Velbastine

Vinblastine sulfate.

Each vial contains: Vinblastine sulfate 10 mg.
Each Diluent for Vinblastine sulfate vial contains: Water for Injection 10 mL, Benzyl alcohol 90 mg, Sodium chloride 90 mg.

Pharmacology: Pharmacodynamics: Although the mechanism of action has not been definitely established, vinblastine appears to bind to or crystallise critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerisation 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 utilisation of glutamic acid and thus inhibits purine synthesis, the citric acid cycle, and the formation of urea. Vinblastine exerts some immunosuppressive activity.
Pharmacokinetics: Vinblastine sulfate is unpredictably absorbed from the GI tract. Following intravenous 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 metabolised, primarily in the liver, to desacetylvinblastine, which is more active than the parent compound on a weight basis. The drug is excreted slowly in urine and in faeces via the bile.

Vinblastine sulfate is effective as a single agent, but its therapeutic effect is enhanced when used in combination with other antineoplastic drugs.
Vinblastine sulfate is used in the treatment of Hodgkin's disease (Stage III and IV); lymphocytic lymphoma; histiocytic lymphoma; advanced stages of mycosis fungoides; advanced carcinoma of the testis; Kaposi's sarcoma and histiocytosis X.
Vinblastine sulfate is used for the treatment of choriocarcinoma resistant to other chemotherapeutic agents; carcinoma of the breast.

There are variations in the depth of the leukopenic response that follows therapy with Vinblastine sulfate. For this reason, it is recommended that the drug be given no more frequently than once every 7 days. It is wise to initiate therapy for adults by administering a single intravenous dose of 3.7 mg/m² of body surface area (BSA); the initial dose for children should be 2.5 mg/m². Thereafter, white-blood counts should be made to determine the patient's sensitivity to Vinblastine sulfate (see Table).

Click on icon to see table/diagram/image

For the adult patients, this dosage will be 5.5 mg/m²-7.4 mg/m². However, the dosage should be carefully considered according to a patient's clinical response (tolerance to vinblastine, hematologic response, etc) in order to obtain maximum therapeutic effect and minimal side effect.
A reduction of 50% in the dose of Vinblastine sulfate is recommended for patients having a direct serum bilirubin value above 3 mg/100 mL.
Prolonged chemotherapy for maintaining remissions involves several risks such as life-threatening infections, sterility and possibly the appearance of other cancers through suppression of immune response.

Adverse reactions following the use of vinblastine sulfate are dose-related. Therefore, following administration of more than the recommended dose, patients can be expected to experience these effects in an exaggerated fashion. There is no specific antidote.
Treatment: Prevention of adverse effects that result from the syndrome of inappropriate secretion of antidiuretic hormone (this would include restriction of the volume of daily fluid intake to that of the urine output plus insensible loss and perhaps the administration of a diuretic affecting the function of the loop of Henle and the distal tubule);
Administration of an anticonvulsant (Phenobarbital); Use of enemas or cathartics to prevent ileus (In some instances, decompression of the gastrointestinal tract may be necessary.);
Monitoring the cardiovascular system; Determining daily blood counts for guidance in transfusion requirements and assessing the risk of infection. If necessary, give a blood transfusion. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc.

Severe hypersensitivity to the drug. Patients with leukopenia; Patients with bacterial infection (such infections should be brought under control with antibiotics before the initiation of therapy with Vinblastine sulfate).

Patients with hepatic disorder; renal disorder; bone marrow depression; infections; history of muscular or neural disease; chickenpox (fatal systemic disorder may occur.)
When cachexia or ulcerated areas of the skin are present, a more profound leukopenic response may be produced by Vinblastine sulfate; therefore, the drug should be avoided in geriatric patients suffering from either of these conditions.
Blood cell counts have sometimes fallen precipitously after moderate doses of Vinblastine sulfate in patients with malignant cell infiltration of the bone marrow. Adverse effects such as bone marrow depression, peripheral nerve disorder may occur; therefore, frequent clinical tests (blood test, liver function, renal function test) should be done and the patients should be observed sufficiently. If any symptoms occur, the administration should be discontinued or reduced. Prolonged therapy may have severe adverse effects; therefore, the administration should be considered.
Manifestation of bleeding tendency and infection should be cautioned.
If leukopenia with less than 2,000 white blood cells/mm³ occurs, following a dose of Vinblastine sulfate, the patient should be observed carefully for evidence of infection until the white-blood-cell count has returned to a safe level.
Others: Vinca alkaloids have been reported to cause myocardial infarction, cerebral infarction in either alone or in combination with other antineoplastic drugs.
Use in Pregnancy & Lactation: Animal studies have demonstrated teratogenic effects, Vinblastine Sulfate should not be administered in pregnant women or women suspected of pregnancy. Safety use in lactation has not been established and therefore breast feeding should be avoided during the therapy.
Use in Children: Use in children should be cautioned about manifestation of adverse effects, and the administration should be considered.
Use in children or patients of child-bearing potential should be considered about effects on gonad.

Animal studies have demonstrated teratogenic effects, Vinblastine Sulfate should not be administered in pregnant women or women suspected of pregnancy.
Safety use in lactation has not been established and therefore breast feeding should be avoided during the therapy.

Hematologic: Leukopenia, thrombocytopenia; occasionally, bleeding, anemia may occur.
Gastrointestinal System: Nausea, vomiting; occasionally, anorexia, dipsia, stomatitis, infection of the lip, abdominal pain, rectal bleeding, ileus, constipation, cacogeusia, and indigestion may occur.
Hypersensitivity: Anaphylactoid syndrome (urticaria, dyspnea, angioedema) may occur. If they occur, the administration should be discontinued and/or appropriate therapy should be initiated.
Dermatologic: Occasionally, alopecia, blister, rash may occur.
Neurologic: Occasionally, paraesthesia, peripheral neuritis, loss of deep tendon reflexes, dysbasia, convulsion, arthralgia, myalgia, headache, dizziness, depression, hyposomnia; rarely, confusion, coma, apprehension may occur.
Gonad: Aspermia, gonad (testis, ovary) disorder may occur.
Respiratory System: Acute shortness of breath and severe bronchospasm has been reported following the administration of this drug. These reactions have been encountered most frequently when this drug was used in combination with mitomycin-C.
Other: Occasionally, dysuria, flush, phlebitis, local pain of injection site, sphacelism, boil or wart, lymph node pain, tachycardia may occur.
Extravasation during intravenous injection may lead to cellulitis and phlebitis. If the amount of extravasation is great, sloughing may occur.

Concomitant administration with other antineoplastics or radiotherapy may cause increase of adverse effects including bone marrow depression.
Concomitant administration with erythromycin has been reported that action of this drug was enhanced.

Vinblastine Sulfate should be administered intravenously only. Intrathecal administration may result in death.
Vinblastine Sulfate should be given intravenously at weekly intervals. The use of small amounts of Vinblastine Sulfate daily for long periods is not advised, even though the resulting total weekly dosage may be similar to that recommended. No added therapeutic effect has been demonstrated and adverse effects (i.e. convulsions, severe CNS toxicity) have been observed when such regimens have been used.
It is extremely important that the needle be properly positioned in the vein before this product is injected. If leakage into surrounding tissue should occur during intravenous administration of Vinblastine Sulfate, it may cause considerable irritation. The injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis. Care must be taken to avoid contamination of the eye with concentrations of Vinblastine Sulfate used clinically. If accidental contamination occurs, severe irritation or corneal ulceration may result. The eye should be washed with water immediately and thoroughly.
The dose should not be diluted in large volumes of diluent (100 to 200 mL) or given intravenously for prolonged periods (ranging from 30 to 60 minutes or more), since this frequently results in irritation of the vein and increases the chance of extravasation.

Preserve in sealed containers at a cool and dark place. Store at 2°C-8°C. Refrigerate. Do not freeze.

Cytotoxic Chemotherapy

L01CA01 - vinblastine ; Belongs to the class of plant alkaloids and other natural products, vinca alkaloids and analogues. Used in the treatment of cancer.

Rx

Powd for inj (vial) 10 mg (white freeze-dried cake; clear solution) x 10 mL x 1's.