Clozaril Dosage/Direction for Use

The dosage must be adjusted individually. For each patient the lowest effective dose should be used. Careful dose titration and a divided dosage schedule are necessary to minimize the risk of hypotension, seizure, and sedation. The total daily amount may be divided into unequal doses, the largest of which should be taken at bedtime.
The following dosages are recommended: Starting dose: 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 dose may then be increased in increments of 25-50 mg/day in order to achieve a daily dose of 300 mg within 2-3 weeks. Thereafter, if required, the daily dose may be further increased in increments of 50-100 mg at half-weekly or, preferably, weekly intervals.
Therapeutic dose range: In most patients the onset of antipsychotic effects occurs at a daily dosage of 300-450 mg, given in two to four divided doses. Some patients require lower daily doses, and others up to 600 mg.
Maximum dose: To obtain full therapeutic benefit, a few patients may require larger doses; in such cases the maximum permissible dose is 900 mg/day, with maximum individual increments of 100 mg. Increased adverse effects (in particular seizures) are possible at doses exceeding 450 mg/day.
Maintenance dose: Once the maximum therapeutic effect has been attained, many patients can be effectively maintained on a lower dose. Careful downward titration is therefore recommended. 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.
Withdrawal of treatment: In the event of planned withdrawal of Clozaril, it is recommended that the dose be reduced gradually over a period of 1-2 weeks. If abrupt discontinuation is necessary (e.g. because of leukopenia), the patient should be closely monitored for recurrence of psychosis and symptoms of cholinergic rebound (e.g. increased sweating, headache, nausea, vomiting and diarrhea).
Resumption of treatment: If more than two days have elapsed since the last dose of Clozaril, treatment should be resumed with 12.5 mg (half a 25 mg tablet) once or twice on the first day. If this dose is well tolerated, titration to the therapeutic level can then proceed more quickly than is recommended for initial treatment. However, re-titration should be carried out with extreme caution in any patient who has previously experienced respiratory or cardiac arrest with initial dosing (see Other precautions), but was then able to be successfully titrated to a therapeutic dose.
Switching from another antipsychotic therapy to Clozaril: It is generally recommended that Clozaril should not be combined with other antipsychotic agents. When Clozaril therapy is to be initiated in a patient undergoing oral antipsychotic therapy, it is recommended that if possible, the other antipsychotic agent should first be discontinued by tapering the dosage downwards over a period of about one week. Once the antipsychotic agent has been completely discontinued for at least 24 hours, Clozaril treatment can be started as described previously.
A lower starting dose and slower build-up are recommended for patients with a history of seizures or with cardiovascular, renal or hepatic disorders.
Dose adjustment is necessary in patients receiving drugs that interact with Clozaril, such as benzodiazepines, carbamazepine or selective serotonin reuptake inhibitors (see Interactions).
(Long-term) reducing the recurrent suicidal behavior in patients with schizophrenia and schizoaffective disorder: The dosage and administration guidelines described previously for the use of Clozaril in patients with treatment-resistant schizophrenia are also valid when Clozaril is used in patients with schizophrenia or schizoaffective disorder who show evidence of a long-term risk for recurrent suicidal behavior.
Special patient groups: Patients with heart disease: The starting dose should be low (1 x 12.5 mg on the first day) in patients with heart disease. It should be increased slowly and in small increments. It is contraindicated for patients with severe cardiovascular disease (see Contraindications).
Patients with renal insufficiency: The starting dose should be low (1 x 12.5 mg on the first day) in patients with mild to moderate renal insufficiency. It should be increased slowly and in small increments.
Patients with hepatic insufficiency: In patients with hepatic insufficiency, Clozaril should only be administered with care and regular monitoring (see Precautions).
Children and adolescents: There are no studies in children and adolescents on the safety and effectiveness of Clozaril.
Elderly patients: In older patients (≥60 years) initiation of treatment at a particularly low dose is recommended (12.5 mg given once on the first day), with subsequent dose increments restricted to 25 mg/day.