Procarbazine (Specialist drug)

COMBINATION USE: procarbazine is usually administered concomitantly with other appropriate cytostatic drugs in repeated four- to six-weekly cycles; in most such regimens currently in use it is given daily on the first 10-14 days of each cycle at 100 mg per square metre of body surface, rounded to the nearest 50 mg. AS SOLE AGENT (adults): treatment should begin with small doses which are increased gradually up to a maximum daily dose of 250 or 300 mg divided as evenly as possible throughout the day. Initial dosage scheme — 1st day 50 mg, 2nd day 100 mg, 3rd day 150 mg, 4th day 200 mg, 5th day 250 mg, 6th day and thereafter 250-300 mg. Treatment should be continued with 250 or 300 mg daily until the greatest possible remission has been obtained, after which a maintenance dose of 50-150 mg daily is given. Treatment should be continued until a total dose of at least 6 g has been given; otherwise a negative result is not significant. MONITORING: procarbazine should be given only under the supervision of a physician experienced in cancer chemotherapy with facilities for regular monitoring of clinical and haematological effects; introduction of therapy should only be effected under hospital conditions. Regular blood counts are of great importance — if during initial treatment the total white cell count falls to 3,000 per mm3 or the platelet count to 80,000 per mm3, treatment should be suspended temporarily until levels recover, when therapy with the maintenance dose may be resumed. Treatment should be interrupted on the appearance of allergic skin reactions. Live vaccines should not be given during or within at least 6 months of treatment. ELDERLY: procarbazine should be used with caution in the elderly; these patients should be observed very closely for signs of early failure or intolerance of treatment. CHILDREN (non-numeric per-kg dose — verbatim intent of SPC): the per-square-metre dose used in most published trials was analogous to the dose used in adults (100 mg/m2 for up to 14 days). The dose should be adjusted according to the chemotherapy protocol used, the functional state of the bone marrow, previous chemo- and radiotherapy cycles, and the myelosuppressive effect of other cytostatics used. Treatment and maintenance doses in children should be determined only by a physician experienced in the use of potent antineoplastic drugs in children. Because the paediatric dose is stated per square metre and not per kilogram, no structured paediatric per-kg dose can be given — verify against a children's formulary and the relevant protocol. CAUTIONS: caution is advisable in hepatic or renal dysfunction, and in cardiovascular or cerebrovascular disease, phaeochromocytoma or epilepsy. US LABELLING DIFFERENCE (from the openFDA Matulane provider in the same bundle, for cross-check only — do not merge with the UK regimen): the US label gives a weight-based single-agent adult regimen of 2 to 4 mg/kg/day for the first week, then 4 to 6 mg/kg/day until maximum response or until the white blood count falls below 4000/cmm or platelets below 100,000/cmm, then a maintenance dose of 1 to 2 mg/kg/day, and states that in the MOPP regimen the dose is 100 mg/m2 daily for 14 days; its paediatric schedule is 50 mg/m2/day for the first week, then 100 mg/m2/day until maximum response or until leukopenia or thrombocytopenia occurs, then maintenance at 50 mg/m2/day, with individualised dosing and mandatory very close clinical monitoring.