VINCRISTINE HOSPIRA Solution for injection Ref.[8340] Active ingredients: 22-Oxovincaleukoblastine

Posology

The following dosage regimens have been used:

Adults

The drug is administered intravenously at weekly intervals. The recommended dose is 1.4 to 1.5 mg/m² up to a maximum weekly dose of 2 mg.

Children

The suggested dose is 1.4 to 2 mg/m² given on a weekly basis with a maximum weekly dose of 2 mg. For children weighing 10 kg or less the starting dose should be 0.05 mg/kg administered as a weekly intravenous injection.

Elderly

The normal adult dose is still appropriate in the elderly.

Hepatic Impairment

Because of the hepatic metabolism and biliary excretion of vincristine, reduced doses are recommended in patients with obstructive jaundice or other hepatic impairment. Patients with liver disease sufficient to decrease biliary excretion may experience an increase in the severity of side-effects. A 50 per cent reduction in the dose of vincristine sulfate is recommended for patients having a direct serum bilirubin value above 3 mg/100 ml (51 micromol/l).

Caution: If leakage into surrounding tissue should occur during intravenous administration of vincristine, 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 the hyaluronidase and the application of moderate heat to the area of leakage help to disperse the drug and are thought to minimise discomfort and the possibility of cellulitis.

Method of administration

Precautions to be taken before handling or administering the medicinal product.

This preparation is for intravenous use only. It should only be administered by individuals experienced in vincristine administration.

FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY ANY OTHER ROUTE.

See section 4.4 for use for the treatment of patients given intrathecal vincristine sulfate.

Vincristine sulfate is administered by intravenous infusion at weekly intervals.

Great care should be exercised in calculating and administering the dose, as overdosage may be extremely serious or even fatal. The dose should not be increased beyond the level which produces therapeutic benefit. Individual doses should not exceed 2 mg; and white cell counts should be carried out before and after giving each dose.

With the vial presentations, do not add extra fluid to the vial prior to removal of the dose. Withdraw the solution of Vincristine Sulfate into an accurate dry syringe, measuring the dose carefully. Do not add extra fluid to the vial in an attempt to empty it completely.

It is recommended to infuse vincristine sulfate over 5 to 10 minutes after dilution in a 50 ml infusion bag with Sodium Chloride 9 mg/ml (0.9%) Solution for Injection. After administration the vein must be flushed through thoroughly. Care should be taken to avoid extravasation as this may cause local ulceration.

Because of the narrow range between therapeutic and toxic levels and variations in response, the dosage must always be adjusted to the individual.

For instructions on dilution of the medicinal product before administration, see section 6.6.

Side effects following the use of vincristine are dose related. In children under 13 years of age, death has occurred following doses of vincristine that were 10 times those recommended for therapy. Severe symptoms may occur in this patient group following dosages of 3 to 4 mg/m². Adults can be expected to experience severe symptoms after single doses of 3 mg/m² or more. Therefore, following administration of doses higher than those recommended patients can be expected to experience side-effects in an exaggerated fashion. Supportive care should include the following: (a) prevention of side-effects resulting from the syndrome of inappropriate antidiuretic hormone secretion (this would include restriction of fluid intake and perhaps the administration of a diuretic affecting the function of the loop of Henle and the distal tubule); (b) administration of anticonvulsants; © use of enemas or cathartics to prevent ileus (in some instances, decompression of the gastrointestinal tract may be necessary); (d) monitoring the cardiovascular system; (e) determining daily blood counts for guidance in transfusion requirements.

Folinic acid has been observed to have a protective effect in normal mice which were administered lethal doses of vincristine. Isolated case reports suggest that folinic acid may be helpful in treating humans who have received an overdose. A suggested schedule is to administer 100 mg of folinic acid intravenously every 3 hours for 24 hours and then every 6 hours for at least 48 hours. Theoretical tissue levels of vincristine derived from pharmacokinetic data are predicted to remain significantly elevated for at least 72 hours. Treatment with folinic acid does not eliminate the need for the above-mentioned supportive measures.

Most of an intravenous dose of vincristine is excreted into the bile after rapid tissue binding. Because only very small amounts of the drug appear in dialysate, haemodialysis is not likely to be helpful in cases of overdosage.

Enhanced faecal excretion of parenterally administered vincristine has been demonstrated in dogs pre-treated with cholestyramine. There are no published clinical data on the use of cholestyramine as an antidote in humans.

There are no published clinical data on the consequences of oral ingestion of vincristine. Should oral ingestion occur, the stomach should be evacuated followed by oral administration of activated charcoal and a cathartic.

2 years.

Store in a refrigerator (2°C–8°C). Keep the vial in the outer carton, in order to protect from light.

2 ml Type I clear glass vials, with rubber closures and aluminium caps in packs of 5 vials.

2 ml Type I clear Onco-Tain vials, with rubber closures and aluminium caps in packs of 5 vials.

2.25 ml Type I clear glass, graduated, barrel syringes with luer lock as a single syringe pack.

Not all pack sizes may be marketed.

Cytotoxic Handling Guidelines

Administration: Should be administered only by or under the direct supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents.

Preparation (Guidelines):

1. Chemotherapeutic agents should be prepared for administration only by professionals who have been trained in the safe use of preparation.
2. Operations such as reconstitution of powder and transfer to syringes should be carried out only in the designated area.
3. The personnel carrying out these procedures should be adequately protected with clothing, gloves and eye shield.
4. Pregnant personnel are advised not to handle chemotherapeutic agents.

Contamination:

• In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat the transient stinging of skin. Medical advice should be sought if the eyes are affected.
• In the event of spillage, operators should put on gloves and mop the spilled material with a sponge kept in the area for that purpose. Rinse the area twice with water. Put all solutions and sponges into a plastic bag and then seal it.

Disposal

Syringes, containers, absorbent materials, solution and any other contaminated material should be placed in a thick plastic bag or other impervious container and incinerated.