Vincristine-Teva (Solution) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Pharmachemie, B.V. (Netherlands)

ATC Code

L01CA02 (Vincristine)

Active Substance

Vincristine (Rec.INN registered by WHO)

Dosage Forms

	Vincristine-Teva	Solution for intravenous administration 1 mg/1 ml: 1 vial.
		Solution for intravenous administration 2 mg/2 ml: 1 vial.
		Solution for intravenous administration 5 mg/5 ml: 1 vial.

Dosage Form, Packaging, and Composition

Solution for intravenous administration clear, from colorless to pale yellow.

Excipients: mannitol, sodium hydroxide, sulfuric acid, water for injections.

1 ml – vials (1) – cardboard packs.

Solution for intravenous administration clear, from colorless to pale yellow.

Excipients: mannitol, sodium hydroxide, sulfuric acid, water for injections.

2 ml – vials (1) – cardboard packs.

Solution for intravenous administration clear, from colorless to pale yellow.

Excipients: mannitol, sodium hydroxide, sulfuric acid, water for injections.

5 ml – vials (1) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agents; plant alkaloids and other natural substances; vinca alkaloids and their analogues

Pharmacological Action

Antineoplastic agent of plant origin.

Vincristine is an alkaloid from the Madagascar periwinkle, belonging to cytostatic chemotherapeutic agents. Vincristine binds to the protein tubulin and leads to disruption of the cell microtubular apparatus and rupture of the mitotic spindle. It suppresses mitosis in the metaphase. It also inhibits glutamate metabolism and possible nucleic acid synthesis, and has an immunosuppressive effect.

Pharmacokinetics

After intravenous administration, Vincristine is rapidly eliminated from the blood. About 90% of the drug binds to plasma proteins. Vincristine is metabolized in the liver and excreted mainly in the bile; 70-80% of the drug is found in the feces unchanged and as metabolites, 10-20% of the drug is determined in the urine. The initial, mean, and terminal half-lives are 5 min, 2.3 h, and 85 h, respectively. The terminal half-life can range from 19 to 155 h. Vincristine poorly penetrates the blood-brain barrier.

Indications

• Acute leukemias;
• Hodgkin’s and non-Hodgkin’s lymphomas;
• Wilms’ tumor;
• Rhabdomyosarcoma;
• Neuroblastoma;
• Myeloma;
• Kaposi’s sarcoma;
• Bone and soft tissue sarcomas;
• Small cell lung cancer;
• Uterine choriocarcinoma;
• Brain tumors.

Vincristine is also used for idiopathic thrombocytopenic purpura (in case of resistance to corticosteroid drugs and ineffectiveness of splenectomy).

ICD codes

Dosage Regimen

Intrathecal administration of vincristine is prohibited.

Vincristine is administered strictly intravenously at intervals of 1 week. The injection duration should be approximately 1 minute.

Before administration, the contents of the vial are diluted in the supplied solvent with the addition of the required amount of 0.9% sodium chloride solution to obtain a concentration of 0.1 mg/ml.

Caution must be exercised during administration to avoid extravasation.

The dose is selected individually. The average dose for adults is 1.4 mg/m² of body surface area, a single dose should not exceed 2 mg; for children – 1.5-2 mg/m² of body surface area. For children weighing less than 10 kg, the initial dose should be 0.05 mg/kg per week.

In patients with impaired liver function and plasma bilirubin concentration above 51.3 µmol/L, a 50% dose reduction is recommended.

Adverse Reactions

From the central and peripheral nervous system: seizures with increased blood pressure, paresthesia, neuralgia, neuropathy, jaw pain, decreased muscle strength, loss of tendon reflexes, ataxia, headache, depression, hallucinations, sleep disorders, diplopia, ptosis, transient blindness and optic nerve atrophy. Neurotoxicity is a dose-limiting factor.

From the digestive system: nausea, vomiting, stomatitis, constipation, paralytic ileus (especially common in children), abdominal pain, small intestine necrosis and/or perforation, diarrhea.

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

From the cardiovascular system: increase or decrease in blood pressure. In patients with previously irradiated mediastinum receiving polychemotherapy including vincristine, angina pectoris and myocardial infarction may occur.

From the respiratory system: acute dyspnea and severe bronchospasm were observed when vincristine was used with mitomycin C.

From the endocrine system: a syndrome due to impaired secretion of antidiuretic hormone is rarely observed, which is characterized by high sodium excretion in the urine and causes hyponatremia. In this case, there are no signs of kidney and adrenal damage, arterial hypotension, dehydration, azotemia and edema.

From the hematopoietic system: does not have a significant effect on hematopoiesis. However, moderate leukopenia, thrombocytopenia and anemia may be observed.

Local reactions: if the drug gets under the skin, cellulitis, phlebitis, and even necrosis may develop.

Other: alopecia, rash, amenorrhea, azoospermia.

Contraindications

• Neurodystrophic diseases (for example, the demyelinating form of Charcot-Marie-Tooth syndrome);
• Pregnancy;
• Lactation period;
• Hypersensitivity to vinca alkaloids.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

In patients with plasma bilirubin concentration above 51.3 µmol/L, a 50% dose reduction is recommended.

Use in Renal Impairment

In patients with impaired liver function a 50% dose reduction is recommended.

Pediatric Use

The dose is selected individually. The average dose for children – is 1.5-2 mg/m² of body surface area. For children weighing less than 10 kg, the initial dose should be 0.05 mg/kg per week.

Special Precautions

Intrathecal administration of vincristine can lead to death.

During treatment, regular hematological monitoring should be carried out. In case of leukopenia development with repeated doses, special caution should be exercised.

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

With an increase in liver test levels, the dose of vincristine should be reduced.

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

Patients with a history of neuropathy require special monitoring.

Vincristine should be prescribed with caution to elderly patients, as neurotoxicity may be more pronounced in them.

Any complaints of eye pain or decreased vision require a thorough ophthalmological examination.

Avoid getting the vincristine solution into the eyes. If this happens, the eyes should be immediately and thoroughly rinsed with plenty of fluid.

Effect on ability to drive vehicles and operate machinery

The neurotoxicity of Vincristine may adversely affect the ability to drive a vehicle.

Overdose

In case of accidental overdose, an increase in the side effects of Vincristine should be expected. A specific antidote is not known.

Treatment is symptomatic and should include fluid restriction, administration of diuretics (to prevent complications associated with the development of the syndrome of inappropriate antidiuretic hormone secretion), use of phenobarbital (to prevent seizures), use of laxatives (to prevent intestinal obstruction). It is also necessary to monitor the activity of the cardiovascular system and carry out hematological control. Hemodialysis is not effective.

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

Drug Interactions

Vincristine may reduce the anticonvulsant effect of phenytoin.

When used concomitantly with neurotoxic drugs (isoniazid, itraconazole, nifedipine), an increase in side effects from the nervous system is observed.

When used concomitantly, Vincristine weakens the effect of antigout drugs. When used concomitantly with drugs that increase the level of uric acid in the blood serum, the risk of nephropathy increases.

When prescribed in combination with mitomycin C, Vincristine may cause severe bronchospasm.

If it is necessary to use the drug in combination with L-asparaginase, Vincristine should be administered 12-24 hours before the administration of L-asparaginase. Administration of asparaginase before vincristine administration may impair its excretion from the liver.

Concomitant use of vincristine with other myelodepressive drugs and prednisolone may enhance the suppression of bone marrow hematopoiesis.

Storage Conditions

Store the solution at a temperature of 2-8°C (17.6°F) in a place inaccessible to children; shelf life – 2 years.

Store the lyophilized powder at a temperature of 2-8°C (17.6°F) in a place inaccessible to children; shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.