Professional Drug Information > Velban

Vinblastine (Systemic)

VA CLASSIFICATION
Primary: AN900

Commonly used brand name(s): Velban; Velbe.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Carcinoma, breast (treatment)
Tumors, trophoblastic, gestational (treatment)
Carcinoma, testicular (treatment)
[Carcinoma, bladder (treatment)]¹
[Carcinoma, lung, non–small cell (treatment)]¹ or
[Carcinoma, renal (treatment)]¹—Vinblastine is indicated for treatment of breast carcinoma unresponsive to appropriate endocrine surgery and hormonal therapy, choriocarcinoma resistant to other chemotherapeutic agents, and advanced testicular germ cell carcinomas (embryonal carcinoma, teratocarcinoma, and choriocarcinoma)^{01}{02}. Vinblastine also is indicated for treatment of bladder carcinoma^{03}{06}, non–small cell lung carcinoma^{03}{07}, and renal carcinoma^{03}{08}.

Lymphomas, Hodgkin's (treatment) or
Lymphomas, non-Hodgkin's (treatment)—Vinblastine is indicated for treatment of generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system) and for treatment of lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated) and histiocytic lymphoma^{01}{02}.

Sarcoma, Kaposi's (treatment)—Vinblastine is indicated for treatment of Kaposi's sarcoma^{01}{02}, including [acquired immunodeficiency syndrome (AIDS)–associated Kaposi's sarcoma]^1{04} by intravenous or intralesional injection^{{11}{12}{13}{14}{15}{16}{17}{18}}.

Histiocytosis X (treatment)^{01}{02}—Vinblastine is indicated for treatment of Histiocytosis X (Letterer-Siwe disease; Langerhans cell histiocytoses).

Mycosis fungoides (treatment)—Vinblastine is indicated for treatment of advanced stages of mycosis fungoides^{01}{02}.

[Carcinoma, prostatic (treatment) ]¹—Vinblastine is indicated as reasonable medical therapy for treatment of prostatic carcinoma^{{19}{20}{21}{22}{23}{24}} (Evidence rating: IIID).

[Melanoma, malignant (treatment)]¹—Vinblastine is indicated for treatment of metastatic malignant melanoma^{03}{05}.

[Tumors, germ cell, ovarian (treatment) ]¹—Vinblastine is indicated for treatment of germ cell ovarian tumors^{03}{09}.

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Vinblastine is a vinca alkaloid ^{01}.
Molecular weight—
    909.07 ^{01}

Mechanism of action/Effect:

Vinblastine blocks mitosis by arresting cells in metaphase, and may also interfere with amino acid metabolism ^{01}; it is cell cycle–specific for the M phase of cell division.

Distribution:

Does not cross the blood-brain barrier in significant amounts ^{01}.

Biotransformation:

Hepatic; metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 3A isoenzymes. ^{01}

Half-life:

Following rapid intravenous administration—

• Initial phase: 3.7 minutes ^{01}.


• Middle phase: 1.6 hours ^{01}.Terminal phase: 24.8 hours ^{01}.


Elimination:
    Primary route—Biliary/fecal ^{01}.
    Secondary route—Renal ^{01}.


Precautions to Consider

Carcinogenicity/Mutagenicity

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effects of dose and duration of therapy are also unknown, although risk seems to increase with long-term use.

In studies in rats and mice, administration of the maximum tolerated dose of vinblastine and half of the maximum tolerated dose for 6 months did not show a clear relationship between vinblastine and tumor development. The test demonstrated that other agents were clearly carcinogenic; however, vinblastine was one of the drugs in the group of drugs that caused slightly increased or the same tumor incidence as controls. ^{01}

Pregnancy/Reproduction
Fertility—
Gonadal suppression, resulting in amenorrhea or azoospermia, has occurred in patients taking vinblastine. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents. Vinblastine also has been reported to cause aspermia. ^{01}

Pregnancy—
In general, use of a contraceptive is recommended during cytotoxic drug therapy.

First trimester: It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered.

Administration of vinblastine to animals early in pregnancy results in fetal resorption with surviving fetuses showing gross deformities ^{01}.

Other hazards to the fetus include adverse reactions seen in adults.

FDA Pregnancy Category D ^{01}.

Breast-feeding

Although very little information is available regarding distribution of antineoplastic agents into breast milk, breast-feeding is not recommended while vinblastine is being administered because of the risks to the infant (adverse effects, mutagenicity, carcinogenicity). It is not known whether vinblastine is distributed into breast milk ^{01}.

Pediatrics

Studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of this medication in children.


Geriatrics


Although appropriate studies with vinblastine have not been performed in the geriatric population, the leukopenic response may be increased in elderly patients suffering from malnutrition or skin ulcers ^{01}.


Dental

The bone marrow depressant effects of vinblastine may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Vinblastine may also cause stomatitis associated with considerable discomfort ^{01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Allopurinol or
Colchicine or
» Probenecid or
» Sulfinpyrazone    (vinblastine may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse vinblastine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents)


Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of vinblastine may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of vinblastine, if necessary, should be based on blood counts)


» Bone marrow depressants, other (see Appendix II ) or
Radiation therapy    (additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by vinblastine therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by vinblastine therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the vinblastine therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Immunization with oral poliovirus vaccine should also be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Uric acid concentrations in blood and urine    (may be increased ^{10})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Bone marrow depression
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


Gout, history of or
Urate renal stones, history of    (risk of hyperuricemia)


» Hepatic function impairment^{01}    (a 50% dosage reduction is recommended for patients with a direct serum bilirubin concentration greater than 3 mg per 100 mL ^{01})


» Infection
Sensitivity to vinblastine
» Tumor cell infiltration of bone marrow    (in patients with malignant-cell infiltration of bone marrow, leukocyte and platelet counts have been reported to fall precipitously following administration of moderate doses of vinblastine; further administration of vinblastine in such patients is not recommended ^{01})


» Caution should be used also in patients who have had previous cytotoxic drug therapy or radiation therapy.

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Alanine aminotransferase (ALT [SGPT]), serum and
Aspartate aminotransferase (AST [SGOT]), serum and
Bilirubin, serum and
Lactate dehydrogenase (LDH)    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently; toxicity may be enhanced in the presence of hepatic insufficiency ^{01})


» Hematocrit or hemoglobin and
» Platelet count and
» Total and, if appropriate, differential leukocyte count    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Uric acid concentrations, serum    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)




Side/Adverse Effects

Note: Many “side effects” of antineoplastic therapy are unavoidable and represent the medication's pharmacologic action. Some of these (for example, leukopenia and thrombocytopenia) are actually used as parameters to aid in individual dosage titration.
Incidence of side effects is generally dose-related.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Leukopenia ^{01}(fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)—usually asymptomatic

Note: With leukopenia, the nadir of the leukocyte count occurs 5 to 10 days after the last day of administration, and recovery is usually complete within another 7 to 14 days ^{01}.


Incidence less frequent
    
Cellulitis (pain or redness at site of injection)—caused by extravasation^{01}
    
hyperuricemia or uric acid nephropathy (joint pain; lower back or side pain; swelling of feet or lower legs)
    
stomatitis ^{01}(sores in mouth and on lips)
    
thrombocytopenia, transient ^{01}(unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)—usually asymptomatic

Note: Hyperuricemia or uric acid nephropathy occurs most commonly during initial treatment of patients with lymphoma as a result of rapid cell breakdown that leads to elevated serum uric acid concentrations ^{10}.


Incidence rare
    
Rectal bleeding, hemorrhagic colitis, or bleeding from a previously existing peptic ulcer ^{01}(black, tarry stools)
    
neurotoxicity ^{01}(difficulty in walking; dizziness; double vision; drooping eyelids; headache; jaw pain; mental depression; numbness or tingling in fingers and toes; pain in fingers and toes; pain in testicles; weakness)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Nausea and vomiting ^{01}
    
pain in bone or tumor-containing tissues ^{01}



Those not indicating need for medical attention
Incidence more frequent
    
Loss of hair

Note: Hair growth should return after treatment has ended and possibly during therapy ^{01}.






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Vinblastine (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
  Conditions affecting use, especially:
Sensitivity to vinblastine

Pregnancy—Advisability of using contraception; telling physician immediately if pregnancy is suspected





Breast-feeding—Not recommended because of risk of serious side effects
Other medications, especially other bone marrow depressants, probenecid, or sulfinpyrazone
Other medical problems, especially chickenpox or recent exposure, hepatic function impairment, herpes zoster, other infections, previous cytotoxic medication or radiation therapy, or tumor cell infiltration of bone marrow

Proper use of this medication
Caution in taking combination therapy; taking each medication at the right time

Importance of ample fluid intake and subsequent increase in urine output to aid in excretion of uric acid

Frequency of nausea and vomiting; importance of continuing medication despite stomach upset

» Proper dosing

Precautions while using this medication
» Importance of close monitoring by physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding other persons who have taken oral poliovirus vaccine within the past several months or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury could occur
» Possibility of local tissue injury and scarring if infiltration of intravenous solution occurs; telling physician or nurse right away about redness, swelling, or pain at site of injection


Side/adverse effects
May cause adverse effects such as blood problems, loss of hair, and cancer; importance of discussing possible effects with physician

Signs of potential side effects, especially leukopenia, cellulitis caused by extravasation, hyperuricemia, uric acid nephropathy, stomatitis, transient thrombocytopenia, rectal bleeding, hemorrhagic colitis, bleeding from existing peptic ulcer, and neurotoxicity

Physician or nurse can help in dealing with side effects

Possibility of hair loss; growth should return after treatment has ended and possibly during therapy


General Dosing Information
Vinblastine may be administered by intravenous push or injected into the tubing of a running intravenous infusion, over a 1-minute period. Do not administer vinblastine intrathecally because death of the patient will occur. ^{01}

Patients receiving vinblastine should be under supervision of a physician experienced in cancer chemotherapy.

Dosage must be adjusted to meet the individual requirements of each patient, on the basis of clinical response and degree of bone marrow depression.

Development of uric acid nephropathy in patients with lymphoma may be prevented by adequate oral hydration and, in some cases, administration of allopurinol. Alkalinization of urine may be necessary if serum uric acid concentrations are elevated.

It is recommended that vinblastine be administered no more frequently than every 7 days, to allow the full effect of each dose on the leukocyte count to be seen ^{01}.

Dilution in larger volumes (100 to 250 mL) or administration over longer periods (30 to 60 minutes and longer) is recommended only with great caution because of irritation to the vein and increased risk of extravasation ^{01}.

To minimize the risk of extravasation, rinsing of the syringe and needle with venous blood before withdrawal of the needle is recommended ^{01}.

If extravasation of vinblastine occurs during intravenous administration, the injection should be stopped immediately and the remaining dose injected into another vein ^{01}.

Injection of vinblastine into an extremity in which circulation is compromised by conditions such as compressing or invading neoplasm, phlebitis, or viscosity is not recommended because of the increased risk of thrombosis ^{01}.

If marked leukopenia (particularly granulocytopenia) or thrombocytopenia occurs, it is recommended that vinblastine therapy be withdrawn until leukocyte counts return to satisfactory levels (at least 4000 per cubic millimeter) ^{01}.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of vinblastine. These may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using caution to prevent falls and other injuries. Such patients should avoid alcohol and aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In neutropenic patients who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.

Safety considerations for handling this medication
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastics may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.


Combination chemotherapy
Vinblastine may be used in combination with other agents in various regimens. As a result, incidence and/or severity of side effects may be altered and different dosages (usually reduced) may be used. For example, vinblastine is part of the following chemotherapeutic combinations (some commonly used acronyms are in parentheses):    —doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
   —carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone (BCVPP).
For specific dosages and schedules, consult the literature. For information regarding each agent, consult the individual monograph.


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

VINBLASTINE SULFATE INJECTION

Usual adult dose
Carcinoma, breast or
Tumors, trophoblastic, gestational or
Carcinoma, testicular or
[Carcinoma, renal]¹ or
Lymphomas, Hodgkin's or
Lymphomas, non-Hodgkin's or
Sarcoma, Kaposi's or
Histiocytosis X or
Mycosis fungoides or
[Tumors, germ cell, ovarian ]¹
Initial: Intravenous, 100 mcg (0.1 mg) per kg of body weight or 3.7 mg per square meter of body surface area a week, with successive weekly doses increased by increments of 50 mcg (0.05 mg) per kg of body weight or 1.8 to 1.9 mg per square meter of body surface area until the leukocyte count falls to 3000 per cubic millimeter, or a decrease in tumor size occurs, or a maximum dose of 500 mcg (0.5 mg) per kg of body weight or 18.5 mg per square meter of body surface area is reached (usual range 150 to 200 mcg [0.15 to 0.2 mg] per kg of body weight or 5.5 to 7.4 mg per square meter of body surface area).

Maintenance: Intravenous, dosage one increment smaller than the final initial dosage every seven days^{01}, or 10 mg one or two times a month.


Note: Each subsequent dose should not be given until the leukocyte count after the preceding dose returns to 4000 per cubic millimeter, even if seven days have passed^{01}.
A reduction in dosage of 50% is recommended in patients with a direct serum bilirubin concentration above 3 mg per 100 mL^{01}.
A variety of dosage schedules and regimens of vinblastine, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature in choosing a specific dosage.

[Carcinoma, bladder]¹ or
[Carcinoma, lung, non–small cell]¹or
[Carcinoma, prostatic]¹ or
[Melanoma, malignant]¹
Consult medical literature or manufacturer's literature for appropriate dosage.


Usual pediatric and adolescent dose
Carcinoma, breast or
Tumors, trophoblastic, gestational or
Carcinoma, testicular or
[Carcinoma, renal]¹ or
Lymphomas, Hodgkin's or
Lymphomas, non-Hodgkin's or
Sarcoma, Kaposi's or
Histiocytosis X or
Mycosis fungoides or
[Tumors, germ cell, ovarian ]¹
Initial: Intravenous, 2.5 mg per square meter of body surface area a week, with successive weekly doses increased by increments of 1.25 mg per square meter of body surface area until the leukocyte count falls to 3000 per cubic millimeter, or a decrease in tumor size occurs, or a maximum dose of 7.5 mg per square meter of body surface area is reached.

Maintenance: Intravenous, dosage one increment smaller than the final initial dosage every seven days^{01}.


Note: Each subsequent dose should not be given until the leukocyte count after the preceding dose returns to 4000 per cubic millimeter, even if seven days have passed^{01}.
A reduction in dosage of 50% is recommended in patients with a direct serum bilirubin concentration above 3 mg per 100 mL^{01}.
A variety of dosage schedules and regimens of vinblastine, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature in choosing a specific dosage.

[Carcinoma, bladder]¹ or
[Carcinoma, lung, non–small cell]¹or
[Carcinoma, prostatic]¹ or
[Melanoma, malignant]¹
Consult medical literature or manufacturer's literature for appropriate dosage.


Strength(s) usually available
U.S.—


1 mg per mL (Rx)[Generic]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F).

Stability:
After withdrawal of the first dose, the remainder of the vial may be stored for 30 days between 2 and 8 °C (36 and 46 °F) without significant loss of potency.


Caution:
When dispensed, the container or the syringe holding the individual dose prepared for administration to the patient must be enclosed in an overwrap bearing the statement: “DO NOT REMOVE COVERING UNTIL THE MOMENT OF INJECTION. FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY.” USP does not specifically define the term “overwrap,” but it is believed a ziplock bag or similar wrap utilized in hospitals may suffice to meet this requirement.

Note: If accidental contamination of the eye with vinblastine occurs, the eye should be immediately and thoroughly flushed with water to prevent severe irritation and possible corneal ulceration.



STERILE VINBLASTINE SULFATE USP

Usual adult dose
Carcinoma, breast or
Tumors, trophoblastic, gestational or
Carcinoma, testicular or
[Carcinoma, renal]¹ or
Lymphomas, Hodgkin's or
Lymphomas, non-Hodgkin's or
Sarcoma, Kaposi's or
Histiocytosis X or
Mycosis fungoides or
[Tumors, germ cell, ovarian ]¹
Initial: Intravenous, 100 mcg (0.1 mg) per kg of body weight or 3.7 mg per square meter of body surface area a week, with successive weekly doses increased by increments of 50 mcg (0.05 mg) per kg of body weight or 1.8 to 1.9 mg per square meter of body surface area until the leukocyte count falls to 3000 per cubic millimeter, or a decrease in tumor size occurs, or a maximum dose of 500 mcg (0.5 mg) per kg of body weight or 18.5 mg per square meter of body surface area is reached (usual range 150 to 200 mcg [0.15 to 0.2 mg] per kg of body weight or 5.5 to 7.4 mg per square meter of body surface area).

Maintenance: Intravenous, dosage one increment smaller than the final initial dosage every seven days^{01}, or 10 mg one or two times a month.


Note: Each subsequent dose should not be given until the leukocyte count after the preceding dose returns to 4000 per cubic millimeter, even if seven days have passed^{01}.
A reduction in dosage of 50% is recommended in patients with a direct serum bilirubin concentration above 3 mg per 100 mL^{01}.
A variety of dosage schedules and regimens of vinblastine, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature in choosing a specific dosage.

[Carcinoma, bladder]¹ or
[Carcinoma, lung, non–small cell]¹or
[Carcinoma, prostatic]¹ or
[Melanoma, malignant]¹
Consult medical literature or manufacturer's literature for appropriate dosage.


Usual pediatric and adolescent dose
Carcinoma, breast or
Tumors, trophoblastic, gestational or
Carcinoma, testicular or
[Carcinoma, renal]¹ or
Lymphomas, Hodgkin's or
Lymphomas, non-Hodgkin's or
Sarcoma, Kaposi's or
Histiocytosis X or
Mycosis fungoides or
[Tumors, germ cell, ovarian ]¹
Initial: Intravenous, 2.5 mg per square meter of body surface area a week, with successive weekly doses increased by increments of 1.25 mg per square meter of body surface area until the leukocyte count falls to 3000 per cubic millimeter, or a decrease in tumor size occurs, or a maximum dose of 7.5 mg per square meter of body surface area is reached.

Maintenance: Intravenous, dosage one increment smaller than the final initial dosage every seven days.


Note: Each subsequent dose should not be given until the leukocyte count after the preceding dose returns to 4000 per cubic millimeter, even if seven days have passed^{01}.
A reduction in dosage of 50% is recommended in patients with a direct serum bilirubin concentration above 3 mg per 100 mL^{01}.
A variety of dosage schedules and regimens of vinblastine, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature in choosing a specific dosage.

[Carcinoma, bladder]¹ or
[Carcinoma, lung, non–small cell]¹or
[Carcinoma, prostatic]¹ or
[Melanoma, malignant]¹
Consult medical literature or manufacturer's literature for appropriate dosage.


Size(s) usually available:
U.S.—


10 mg (Rx) [Velban][Generic]

Canada—


10 mg (Rx) [Velbe]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F)^{01}.

Preparation of dosage form:
Sterile Vinblastine Sulfate USP is reconstituted for intravenous use by adding 10 mL of 0.9% sodium chloride injection preserved with benzyl alcohol to the vial to produce a solution containing 1 mg of vinblastine sulfate per mL. It is not necessary to use preservative-containing 0.9% sodium chloride injection if unused solution is discarded immediately.^{01}

Stability:
Solutions of vinblastine that are reconstituted with sodium chloride injection containing a preservative may be stored for 28 days between 2 and 8 °C (36 and 46 °F). Preservative-free solutions should be discarded immediately.^{01}


Caution:
When dispensed, the container or the syringe holding the individual dose prepared for administration to the patient must be enclosed in an overwrap bearing the statement: “DO NOT REMOVE COVERING UNTIL THE MOMENT OF INJECTION. FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY^{01}.” USP does not specifically define the term “overwrap,” but it is believed a ziplock bag or similar wrap utilized in hospitals may suffice to meet this requirement.

Use of diluents containing benzyl alcohol is not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, central nervous system (CNS) depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use.

Note: If accidental contamination of the eye with vinblastine occurs, the eye should be immediately and thoroughly flushed with water to prevent severe irritation and possible corneal ulceration^{01}.

Revised: 07/19/2000

References

Note: References used in the development and subsequent revisions of this monograph have not been incorporated into the database and therefore are not listed below.

1. Velban package insert (Lilly—US), Rev 11/20/96.
   

2. Velbe package insert (Lilly—Canada), Rev 11/16/92.
   

3. Reviewers' responses to Hematologic-Oncologic Disease Advisory Panel Memo #9 of 1/30/97.
   

4. Miles SA, Mitsuyasu RI, Aboulafia DM. AIDS-related malignancies. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 2445-67.
   

5. Albino AP, Reed JA, McNutt NS. Malignant melanoma. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 1935-2001.
   

6. Scher HI, Shiply WU, Herr HW. Cancer of the bladder. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 1300-22.
   

7. Ginsberg RJ, Vokes EE, Raben A. Non–small cell lung cancer. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 858-911.
   

8. Linehan WM, Shipley WU, Parkinson DR. Cancer of the kidney and ureter. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 1271-300.
   

9. Ovarian germ cell tumor. National Cancer Institute. Available from: URL: http://cancernet.nci.nih.gov
   

10. Warrell RP. Metabolic emergencies. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 2493-4.
    

11. Friedman M, Venkatesan TK, Caldarelli DD. Intralesional vinblastine for treating AIDS-associated Kaposi's sarcoma of the oropharynx and larynx. Ann Otol Rhinol Laryngol 1996; 105: 272-4.
    

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