Source: Health Products Regulatory Authority (ZA) Revision Year: 2021 Publisher: Pfizer Laboratories (Pty) Ltd, 85 Bute Lane, Sandton 2196, South Africa Tel: +27(0)11 320 6000 / 0860 734 937 (Toll-free South Africa)
CYTOSAR is indicated for induction and maintenance of remission in acute non-lymphocytic leukaemia of both adults and children. It is also indicated in the treatment of acute lymphocytic leukaemia (ALL) and chronic myelocytic leukaemia (CML) (blast phase).
CYTOSAR may be used alone or in combination with other antineoplastic medicines. It is more effective when used in combination therapy with other medicines.
Children with non-Hodgkin’s lymphoma have benefited from a combination medication programme that included CYTOSAR.
CYTOSAR alone or in combination with other medicines is used intrathecally for prophylaxis or treatment of meningeal leukaemia.
CYTOSAR in high doses (2–3 g/m²) may be effective in some cases of refractory leukaemia and relapsed acute leukaemia, although systemic toxicity, especially of the central nervous system, may be high.
CYTOSAR is not active orally. The schedule and method of administration varies with the programme of therapy to be used.
Thrombophlebitis has occurred at the site of injection or infusion and patients have noted pain and inflammation at subcutaneous injection sites.
Patients can sometimes tolerate higher total doses when they receive the medicine by rapid intravenous injection as compared to slow infusion, but no clear-cut clinical advantage has been demonstrated by either. Toxicity necessitating dose alteration almost always occurs.
In many chemotherapeutic programmes, CYTOSAR is used in combination with other cytotoxic medicines. The addition of these cytotoxic medicines has necessitated changes and dose alterations. The dosage schedules for combination therapy have been reported in the literature.
100 mg/m² day by continuous infusion (Days 1–7) or 100 mg/m² infusion every 12 hours (Days 1–7) or until bone hyperplasia occurs.
Adults:
Maintenance programmes are modifications of induction programmes and in general, use similar schedules of medicine therapy as were used during induction. Most programmes have a greater time spacing between courses of therapy during remission maintenance.
Children:
Where the adult dosage is stated in terms of body mass or surface area, the children’s dosage may be calculated on the same basis. When specified amounts of a medicine are indicated for the adult dosage, these should be adjusted for children on the basis of factors such as age, body mass or body surface area.
In general, dosage schedules are similar to those used in acute non-lymphocytic leukaemia with some modifications. Meningeal leukaemia – intrathecal use The most frequently used dose was 30 mg/m² every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment.
Intrathecal CYTOSAR should not be used to treat focal leukaemic involvement of the central nervous system.
Before instituting a programme of combined chemotherapy or high dose therapy, the medical practitioner should be familiar with the literature, adverse reactions, precautions, contraindications and warnings applicable to all the medicines involved in the programme.
2–3 g/m² as an infusion over 1–3 hours given every 12 hours for 2–6 days with or without additional cancer chemotherapeutic medicines, has been shown to be effective in the treatment of poor-risk leukaemia, refractory leukaemia and relapsed acute leukaemia.
CYTOSAR has been used as part of a multi-medicine programme to treat non-Hodgkin’s lymphoma in children.
The dosage of CYTOSAR must be modified or suspended when signs of serious haematologic depression appear. In general, consider discontinuing the medicine if the patient has less than 50 000 platelets or 1 000 polymorphonuclear granulocytes/mm³ in the peripheral blood. These guidelines may be modified depending on signs of toxicity in other systems and on the rapidity of fall in formed blood elements. Re-start the medicine when there are signs of marrow recovery and the above platelet and granulocyte levels have been attained.
Withholding therapy until the patient’s blood values are normal may result in escape of the patient’s disease from control by the medicine.
CYTOSAR may be given by intravenous infusion, injection, intrathecally or subcutaneously.
When preparing CYTOSAR for intrathecal use, do not use diluents containing benzyl alcohol (see section 4.4). Many medical practitioners reconstitute with preservative-free 0,9% sodium chloride for injection and use immediately.
CYTOSAR given intrathecally may cause systemic toxicity and careful monitoring of the haemopoietic system is indicated. Modification of the anti-leukaemia therapy may be necessary (see section 4.4 and section 4.8). When CYTOSAR is administered both intrathecally and intravenously within a few days, there is an increased risk of spinal cord toxicity.
If high dose therapy is used, do not use diluents containing benzyl alcohol (see section 6.6).
There is no antidote for overdosage of CYTOSAR.
Doses of 4,5 g/m² by intravenous infusion over 1 hour every 12 hours for 12 doses has caused an unacceptable increase in irreversible CNS toxicity and death.
Cessation of therapy followed by management of ensuing bone marrow depression including whole blood platelet transfusion and antibiotics as required.
Treatment is symptomatic and supportive.
Powder for solution for injection: 60 months.
CYTOSAR is stable for seven days at room temperature when admixed at 0,5 mg/mL in glass IV bottles and plastic intravenous bags with water for injection, 5% dextrose injection, and 0,9% sodium chloride injection solutions. Also when similarly admixed at 8-32 mg/mL in glass intravenous bottles and plastic intravenous bags, CYTOSAR is stable for seven days at room temperature -20°C and 4°C in 5% dextrose injection, 5% dextrose in 0,2% sodium chloride injection, and in 0,9% sodium chloride injection solutions.
CYTOSAR 2 mg/mL is chemically stable in the presence of KCl equivalent to 50 mmoL/500 mL in dextrose 5% in water and 0,9% sodium chloride for up to 8 days.
CYTOSAR is also stable at room temperature and at refrigerated temperature (8°C) at a concentration of 0,2–1,0 mg/mL in the presence of sodium bicarbonate equivalent to 50 mmoL/L in dextrose 5% in water or dextrose 5% in 0,2% sodium chloride for seven days in Travenol glass bottles or viaflex bags.
Store at room temperature between 15°C and 30°C.
Once reconstituted, store at room temperature between 15°C and 30°C and use within 48 hours.
Discard any solution in which a slight haze develops.
CYTOSAR 100 mg: 100 mg vial plus 5 mL water for injection (with benzyl alcohol 0,9% m/v).
CYTOSAR 500 mg: 500 mg vial plus 10 mL water for injection (with benzyl alcohol 0,9% m/v).
CYTOSAR 100 mg and 500 mg are in multidose vials.
Bacteriostatic water for injection plus benzyl alcohol 0,9% m/v is available in ampoules of 5 mL and 10 mL.
Not all pack sizes may be marketed.
CYTOSAR is compatible with the following medicines at the specified concentrations, in dextrose 5% in water for eight hours: CYTOSAR 0,8 mg/mL and cephalothin 1,0 mg/mL; CYTOSAR 0,4 mg/mL and prednisolone sodium phosphate 0,2 mg/mL; CYTOSAR 16 µg/mL and vincristine sulphate 4 µg/mL is compatible in dextrose 5% in water for 8 hours.
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