This preparation is for intravenous use only. It should be administered only by individuals experienced in vindesine administration. 4 for the treatment of patients given intrathecal vindesine sulphate Extreme care must be used in calculating and administering the dose of vindesine, since overdosage may have a very serious or fatal outcome.
It is recommended that the drug be administered intravenously in a single rapid bolus injection at weekly intervals. The size of the dose is determined by body surface area. In adults and the elderly, the recommended starting dose is 3mg/m2, and children may be started at 4mg/m2.
Thereafter, granulocyte counts should be made prior to each subsequent dose to determine the patient's sensitivity to the drug. 5mg/m2 steps at weekly intervals. In adults, the maximum total weekly dosage for which data exists is 4mg/m2.
The optimum dose of vindesine is that which produces mild to modest granulocytopenia. Sustained granulocyte counts lower than 2,500 cells/mm3 are to be avoided. Those with decreased marrow function from leukaemia infiltration or replacement will require full doses to attempt to restore marrow function.
This must be done under close supervision. 4). On each of the above occasions there should be full recovery before administering the next dose, which should be reduced from the one causing the adverse reaction. 0mg/m2 in children. The use of small amounts of vindesine daily for long periods is not advised, even though the resulting total weekly dosage may be similar to that recommended.
Little or no added therapeutic advantage has been demonstrated when such regimens have been used, and side effects are increased. Strict adherence to the recommended dosage schedule is very important. As vindesine is excreted principally by the liver, it may be necessary to reduce initial doses in the presence of significantly impaired hepatic or biliary function.
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.
5). 9% sodium chloride intravenous infusion to the 5mg of Eldisine in the sterile vial. The drug dissolves rapidly to give a clear solution. The dose of Eldisine solution (calculated to provide the desired number of milligrams per square metre of the patient's surface area) may be injected either into the tubing of a running intravenous infusion (compatible infusions are 5% Dextrose Intravenous Infusion BP, Sodium Chloride Intravenous Infusion BP and dextrose/saline infusions) or directly into a vein.
The latter procedure is readily adaptable to outpatient therapy. In either case, the injection should be completed in 1 to 3 minutes. If care is taken to ensure that the needle is securely within the vein and that no solution containing vindesine is spilled extravascularly, cellulitis and/or phlebitis is unlikely to occur.
Because of the enhanced possibility of thrombosis, it is considered inadvisable to inject a solution into an extremity in which the circulation is impaired, or potentially impaired, by such conditions as compressing or invading neoplasm, phlebitis or varicosity.
Caution It is extremely important to choose the largest accessible vein and to be certain that the needle is properly positioned in the vein before any vindesine is injected. If leakage into surrounding tissues should occur during intravenous administration, it may cause considerable irritation.
The injection should be discontinued as soon as leakage occurs, 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 minimise discomfort and the possibility of cellulitis.