CYTOCRISTIN AQUEOUS 1MG/ML INJECTION

Indications

• Acute lymphoblastic leukemia (ALL)
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Wilms' tumor
• Neuroblastoma
• Kaposi's sarcoma
• Breast cancer
• Testicular cancer

Dosage

Adults: The recommended starting dose of vincristine for adult patients is typically 1.4 mg/m2 as an intravenous bolus, not to exceed 2 mg per dose. This may be adjusted based on clinical response and tolerability.

Mechanism of action

Vincristine inhibits mitosis at metaphase by binding to tubulin, preventing its polymerization into microtubules, which disrupts the mitotic spindle. This leads to metaphase arrest, as chromosomes fail to segregate properly during cell division. Additionally, vincristine may interfere with amino acid metabolism, cellular respiration, and nucleic acid and lipid biosynthesis.

Pharmacodynamics

As a vinca alkaloid, vincristine demonstrates cell cycle specificity, primarily impacting cells in the M phase. It has antitumor activity against a range of cancers, including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The drug's structural components, vindoline and catharanthine, contribute to its efficacy in cancer therapy, while its immunosuppressive properties may affect the immune response.

Pharmacokinetics

Vincristine is administered intravenously and is highly bound to plasma proteins. It undergoes hepatic metabolism, primarily by the cytochrome P450 system, and has a variable half-life. The drug's clearance can be affected by co-administered medications, such as rifampicin and certain asparaginases, which may alter its exposure and efficacy.

Contra-indications

• Hypersensitivity to vincristine or any of its components
• Active infections
• Severe bone marrow depression

Adverse effects

• Neurotoxicity, including peripheral neuropathy
• Constipation
• Alopecia
• Nausea and vomiting
• Myelosuppression
• Severe hypersensitivity reactions

Interactions

• Asparaginase: Unknown (increases risk of neurotoxicity)
• Crisantaspase: Unknown (increases risk of neurotoxicity)
• Mitotane: Unknown (decreases exposure)
• Pegaspargase: Unknown (increases risk of neurotoxicity)
• Rifampicin: Unknown (decreases exposure)
• St John's Wort: Unknown (decreases exposure)

Precautions

• Use caution in patients with hepatic impairment
• Monitor for signs of neurotoxicity
• Regularly assess blood counts due to myelosuppression risk
• Avoid use in patients with significant infections

Pregnancy

Safety in pregnancy has not been established, use only if clearly needed.

Breast-feeding

Use with caution, as it may be excreted in breast milk.

Storage

Store in a cool, dry place away from light. Protect from freezing.

Formulations

• Vincristine sulfate injection

Indications

• Acute lymphoblastic leukaemia (ALL)
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Wilms' tumor
• Neuroblastoma
• Breast cancer
• Lung cancer

Dosage

Children: For paediatric patients, the dosage is also based on body surface area, commonly starting at 1.5 mg/m

Adults: The dosage of vincristine sulfate in adults is typically determined by local protocols, often starting at 1.4 mg/m² of body surface area, administered intravenously, with a maximum dose not exceeding 2 mg per administration. Refer to local guidelines for specific dosing information.

Mechanism of action

Vincristine sulfate exerts its antineoplastic effect by binding to tubulin, inhibiting microtubule formation, which is essential for mitosis. This disruption of the mitotic spindle prevents proper cell division, leading to cell cycle arrest in the metaphase stage and ultimately triggering apoptosis in susceptible cancer cells.

Pharmacodynamics

The pharmacodynamics of vincristine involve its ability to alter the structure and function of the mitotic spindle. The drug shows a dose-dependent response, with efficacy correlated to the concentration of vincristine in the bloodstream. Importantly, its cytotoxic effects are more pronounced in rapidly dividing cells, such as those found in tumors.

Pharmacokinetics

Vincristine is characterized by a complex pharmacokinetic profile. After intravenous administration, it has a rapid distribution phase and a terminal elimination half-life of approximately 20 to 50 hours. The drug is extensively metabolized by the liver, with biliary excretion of metabolites. Renal clearance is minimal, which is important for patients with renal impairment. Caution is advised in patients with hepatic dysfunction, as this may lead to increased toxicity due to reduced clearance.

Contra-indications

• Intrathecal injection
• Severe neurotoxicity

Adverse effects

• Diarrhoea
• Dizziness
• Dyspnoea
• Headache
• Bronchospasm
• Hypertension
• Ileus
• Increased risk of infection
• Leucopenia
• Malaise
• Myalgia
• Myocardial infarction
• Nausea
• Nystagmus
• Oral blistering
• Neurotoxicity
• Sensory and motor neuropathies
• Raynaud's phenomenon
• Absent reflexes
• Respiratory disorders
• Seizure
• Abnormal sensation
• SIADH
• Skin reactions
• Stroke
• Thrombocytopenia
• Vertigo
• Vomiting

Precautions

• Caution in handling as it is an irritant to tissues
• Caution in patients with impaired hepatic or biliary function
• Monitoring for symptoms of neuropathy is advised

Pregnancy

Avoid use during pregnancy as it is teratogenic in animal studies and may cause fetal harm.

Breast-feeding

Discontinue breastfeeding during treatment.

Storage

Store below 25 degrees Celsius. Protect from light.

Formulations

• Vincristine sulfate 1 mg per 1 ml solution for injection
• Vincristine sulfate 2 mg per 2 ml solution for injection

Mechanism of action

The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca²⁺-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis. Vinca alkaloids are cell cycle specific agents ... /which/ block mitosis and produce metaphase arrest. Biological activities of these drugs can be explained by their ability to bind specifically tubulin, and to block ability of the protein to polymerize into microtubules ... through disruption of microtubules of mitotic apparatus, cell division is arrested in metaphase. In absence of intact mitotic spindle, chromosomes may disperse throughout cytoplasm ... or may occur in unusual groupings ... inability to segregate chromosomes correctly during mitosis presumably leads to cellular death. /Vinca alkaloids/ Although the mechanism of action has not been definitely established, vincristine appears to bind to or crystallize critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerization and causing metaphase arrest. In high concentrations, the drug also exerts complex effects on nucleic acid and protein synthesis. Vincristine exerts some immunosuppressive activity.

Pharmacodynamics

Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects <i>in vitro</i>. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.