Usual Adult Dose for Schizophrenia

Initial dose: 50 to 100 mg orally 3 times a day
Maintenance dose: 200 to 800 mg/day, divided into 2 to 4 doses
Maximum dose: 800 mg/day

Comment: Once control is attained, the dose should be gradually lowered to determine the minimum effective maintenance dose.

Use: Patients with schizophrenia who have failed to respond to treatment with at least 2 other antipsychotic agents due to insufficient effectiveness or inability to achieve an effective dose due to intolerable side effects

Usual Pediatric Dose for Schizophrenia

Initial dose: 0.5 mg/kg/day orally, in divided doses
Maximum dose: 3 mg/kg/day, in divided doses

Comment: The dose should be increased gradually until therapeutic effects are observed and/or the maximum dose is reached.

Use: Patients with schizophrenia who have failed to respond to treatment with at least 2 other antipsychotic agents due to insufficient effectiveness or inability to achieve an effective dose due to intolerable side effects

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Patients at risk of QT Prolongation and/or CYP450 2D6 poor metabolizers:

• QT interval greater than 450 msec at baseline: Not recommended; if used, monitoring (e.g., ECG, serum potassium) should be considered, especially during dose adjustments.
• QT interval greater than 500 msec during treatment: Discontinue use

Precautions

CONTRAINDICATIONS:

• Hypertensive or hypotensive heart disease of extreme degree
• In combination with other drugs known to prolong the QTc interval
• Inhibitors of CYP450 2D6 (e.g., fluvoxamine, fluoxetine, paroxetine, pindolol, propranolol)
• Patients with congenital long QT syndrome/history of cardiac arrhythmias
• Patients with decreased CYP450 2D6 activity
• Severe central nervous system (CNS) depression or comatose states from any cause (e.g., drug-induced CNS depression)

• Dose-related QTc interval prolongation, Torsade de pointes-type arrhythmias, and sudden death has been shown to occur with this drug.

• Due to its potential for significant, life-threatening proarrhythmic effects, this drug should be reserved for use in the treatment of patients with schizophrenia who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness OR the inability to achieve an effective dose due to intolerable adverse effects from those drugs.

• Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
• Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.
• Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
• Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
• Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality.
• The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

• This drug is not approved for the treatment of patients with dementia-related psychosis.

Dialysis

Data not available

Other Comments

Administration advice:

• See manufacturer product information.

• Protect from light and moisture.

• Safety and efficacy of treatment in patients for refractory schizophrenia is not known.
• Use should be limited to patients who have failed treatment with at least 2 other antipsychotic drugs given at adequate doses for appropriate durations.
• The lowest effective dose should be used due to a dose-related risk of QT prolongation, arrhythmia, and death.

• CARDIOVASCULAR: ECGs, especially before starting treatment, during dose adjustments, and periodically thereafter
• HEMATOLOGIC: Periodic WBC with differential tests, especially in patients with signs/symptoms of infection/sore throat or with a history of low WBCs or drug-induced neutropenia/leukopenia
• METABOLIC: Potassium, especially before starting treatment and periodically thereafter; periodic electrolyte levels, especially in patients with a high risk of developing cardiovascular events and/or those taking diuretics
• OCULAR: Eye examinations, especially in patients on prolonged treatment

• Warn patients to avoid abrupt discontinuation of this drug.
• Tell patients to immediately report any signs/symptoms of neutropenia/leukopenia, neuroleptic malignant syndrome, tardive dyskinesia, or Torsades de pointes.
• Advise patients, and families/caregivers to monitor and report signs/symptoms of unusual behavior immediately to their healthcare provider (e.g., agitation, irritability, anxiety, panic attacks, insomnia, hostility, aggressiveness, impulsivity, akathisia, hypomania/mania).
• Patients should be advised to report all concurrent prescription and nonprescription medications or herbal products they are taking.
• Patients should be instructed to speak to a healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding.
• Inform patients that this drug may cause drowsiness, and they should avoid driving or operating machinery until the full effects of the drug are seen.