INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo P&U VINCRISTINE CSV
SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

P&U VINCRISTINE CSV

P&U VINCRISTINE CSV 1 mg/1 mL INJECTION
P&U VINCRISTINE CSV 2 mg/2 mL INJECTION
P&U VINCRISTINE CSV 5 mg/5 mL INJECTION

COMPOSITION:
P&U VINCRISTINE CSV 1 mg/1 mL INJECTION: Each one mL contains 1 mg vincristine sulphate.
P&U VINCRISTINE CSV 2 mg/2 mL INJECTION: Each one mL contains 1 mg vincristine sulphate.
P&U VINCRISTINE CSV 5 mg/5 mL INJECTION: Each one mL contains 1 mg vincristine sulphate.

PHARMACOLOGICAL CLASSIFICATION:
A 26. Cytostatic agents

PHARMACOLOGICAL ACTION:
VINCRISTINE is a vinca alkaloid which is a cell-cycle-specific agent and blocks mitosis with metaphase arrest. Most of the biological activities of VINCRISTINE can be explained by its ability to bind specifically with the protein tubulin and to block the ability of the protein to polymerize into microtubules. Through disruption of the microtubules of the mitotic apparatus, cell division is arrested in metaphase and leads to cell death.

INDICATIONS:
VINCRISTINE is effective in Hodgkins disease and other lymphomas. In Hodgkins disease it is effective for the advanced stages (III and IV) when used in the MOPP regime (mechlorethamine, oncovin, prednisone, procarbazine).
In non-Hodgkins lymphomas, vincristine is an important agent, particularly when used with cyclophosphamide, bleomycin, doxorubicin and prednisone. Vincristine is also effective in lymphocytic leukemia. Beneficial responses have been reported in patients with a variety of other neoplasms, particularly Wilms tumour, neuroblastoma, brain tumours, rhabdomyosarcoma and carcinomas of the breast, bladder, and the female and male reproductive systems.

CONTRA-INDICATIONS:
Hypersensitivity to vincristine or vinca alkaloids
VINCRISTINE is contra-indicated in patients with the demyelinating form of Charcot-Marie-Tooth disease. Patients with bacterial infection.
Should not be taken during pregnancy and lactation.

WARNINGS:
This preparation should only be administered by individuals experienced in the administration of vincristine.
Care should be taken to avoid extravasation and the injection may be given into a freely-running intravenous infusion of sodium chloride injection if preferred.
It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration may cause considerable irritation.
If extravasation occurs during intravenous administration the injection should be stopped immediately and the remaining dose injected into another vein. Local discomfort and the possibility of cellulitis may be minimized by local injection of hyaluronidase and application of moderate heat or by application of cold compress.

When dispensed, the container or the syringe holding the individual dose prepared for administration to the patient must be enclosed in an overwrap bearing the statement:
“DO NOT REMOVE COVERING UNTIL THE MOMENT OF INJECTION. FATAL IF GIVEN INTRATHECALLY; FOR INTRAVENOUS USE ONLY”

Caution should be used in patients who have had previous cytotoxic drug therapy or radiation therapy and in those with existing neuromuscular problems who appear to be more susceptible to the neurotoxic effects of vincristine.
Doses may need to be adjusted in patients with impaired liver function. Care should be taken in elderly patients, who may be more susceptible to neurotoxicity.
FATAL IF GIVEN INTRATHECALLY; FOR INTRAVENOUS USE ONLY

DOSAGE AND DIRECTIONS FOR USE (SEE WARNINGS):
This preparation is for intravenous use only.
The prescriber should consult the current medical literature in choosing a specific dosage. Extreme care must be taken in calculating and administering the dose of vincristine since overdosage may have a very serious or fatal outcome.
Vincristine sulphate is administered by intravenous injection and solutions containing 0,01 to 1 mg per mL in sodium chloride injection (0,9%) have been used.
Vincristine must be administered via an intact free-flowing intravenous needle or catheter. Care should be taken that there is no leakage or that swelling does not occur during administration (see “WARNINGS”).
In acute leukaemia the usual weekly dose of vincristine sulphate for induction of remission in children is 2 mg per m² body surface, or 50 micrograms per kg body weight, increasing by weekly increments of 25 micrograms per kg, to a maximum of 150 micrograms per kg. Adults may be given about 1,4 mg per m² or 25 to 75 micrograms per kg weekly; a maximum weekly dose of 2 mg has been suggested. For other malignancies 25 micrograms per kg may be given weekly and reduced to 5 to 10 micrograms per kg for maintenance.
Blood counts should be carried out before giving each dose.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects are dose related. The most common side-effect is hair loss; the most troublesome side-effects are neuromuscular in origin.
The following side effects have been reported:
Neurotoxicity:
Neurotoxicity most typically presents as mixed sensorimotor neuropathy of the distal type.
The earliest symptoms are sensory changes in the form of paresthesias accompanied by impairment and ultimately, loss of deep and tendon reflexes. In more severe forms, impairment of motor function occurs with foot and wrist drop, ataxia and gait abnormalities and occasionally progressive quadriplegia.
Progressive neurotoxicity may frequently present as blurred or double vision, difficulty in walking, drooping eyelids, headache, jaw pain, numbness or tingling in fingers and toes, pain in fingers and toes, pain in testicles and weakness.
Progressive neurotoxicity develops after about 2 months of treatment and may persist for several days to several months.
Incidences less frequently reported include:- central nervous system toxicity, agitation, confusion, dizziness, hallucinations, loss of appetite, mental depression, seizures, trouble in sleeping and unconsciousness.
Cranial nerve manifestations, including ptosis, hoarseness or optic neuropathies have been reported. Bilateral optic atrophy, blindness and profound neurological deafness have been reported. Convulsions, frequently with hypertension, have been reported. Several instances of convulsions followed by coma have been reported in children.
Gastro-intestinal effects:
Gastro-intestinal effects include stomatitis, constipation, nausea, vomiting and gastro-intestinal bleeding. Because of severe constipation and impaction of faeces, laxatives or enemas may be necessary.
Paralytic ileus may occur, particularly in young children and in the elderly.
Cardiovascular effects:
Ischaemic cardiac toxicity, hypotension, hypertension have been reported.
Renal:
Hyperuricaemia or uric acid nephropathy occurs most commonly during initial treatment of patients with leukemia or lymphoma.
Hematologic:
Anemia, leucopenia and thrombocytopenia have been reported.
Other reported effects include skin reactions, alopecia, dyspnoea and bronchospasm, bone and tumour pain. A syndrome of inappropriate secretion of antidiuretic hormone has occurred at high doses and may be relieved by fluid restriction and if necessary, a suitable diuretic.
Precautions:
Vincristine should be given with caution to patients with pre-existing neuromuscular disease.
Because severe constipation and impaction of faeces often occurs with vincristine, laxatives or enemas may be necessary to ensure regular bowel function. Vincristine should be given with caution to patients with pre-existing neuromuscular disease.
If vincristine is used in combination with asparaginase it should be given 12 to 24 hours before the enzyme: administration of asparaginase with or before vincristine may reduce vincristine clearance and increase toxicity.
Interactions:
Acute uric acid nephropathy has been reported with the administration of oncolytic agents. Acute shortness of breath and severe bronchospasm have been reported most frequently when vinca alkaloids are used in combination with mitomycin-C and may require aggressive treatment, particularly with pre-existing pulmonary dysfunction.
This reaction may occur within minutes or several hours after and may continue for up to 2 weeks following the dose of mitomycin-C. Vincristine should not be readministered.
Sequential administration of vincristine prior to bleomycin arrests cells in mitosis so that they are more susceptible to bleomycin. Blood dyscrasia-causing medications, doxorubicin, neurotoxic medication, spinal cord irradiation, killed and live virus vaccinations.
Vincristine has been reported to reduce blood levels of phenytoin and to increase seizure activity.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See “SIDE-EFFECTS AND SPECIAL PRECAUTIONS.”Treatment is symptomatic and supportive.

IDENTIFICATION:
Clear, colourless solution.

PRESENTATION:
P&U VINCRISTINE CSV 1 mg/1 mL INJECTION: A single dose plastic vial containing 1 mg of vincristine sulphate per mL of solution.
P&U VINCRISTINE CSV 2 mg/2 mL INJECTION: A single dose plastic vial containing 2 mg of vincristine sulphate per 2 mL solution.
P&U VINCRISTINE CSV 5 mg/5 mL INJECTION(IV INJECTION): A single dose plastic vial containing 5 mg of vincristine sulphate per 5 mL of solution.

STORAGE INSTRUCTIONS:
Store between 2° and 8°C in a fridge. Do not freeze. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
P&U VINCRISTINE CSV 1 mg/1 mL INJECTION:        29/26/0503
P&U VINCRISTINE CSV 2 mg/2 mL INJECTION:        30/26/0312
P&U VINCRISTINE CSV 5 mg/5 mL INJECTION:        30/26/0313

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pharmacia South Africa (Pty) Ltd
Alphen West G
George Street
MIDRAND
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
March 1996

New addition to this site: February 2005
Source: Pharmaceutical Industry

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