VA Class:AN900
Vinblastine sulfate, a naturally occurring vinca alkaloid, is an antineoplastic agent.134, 139
Vinblastine is used in combination chemotherapy for the treatment of Hodgkin's disease.127, 135 Various regimens have been used in combination therapy and comparative efficacy is continually being evaluated.138 Vinblastine often is used with doxorubicin, bleomycin, and dacarbazine (known as the ABVD regimen) for the treatment of patients with Hodgkin's disease.135, 138 The use of vinblastine 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 is being investigated.135, 138
For the treatment of advanced nonseminomatous testicular carcinoma, combination chemotherapy regimens containing vinblastine, cisplatin, and bleomycin have been used;127, 128, 129, 130 however, most clinicians recommend regimens containing cisplatin and bleomycin, in combination with etoposide rather than vinblastine, particularly because of the reduced risk of neuromuscular toxicity and evidence suggesting greater efficacy in poor-risk patients.128, 129, 130, 135 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.128, 135 The best combination or sequential therapy in the treatment of advanced nonseminomatous testicular tumors has not been established, and comparative efficacy is continually being evaluated.128
Vinblastine sulfate has been used alone135, 140, 141 or in combination140, 142, 143, 144, 145, 146 chemotherapy for the palliative treatment of AIDS-related Kaposi's sarcoma. Single-agent therapy with vinblastine is considered an alternative regimen for treatment of such sarcoma.135 Combination chemotherapy with a vinca alkaloid (vinblastine or vincristine) also has been a preferred regimen,135, 140, 145, 146 but many clinicians currently consider a liposomal anthracycline (doxorubicin or daunorubicin) the first-line therapy of choice for advanced AIDS-related Kaposi's sarcoma (see Uses: AIDS-related Kaposi's Sarcoma in Doxorubicin 10:00 for overview and further discussion; also see Daunorubicin 10:00).135, 140, 180, 193, 199
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).140, 145, 146, 182, 194 However, the results of several randomized, multicenter trials indicate that patients receiving a liposomal anthracycline for the treatment of advanced AIDS-related Kaposi's sarcoma experience similar or higher response rates with a more favorable toxic effects profile than those receiving combination therapy with conventional chemotherapeutic agents.140, 180, 193, 199
Vinblastine is used in combination regimens with cisplatin and methotrexate, with or without doxorubicin, for the treatment of invasive and advanced bladder cancer†.135, 188, 189, 190, 191 (See Uses: Bladder Cancer, Cisplatin 10:00.)
Vinblastine used in combination with cisplatin and mitomycin (MVP)126 is an alternative regimen for the treatment of non-small cell lung cancer†.135, 192 Currently preferred regimens for the treatment of advanced non-small cell lung cancer include the combination of cisplatin with another agent, such as paclitaxel, vinorelbine, or gemcitabine.135, 192 (See Uses: Non-small Cell Lung Cancer in Cisplatin 10:00.)
Vinblastine is used in combination regimens (e.g., cisplatin, vinblastine, and dacarbazine, with or without interferon alfa and aldesleukin) for the treatment of metastatic melanoma†.135, 216, 218, 219 Evidence from large, randomized trials has not established the superiority of combination regimens compared with dacarbazine alone,212, 215, 217 and dacarbazine monotherapy currently is a systemic treatment of choice for metastatic melanoma. (See Uses: Metastatic Melanoma, in Dacarbazine 10:00.)135, 213, 214, 215, 217
Vinblastine sulfate is labeled for use in the palliative treatment of non-Hodgkin's lymphomas, including lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated) and histiocytic lymphoma, and in advanced stages of mycosis fungoides;127 however, other agents currently are preferred for the treatment of these cancers.135 Vinblastine also is labeled for use in the treatment of Letterer-Siwe disease (histiocytosis X).127
Single-agent vinblastine has been used for the treatment of classic Kaposi's sarcoma.127, 140
Vinblastine in combination with cisplatin and bleomycin has been used for the treatment of intracranial germ cell tumors†.135, 187
Although not as effective as for the previous indications, vinblastine also may be of some use in the palliative treatment of choriocarcinoma127 resistant to other chemotherapeutic agents and cancer of the breast127 which is unresponsive to appropriate endocrine surgery and hormonal therapy.
Vinblastine has been used in the treatment of immune thrombocytopenic purpura†.224 Slow IV infusions of vinblastine106 or the use of vinblastine-loaded platelets107, 108 has reportedly been effective in some cases for the treatment of autoimmune hemolytic anemia†.106, 107, 108
Reconstitution and Administration
Vinblastine sulfate is administered only by IV injection by individuals experienced in the administration of the drug.127 Vinblastine sulfate is very irritating and must not be given IM, subcutaneously, or intrathecally. Intrathecal administration of vinblastine usually results in death .127 When dispensed, the container or syringe holding the individual dose prepared for administration to the patient must be labeled with the statement “Fatal if given intrathecally. For intravenous use only.” and enclosed 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.”127
In addition to the use of the warning labels and overwrap, other protective measures to prevent inadvertent intrathecal administration of vinblastine or other vinca alkaloids include: administering diluted vinca alkaloid solutions in minibags, preparing the medication at the time of administration, attaching a unique filter, dispensing the vinca alkaloid separately from all other medications, dispensing the vinca alkaloid 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 of the drug, and administering the vinca alkaloid in a separate room from rooms where other medications are administered.225
Management of patients mistakenly receiving intrathecal vinblastine is a medical emergency.127 Immediate neurosurgical intervention is required to prevent ascending paralysis leading to death.127 Unfortunately, the prognosis to date (principally with patients inadvertently administered vincristine intrathecally) generally has been poor despite immediate efforts at removing spinal fluid and flushing with lactated Ringer's injection, with such efforts failing to prevent ascending paralysis and death in almost all cases.133 In a very small number of patients, life-threatening paralysis and subsequent death have been averted; however, devastating neurologic sequelae, with limited recovery afterwards, have resulted.127 There are no published cases of survival following intrathecal administration of vinblastine to use as guidance for treatment.127 However, according to the 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.127 When available upon request, fresh frozen plasma (25 mL) should be added to every 1 liter of lactated Ringer's solution.127 An intraventricular drain or catheter should be inserted by a neurosurgeon, and CSF irrigation should be continued with fluid removal through the lumbar access connected to a closed drainage system.127 Lactated Ringer's solution should be given by continuous infusion at a rate of 150 mL/hour, or at a rate of 75 mL/hr when fresh frozen plasma has been added.127 The rate of infusion should be adjusted to maintain a CSF protein concentration of 150 mg/dL.127 Additional measures which also have been used but may not be essential include the administration of glutamic acid, leucovorin, and pyridoxine.127, 133 Glutamic acid has been administered in a dose of 10 g given IV over 24 hours, followed by 500 mg orally 3 times daily for 1 month.127, 133 Leucovorin has been administered as a 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.127 Pyridoxine hydrochloride 50 mg has been administered as an IV infusion over 30 minutes every 8 hours.127 The contribution of these additional therapies to the reduction of neurotoxicity is unclear.127
Vinblastine sulfate powder is reconstituted 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.127 The manufacturers state that other diluents should not be used.127 The appropriate quantity of solution reconstituted from the powder or vinblastine sulfate injection may be injected into the tubing of a running IV infusion or directly into a vein over about a 1-minute period. To minimize the risk of extravasation and/or venous irritation, the manufacturers recommend that vinblastine sulfate not be diluted in large volumes of IV solution (i.e., 100-250 mL) or infused over long periods of time (i.e., from 30-60 minutes or longer); however, the drug has been diluted in larger volumes of IV solution and infused over periods of 3-8 hours in the treatment of refractory idiopathic thrombocytopenic purpura†102, 103 or autoimmune hemolytic anemia†.106 Care should be taken to ensure that the needle or catheter is securely within the vein in order to avoid extravasation.127 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, the injection should be discontinued immediately and the remainder of the dose given through another vein; local treatment of the area of leakage may minimize discomfort and the possibility of cellulitis. (See Cautions: Local Effects.) Because of the enhanced possibility of thrombosis, vinblastine sulfate solutions should not be injected into an extremity with impaired or potentially impaired circulation caused by compression or invading neoplasm, phlebitis, or varicosity.
Vinblastine sulfate injection and solutions reconstituted from the powder should be inspected visually for particulate matter and discoloration whenever solution and container permit.
Although various dosages have been used, the usual adult dosage of vinblastine sulfate recommended by the manufacturers for initiation of therapy is 3.7 mg/m2 given as a single dose.127
According to the manufacturer, a review of published literature from 1993-1995 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.127 When used as monotherapy for the treatment of Letterer-Siwe disease (histiocytosis X), an initial vinblastine sulfate dosage of 6.5 mg/m2 was reported.127 When used in combination with other chemotherapeutic agents for the treatment of Hodgkin's disease, an initial vinblastine sulfate dosage of 6 mg/m2 was used.127 For the treatment of testicular germ cell carcinoma, an initial vinblastine sulfate dosage of 3 mg/m2 has been used in a combination regimen.127
Dosage Modification for Toxicity
Subsequent dosage of vinblastine sulfate must be determined by the clinical and hematologic response and tolerance of the patient in order to obtain optimum therapeutic results with minimum adverse effects.127 Because of the possible leukopenic response that follows administration of vinblastine, the drug is given at intervals of at least 7 days; however, even if 7 days have elapsed, the next dose of vinblastine should not be given until the leukocyte count has returned to at least 4000/mm3.127 Doses are usually increased at weekly intervals in increments of about 1.8 mg/m2 in adults until the desired therapeutic response is obtained, the leukocyte count decreases to about 3000/mm3, or a maximum weekly dose of 18.5 mg/m2 is being administered to adults.127
For most adult patients, the optimum weekly dose of vinblastine sulfate 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 18.5 mg/m2 per week.127 Dosage is generally reduced in patients with recent exposure to radiation therapy or chemotherapy; single doses in these patients usually do not exceed 5.5 mg/m2.
Dosage modifications in pediatric patients should be guided by hematologic tolerance.127
Once the dose required to produce a leukocyte count of 3000/mm3 has been determined, a maintenance dose of one increment (about 1.8 mg/m2 in adults) less than this amount should be administered at weekly intervals.127 Thus, the patient receives the maximum dose of vinblastine sulfate that does not cause leukopenia (leukocyte count of 3000/mm3 or less).
To ensure an adequate trial, vinblastine 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.
Strict adherence to the recommended dosage interval is important. The 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. 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.
The duration of maintenance therapy varies according to the disease being treated and the combination of chemotherapeutic agents being used. Some clinicians have reported successful maintenance with vinblastine sulfate doses administered at intervals as long as 3-8 weeks, but most reports indicate that patients frequently relapse if maintenance dosage intervals exceed 2 weeks. Clinicians should consult published protocols for the dosage of vinblastine and other chemotherapeutic agents and the method and sequence of administration. There are differences of opinion regarding the duration of maintenance therapy with the same protocol for a particular disease. Prolonged chemotherapy for maintaining remissions involves several risks, including life-threatening infectious diseases, sterility, and possibly the appearance of other neoplasms as a result of suppression of the immune system. 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.
Dosage in Renal and Hepatic Impairment
The effect of renal and/or hepatic impairment on the disposition of vinblastine has not been fully determined.127 Reduction of vinblastine dosage in patients with renal impairment does not appear to be necessary.127 Because the drug is extensively metabolized in the liver, doses of vinblastine should be reduced and the drug should be administered with caution in patients with hepatic impairment.127 A 50% reduction in vinblastine sulfate dose is recommended for patients with a direct serum bilirubin exceeding 3 mg/dL.127
In general, adverse reactions to vinblastine are dose related and reversible. Toxicity may be enhanced by the presence of hepatic insufficiency.
The major adverse effect of vinblastine is hematologic toxicity which occurs much more frequently than with vincristine therapy. Leukopenia (granulocytopenia) occurs most commonly and is usually the dose-limiting factor in vinblastine therapy; however, numerous patients have achieved a sustained remission without leukopenia. Leukopenia may not be a problem with small doses used for maintenance therapy; however, the possibility of a cumulative effect should be considered. The nadir in the leukocyte count usually occurs 4-10 days after administration of vinblastine. Recovery occurs rapidly, usually within another 7-14 days; however, following administration of high doses of vinblastine, recovery may take 21 days or more. The patient's hematologic status must be carefully monitored. (See Cautions: Precautions and Contraindications.)
Although thrombocytopenia is usually slight and transient, substantial platelet count depression may occur, particularly in patients who have received prior radiation therapy or chemotherapy. In patients whose bone marrow has been infiltrated with malignant cells, vinblastine may produce an abrupt fall in the leukocyte and thrombocyte counts. If this occurs, the manufacturers recommend that vinblastine therapy be discontinued; however, many clinicians consider it appropriate to continue vinblastine therapy in these patients if the drug is clearly destroying tumor cells in the bone marrow. Anemia also may occur in patients receiving vinblastine.
Acute shortness of breath and bronchospasm, which can be severe or life threatening, have occurred following administration of vinca alkaloids (e.g., vinblastine), and have been reported most frequently when mitomycin was administered concomitantly.127 Such reactions may occur a few minutes to several hours after administration of a vinca alkaloid or up to 2 weeks after a dose of mitomycin.127 Aggressive treatment may be required, particularly in patients with preexisting pulmonary dysfunction.127 Progressive dyspnea, which may require chronic therapy, can occur in patients receiving vinblastine; the drug should not be readministered to these patients.127
Nausea and vomiting are the most frequently occurring adverse GI effects of vinblastine. Nausea and vomiting usually last less than 24 hours, and are reported to be easily controlled by administration of antiemetics. Other adverse GI effects of vinblastine include anorexia, diarrhea, constipation, epigastric and abdominal pain, adynamic ileus, pharyngitis, stomatitis, vesiculation of the mouth, hemorrhagic enterocolitis, rectal bleeding, and bleeding from old peptic ulcers. GI symptoms, particularly constipation, abdominal pain, and adynamic ileus, may be related to the neurotoxicity of vinblastine. Stomatitis, although reversible, can be disabling.
Neurotoxicity occurs occasionally in patients receiving vinblastine, especially with high doses or prolonged therapy, but less frequently than with vincristine therapy. Neurotoxicity can be disabling. Adverse neurologic effects of vinblastine include numbness, paresthesia, peripheral neuropathy and neuritis, mental depression (usually 2-3 days after administration of the drug), loss of deep tendon reflexes, headache, malaise, weakness, dizziness, seizures, psychoses, severe face and jaw pain, severe immediate or delayed pain at the tumor site, bone pain, vocal cord paralysis, and dysfunction of the autonomic nervous system with such symptoms as urinary retention, sinus tachycardia, orthostatic hypotension, and tender parotid glands associated with dry mouth. In some studies, patients who showed marked neurotoxicity following vinblastine therapy later received vincristine without evidence of neuropathy. GI symptoms, headache, and paresthesia may appear 4-6 hours after administration of vinblastine and usually persist for 2-10 hours.
Hypertension is the most common adverse cardiovascular effect of vinblastine.127 Myocardial infarction, angina pectoris, and transient ECG abnormalities related to coronary ischemia have been reported rarely in patients receiving the drug.127 Caution is advised when using vinblastine in patients with ischemic cardiovascular disease, and care of this condition should be recommended.127 Cases of unexpected myocardial infarction and cerebrovascular accident have been reported in patients receiving vinblastine in combination with bleomycin and cisplatin.127 Raynaud's phenomenon has been reported in patients receiving vinblastine and bleomycin, with or without cisplatin; a few cases have been reported in patients receiving bleomycin alone.127, 223
Vinblastine is a tissue irritant and 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. The 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.
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. Fever has also occurred in patients receiving vinblastine.
Eighth cranial nerve damage, which may be manifested by vestibular manifestations such as dizziness, nystagmus, and vertigo, and by auditory manifestations such as varying degrees of hearing impairment (including partial or total deafness) that may be temporary or permanent, has been reported in patients receiving vinca alkaloids.127 Vinca alkaloids should be used concomitantly with other potentially ototoxic drugs such as platinum-containing antineoplastic agents with extreme caution.127
Precautions and Contraindications
Vinblastine sulfate is a highly toxic drug with a low therapeutic index, and a therapeutic response is not likely to occur without some evidence of toxicity. The drug must be used only under constant supervision by clinicians experienced in therapy with cytotoxic agents. Patients and/or their parents or guardians should be advised of the possibility of adverse effects and associated manifestations.
Patients with cachexia or ulcerated areas of the skin may be more susceptible to the leukopenic effects of vinblastine; therefore, the drug should be administered with extreme caution to patients (especially geriatric patients) with these conditions.
Patients who receive myelosuppressive drugs experience an increased frequency of infections as well as possible hemorrhagic complications. Because these complications are potentially fatal, the patient should be instructed to notify the physician if fever, sore throat, or unusual bleeding or bruising occurs. Blood counts should be performed weekly or at least before administration of each dose of vinblastine. The manufacturers state that if the leukocyte count falls below 2000/mm3, patients should be observed carefully for signs of infection. The effect of vinblastine on the erythrocyte count and hemoglobin is usually insignificant; however, it should be remembered that patients with malignant disease may exhibit anemia in the absence of any therapy.
Patients with preexisting pulmonary dysfunction may be particularly susceptible to severe or life-threatening pulmonary effects of vinblastine.127 (See Cautions: Respiratory Effects.)
Caution is advised when using vinblastine in patients with ischemic cardiovascular disease, and care of this condition should be recommended.127
Care must be taken to avoid contact of vinblastine sulfate solutions with the eyes as severe irritation and possibly corneal ulceration can result; if contact occurs, the eye should be thoroughly washed with water immediately.
As a result of extensive purine catabolism accompanying rapid cellular destruction, hyperuricemia may occur in some patients receiving vinblastine, especially those with non-Hodgkin's lymphomas or leukemia. In some patients, uric acid nephropathy may result. These effects may be minimized by adequate hydration, alkalinization of the urine, and/or administration of allopurinol.
For additional information on precautions associated with the use of vinblastine, see Cautions: Hematologic Effects and Cautions: Local Effects.
Because of the hepatic metabolism and biliary excretion of vinblastine, some clinicians recommend reduced doses in patients with obstructive or hepatocellular jaundice. Metabolism of vinblastine via cytochrome P-450 (CYP) isoenzymes may be impaired in patients with hepatic dysfunction.127
The manufacturers state that vinblastine is contraindicated in patients who are severely leukopenic. The manufacturers also state that the drug should not be administered in the presence of bacterial infections; infections should be controlled prior to initiation of vinblastine therapy.
Pregnancy, Fertility, and Lactation
Although information on the use of vinblastine during pregnancy is limited, the drug may cause fetal toxicity when administered to pregnant women. The drug causes resorption of fetuses in animals and produces gross fetal abnormalities in surviving offspring. There are no adequate and controlled studies to date using vinblastine in pregnant women, and the drug should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug. When vinblastine is administered during pregnancy or the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.
The effect of vinblastine on fertility in humans is not fully known. Aspermia has occurred in some individuals during vinblastine therapy. Reproduction studies in animals have revealed evidence of metaphase arrest and degenerative changes in germ cells.
It is not known whether vinblastine is distributed in milk.127 Because of the potential for serious adverse reactions to vinblastine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.127
Drugs Affecting Hepatic Microsomal Enzymes
Metabolism of vinca alkaloids (e.g., vincristine, vinblastine) is mediated by the cytochrome P-450 isoenzyme CYP3A, and caution should be exercised when vinca alkaloids are used concurrently with inhibitors of this isoenzyme.127, 185
Increased toxicity has been reported in patients receiving concomitant erythromycin and vinblastine.127
Concomitant administration of vincristine and the antifungal agent itraconazole, a potent inhibitor of CYP3A, has been associated with earlier onset and/or increased severity of adverse neuromuscular effects, presumably because of inhibition of vincristine metabolism.184, 185 In vitro studies demonstrate that antifungal agent voriconazole is a less potent inhibitor of CYP3A4 than ketoconazole or itraconazole.220 Because concomitant use of voriconazole or other azole antifungal agents may increase plasma concentrations of vinblastine and lead to neurotoxicity, dosage reduction of vinblastine should be considered.220 Patients receiving a vinca alkaloid and itraconazole or other azole antifungal agent concomitantly should be monitored for increases in and/or prolongation of the effects of the vinca alkaloid, including adverse effects such as peripheral neuropathy and ileus, and dosage of the vinca alkaloid should be reduced accordingly.186, 220
Because it is a potent CYP3A4 inhibitor, vinblastine may cause increased plasma concentrations of tolterodine during concomitant use; reduction to 50% of the recommended dose for tolterodine is recommended.222
Caution and careful monitoring are advised during concomitant use of vinblastine and aprepitant, an antiemetic agent, which may inhibit or induce CYP3A.221
Since varying degrees of permanent or temporary hearing impairment (including partial or total deafness) associated with eighth cranial nerve damage have been reported in patients receiving vinca alkaloids, vinblastine should be used concomitantly with other potentially ototoxic drugs such as platinum-containing antineoplastic agents with extreme caution.127
In patients receiving phenytoin and combination regimens containing vinblastine, decreased serum concentrations of phenytoin and increased seizure activity have been reported, possibly as a result of decreased absorption and/or increased metabolism of phenytoin.127, 131 The contribution of vinblastine to this interaction is uncertain;127 however, in patients receiving phenytoin and vinblastine concomitantly, serum concentrations of phenytoin should be monitored and dosage adjustments made as necessary.127, 131
Although the mechanism of action has not been 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.134, 139 The 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.134 In high concentrations, vinblastine also exerts complex effects on nucleic acid and protein synthesis. Vinblastine reportedly 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. Vinblastine exerts some immunosuppressive activity.
Vinblastine sulfate is unpredictably absorbed from the GI tract. Following IV administration, the drug is rapidly cleared from the blood and distributed into body tissues. Vinblastine crosses the blood-brain barrier poorly and does not appear in the CSF in therapeutic concentrations. Vinblastine is reported to be extensively metabolized, primarily in the liver, to desacetylvinblastine, which is more active than the parent compound on a weight basis. Metabolism of vinca alkaloids (e.g., vinblastine, vincristine) is mediated by the cytochrome P-450 isoenzymes in the CYP3A subfamily.127 The drug is excreted slowly in urine and in feces via the bile.
Vinblastine sulfate, a naturally occurring vinca alkaloid, is an antimicrotubule antineoplastic agent.134, 139 Vinblastine sulfate is the salt of a dimeric alkaloid isolated from Cantharanthus roseus. Vinblastine sulfate occurs as a white, off-white, or slightly yellow, hygroscopic, amorphous or crystalline powder and is freely soluble in water, soluble in methanol, and slightly soluble in ethanol.127 Vinblastine sulfate is insoluble in benzene, ether, and naphtha.127 Commercially available vinblastine sulfate powder occurs as a yellowish white solid having the characteristic appearance of a lyophilized preparation. Vinblastine sulfate injection is a clear, colorless solution with a pH of 3-5.5; the injection also contains sodium chloride and benzyl alcohol. Vinblastine reportedly has pKas of 5.4 and 7.4.
Vinblastine sulfate powder, vinblastine sulfate injection, and solutions of the drug are light-sensitive and must be protected from light. Vinblastine sulfate powder and injection should be refrigerated at 2-8°C. Following reconstitution of the powder with bacteriostatic sodium chloride injection which contains benzyl alcohol as a preservative, solutions of the drug have a pH of 3.5-5 and are stable for 28 days when refrigerated at 2-8°C.127 Sodium chloride injection (without preservatives) also may be used as a diluent.127 The manufacturer states that other diluents should not be used.127 When vinblastine sulfate powder is reconstituted with a diluent that does not contain a preservative, any unused portions of reconstituted solution of the drug should be discarded immediately.127
Additional Information
For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV use only | 1 mg/mL* | Vinblastine Sulfate Injection | |
For injection, for IV use only | 10 mg* | Vinblastine Sulfate for Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
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