|The dosage must be adjusted individually. For each patient the lowest effective dose should be used. In patients with a history of seizures or suffering from renal or cardiovascular disorders (note: severe renal or cardiovascular disorders are contraindications) the initial dose should be 12.5 mg given once on the first day, and dosage increase should be slow and in small increments.
Clozaril should be started with 12.5 mg (half a 25 mg tablet) once or twice on the first day, followed by one or two 25 mg tablets on the second day. If well tolerated, the daily dose may then be increased slowly in increments of 25 mg to 50 mg in order to achieve a dose level of up to 300 mg/day within 2 to 3 weeks. Thereafter, if required, the daily dose may be further increased in increments of 50 mg to 100 mg at half-weekly or, preferably, weekly intervals.
Therapeutic dose range:
In most patients, antipsychotic efficacy can be expected with 200 to 450 mg/day given in divided doses. Some patients may be treated with lower doses, and some patients may require doses up to 600 mg/day. The total daily dose may be divided unevenly, with the larger portion being taken at bedtime.
To obtain full therapeutic benefit, a few patients may require larger doses, in which case judicious increments (not exceeding 100 mg) are permissible up to 900 mg/day. The possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind.
After achieving maximum therapeutic benefit, patients can be maintained effectively on lower doses. Careful downward titration is recommended to the lowest effective dose for the individual patient. Treatment should be maintained for at least 6 months. If the daily dose does not exceed 200 mg, once daily administration in the evening may be appropriate.
In the event of planned termination of Clozaril therapy, a gradual reduction in dose over a 1- to 2- week period is recommended.
In patients in whom the interval since the last dose of Clozaril exceeds 2 days, treatment should be re-initiated with 12.5 mg (half a 25 mg tablet) given once or twice on the first day.