Usage
Vinblastine is prescribed for the treatment of various cancers, including:
- Hodgkin’s disease
- Non-Hodgkin’s lymphoma (including histiocytic lymphoma and lymphocytic lymphoma)
- Breast cancer
- Methotrexate-resistant choriocarcinoma
- Renal cell carcinoma
- Testicular cancer (including teratoma and seminoma)
- Kaposi’s sarcoma
- Mycosis fungoides (advanced stages)
- Langerhans cell histiocytosis (Letterer-Siwe disease)
Pharmacological Classification: Vinblastine is classified as an antineoplastic agent, specifically a vinca alkaloid.
Mechanism of Action: Vinblastine inhibits microtubule formation by binding to tubulin, thereby disrupting cell division at the metaphase stage. This primarily affects rapidly dividing cells, such as cancer cells.
Alternate Names
- Generic Name: Vinblastine Sulfate
- Brand Names: Velban, DBL Vinblastine Injection, VinBLAStine
How It Works
Pharmacodynamics: Vinblastine’s primary effect is to block cell division by disrupting microtubule polymerization. This leads to metaphase arrest and ultimately cell death, particularly in rapidly dividing cells.
Pharmacokinetics:
- Absorption: Vinblastine is administered intravenously, therefore absorption is not a relevant factor.
- Metabolism: Primarily metabolized in the liver by the CYP3A4 enzyme system.
- Elimination: Excreted slowly in urine and feces via biliary excretion. Vinblastine has a long half-life, making breastfeeding generally contraindicated.
Mode of Action: Vinblastine binds to tubulin dimers, preventing their assembly into microtubules which are essential for cell division (mitosis). This results in mitotic arrest at metaphase, leading to cell death.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Vinblastine directly targets tubulin, a structural protein, rather than a receptor, enzyme, or neurotransmitter. It does, however, have a potent inhibitory effect on the CYP3A4 enzyme system which may impact the metabolism of co-administered drugs.
Elimination Pathways: Primarily hepatic metabolism followed by biliary excretion into the feces. Some renal excretion also occurs.
Dosage
Standard Dosage
Adults:
Initial dose: 3.7 mg/m² intravenously once weekly. Subsequent doses may be increased incrementally by 1.8 mg/m² weekly, based on the patient’s white blood cell count, with a maximum dose of 18.5 mg/m² weekly. Most adult patients receive a dose between 5.5 to 7.4 mg/m² weekly.
Children:
Initial dose: 2.5 mg/m² intravenously once weekly. Dosage may be incrementally increased by approximately 1.25 mg/m² weekly, based on tolerance and white blood cell count, not to exceed 12.5 mg/m² weekly.
Special Cases:
- Elderly Patients: Use with caution due to potential for increased toxicity. Close monitoring is recommended.
- Patients with Renal Impairment: No dose adjustment is typically necessary.
- Patients with Hepatic Dysfunction: Dosage reduction may be required depending on the degree of impairment. For bilirubin >1 to 2.5 times the upper limit of normal (ULN), use 50% of the usual dose. For bilirubin >2.5 times ULN, use 25% of the usual dose.
- Patients with Comorbid Conditions: Caution should be used in patients with pre-existing bone marrow suppression, infections, or ischemic heart disease.
Clinical Use Cases
Vinblastine’s dosage is determined based on the specific cancer being treated, typically as part of a combination chemotherapy regimen. Specific dosages for use in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations are not relevant as its usage is primarily within oncology protocols.
Dosage Adjustments
Dose modifications may be required based on hematologic toxicity (e.g., neutropenia, thrombocytopenia) or other adverse effects.
Side Effects
Common Side Effects
- Nausea and vomiting
- Constipation
- Hair loss (alopecia)
- Fatigue
- Loss of appetite
- Headache
- Jaw pain
- Peripheral neuropathy (numbness or tingling in hands and feet)
Rare but Serious Side Effects
- Myelosuppression (decreased production of blood cells leading to anemia, increased risk of infection, and bleeding)
- Severe allergic reactions
- Neurotoxicity (including autonomic neuropathy, cranial nerve palsies)
- Pulmonary toxicity
- Ileus
Long-Term Effects
- Secondary malignancies (e.g., leukemia)
- Infertility
Adverse Drug Reactions (ADR)
- Severe hypersensitivity reactions
- Febrile neutropenia
- Extravasation injury (tissue damage at the injection site)
Contraindications
- Hypersensitivity to vinblastine
- Severe myelosuppression
- Active bacterial infections
- Pregnancy
- Intrathecal administration
Drug Interactions
Vinblastine is metabolized by CYP3A4 and can interact with drugs that inhibit or induce this enzyme, leading to either increased toxicity (inhibitors) or reduced efficacy (inducers). Examples include:
- CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir)
- CYP3A4 inducers (carbamazepine, phenytoin, rifampin)
Other significant interactions include those with:
- Mitomycin (increased risk of bronchospasm)
- Phenytoin (decreased phenytoin levels)
- Myelosuppressive agents (additive bone marrow suppression)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (FDA) – positive evidence of human fetal risk, but potential benefits may warrant use in pregnant women despite potential risks.
- Fetal Risks: Vinblastine is teratogenic and can cause birth defects.
- Breastfeeding: Contraindicated due to the potential for serious adverse reactions in infants and vinblastine’s long half-life.
Drug Profile Summary
- Mechanism of Action: Inhibits microtubule polymerization, disrupting cell division.
- Side Effects: Myelosuppression, neurotoxicity, nausea, vomiting, hair loss, constipation.
- Contraindications: Hypersensitivity, severe myelosuppression, active infections, pregnancy, intrathecal administration.
- Drug Interactions: CYP3A4 inhibitors/inducers, mitomycin, phenytoin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adult: 3.7-18.5 mg/m² IV weekly; Pediatric: 2.5-12.5 mg/m² IV weekly.
- Monitoring Parameters: Complete blood count, liver function tests, neurological assessment.
Popular Combinations
Vinblastine is commonly used in combination chemotherapy regimens, such as:
- ABVD: Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine (for Hodgkin’s lymphoma).
- BEACOPP: Bleomycin, Etoposide, Adriamycin (doxorubicin), Cyclophosphamide, Vincristine, Procarbazine, Prednisone (for Hodgkin’s lymphoma).
- Stanford V: Doxorubicin, Vinblastine, Mechlorethamine, Vincristine, Bleomycin, Etoposide, Prednisone (for Hodgkin’s lymphoma).
Precautions
- General Precautions: Careful monitoring of blood counts, hepatic function, and neurological status. Avoid extravasation during administration.
- Specific Populations: Avoid use in pregnant or breastfeeding women. Use with caution in elderly patients and those with hepatic dysfunction.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Vinblastine?
A: Adults: Initial dose 3.7 mg/m² IV weekly, increasing as tolerated up to 18.5 mg/m² weekly. Children: Initial dose 2.5 mg/m² IV weekly, increasing as tolerated up to 12.5 mg/m² weekly.
Q2: What are the most serious side effects of Vinblastine?
A: Myelosuppression, neurotoxicity, severe allergic reactions.
Q3: Can Vinblastine be administered intrathecally?
A: No, intrathecal administration is contraindicated and can be fatal.
Q4: How should Vinblastine be administered?
A: As a slow intravenous push or short infusion.
Q5: What are the main drug interactions with Vinblastine?
A: CYP3A4 inhibitors/inducers, myelosuppressive agents, mitomycin, phenytoin.
Q6: Can Vinblastine be used during pregnancy or breastfeeding?
A: No, Vinblastine is contraindicated in both pregnancy and breastfeeding.
Q7: How is Vinblastine eliminated from the body?
A: Primarily hepatic metabolism followed by biliary excretion and some renal excretion.
Q8: What is the mechanism of action of Vinblastine?
A: Inhibits microtubule polymerization, leading to mitotic arrest and cell death.
Q9: What should be monitored during Vinblastine treatment?
A: Complete blood count, liver function tests, and neurological status.
Q10: What are the common cancers treated with Vinblastine?
A: Hodgkin’s disease, non-Hodgkin’s lymphoma, testicular cancer, breast cancer, Kaposi’s sarcoma.
