Leponex Dosage/Direction for Use

Dosage information: The dosage must be adjusted individually. For each patient the lowest effective dose should be used. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure, and sedation.
Initiation of treatment must be restricted to those patients with a WBC count ≥3500/mm³ (3.5 x 10⁹/L) and an ANC ≥2000/mm³ (2.0 x 10⁹/L), and within standardized normal limits.
Dose adjustment is indicated in patients who are also receiving medicinal products that have pharmacokinetic interactions with clozapine, such as benzodiazepines or selective serotonin re-uptake inhibitors (see Interactions).
Switching from a previous antipsychotic therapy to Clozapine (Leponex): It is generally recommended that clozapine should not be used in combination with other antipsychotics. When clozapine (Leponex) therapy is to be initiated in a patient undergoing oral antipsychotic therapy, it is recommended that the dosage of other antipsychotics be reduced or discontinued by gradually tapering it downwards. Based on the clinical circumstances, the prescribing physician should judge whether or not to discontinue the other antipsychotic therapy before initiating treatment with clozapine.
Treatment resistant schizophrenia: Starting therapy: Clozapine (Leponex) 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 300 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.
Maximum dose: 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. However the possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind.
Maintenance dose: After achieving maximum therapeutic benefit, many patients can be maintained effectively on lower doses. 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.
Ending therapy: In the event of planned termination of clozapine therapy, a gradual reduction in dose over a 1- to 2-week period is recommended. If abrupt discontinuation is necessary (e.g. because of leucopenia), the patient should be carefully observed for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound (see Precautions).
Restarting therapy: In patients in whom the interval since the last dose of clozapine (Leponex) 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. If this dose is well tolerated, it may be feasible to titrate the dose to the therapeutic level more quickly than is recommended for initial treatment. However, in any patient who has previously experienced respiratory or cardiac arrest with initial dosing (see Precautions), but was then able to be successfully titrated to a therapeutic dose, re-titration should be done with extreme caution.
Reducing the risk of suicidal behavior in schizophrenia and schizoaffective disorder: The dosage and administration recommendations described in the preceding subsection regarding the use of clozapine (Leponex) in patients with treatment-resistant schizophrenia should also be followed when treating patients with schizophrenia or schizoaffective disorder at risk for recurrent suicidal behaviour.
A course of treatment with clozapine (Leponex) of at least two years is recommended in order to maintain the reduction of risk for suicidal behaviour. It is recommended that the patient's risk of suicidal behaviour be reassessed after two years of treatment and that thereafter the decision to continue treatment with clozapine be re-visited at regular intervals, based on thorough assessments of patient's risk for suicidal behaviour during treatment.
Psychotic disorders occurring during the course of Parkinson's disease, in cases where standard treatment has failed: Starting therapy: The starting dose must not exceed 12.5 mg/day (half a 25 mg tablet), taken in the evening. Subsequent dose increases must be by 12.5 mg increments, with a maximum of two increments a week up to a maximum of 50 mg, a dose that cannot be reached until the end of the second week. The total daily amount should preferably be given as a single dose in the evening.
Therapeutic dose range: The mean effective dose is usually between 25 and 37.5 mg/day. In the event that treatment for at least one week with a dose of 50 mg fails to provide a satisfactory therapeutic response, dosage may be cautiously increased by increments of 12.5 mg/week.
Maximum dose: The dose of 50 mg/day should only be exceeded in exceptional cases, and the maximum dose of 100 mg/day must never be exceeded.
Dose increases should be limited or deferred if orthostatic hypotension, excessive sedation or confusion occurs. Blood pressure should be monitored during the first weeks of treatment.
Maintenance dose: When there has been complete remission of psychotic symptoms for at least 2 weeks, an increase in anti-parkinsonian medication is possible if indicated on the basis of motor status. If this approach results in the recurrence of psychotic symptoms, Clozapine (Leponex) dosage may be increased by increments of 12.5 mg/week up to a maximum of 100 mg/day, taken in one or two divided doses (see previously mentioned).
Ending therapy: When ending therapy, a gradual reduction in dose by steps of 12.5 mg over a period of at least one week (preferably two) is recommended.
Treatment must be discontinued immediately in the event of neutropenia or agranulocytosis as indicated in Precautions. In this situation, careful psychiatric monitoring of the patient is essential since symptoms may recur quickly.
Special Populations: Cardiovascular disorders: In patients suffering from cardiovascular disorders (note: severe 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.
Renal impairment: In patients with mild to moderate renal impairment the initial dose should be 12.5 mg given once on the first day, and dosage increase should be slow and in small increments.
Hepatic impairment: Patients with hepatic impairment should receive clozapine (Leponex) with caution along with regular monitoring of liver function tests (see Precautions).
Pediatrics: No pediatric studies have been performed. The safety and efficacy of clozapine (Leponex) in children and adolescents have not been established.
Patients 60 years of age and older: It is recommended that treatment in patients 60 years and older is initiated at a particularly low dose (12.5 mg given once on the first day) with subsequent dose increments restricted to 25 mg/day.
Method of administration: Clozapine (Leponex) is administered orally.