You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search
A - Drug Name

vinBLAStine

SYNONYM(S):   VBL; Vincaleukoblastine; VLB

COMMON TRADE NAME(S):   Velban® (multiple brands available)

 
B - Mechanism of Action and Pharmacokinetics

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 in vitro. Similar to other vinca alkaloids, vinblastine binds to the microtubular proteins of the mitotic spindle, leading to depolymerization of the microtubule and mitotic arrest at metaphase or cell death. Vinblastine has some immunosuppressant effects. The vinca alkaloids are considered to be cell cycle phase-specific (M and S phases).



Absorption
Oral absorption is erratic.
Distribution

Rapid and extensive binding to tissues and to formed elements of peripheral blood.  Distributes to the liver.

PPB 99%
Cross blood brain barrier? poorly
Metabolism

Extensively metabolized in liver via CYP3A subfamilies, including CYP3A4. Inhibits CYP3A4 and 2D6.

Active metabolites Desacetylvinblastine
Inactive metabolites Yes
Elimination

Slowly excreted in urine and feces (via bile).

Urine < 1% unchanged
Feces 95%
Half-life 25 hours (terminal)
 
C - Indications and Status
Health Canada Approvals:

  • Frequently responsive:
    • Hodgkin's disease
    • Lymphocytic lymphoma
    • Histolytic lymphoma
    • Mycosis fungoides
    • Testicular cancer
    • Kaposi's sarcoma
    • Letterer-Siwe disease (histiocytosis-X)
  • Less frequently responsive:
    • Choriocarcinoma resistant to other chemotherapy
    • Breast cancer (unresponsive to endocrine surgery and hormonal therapy)


Other Uses:

  • Bladder cancer
  • Non-small cell lung cancer
  • Desmoid tumour
  • CNS cancer 
 
D - Adverse Effects

Emetogenic Potential:  

Minimal

Extravasation Potential:   Vesicant

ORGAN SITE SIDE EFFECT* (%) ONSET**
Auditory Hearing impaired (rare) E
Cardiovascular Arterial thromboembolism E
ECG changes (transient; rare) E
Hypertension (<10%) I  E
Dermatological Alopecia (>10%) E
Photosensitivity (<10%) E
Rash (<10%) E
Gastrointestinal Abdominal pain (>10%) E
Anorexia (>10%) E
Constipation (>10%) E
Diarrhea (<10%) E
Mucositis (>10%) E
Nausea, vomiting (>10%) I
General Fatigue (<10%) E
Pain (tumour pain) I
Hematological Immunosuppression E
Myelosuppression ± infection, bleeding (>10%) E
Hypersensitivity Hypersensitivity (rare) I
Injection site Phlebitis I  E
Metabolic / Endocrine Hyperuricemia (during periods of active cell lysis) I
SIADH (<1%) E
Musculoskeletal Musculoskeletal pain (<10%, including jaw pain, may be severe) E
Nervous System Depression (<10%) E
Dysgeusia (>10%) E
Headache (<10%) E
Neuropathy E
Seizure (<10%) E
Reproductive and breast disorders Infertility L
Respiratory Bronchospasm (or shortness of breath, especially in combination with mitomycin; <10%) I
Pneumonitis (rare) E
Vascular Peripheral ischemia (<10%) D


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

Myelosuppression and neurotoxicity are the main dose-limiting effects of vinblastine.

Hyperuricemia during periods of active cell lysis, which is caused by cytotoxic chemotherapy of highly proliferative tumours of massive burden (e.g. some leukemias and lymphomas), can be minimized with allopurinol and hydration.  In hospitalized patients the urine may be alkalinized, by addition of sodium bicarbonate to the IV fluids, if tumour lysis is expected.

Neurotoxicity with the vinca alkaloids is qualitatively similar but quantitatively different (vincristine> vinblastine>vinorelbine). Symptoms tend to be worse with prolonged exposure. Neurotoxicity may be manifested as numbness, paresthesia, mental depression, loss of deep tendon reflex, headache, malaise, dizziness, seizures or psychosis. Cranial nerve neuropathy may lead to vocal cord paresis or paralysis, oculomotor nerve dysfunction and bilateral facial nerve palsies.

Cranial nerve toxicities tend to be bilateral and reversible when treatment with vinblastine is discontinued.

Severe jaw pain or parotid gland pain can occur within a few hours of the first dose of vinblastine. This is not an indication to stop or modify the dose; treat with analgesics. Autonomic neuropathy is manifested as constipation, abdominal pain, urinary retention and paralytic ileus. These gastrointestinal symptoms are seen especially when high doses are used (e.g. >20 mg) and are rare with doses <10 mg.

Toxicity and hematologic toxicity may be more severe in patients with severe cachexia, skin ulcers or marrow infiltration.

 
E - Dosing

Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of white blood cell count. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxic/radiation therapy. Do not re-treat with vinblastine until marrow recovery has occurred.

 



Adults:

Intravenous: 6 mg/m² Every 1 week
(range 3.7-18.5 mg/m2; usual weekly dose: 5.5 – 7.4 mg/m2; maximum weekly dose: 18.5 mg/m2)
Intravenous: 6 mg/m² Every 2 weeks (ABVD)

Intravenous: 4 mg/m² days 1 and 8 Every 3 weeks (CMV)

Intravenous: 0.11 mg/kg days 1 and 2 Every 3 weeks (VIP)

Intravenous: 3 mg/m² days 2, 15, 22 Every 4 weeks (MVAC)

Dosage with Toxicity:

Dosage with toxicity:

  • Modify according to protocol by which patient is being treated; if no guidelines available, refer to Appendix 6 "Dosage Modification for Hematologic and Non-Hematologic Toxicities."

Suggested:

Worst Toxicity / Counts in Previous Cycle (x 109/L)
Dose (% previous dose)*

Febrile neutropenia, grade 4 ANC for ≥ 5-7 days or thrombocytopenic bleeding

Grade 3  related organ / non-hematologic
Hold, then 75%*

Grade 4  related organ / non-hematologic

Discontinue

*Do not retreat until ANC ≥ 1-1.5 x 109L, platelets ≥ 100 x 109L and toxicity ≤ grade 2



Dosage with Hepatic Impairment:

Bilirubin %  Usual dose
1 - 2.5 x ULN 50%
> 2.5 x ULN 25%


Dosage with Renal Impairment:

No adjustment required.

Dosage in the elderly:

Toxicity may be increased; used with caution.

Children:

Refer to protocol being used.

 



 
F - Administration Guidelines

FOR INTRAVENOUS USE ONLY.
Intrathecal administration of other vinca alkaloids has resulted in death. Syringes containing this product should be labelled
WARNING – FOR INTRAVENOUS USE ONLY.  FATAL if given intrathecally.

  • Quick push through sidearm of free flowing IV (5% Dextrose or Normal Saline); Inject over 1 minute. Do not admix with solutions that can change pH (e.g. lactate containing solutions).
  • May mix in 50 mL minibag (NS or D5W); infusions over ≥30-60 minutes are not recommended.
  • If any signs or symptoms of extravasation occur, the injection or infusion should be immediately terminated and restarted in another vein. Any known or suspected extravasation should be managed promptly.


 
G - Special Precautions
Other:

Vinblastine is contraindicated in patients who have hypersensitivity to vinblastine or its formulation and in patients with severe myelosuppression or infection. Intrathecal vinblastine administration is absolutely contraindicated.

Myelosuppressive effects are more marked in patients with bone marrow infiltration and in elderly/cachectic patients. Use with caution in patients with ischemic heart disease and in combination with neurotoxic drugs.  Do not give vinblastine more frequently than once every 7 days.

Standard doses of vinblastine given for prolonged periods (e.g. daily for 7 days) may result in permanent or fatal neurologic toxicity and should not be used.

Vinblastine is teratogenic, embryotoxic, potentially mutagenic and carcinogenic; therefore, it is contraindicated in pregnancy. Adequate contraception should be used by both sexes during vinblastine treatment and for at least 6 months after the last dose. Vinblastine affects fertility in humans, which may be reversible in some cases. Breast feeding is not recommended due to the potential secretion into breast milk.

 

 

 

 
H - Interactions

 

 

AGENT EFFECT MECHANISM MANAGEMENT
Mitomycin Acute bronchospasm has occurred minutes to hours after administration. Reaction may occur up to 2 weeks after mitomycin. Unknown Caution
Phenytoin ↓ serum concentration of phenytoin Possibly ↓ absorption or increased metabolism of phenytoin Monitor serum levels of phenytoin and adjust dose prn
CYP3A4 inhibitors (i.e. ketoconazole, voriconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges, starfruit or pomegranate ) ↑ risk of neurotoxicity inhibits CYP3A4 and interferes with metabolism of vinblastine Avoid concomitant use
CYP3A4 substrates (i.e., aprepitant, tolterodine) ↑ toxicity ↓ metabolism (vinblastine a a potent CYP3A4 inhibitor) Avoid if possible. If must use, monitor or adjust dose.
CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc) ↓ vinblastine effect ↑ metabolism (CYP3A4) Caution
Bleomycin +/- cisplatin Raynaud's phenomenon, MI, CVA reported Unknown Caution
Ototoxic drugs (i.e., cisplatin, aminoglycosides) ↑ ototoxicity (reported with other vinca alkaloids) Additive Caution
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type Monitor Frequency
CBC Baseline and regular
Liver function tests Baseline and regular

Clinical assessment for neurotoxicity, infection, bleeding, local toxicity.

At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version



 
K - References

CPhA Monograph:  Vinblastine.  Compendium of Pharmaceuticals and Specialties, March 2009.

Johnson IS, Armstrong JG, Gorman M, et al.  The vinca alkaloids:  a new class of oncolytic agents. Cancer Research 1963;23:1390-427.

McEvoy GK, editor. AHFS Drug Information 2011. Bethesda: American Society of Health-System Pharmacists, p. 1263-5.

Prescribing information:  Vinblastine. Bedford Laboratories (US)., December 2001.

Product Monograph: Vinblastine. Hospira Corporation, June 18, 2007.

Scripture CD, Figg WD. Drug interactions in cancer therapy. Nature Reviews Cancer 2006;6:546-58.

Vinblastine:  BC Cancer Agency Cancer Drug Manual.  March 2008.

Zidan J, Robenstein W, Abzah A, et al. Treatment of Kaposi's Sarcoma with Vinblastine in Patients with Disseminated Dermal Disease. IMAJ 2001;3:251-3.

 


October 2017 edited indications

 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.