Iloperidone
Indications
Iloperidone is indicated for the treatment of schizophrenia in adults.
When deciding among the alternative treatments available for this condition, the prescriber should consider the finding that iloperidone is associated with prolongation of the QTc interval. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointestype arrhythmia, a potentially fatal polymorphic ventricular tachycardia which can result in sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether iloperidone will cause torsade de pointes or increase the rate of sudden death is not yet known.
Patients must be titrated to an effective dose of iloperidone. Thus, control of symptoms may be delayed during the first 1 to 2 weeks of treatment compared to some other antipsychotic drugs that do not require a similar titration. Prescribers should be mindful of this delay when selecting an antipsychotic drug for the treatment of schizophrenia
When deciding among the alternative treatments available for this condition, the prescriber should consider the finding that iloperidone is associated with prolongation of the QTc interval. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointestype arrhythmia, a potentially fatal polymorphic ventricular tachycardia which can result in sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether iloperidone will cause torsade de pointes or increase the rate of sudden death is not yet known.
Patients must be titrated to an effective dose of iloperidone. Thus, control of symptoms may be delayed during the first 1 to 2 weeks of treatment compared to some other antipsychotic drugs that do not require a similar titration. Prescribers should be mindful of this delay when selecting an antipsychotic drug for the treatment of schizophrenia
Pharmacology
Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors.
Dosage & Administration
Initial dose: 1 mg orally twice a day
Titration: Increase in increments of not more than 2 mg twice daily as tolerated.
Target dose: 6 to 12 mg twice a day
Maximum dose: 24 mg/day
This drug must be titrated slowly to avoid orthostatic hypotension; because of the need to titrate slowly, control of symptoms may be delayed during the first 1 to 2 weeks of treatment.
Titration: Increase in increments of not more than 2 mg twice daily as tolerated.
Target dose: 6 to 12 mg twice a day
Maximum dose: 24 mg/day
This drug must be titrated slowly to avoid orthostatic hypotension; because of the need to titrate slowly, control of symptoms may be delayed during the first 1 to 2 weeks of treatment.
Interaction
There are no known drug interactions and none well documented.
Contraindications
Hypersensitivity.
Side Effects
Dizziness (20%), Dry mouth (15%), Nausea (10%), Somnolence (10%), Tachycardia, Diarrhea, Ejaculation failure, Myalgia, Nasal congestion, Orthostatic hypotension, Palpitations, Urinary incontinence, Weight gain
Pregnancy & Lactation
Pregnancy Category-C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Lactation: Not known if excreted in breast milk, do not nurse.
Lactation: Not known if excreted in breast milk, do not nurse.
Precautions & Warnings
This drug is not approved for the treatment of patients with dementia-related psychosis. Prolongs QT interval; caution with other drugs/conditions that increase QTc. Risk of neuroleptic malignant syndrome and extrapyramidal symptoms. May cause anticholinergic side effects (eg., confusion, agitation). Blood dyscrasias (leukopenia, neutropenia, agranulocytosis) may occur. Orthostatic hypotension may occur.
Use in Special Populations
Renal Dose Adjustments: No adjustment recommended.
Liver Dose Adjustments-
Liver Dose Adjustments-
- Mild hepatic impairment: No adjustment recommended.
- Moderate hepatic impairment: Use with caution.
- Severe hepatic impairment: Not recommended.
Therapeutic Class
Piperidinyl-benzisoxazole derivative
