Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Genus Pharmaceuticals Limited, T/A Genus Pharmaceuticals, Linthwaite, Huddersfield, HD7 5QH, UK
Eldisine is an anti-neoplastic drug for intravenous use which can be used alone or in combination with other oncolytic drugs. Information available at present suggests that Eldisine as a single agent may be useful for the treatment of:
This preparation is for intravenous use only. It should be administered only by individuals experienced in vindesine administration.
FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES.
See special warnings in section 4.4 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. Provided there is no granulocytopenia or other toxicity (see ‘Undesirable Effects’) the dosage may be increased in 0.5mg/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.
The dose should not be increased after that dose which: (i) reduces the granulocyte count to below l500 cells/mm³ or, on rare occasions, (ii) reduces the platelet count to below 100,000/mm³; (iii) causes acute abdominal pain (see section 4.4).
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. For most patients, however, the weekly dosage will prove to be in the range of 3.0 to 4.0mg/m² in adults and 4.0 to 5.0mg/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. (see section 4.5).
To prepare a solution containing 1mg/ml add 5ml of sterile 0.9% 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.
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.
Side effects following the use of vindesine are dose related. Therefore, following administration of more than the recommended dose, patients can be expected to experience these effects in an exaggerated fashion.
Supportive care should include: (a) daily blood counts for guidance in transfusion requirement; (b) prevention of the side effects that result from the syndrome of inappropriate secretion of antidiuretic hormone. This includes restriction of fluid intake and, perhaps, the use of a diuretic drug acting on the loop of Henle and distal tubule function; © use of cathartics to prevent ileus; (d) administration of an anticonvulsant; (e) monitoring the patient’s cardiovascular system.
The use of folinic acid in addition to the other supportive measures recommended may be considered although, unlike vincristine, studies have not been conducted to confirm its protective action. Clinical experience of vindesine overdosage is extremely limited, with only one published case.
5 years.
Vials of Eldisine should be stored in a refrigerator between 2° and 8°C.
After reconstitution: After a portion of the solution has been removed from a vial, the remainder of the contents of the vial may be stored in a refrigerator for future use for 24 hours without significant loss of potency. When the reconstituted vial of Eldisine is to be stored for more than 24 hours, it is essential to reconstitute with sterile 0.9% sodium chloride intravenous infusion preserved with 2.0% benzyl alcohol. Where preserved diluent is used, the reconstituted solution may be stored in a refrigerator for up to 28 days without significant loss of potency.
Single vials comprising Type I glass each with a rubber stopper, an aluminium sealing ring and a polypropylene cap.
Cytotoxic preparations should not be handled by pregnant staff.
Trained personnel should reconstitute the drug. This should be performed in a designated area. The work surface should be covered with disposable plastic-backed absorbent paper.
Adequate protective gloves, masks and clothing should be worn. Precautions should be taken to avoid the drug accidentally coming into contact with the eyes. If accidental contamination occurs, the eye should be washed with water or saline thoroughly and immediately.
Use Luer-lock fittings on all syringes and sets. Large bore needles are recommended to minimise pressure and the possible formation of aerosols. The latter may also be reduced by the use of a venting needle.
Adequate care and precaution should be taken in the disposal of items (syringes, needles, etc.) used to reconstitute cytotoxic drugs.
When dispensing vindesine sulphate in other than the original container, e.g., a syringe containing a specific dose, it is imperative that it be packaged in an overwrap bearing the statement “DO NOT REMOVE COVER UNTIL MOMENT OF INJECTION. FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES”. A syringe containing a specific dose must be labelled, using the auxiliary sticker provided in the pack, with this warning.
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