Uses
Schizophrenia
Management of treatment-resistant schizophrenia in severely ill patients who fail to respond adequately to other antipsychotic therapy and/or in whom such therapy produces intolerable adverse effects. (See Boxed Warning and see Agranulocytosis under Cautions.)
Has been used in the management of childhood-onset schizophrenia in a limited number of treatment-resistant children and adolescents†.
Suicide Risk Reduction in Schizophrenia and Schizoaffective Disorder
Reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for reexperiencing suicidal behavior, based on history and recent clinical state.
In the principal supportive study for this use, most patients also received other treatments to reduce suicide risk, including concomitant psychotropic agents (i.e., antipsychotics, anxiolytics, antidepressants, mood stabilizers), hospitalization, and/or psychotherapy; contributions to efficacy unknown.
Parkinsonian Syndrome
Has been used in a limited number of patients with advanced, idiopathic parkinsonian syndrome for management of dopaminomimetic psychosis† associated with antiparkinsonian drug therapy, but adverse effects (e.g., sedation, confusion, increased parkinsonian manifestations) may limit benefit.
Dosage and Administration
Administration
Restricted Distribution
Available only through distribution systems that ensure periodic blood tests prior to delivery of next supply of medication; dispensing is contingent on results of WBC count and ANC. (See Agranulocytosis under Cautions.)
Upon initiating therapy, may dispense up to an additional 1-week supply to the patient to be held for emergencies (e.g., weather, holidays). Dispense ≤1 week supply ordinarily, but may dispense supply sufficient for therapy for a period of time equal to that of the monitoring period; patients monitored weekly may receive a 1-week (7-day) supply of medication, patients monitored biweekly may receive a 2-week supply, and patients eligible for monitoring every 4 weeks may receive a 28-day supply of medication, depending on WBC count and ANC results.
Before initiating therapy in any patient, check Clozaril National Registry (phone number: 800-448-5938) to ensure patient does not have history of clozapine-induced agranulocytosis or severe leukopenia/granulocytopenia; do not administer to patients with such a history. (See Contraindications under Cautions.)
Contact individual manufacturers for additional information on current mechanisms for obtaining drug.
Oral Administration
Administer orally as conventional or orally disintegrating tablets without regard to meals.
Administer in divided doses to minimize risk of certain adverse effects (e.g., hypotension, seizures, sedation).
Just prior to administration of orally disintegrating tablet, peel blister backing completely off the blister and gently remove tablet; immediately place on the tongue to dissolve and swallow with or without liquid. When clozapine orally disintegrating tablets are divided, destroy the remaining half of the tablet.
Dosage
Carefully adjust dosage according to individual requirements and response using lowest possible effective dosage. Avoid extended treatment in patients failing to show acceptable level of clinical response.
Due to possibility that high dosages may increase risk of adverse reactions, particularly seizures, allow adequate time to respond to a given dosage before dosage escalation is considered.
Pediatric Patients
Schizophrenia
Oral
Dosage not established in children <16 years of age.†
In a clinical study conducted by the National Institute of Mental Health (NIMH) in children (mean: 14 years of age), an initial dosage of 6.25–25 mg daily (depending on patient’s weight) was used; dosages could be increased every 3–4 days by 1–2 times the initial dose on an individual basis up to a maximum of 525 mg daily.†
Adults
Schizophrenia
Oral
Initially, 12.5 mg (one-half of a 25-mg tablet) once or twice daily. If therapy is initiated with orally disintegrating tablets, destroy the remaining half tablet. If well tolerated, increase by 25–50 mg daily over a 2-week period until dosage of 300–450 mg daily is achieved.
Make subsequent dosage increases no more than once or twice weekly, in increments ≤50–100 mg.
Continue daily administration in divided doses (e.g., 2–3 times daily) until effective and tolerable dosage reached, usually within 2–5 weeks, up to a maximum dosage of 900 mg daily.
Many respond adequately to dosages between 200–600 mg daily, but 600–900 mg daily may be required in some.
Optimum duration currently is not known, but maintenance therapy with antipsychotic agents is well established. In responsive patients, continue as long as clinically necessary and tolerated, but at lowest possible effective dosage; reassess need for continued therapy periodically.
Suicide Risk Reduction
Oral
Initially, 12.5 mg once or twice daily. If therapy is initiated with orally disintegrating tablets, destroy the remaining half tablet. If well tolerated, increase by 25–50 mg daily over a 2-week period until a dosage of 300–450 mg daily is achieved.
Make subsequent dosage increases no more than once or twice weekly, in increments ≤50–100 mg.
In the principal supportive study, mean dosage was about 300 mg daily (range: 12.5–900 mg daily).
Continue therapy for ≥2 years; after 2 years, reassess patient’s risk of suicidal behavior. If clinician’s assessment indicates that risk for suicidal behavior is still present, continue therapy. Thereafter, reevaluate need to continue therapy at regular intervals.
If the clinician determines the patient is no longer at risk for suicidal behavior, discontinue gradually and resume treatment of underlying disorder with an antipsychotic agent to which patient has previously responded.
Discontinuance of Therapy
Oral
For planned termination of therapy, reduce dosage gradually over a 1- to 2-week period.
If abrupt discontinuance is required (e.g., due to leukopenia or agranulocytosis), observe carefully for recurrence of psychotic symptoms and symptoms related to cholinergic rebound (e.g., headache, nausea, vomiting, diarrhea). Sudden withdrawal can lead to rapid decompensation and rebound psychosis.
Reinitiation of Therapy
Oral
Do not reinitiate in patients in whom therapy was discontinued due to WBC count <2000/mm3 or an ANC <1000/mm3.
If restarted after brief interruption (i.e., ≥2 days) in therapy, reinitiate at dosage of 12.5 mg once or twice daily. If dosage well tolerated, it may be feasible to titrate back to therapeutic dosage more quickly than during initial treatment. However, reinitiate with extreme caution, even after brief interruptions of only 24 hours, in patients who have previously experienced respiratory or cardiac arrest during initial dosing but were subsequently titrated to therapeutic dosage.
Reexposure might enhance risk of an adverse effect and/or increase its severity (e.g., when immune-mediated mechanisms are involved); additional caution advised during reinitiation of treatment.
When reinitiating therapy, consider WBC count and ANC monitoring recommendations. (See Table 2: WBC and ANC Monitoring for Clozapine Reinitiation under Cautions.)
Prescribing Limits
Adults
Oral
Maximum 900 mg daily.
Special Populations
Geriatric Patients
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
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