vinBLAStine (Monograph)

Brand name: Velban
Drug class: Antineoplastic Agents
- Antimitotic Agents
- Vinca Alkaloids
VA class: AN900
CAS number: 143-67-9

Medically reviewed by Drugs.com on Mar 22, 2024. Written by ASHP.

Introduction

Antineoplastic agent; vinca alkaloid.

Uses for vinBLAStine

Hodgkin’s Disease

In combination chemotherapy as first- or second-line therapy for Hodgkin’s disease.

Often used with doxorubicin, bleomycin, and dacarbazine (known as the ABVD regimen) as first-line therapy for Hodgkin’s disease.

Under investigated in other combination regimens (e.g., Stanford V regimen: doxorubicin, bleomycin, vinblastine, vincristine, mechlorethamine, etoposide, and prednisone) for the treatment of advanced Hodgkin's disease.

Testicular Cancer

For the treatment of advanced nonseminomatous testicular carcinoma, combination chemotherapy regimens containing vinblastine, cisplatin, and bleomycin have been used; however, most clinicians recommend regimens containing cisplatin and bleomycin, in combination with etoposide rather than vinblastine, as first-line therapy, particularly because of the reduced risk of neuromuscular toxicity and evidence suggesting greater efficacy in poor-risk patients.

A regimen of cisplatin, ifosfamide, and either vinblastine or etoposide currently is considered by most clinicians to be the standard initial salvage (i.e., second-line) regimen in patients with recurrent testicular cancer.

AIDS-related Kaposi’s Sarcoma

Has been used alone or in combination chemotherapy for the palliative treatment of AIDS-related Kaposi’s sarcoma.

Single-agent therapy with vinblastine is considered an alternative regimen.

Combination chemotherapy with a vinca alkaloid (vinblastine or vincristine) also has been a preferred regimen, but many clinicians currently consider a liposomal anthracycline (doxorubicin or daunorubicin) the first-line therapy of choice for advanced AIDS-related Kaposi’s sarcoma.

Combination chemotherapy with conventional antineoplastic agents (e.g., bleomycin, conventional doxorubicin, etoposide, vinblastine, vincristine) has been used for more advanced disease (e.g., extensive mucocutaneous disease, lymphedema, symptomatic visceral disease).

A liposomal anthracycline for the treatment of advanced AIDS-related Kaposi’s sarcoma produces similar or higher response rates with a more favorable toxic effects profile than combination therapy with conventional chemotherapeutic agents.

Classic Kaposi’s Sarcoma

Single-agent vinblastine has been used for the treatment of classic Kaposi's sarcoma.

Bladder Cancer

In combination regimens with cisplatin and methotrexate, with or without doxorubicin, as first- or second-line therapy for invasive and advanced bladder cancer^{† [off-label]}.

Non-small Cell Lung Cancer

In combination with cisplatin and mitomycin (MVP) as an alternative regimen for the treatment of non-small cell lung cancer^{† [off-label]}.

Currently preferred regimens for the treatment of advanced non-small cell lung cancer include the combination of cisplatin or carboplatin, with another agent, such as paclitaxel, docetaxel, vinorelbine, or gemcitabine.

Melanoma

Used in combination regimens (e.g., cisplatin, vinblastine, and dacarbazine, with or without interferon alfa and aldesleukin) for the treatment of metastatic melanoma^{† [off-label]}.

Superiority of combination regimens compared with dacarbazine alone not established, and dacarbazine monotherapy currently is a systemic treatment of choice for metastatic melanoma.

Brain Tumors

In combination with cisplatin and bleomycin or as monotherapy (second-line) for the treatment of intracranial germ cell tumors^{† [off-label]}.

Immune Thrombocytopenic Purpura

Has been used in the treatment of immune thrombocytopenic purpura^{† [off-label]}.

Autoimmune Hemolytic Anemia

Slow IV infusions of vinblastine or the use of vinblastine-loaded platelets has reportedly been effective in some cases for the treatment of autoimmune hemolytic anemia^†.

Non-Hodgkin’s Lymphoma

Palliative treatment of non-Hodgkin’s lymphomas, including lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated), histiocytic lymphoma, and advanced stages of mycosis fungoides; however, other agents currently are preferred.

Letterer-Siwe Disease

Treatment of Letterer-Siwe disease.

vinBLAStine Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.

• Care must be taken to avoid contact with the eyes as severe irritation and possibly corneal ulceration (especially if administered under pressure) can result; if contact occurs, immediately wash eyes thoroughly.

• Administration of antiemetics may easily control nausea and vomiting.

Administration

For solution and drug compatibility information, see Compatibility under Stability.

IV Administration

Administer IV only by individuals experienced in the administration of the drug.

Very irritating; must not be given IM, sub-Q, or intrathecally. Intrathecal administration usually results in death. (See Boxed Warning.)

Management of patients mistakenly receiving intrathecal vinblastine is a medical emergency. If administered intrathecally, immediate neurosurgical intervention is required to prevent ascending paralysis leading to death. (See Intrathecal Administration under Cautions.)

Administer appropriate quantity of commercially available or reconstituted solution by IV injection into the tubing of a running IV infusion or directly into a vein.

Because of the enhanced possibility of thrombosis, do not inject into an extremity with impaired or potentially impaired circulation caused by compression or invading neoplasm, phlebitis, or varicosity.

Because of possible leukopenic response, administer at intervals of at least 7 days; however, even if 7 days have elapsed, do not give next dose until leukocyte count has returned to ≥4000/mm³. Strict adherence to recommended dosage interval is important.

To ensure an adequate trial, therapy must be continued for at least 4–6 weeks. Some experts advocate a trial of at least 12 weeks, particularly in patients with carcinomas.

Extravasation

Extremely important to ensure that the needle or catheter is securely within the vein in order to avoid extravasation.

The manufacturers recommend rinsing the syringe and needle with venous blood after administration of the drug and before withdrawal of the needle to further minimize the possibility of extravasation.

If leakage occurs, discontinue injection immediately and administer remainder of the dose through another vein; local treatment of the area of leakage may minimize discomfort and the possibility of cellulitis. (See Boxed Warning and also see Local Effects under Cautions.)

Reconstitution

Reconstitute powder for injection by adding 10 mL of bacteriostatic sodium chloride injection containing benzyl alcohol as a preservative or 10 mL of sodium chloride injection (without preservatives) to a vial labeled as containing 10 mg of the drug to provide a solution containing 1 mg/mL.

Do not use other diluents; do not combine with any other chemical.

Dilution

To minimize the risk of extravasation and/or venous irritation, do not dilute in large volumes of IV solution (e.g., 100–250 mL).

Rate of Administration

Inject appropriate quantity of commercially available or reconstituted solution into the tubing of a running IV infusion or directly into a vein over about a 1-minute period.

To minimize risk of extravasation and/or venous irritation, do not infuse over long periods of time (i.e., from 30–60 minutes or longer).

Dispensing Precautions

When dispensing, must label syringe or container holding the individual dose with the statement: “Warning: Fatal if given intrathecally. For intravenous use only.”

Enclose container or syringe holding the individual dose in an overwrap (e.g., plastic bag or similar wrap with typed label) bearing the statements: “Do not remove covering until moment of injection. Fatal if given intrathecally. For intravenous use only.” (See Intrathecal Administration under Cautions.)

Consider additional measures to prevent inadvertent intrathecal administration, including: administering diluted vinblastine solutions in minibags; preparing the medication at the time of administration; attaching a unique filter; dispensing separately from all other medications; dispensing directly to the individual who is administering the drug; conducting an independent check of the dose and route of administration for the drug both at the time of preparation and prior to administration; and administering vinblastine in a separate room from rooms where intrathecal medications are administered.

Dosage

Available as vinblastine sulfate; dosage expressed in terms of the salt.

Dosage varies depending on the schedule used and whether vinblastine is administered as a single agent or incorporated within a particular chemotherapeutic regimen. Consult published protocols for dosages in combination regimens.

Use of small daily doses for prolonged periods (even if equivalent to the total weekly dosage) is not recommended because it has produced severe toxicity with little or no added therapeutic benefit.

Pediatric Patients

General Dosage

Some evidence indicates that the usual initial pediatric dosage varies depending on the schedule used and whether vinblastine is administered as a single agent or incorporated within a particular chemotherapeutic regimen.

Hodgkin’s Disease

IV

In combination with other chemotherapeutic agents, an initial dosage of 6 mg/m² has been used. Adjust dosage based on hematologic tolerance. Consult published protocols for additional information on dosage.

Testicular Germ Cell Carcinoma

IV

An initial dosage of 3 mg/m² has been used in a combination regimen. Adjust dosage based on hematologic tolerance. Consult published protocols for additional information on dosage.

Letterer-Siwe Disease

IV

As monotherapy, an initial dosage of 6.5 mg/m² reportedly has been used. Adjust dosage based on hematologic tolerance. Consult published protocols for additional information on dosage.

Adults

General Dosage

Initial Dosage

IV

Initially, 3.7 mg/m² given as a single dose.

Dosage Modification

Determine subsequent dosage by clinical and hematologic response and patient tolerance to obtain optimum therapeutic results with minimum adverse effects.

Increase dosage at weekly intervals in increments of about 1.8–1.9 mg/m² until desired therapeutic response is obtained, the leukocyte count decreases to about 3000/mm³, or a maximum weekly dose of 18.5 mg/m² is reached.

In most adults, the optimum weekly dose will be 5.5–7.4 mg/m²; however, leukopenia (leukocyte count of 3000/mm³) may occur in some patients with 3.7 mg/m² per week, whereas other patients may tolerate 11.1–18.5 mg/m² per week.

Once the dose required to produce a leukocyte count of 3000/mm³ has been determined, administer a maintenance dose of one increment (1.8 mg/m²) less than this amount (e.g., the maximum dose that does not cause leukopenia) at weekly intervals.

Dosage generally is reduced in patients with recent exposure to radiation therapy or chemotherapy; single doses in these patients usually do not exceed 5.5 mg/m².

Maintenance Dosage

Duration of maintenance therapy varies according to disease being treated and combination of chemotherapeutic agents being used; there are differences of opinion regarding duration of maintenance therapy with the same protocol for a particular disease.

Prolonged chemotherapy for maintaining remissions involves several risks (i.e., life-threatening infectious diseases, sterility, possible appearance of other neoplasms resulting from immune system suppression).

In some disorders, survival following complete remission may not be as prolonged as that achieved with shorter periods of maintenance therapy; however, failure to provide maintenance therapy in some patients may lead to unnecessary relapse.

Prescribing Limits

Adults

IV

Maximum 18.5 mg/m² weekly.

Special Populations

Hepatic Impairment

In patients with a direct serum bilirubin >3 mg/dL, dosage reduction of 50% recommended.

Renal Impairment

No dosage reduction recommended.

Cautions for vinBLAStine

Contraindications

• Substantial leukopenia (granulocytopenia).

• Presence of bacterial infections; control infection prior to initiation of therapy.

Warnings/Precautions

Warnings

Intrathecal Administration

Fatal if administered intrathecally; immediate neurosurgical intervention required to prevent ascending paralysis leading to death.

Prognosis to date (principally with patients inadvertently administered vincristine intrathecally) generally has been poor despite immediate efforts to remove spinal fluid and flush with lactated Ringer's injection, with such efforts failing to prevent ascending paralysis and death in almost all cases.

In a very small number of patients, life-threatening paralysis and subsequent death have been averted, but devastating neurologic sequelae, with limited recovery afterwards, have resulted.

There are no published cases of survival following intrathecal administration of vinblastine to use as guidance for treatment.

According to published reports of survivors of inadvertent intrathecal administration of vincristine, treatment consists of immediate removal of as much CSF as safely possible via lumbar access, followed by insertion of an epidural catheter into the subarachnoid space via the intervertebral space above initial lumbar access and then CSF irrigation with lactated Ringer’s solution; add fresh frozen plasma (25 mL) to every L of lactated Ringer’s solution when available.

Insert intraventricular drain or catheter (by a neurosurgeon), continue CSF irrigation with fluid removal through the lumbar access connected to a closed drainage system. Give lactated Ringer’s solution by continuous infusion at the rate of 150 mL/hour, or at a rate of 75 mL/hour when fresh frozen plasma has been added. Adjust rate to maintain CSF protein concentration of 150 mg/dL.

Additional measures have been used but may not be essential, including glutamic acid (10 g IV over 24 hours, followed by 500 mg orally 3 times daily for 1 month), leucovorin (100-mg IV bolus followed by an infusion of 25 mg/hour for 24 hours, then 25 mg by IV bolus every 6 hours for 1 week), or pyridoxine hydrochloride (50 mg has been administered as an IV infusion over 30 minutes every 8 hours). The contribution of these additional therapies to reduction of neurotoxicity is unclear.

Hematologic Effects

Leukopenia occurs commonly and is usually the dose-limiting factor in therapy. Nadir in leukocyte count generally occurs 5–10 days after administration and recovery usually occurs within another 7–14 days; however, following administration of high doses, recovery may take ≥21 days.

Perform blood counts weekly or at least before administration of each dose.

If leukopenia with <2000/mm³ occurs following a dose, carefully monitor patient for signs of infection.

More profound leukopenia possible in patients with cachexia or ulcerated areas of skin; avoid use in patients (especially geriatric patients) with these conditions.

In patients with malignant-cell infiltration of the bone marrow, an abrupt decrease in leukocyte and platelet counts may occur after moderate doses; manufacturers recommend discontinuance in such patients, but many clinicians consider it appropriate to continue therapy if the drug is clearly destroying tumor cells in the bone marrow.

Anemia also may occur.

Patients who receive myelosuppressive drugs experience an increased frequency of infections as well as possible hemorrhagic complications.

Nervous System Effects

Possible neurotoxicity, sometimes disabling; occurs occasionally in patients receiving vinblastine, especially with high doses or prolonged therapy, but less frequently than with vincristine therapy.

When doses several times the recommended weekly dosage were administered daily for long periods, seizures, permanent CNS damage, and death occurred; however, some clinicians believe that patients with rapidly progressing tumors with short generation times should receive large divided doses over several days, repeated as often as toxicity permits.

GI Effects

Possible stomatitis; although reversible, can be disabling.

GI symptoms, particularly constipation, abdominal pain, and adynamic ileus, may be related to neurotoxicity.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Genitourinary Effects

Aspermia reported during therapy; reproductive studies in animals have revealed evidence of metaphase arrest and degenerative changes in germ cells.

General Precautions

Highly toxic drug with low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity. Administer only under constant supervision by clinicians experienced in therapy with cytotoxic agents.

Respiratory Effects

Acute shortness of breath and bronchospasm, which can be severe or life threatening, have occurred; reported most frequently when mitomycin was administered concomitantly.

Such reactions may occur a few minutes to several hours after administration of a vinca alkaloid, or up to 2 weeks after mitomycin dose.

Aggressive treatment may be required, particularly in patients with preexisting pulmonary dysfunction.

Progressive dyspnea, which may require chronic therapy, can occur in patients receiving vinblastine; do not readminister to these patients.

Patients with preexisting pulmonary dysfunction may be particularly susceptible to severe or life-threatening pulmonary effects.

Cardiovascular Effects

Caution is advised when using vinblastine in patients with ischemic cardiovascular disease, and care of this condition should be recommended.

Hypertension is the most common adverse cardiovascular effect of vinblastine.

Cases of unexpected MI and cerebrovascular accident reported in patients receiving vinblastine in combination with bleomycin and cisplatin.

Raynaud's phenomenon reported in patients receiving vinblastine and bleomycin, with or without cisplatin.

Local Effects

Tissue irritant; may cause phlebitis and necrosis. Extravasation can result in pain and cellulitis.

If extravasation of large amounts of the injection occurs, sloughing may result; local reactions may be severe and can persist for several weeks to months.

Manufacturers state that local injection of hyaluronidase and application of moderate heat may decrease local reactions resulting from extravasation; however, some clinicians prefer to treat extravasation with cold compresses, dilution with 0.9% sodium chloride injection, and/or local injection of hydrocortisone.

Otic Effects

Eighth cranial nerve damage, which may be evident as vestibular manifestations (e.g., dizziness, nystagmus, vertigo) and by auditory manifestations (e.g., varying degrees of hearing impairment) that may be temporary or permanent, reported in patients receiving vinca alkaloids.

Use vinca alkaloids concomitantly with other potentially ototoxic drugs (e.g., platinum-containing antineoplastic agents) with extreme caution. (See Specific Drugs under Interactions.)

Hyperuricemia

Hyperuricemia may result from extensive purine catabolism accompanying rapid cellular destruction in some patients receiving vinblastine, especially those with non-Hodgkin’s lymphomas or leukemia.

In some patients, uric acid nephropathy may result.

Minimize by adequate hydration, alkalinization of the urine, and/or administration of allopurinol.

Dermatologic Effects

Vinblastine-induced alopecia is common; other adverse dermatologic effects occur infrequently following vinblastine therapy and include dermatitis and vesiculation of the skin, phototoxicity, and epilation.

Epilation is partial and almost always reversible; in some cases, hair may regrow during maintenance therapy.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether vinblastine is distributed in milk. Discontinue nursing or the drug.

Geriatric Use

Avoid use in geriatric patients with cachexia or ulcerated areas of skin; more profound leukopenia is possible in such patients.

Hepatic Impairment

In patients with hepatic impairment, toxicity may be enhanced. Caution advised. (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Leukopenia, alopecia, constipation, nausea, vomiting, hypertension, malaise, bone pain, pain in tumor-containing tissue, jaw pain, paresthesia, peripheral neuropathy and neuritis, numbness, loss of deep tendon reflexes, muscle pain and weakness, ileus, anorexia, stomatitis, weight loss, anemia.

Drug Interactions

Metabolized by CYP3A.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A: potential pharmacokinetic interaction (inhibition of vinblastine metabolism); earlier onset and/or increased severity of adverse effects of vinblastine may occur. Use concomitantly with caution.

Ototoxic Drugs

Since varying degrees of permanent or temporary hearing impairment associated with eighth cranial nerve damage have been reported in patients receiving vinca alkaloids, use concomitantly with other potentially ototoxic drugs with extreme caution. (See Specific Drugs under Interactions.)

Specific Drugs

vinBLAStine Pharmacokinetics

Absorption

Bioavailability

Unpredictably absorbed from the GI tract.

Distribution

Extent

Following IV administration, rapidly cleared from the blood and distributed into body tissues. Crosses the blood-brain barrier poorly and does not appear in the CSF in therapeutic concentrations.

Elimination

Metabolism

Reported to be extensively metabolized, mainly in the liver, to desacetylvinblastine, which is more active than the parent compound on a weight basis.

Mediated by CYP3A.

Elimination Route

Excreted slowly in urine and in feces via bile.

Special Populations

Metabolism via CYP isoenzymes may be impaired in patients with hepatic dysfunction.

Stability

Storage

Parenteral

Injection

2–8°C. Protect from light.

Powder for Injection

Store vials at 2–8°C to assure extended stability. Protect from light.

After reconstitution with bacteriostatic sodium chloride injection (preserved with benzyl alcohol), solutions are stable for 28 days when refrigerated at 2–8°C.

When reconstituted with a diluent that does not contain a preservative, discard any unused portions immediately.

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions

• Mechanism of action not fully elucidated; vinblastine and other vinca alkaloids exert their cytotoxic effects by binding to tubulin, the protein subunit of the microtubules that form the mitotic spindle.

• Formation of vinblastine-tubulin complexes prevents the polymerization of the tubulin subunits into microtubules and induces depolymerization of microtubules resulting in inhibition of microtubule assembly and cellular metaphase arrest.

• In high concentrations, also exerts complex effects on nucleic acid and protein synthesis.

• 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.

• Exerts some immunosuppressive activity.

Advice to Patients

• Importance of notifying a clinician if fever, sore throat, unusual bleeding or bruising, or any other serious adverse event occurs.

• Advise patients regarding avoidance of constipation.

• Advise patients that alopecia may occur, but that scalp hair may regrow to its pretreatment extent even with continued therapy.

• Advise patients that jaw pain and pain in the organs containing tumor tissue (possibly resulting from swelling of tumor tissue during treatment response) may occur.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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