Vinblastine Sulfate

Indications

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Breast cancer
• Lung cancer
• Neuroblastoma
• Kaposi's sarcoma

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to product literature or local protocols for dosage guidance.

Mechanism of action

Vinblastine sulfate exerts its antitumor effects by binding to tubulin, a protein that is critical for microtubule formation. This binding disrupts the assembly of microtubules, leading to cell cycle arrest in the metaphase stage of mitosis. This mechanism ultimately results in apoptosis of the cancer cells.

Pharmacodynamics

Vinblastine demonstrates dose-dependent cytotoxicity against rapidly dividing cells. Its action on the mitotic spindle prevents normal cell division, making it particularly effective in treating cancers characterized by high mitotic rates. Common side effects include bone marrow suppression, resulting in leukopenia, thrombocytopenia, and anemia, as well as gastrointestinal disturbances.

Pharmacokinetics

Vinblastine is administered intravenously and is widely distributed throughout the body. It is metabolized in the liver, primarily by the cytochrome P450 system, and has a half-life of approximately 24 hours. The drug is eliminated predominantly through biliary excretion. Its pharmacokinetics can be influenced by factors such as hepatic function and concurrent medications.

Contra-indications

• Hypersensitivity to vinblastine or any of its excipients
• Severe bone marrow depression
• Pregnancy

Adverse effects

• Alopecia
• Anaemia
• Appetite decrease
• Asthenia
• Colitis
• Constipation
• Diarrhoea
• Fever
• Gastrointestinal discomfort
• Hyperbilirubinaemia
• Hypersensitivity reactions
• Infection
• Leucopenia
• Malaise
• Mucositis
• Nausea
• Neutropenia
• Pancytopenia
• Sepsis
• Skin reactions
• Thrombocytopenia
• Very rare: Angioedema, interstitial lung disease

Interactions

• Caution with other myelosuppressive agents
• Avoid using with live vaccines due to immunosuppression
• Careful monitoring required when used with CYP3A4 inhibitors or inducers

Precautions

• Monitor blood counts regularly
• Use with caution in patients with liver impairment
• Ensure adequate hydration to prevent constipation
• Avoid exposure to infections due to immunosuppression

Pregnancy

Vinblastine is contraindicated in pregnancy. It may cause fetal harm.

Breast-feeding

It is not known if vinblastine is excreted in human milk. Caution is advised.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Vinblastine sulfate powder for solution for injection
• Vinblastine sulfate solution for infusion

Mechanism of action

The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Although the mechanism of action has not been definitely established, vinblastine 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, vinblastine also exerts complex effects on nucleic acid and protein synthesis. Vinblastine reportedly also interferes with amino acid metabolism by blocking cellular utilization of glutamic acid and thus inhibits purine synthesis, the citric acid cycle, and the formation of urea. Vinblastine exerts some immunosuppressive activity. Experimental data indicate that the action of vinblastine sulfate is different from that of other recognized antineoplastic agents. Tissue-culture studies suggest an interference with metabolic pathways of amino acids leading from glutamic acid to the citric acid cycle and to urea. In vivo experiments tend to confirm the in vitro results. A number of in vitro and in vivo studies have demonstrated that vinblastine sulfate produces a stathmokinetic effect and various atypical mitotic figures. ... Studies indicate that vinblastine sulfate has an effect on cell-energy production required for mitosis and interferes with nucleic acid synthesis. The mechanism of action of vinblastine sulfate has been related to the inhibition of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Reversal of the antitumor effect of vinblastine sulfate by glutamic acid or tryptophan has been observed. In addition, glutamic acid and aspartic acid have protected mice from lethal doses of vinblastine sulfate. Aspartic acid was relatively ineffective in reversing the antitumor effect.

Pharmacodynamics

Vinblastine is a vinca alkaloid antineoplastic agent. 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 (<i>Catharanthus roseus</i>) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects <i>in vitro</i>. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.