Vinblastine

810.97

810.97

212-734-0

5V9KLZ54CY

DTXSID8021430

C930

Solvated needles from methanol

L01CA01|L - Antineoplastic and immunomodulating agents

154.10000

4.18

POWDER

1.4±0.1 g/cm3

211-216 °C

1.671

Negligible

Vinblastine sulfate sterile powder, vinblastine sulfate injection, and solutions of the drug are light sensitive and must be protected from light. Vinblastine sulfate sterile powder and injection should be refrigerated at 2-8 °C. Following reconstitution of the sterile powder with bacteriostatic sodium chloride injection which contains phenol or 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.

1.03X10-27 mm Hg at 25 °C (est)

LD50 intraperitoneal in mouse: 3120ug/kg

D23 -32° (c = 0.88 in methanol)

pKa1 = 5.4; pKa2 = 7.4

DECOMP AT 244-246 °C; CRYSTALS /VINBLASTINE DIHYDROCHLORIDE DIHYDRATE/|Hydroxyl radical reaction rate constant = 6.44X10-10 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 1.13X10-17 cu cm/molec-sec at 25 °C (est)

II

6.1(a)

1544

YY8050000

SOLN MAY BE STORED IN REFRIGERATOR FOR PERIODS OF 30 DAYS WITHOUT SIGNIFICANT LOSS OF POTENCY /VINBLASTINE SULFATE/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/|For more Disposal Methods (Complete) data for VINBLASTINE (8 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl vinblastine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /Vinblastine sulfate/

Weisburger EK; Bioassay Program for Carcinogenic Hazards of Cancer Chemotherapeutic Agents; Cancer 40: 1935-49 (1977). Route: ip injection; Species: rats and mice.|Zhou XJ, Rahmani R; Preclinical and Clinical Pharmacology of Vinca Alkaloids. Drugs 44 (Suppl 4): 1-16; 66-9 (1992). Vinca alkaloids, including vinblastine, vincristine, vindesine and vinorelbine, are widely used antineoplastic drugs, either as single agents or in combination with other drugs. Numerous studies have been conducted in animals and humans, using various in vivo and in vitro models, to investigate the pharmacological behavior of this class of antitumor drug.|Smith BD; Antitumor Update: Vinca Alkaloids and Epipodophyllotoxins. Hosp Formul22 (Apr): 363-4, 367-8 (1987). A review of the toxicity, dosage and administration and indications of vincristine sulfate (Oncovin), vinblastine sulfate (Velban), vindesine, vinzolidine sulfate, etoposide (VP-16-213; Vepesid) and teniposide (VM-26) in the treatment of malignancies is presented.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/|For more Preventive Measures (Complete) data for VINBLASTINE (19 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

Care must be taken to avoid contact of vinblastine sulfate solutions with the eyes as severe irritation and possibly corneal ulceration can result.|... A nurse who sought attention 6 days after squirting vinblastine solution in one eye, having developed by this time photophobia, pain, tearing, and redness of the eye, with vision reduced to 1/10 /is described/. Microcystic edema involved the entire corneal epithelium, and in the following days the epithelium ulcerated and came off in small sheets. Healing from the periphery toward the center began 2 wk after the accident, and in 3.5 wk the eye returned to normal.

Vinblastine was detected, not quantified in hospital waste water from Ruhr University, Germany (detection limit 0.01 mg/L)(1).

Oral, mouse: LD50 = 423 mg/kg; Oral, rat: LD50 = 305 mg/kg.

Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily, or in patients with hepatic dysfunction. Concurrent administration of vinblastine sulfate with an inhibitor of this metabolic pathway may cause an earlier onset and/or an increased severity of side effects.|The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vinblastine sulfate has been reported to have reduced blood levels of the anticonvulsant and to have increased seizure activity.|Potential synergistic interactions between vinblastine and recombinant interferon-beta were assessed using median effect analysis. Calculation of the combination index demonstrated values less than 1 (indicating synergy) over a wide range of drug induced growth inhibition for each of four different renal carcinoma cell lines. The degree of synergy observed could not be predicted from the morphology, doubling time, or relative sensitivity of the renal carcinoma cell lines to vinblastine and recombinant interferon-beta. The optimal ratio of vinblastine to recombinant interferon-beta in the combination appeared to be close to the ratio of the concn of each agent which yielded a 50% inhibition of growth. Although simultaneous presence of vinblastine and recombinant interferon-beta in the culture medium was not required to demonstrate a synergistic effect, the minimum exposure time for recombinant interferon-beta was determined to be 7 days. The uptake but not the egress of tritiated vinblastine into renal carcinoma cell line cells was enhanced after growth for 4 days in 2.25 ng/mL of recombinant interferon-beta. Median effect analysis can be shown to be independent of the mechanism of action of vinblastine and recombinant interferon-beta and gives an indication of potential synergistic interactions over a wide range of drug effects. This method may prove useful in the selection of combinations of IFNs and antitumor drugs for clinical study.|A HIV infected patient was treated for stage IVB Hodgkin's lymphoma by ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy and lopinavir-ritonavir based antiretroviral therapy inducing profound life-threatening neutropenia. Vinblastine and lopinavir-ritonavir interaction was managed with lopinavir-ritonavir interruption around chemotherapy administration, with complete remission and immunovirological success after six cycles.|For more Interactions (Complete) data for VINBLASTINE (6 total), please visit the HSDB record page.

Because of the hepatic metabolism and biliary excretion of vinblastine, some clinicians recommend reduced doses in patients with obstructive or hepatocellular jaundice.|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.

98-99%

Vinblastine is derived from periwinkle, Vinca rosea, Linn(1).

Vinblastine's production and use as an antineoplastic drug(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2,400(SRC), determined from a log Kow of 3.70(2) and a regression-derived equation(3), indicates that vinblastine is expected to have slight mobility in soil(SRC). The pKa1 and pKa2 of vinblastine are 5.4 and 7.4, respectively(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the base exists as a cation and cations do not volatilize. Vinblastine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of <10-8 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2008).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2,400(SRC), determined from a log Kow of 3.70(2) and a regression-derived equation(3), indicates that vinblastine is expected to adsorb to suspended solids and sediment(SRC). pKa values of 5.4 and 7.4(4) indicate vinblastine will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 140(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC). Biodegradation data were not available(SRC, 2008).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), vinblastine, which has an estimated vapor pressure of <10-8 mm Hg a 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase vinblastine may be removed from the air by wet or dry deposition(SRC). Vinblastine contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 4.2X10-2 L/mole-sec(SRC) for the ester functional groups was estimated using a structure estimation method(1); this corresponds to half-lives of 5 years and 200 days at pH values of 7 and 8, respectively(1). Therefore, hydrolysis is not expected to be an important environmental fate process(SRC). Vinblastine contains chromophores that absorb at wavelengths >290 nm(2) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 140 was calculated in fish for vinblastine(SRC), using a log Kow of 3.70(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of vinblastine is estimated as 2,400(SRC), using a log Kow of 3.70(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that vinblastine is expected to have slight mobility in soil. The pKa1 and pKa2 of vinblastine are 5.4 and 7.4(4), respectively, indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

A pKa1 of 5.4 and a pKa2 of 7.4(1) indicate vinblastine will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces or moist soil is not expected to be an important fate process(2). Vinblastine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of <10-8 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 2,136 workers (1,159 of these were female) were potentially exposed to vinblastine in the US(1). Occupational exposure to vinblastine may occur through inhalation and dermal contact with this compound at workplaces where vinblastine is produced or used. Exposure to vinblastine among the general population may be limited to those administered this drug, an antitumor alkaloid(SRC).

For treatment of breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin's and non-Hodgkin's lymphomas, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.|Drug: Veip

Antineoplastic Agents, Phytogenic|Vinblastine sulfate is indicated in the palliative treatment of the following: Frequently Responsive Malignancies: Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system), Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated), histiocytic lymphoma, mycosis fungoides (advanced stages), advanced carcinoma of the testis, Kaposi's sarcoma, Letterer-Siwe disease (histiocytosis X). Less Frequently Responsive Malignancies: Choriocarcinoma resistant to other chemotherapeutic agents, carcinoma of the breast, unresponsive to appropriate endocrine surgery and hormonal therapy. Current principles of chemotherapy for many types of cancer include the concurrent administration of several antineoplastic agents. For enhanced therapeutic effect without additive toxicity, agents with different dose-limiting clinical toxicities and different mechanisms of action are generally selected. Therefore, although vinblastine sulfate is effective as a single agent in the aforementioned indications, it is usually administered in combination with other antineoplastic drugs. /Included in US product label/|Vinblastine sulfate has been shown to be one of the most effective single agents for the treatment of Hodgkin's disease. Advanced Hodgkin's disease has also been successfully treated with several multiple-drug regimens that included vinblastine sulfate. /Included in US product label/|Advanced testicular germinal-cell cancers (embryonal carcinoma, teratocarcinoma, and choriocarcinoma) are sensitive to vinblastine sulfate alone, but better clinical results are achieved when vinblastine sulfate is administered concomitantly with other antineoplastic agents. /Included in US product label/|For more Therapeutic Uses (Complete) data for VINBLASTINE (11 total), please visit the HSDB record page.

This preparation is for intravenous use only. It should be administered by individuals experienced in the administration of vinblastine sulfate injection. The intrathecal administration of vinblastine sulfate injection usually results in death. Syringes containing this product should be labeled, using the auxiliary sticker provided, to state "FATAL IF GIVEN INTRATHECALLY. FOR INTRAVENOUS USE ONLY."|Vinblastine sulfate is contraindicated in patients who have significant granulocytopenia unless this is a result of the disease being treated.|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. ... 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. ... 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), being 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 wk after a dose of mitomycin. Progressive dyspnea ... can occur in patients receiving vinblastine; the drug should not be readministered to these patients.|For more Drug Warnings (Complete) data for VINBLASTINE (21 total), please visit the HSDB record page.

Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units: vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.

Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. (See all compounds classified as Antineoplastic Agents, Phytogenic.)|Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES. (See all compounds classified as Tubulin Modulators.)

The major route of excretion may be through the biliary system.|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.|The volume of the central compartment is 70% of body weight, probably reflecting very rapid tissue binding to formed elements of the blood. Extensive reversible tissue binding occurs. Low body stores are present at 48 and 72 hours after injection.|Following injection of tritiated vinblastine in the human cancer patient, 10% of the radioactivity was found in the feces and 14% in the urine; the remaining activity was not accounted for. Similar studies in dogs demonstrated that, over 9 days, 30% to 36% of radioactivity was found in the bile and 12% to 17% in the urine. A similar study in the rat demonstrated that the highest concentrations of radioactivity were found in the lung, liver, spleen, and kidney 2 hours after injection.|It is not known whether this drug is excreted in human milk.|For more Absorption, Distribution and Excretion (Complete) data for VINBLASTINE (9 total), please visit the HSDB record page.

Hepatic. Metabolism of vinblastine has been shown to be mediated by hepatic cytochrome P450 3A isoenzymes.|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.|Since the major route of excretion may be through the biliary system, toxicity from this drug may be increased when there is hepatic excretory insufficiency. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes such as erythromycin.

Triphasic: 35 min, 53 min, and 19 hours|Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle, and terminal half-lives are 3.7 minutes, 1.6 hours, and 24.8 hours, respectively.|The elimination of VLB from the plasma of patients who received it by 5-day iv infusion at 1 to 2 mg/sq m daily was biphasic. In four patients who achieved partial remission, the average plasma half-life of VLB during the terminal phase was 29.4 +/- 14.6 days ... However, in three patients whose disease merely stabilized, the plasma half-life was 6.4 +/- 1.6 days ... In contrast, in five patients with refractory disease, this parameters was 2.3 +/- 0.3 days...|The pharmacokinetics of vinblastine in humans was examined using a radioimmunoassay specific for both the Vinca alkaloids and aromatic ring [3H]vinblastine. The data were consistent with a three-compartment open model system with the following values, alpha phase: t1/2=3.90+/-1.46 min; Vc=16.8+/-7.1 liters. beta phase:t1/2=53.0+/-13.0 min; Vbeta=79.0+/-52.0 liters; gamma phase:t1/2=1173.0+/-65.0 min; Vgamma=1656.0+/-717.0 liters. ...

The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.|Although the mechanism of action has not been definitely established, vinblastine appears to bind to or crystallize critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerization and causing metaphase arrest. 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.|Experimental data indicate that the action of vinblastine sulfate is different from that of other recognized antineoplastic agents. Tissue-culture studies suggest an interference with metabolic pathways of amino acids leading from glutamic acid to the citric acid cycle and to urea. In vivo experiments tend to confirm the in vitro results. A number of in vitro and in vivo studies have demonstrated that vinblastine sulfate produces a stathmokinetic effect and various atypical mitotic figures.|... Studies indicate that vinblastine sulfate has an effect on cell-energy production required for mitosis and interferes with nucleic acid synthesis. The mechanism of action of vinblastine sulfate has been related to the inhibition of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage.|Reversal of the antitumor effect of vinblastine sulfate by glutamic acid or tryptophan has been observed. In addition, glutamic acid and aspartic acid have protected mice from lethal doses of vinblastine sulfate. Aspartic acid was relatively ineffective in reversing the antitumor effect.

Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. Extravasation: Immediately stop the infusion and withdraw as much fluid as possible by negative pressure on the syringe. Then give the following specific treatment: Place a heating pad over the area and apply heat intermittently for 24 hours; elevate the limb. Local injection of hyaluronidase may be beneficial. Do not use ice packs. /For/ decontamination administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Because of the rapid intracellular incorporation of these agents, dialysis and other extracorporeal removal procedures are generally not effective. /Antineoplastic agents/|Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Treatment with vinca alkaloids has resulted ... in both vestibular and auditory damage to the eighth cranial nerve. Manifestations include partial or total deafness which may be temporary or permanent, and difficulties with balance including dizziness, nystagmus, and vertigo.|/SIGNS AND SYMPTOMS/ Symptoms of overdose will appear when greater-than-recommended doses are given. Any dose of vinblastine sulfate that results in elimination of platelets and neutrophils from blood and marrow and their precursors from marrow should be considered life-threatening. The exact dose that will do this in all patients is unknown.|/SIGNS AND SYMPTOMS/ Clinical as well as experimental studies ... demonstrated that bone-marrow depression, chiefly manifested by leukopenia, is most important cytotoxic effect on normal cells. ... Neurological manifestations /are characterized by/ ... temporary mental depression, paresthesias, loss of deep-tendon reflexes, and more rarely, headache, convulsions, and psychoses ... .|/SIGNS AND SYMPTOMS/ ... Dysfunction of autonomic nervous system, with marked constipation, paralytic ileus, urinary retention, bilateral pain and tenderness of parotid glands associated with dryness of mouth, and sinus tachycardia, has been reported at higher doses. GI disturbances, including nausea, vomiting, anorexia, and diarrhea... Dermatological manifestations are infrequent, but loss of hair, vesicular mucositis of mouth, and dermatitis may occur. Extravasation during injection may lead to cellulitis and phlebitis.|For more Human Toxicity Excerpts (Complete) data for VINBLASTINE (15 total), please visit the HSDB record page.

cellblastin

Parenteral Injection, for IV use only 1 mg/mL, Vinblastine Sulfate Injection (with benzyl alcohol 0.9%), Abraxis; Sterile, for IV use only 10 mg, Bedford|Vials, 10 mg /Vinblastine sulfate/

VINBLASTINE IS CLASS II IMMUNOSUPPRESSIVE DRUG, BUT IT HAS NOT BEEN EXPLOITED FOR THIS PURPOSE. /VINBLASTINE SULFATE/|Antitumor alkaloid

Analyte: vinblastine sulfate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /vinblastine sulfate/|Analyte: vinblastine sulfate; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 262 nm with comparison to standards /vinblastine sulfate/|Analyte: vinblastine sulfate; matrix: pharmaceutical preparation (injection); procedure: liquid chromatography with ultraviolet detection at 262 nm with comparison to standards (chemical purity) /vinblastine sulfate/|For more Analytic Laboratory Methods (Complete) data for VINBLASTINE (7 total), please visit the HSDB record page.

RADIOIMMUNOASSAY IS USED TO ANALYZE BIOLOGICAL FLUIDS. LIMIT OF DETECTION IS 450NG. /VINBLASTINE SULFATE/|Analyte: vinblastine; matrix: blood (plasma, whole); procedure: high-performance liquid chromatography with ultraviolet detection at 268 nm; limit of detection: less than 120 ng/mL|Analyte: vinblastine; matrix: blood (plasma), urine; procedure: high-performance liquid chromatography with fluorescence detection at 270 nm (excitation) and 320 nm (emission); limit of detection: 1 ng/mL|Analyte: vinblastine; matrix: blood (whole), urine; procedure: high-performance liquid chromatography with ultraviolet detection at 200.5 nm|Analyte: vinblastine; matrix: tissue (heart, kidney, liver, lung, muscle); procedure: high-performance liquid chromatography with ultraviolet detection at 220 nm; limit of detection: 10 ng/g

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