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vinBLAStine
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. It also has complex effects on nucleic acid and protein synthesis in high concentrations. Vinblastine has some immunosuppressant effects. The vinca alkaloids are considered to be cell cycle phase-specific (M and S phases).
Rapid and extensive binding to tissues and to formed elements of peripheral blood. Distributes to the liver.
PPB | 99% |
Cross blood brain barrier? | poorly |
Extensively metabolized in the liver
Active metabolites |
Yes |
Inactive metabolites | Yes |
Slowly excreted in urine and feces (via bile).
Urine | < 1% unchanged |
Feces | 95% |
Half-life | 25 hours (terminal) |
- Frequently responsive:
- Hodgkin 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
Emetogenic Potential:
Extravasation Potential: Vesicant
The incidences for the adverse effects are based on product monographs where available. Adverse events from other trial data or severe / post-marketing events may also be included.
ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
---|---|---|---|---|---|
Auditory | Hearing impaired (rare) | E | |||
Cardiovascular | Arterial thromboembolism (in combination with cisplatin and bleomycin) | E | |||
ECG changes (transient; rare) | E | ||||
Hypertension (≤10%) | I E | ||||
Dermatological | Alopecia (>10%) (usually incomplete; re-growth in some cases while on treatment) | E | |||
Photosensitivity (≤10%) | E | ||||
Rash (≤10%) | E | ||||
Gastrointestinal | Abdominal pain (>10%) | E | |||
Anorexia (>10%) | E | ||||
Constipation (>10%) (may be severe) | E | ||||
Diarrhea (≤10%) | E | ||||
Mucositis (>10%) | E | ||||
Nausea, vomiting (>10%) | I | ||||
General | Fatigue (≤10%) | E | |||
Pain (in tumour-containing tissue, rare) | I | ||||
Hematological | Immunosuppression | E | |||
Myelosuppression ± infection, bleeding (>10%) | E | ||||
Hypersensitivity | Hypersensitivity (rare) | I | |||
Injection site | Phlebitis (≤10%) | I E | |||
Metabolic / Endocrine | Hyperuricemia (≤10%) (during periods of active cell lysis) | I | |||
SIADH (rare) | E | ||||
Musculoskeletal | Musculoskeletal pain (≤10%) (including jaw pain, may be severe) | E | |||
Nervous System | Depression (≤10%) | E | |||
Dysgeusia (>10%) | E | ||||
Headache (≤10%) | E | ||||
Paresthesia (20%) (autonomic, loss of deep tendon reflex, cranial neuropathy - rare) | E | ||||
Seizure (≤10%) | E | ||||
Respiratory | Bronchospasm / pneumonitis (or shortness of breath, especially in combination with mitomycin; ≤10%) | I | |||
Vascular | Peripheral ischemia (≤10%) (Raynauds; in combination with cisplatin and bleomycin) | 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.
** 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 manifest 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, hearing impairment and facial nerve palsies. Vocal cord effects or facial nerve palsies tend to be bilateral and reversible when treatment with vinblastine is discontinued. High doses (> 20 mg) may be associated with autonomic neuropathy, which manifests as constipation, abdominal pain, urinary retention and paralytic ileus.
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.
Refer to protocol by which patient is being treated.
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.
(range 3.7-18.5 mg/m2; usual weekly dose: 5.5 – 7.4 mg/m2; maximum weekly dose: 18.5 mg/m2)
Modify according to protocol by which patient is being treated.
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
Bilirubin | % Usual dose |
>1 - 2.5 x ULN | 50% |
> 2.5 x ULN | 25% |
No adjustment required.
Toxicity may be increased; used with caution.
Refer to protocol being used.
FOR INTRAVENOUS USE ONLY.
Intrathecal administration of other vinca alkaloids has resulted in death. Containers with this product should be labelled:
“WARNING – FOR INTRAVENOUS USE ONLY. FATAL if given intrathecally.”
- Direct IV push is not recommended to reduce the risk of inadvertently administering vinca alkaloids via intrathecal route.
- Mix in 50 mL minibag (NS or D5W).
- Dilutions in large volumes (≥ 100mL) and infusions over ≥30-60 minutes are not recommended, since these can increase the risk of vein irritation and extravasation.
- 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 according to local guidelines.
- Store unopened vials at 2 to 8ºC; protect from light.
- Patients who have hypersensitivity to vinblastine or its formulation
- Patients with severe myelosuppression or infection
- Intrathecal vinblastine administration is absolutely contraindicated.
- Myelosuppressive effects are more marked in patients with bone marrow infiltration, cachexia or skin ulcers
- Use with caution in hepatic impairment due to an increased risk of neurotoxicity.
- 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.
Other Drug Properties:
-
Carcinogenicity:
Yes
-
Mutagenicity:
Yes
-
Embryotoxicity:
Yes
-
Teratogenicity:
Yes
Vinblastine 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 (general recommendation).
-
Breastfeeding:
Breast feeding is not recommended due to the potential secretion of vinblastine into breast milk.
-
Fertility effects:
Yes
Aspermia and amenorrhea have been reported. Recovery of menses is variable.
Vinblastine is metabolized by CYP3A4 and is a potent CYP3A4 inhibitor.
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; discontinue vinblastine if this occurs |
Phenytoin | ↓ serum concentration of phenytoin | Possibly ↓ absorption or increased metabolism of phenytoin | Monitor serum levels of phenytoin and adjust dose as needed |
CYP3A4 inhibitors (i.e. ketoconazole, voriconazole, clarithromycin, erythromycin, ritonavir, fruit or juice from grapefruit, Seville oranges, starfruit or pomegranate ) | ↑ risk of neurotoxicity | inhibition of vinblastine metabolism | Avoid concomitant use |
CYP3A4 substrates (i.e., aprepitant, tolterodine) | ↑ toxicity of CYP3A4 substrates | ↓ metabolism of CYP3A4 substrates | 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 of vinblastine | Caution |
Bleomycin +/- cisplatin | Raynaud's phenomenon, nephrotoxicity, neurotoxicity, MI, CVA reported | Unknown | Caution |
Ototoxic drugs (i.e., cisplatin, aminoglycosides) | ↑ ototoxicity (reported with other vinca alkaloids) | Additive | Caution |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Monitor Type | Monitor Frequency |
---|---|
CBC |
Baseline and before each dose |
Liver function tests |
Baseline and before each cycle |
Clinical assessment for neurotoxicity, infection, bleeding, GI, local toxicity (i.e. extravasation), hypersensitivity, hyperuricemia |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Vinblastine sulfate: ASHP's Interactive Handbook on Injectable Drugs. Accessed April 16, 2020.
Bouffet E, Jakacki R, Goldman S, et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 2012; 30(12):1358-63.
CPhA Monograph: Vinblastine. Canadian Pharmacists Association, October 2017.
ISMP 2018-2019 Targeted Medication Safety Best Practices for Hospitals. (From http://www.ismp.org/tools/bestpractices)
Johnson IS, Armstrong JG, Gorman M, et al. The vinca alkaloids: a new class of oncolytic agents. Cancer Research 1963;23:1390-427.
Lafay-Cousin L, Holm S, Qaddoumi I, et al. Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction. Cancer 2005;103:2636-42.
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. Pfizer Canada, April 2019.
Scripture CD, Figg WD. Drug interactions in cancer therapy. Nature Reviews Cancer 2006;6:546-58.
Summary of Product Characteristics: Vinblastine. Hospira UK Ltd., October 2018.
Vinblastine: BC Cancer Agency Cancer Drug Manual, February 2015.
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.
April 2020 Updated adverse effects, dosing, warnings/precautions, administration, interactions and monitoring sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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