcinoma of the uterus;
- non-Hodgkin lymphomas;
- neuroblastoma;
- rhabdomyosarcoma.
Contraindications
Absolute:
- severe liver dysfunction;
- threatening intestinal obstruction, especially in children;
- neuromuscular disorders, including the demyelinating form of Charcot-Marie-Tooth syndrome;
- simultaneous radiation therapy involving the liver area;
- pregnancy and lactation;
- individual intolerance to the components of the drug.
Relative (Vincristine-Teva is prescribed under medical supervision):
- decreased liver function;
- acute infectious diseases;
- constipation;
- burdened history of neuropathy;
- oppression of bone marrow hematopoiesis;
- previous chemotherapy or radiotherapy;
- elderly age.
Vincristin-Teva, instructions for use: method and dosage
Vincristine-Teva solution is administered strictly intravenously (avoiding extravasation) at intervals of 7 days. The duration of the injection is about 1 minute. Intrathecal administration is prohibited.
The dose is determined individually, depending on the therapy regimen and the patient's clinical condition.
Recommended dosage regimen:
- adults: 1-1.4 mg / m 2, single dose - up to 2 mg / m 2. The total maximum dose is 10–12 mg / m 2;
- children: 1.5–2 mg / m 2, the initial dose in children weighing ≤ 10 kg is 0.05 mg / kg per week.
The course usually lasts 4-6 weeks.
With a decrease in hepatic function (in patients with a direct serum bilirubin concentration of ≥ 3 mg / dL), the dose of Vincristine-Teva is reduced by 2 times.
If signs of severe damage to the nervous system appear, especially with the development of paresis, vincristine should not be used. After discontinuation of Vincristine-Teva, neurological symptoms disappear, treatment can be resumed at a dose that is halved from the initial dose.
Side effects
Against the background of the use of Vincristine-Teva, the following adverse events can develop (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rarely):
- hepatobiliary system: primary hepatic vein thrombosis (especially in children);
- nervous system: often - peripheral sensorimotor neuropathy (in the form of paresthesia, loss of deep tendon reflexes, sagging feet, ataxia, muscle weakness, paralysis), diplopia, neuralgia (including pain in the pharynx, jaws, parotid glands, bones, muscles, back, male gonads), dysfunction of the cranial nerves (in the form of hoarseness, paresis of the vocal cords, ptosis, neuropathy of the optic nerve, etc.), nystagmus, transient cortical blindness, atrophy of the optic nerve; infrequently - convulsions with increased blood pressure, dizziness, depression, headache, increased drowsiness, hallucinations, hearing loss, sleep disturbances, psychosis, agitation, confusion;
- urinary system: infrequently - urinary retention (due to bladder atony), polyuria, dysuria, urate nephropathy, hyperuricemia; rarely - syndrome of inadequate secretion of antidiuretic hormone (manifests itself as hyponatremia in combination with a high level of sodium excretion in the urine, while there are no signs of renal and adrenal dysfunction, dehydration, hypotension, edema or azotemia);
- digestive system: often - abdominal pain, constipation; infrequently - nausea, diarrhea, vomiting, anorexia, paralytic intestinal obstruction (especially common in children), weight loss; rarely - perforation and / or necrosis of the small intestine, stomatitis;
- immune system: often - bronchospasm and acute respiratory failure, sometimes they are pronounced and life-threatening (the development of these disorders was noted when using vincristine in combination with mitomycin C); rarely - edema, anaphylactic shock, skin rash;
- cardiovascular system: infrequently - ischemic heart disease, myocardial infarction (in patients who have previously received radiotherapy in the mediastinal region, when using vincristine as part of combination therapy); rarely - a decrease or increase in blood pressure;
- reproductive system: very often - amenorrhea, azoospermia;
- hematopoietic system: often - transient thrombocytosis; infrequently - thrombocytopenia, anemia, leukopenia, pronounced inhibition of bone marrow function (most often vincristine does not have a significant effect on hematopoiesis);
- skin and skin appendages: very often - alopecia;
- local reactions: often - irritation at the injection site; infrequently (if the solution gets under the skin) - necrosis of the surrounding tissues, inflammation of the subcutaneous fat, pain, phlebitis;
- others: myalgia, fever, arthralgia.
The dose-limiting factor for Vincristine-Teva is neurotoxicity.
Overdose
The main symptoms of vincristine overdose are manifested in the form of increased adverse reactions.
Therapy: symptomatic, should include limiting fluid intake, therapy with drugs with a diuretic effect (in order to prevent antidiuretic hormone secretion syndrome), phenobarbital (to prevent the development of seizures), as well as the use of enemas and laxatives (prevention of intestinal obstruction). Monitoring of the cardiovascular system and hematological control is necessary.
Additionally, calcium folinate can be prescribed intravenously at a dose of 100 mg every 3 hours throughout the day, then every 6 hours for at least two days.
Hemodialysis is ineffective. The specific antidote is unknown.
special instructions
Treatment with Vincristine-Teva should be carried out under the supervision of a physician who has experience in cytotoxic therapy.
The solution is administered intravenously only. With the intrathecal route of administration, fatal neurotoxicity may develop.
In case of increased activity of liver enzymes, the dose of the drug is reduced.
During the period of application of Vincristine-Teva, regular hematological control should be carried out. When leukopenia is detected with the introduction of repeated doses, special care must be taken.
Periodically it is necessary to determine the serum concentration of sodium ions in the blood. For the correction of hyponatremia, the use of appropriate solutions is recommended.
With a burdened history of neuropathy, the patient's condition should be monitored. When signs of neurotoxicity appear, Vincristine-Teva is canceled.
In order to maintain regular bowel function, it is recommended to follow an appropriate diet, use enemas or take laxatives.
In case of extravasation, the administration of the solution must be stopped immediately. The remaining dose of Vincristine-Tev should be injected into another vein. The extravasation area can be pricked with a hyaluronidase solution.
Elderly patients Vincristine-Teva is prescribed with caution, since in this group of patients neurotoxicity may occur in a more pronounced form.
If the patient has any complaints of decreased vision or eye pain, a thorough ophthalmologic examination should be performed.
To prevent the development of urate nephropathy, regular monitoring of serum uric acid levels is required. If uric acid levels are elevated, it is recommended that uricosynthesis inhibitors and urine alkalinization be given.
Women and men should use reliable methods of contraception while using Vincristine-Teva and for at least three months after the end of therapy.
The diluted Vincristine-Teva solution is physically and chemically stable when stored at 2–8 ° C for 48 hours. It is recommended to use the diluted solution immediately; it can be stored for no longer than 24 hours, subject to the specified conditions.
When working with Vincristine-Teva solution, the rules for handling cytotoxic agents must be observed. Contact with the solution should be avoided. In case of contact with eyes, skin or mucous membranes, rinse thoroughly with plenty of water. If vincristine gets into the eyes, severe irritation and ulcerative lesions of the cornea may develop.
Influence on the ability to drive vehicles and complex mechanisms
Against the background of the use of Vincristine-Teva, neurotoxicity may develop, which must be taken into account when driving motor vehicles.
Application during pregnancy and lactation
Vincristine-Teva is not prescribed during pregnancy / lactation.
For violations of liver function
- severe hepatic dysfunction: Vincristine-Teva is contraindicated;
- reduced liver function: therapy should be performed with caution.
Use in the elderly
Vincristine-Teva should be used with caution in elderly patients.
Drug interactions
Vinca alkaloids are metabolized by the cytochrome P 450 isoenzyme - CYP3A4. Therefore, when combined with CYP3A4 inhibitors, including itraconazole, ritonavir, ketoconazole, nelfinavir, erythromycin, nefazodone, fluoxetine, an increase in the plasma concentration of vincristine in the blood is possible.
Do not mix Vincristine-Teva with other solutions in the same syringe.
Radiation therapy may increase the peripheral neurotoxicity of vincristine.
Due to the possible suppression of the function of the immune system associated with the use of Vincristine-Teva, the formation of antibodies in response to the vaccine may be reduced. If a live viral vaccine is administered during the treatment period, the production of antibodies may decrease, an intensification of the replication of the vaccine virus may be observed, and its side / adverse effects may increase.
Other possible interactions when combined with vincristine:
- itraconazole: neuromuscular disorders may develop faster and / or be more pronounced, which is probably associated with inhibition of vincristine metabolism;
- phenytoin: its content in the blood may decrease, which accordingly leads to a decrease in its anticonvulsant effect;
- other myelodepressive drugs and prednisolone: it is possible to increase the inhibition of bone marrow hematopoiesis;
- ototoxic and neurotoxic drugs (itraconazole, isoniazid, nifedipine): against the background of combined use with ototoxic and neurotoxic drugs, there may be an increase in adverse events from the hearing system and the nervous system, respectively;
- digoxin, ciprofloxacin: their effectiveness decreases;
- verapamil: the toxicity of vincristine increases;
- drugs with anti-gouty action: there may be a weakening of their action;
- uricosuric drugs: the likelihood of developing nephropathy increases;
- mitomycin C: combination therapy can lead to severe bronchospasm;
- L-asparaginase: when administered before Vincristine-Teva, the renal clearance of the latter may be impaired, so vincristine should be administered 12-24 hours prior to L-asparaginase administration.
Analogs
Vincristine-Teva analogs are Vincristine, Vero-Vincristine, Vincristine-Richter, Oncocristine, etc.
Terms and conditions of storage
Store in a place protected from light at a temperature of 2-8 ° C. Do not freeze. Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Vincristine-Teva
Reviews of Vincristine-Teva are few, they indicate that the drug has the claimed therapeutic effect.
Price for Vincristine-Teva in pharmacies
Approximate price for Vincristine-Teva: 2 ml of solution in a bottle - 215-280 rubles., 1 ml in a bottle - 146-212 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
