Iloperidone

Uses

Iloperidone is used 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

Iloperidone is also used to associated treatment for these conditions: Schizophrenia

How Iloperidone works

Iloperidone is a dopamine D2 and 5-HT2A receptor antagonist and acts as a neuroleptic agent.

Dosage

Iloperidone dosage

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/dayThis 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.

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

Toxicity

Commonly observed adverse reactions (incidence ≥5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.

Precaution

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.

Interaction

There are no known drug interactions and none well documented.

Food Interaction

• Take with or without food. High fat meals may delay the Tmax of iloperidone and its metabolites P88, P95 by 1,2, and 6 hours respectively, without significantly changing the Cmax or AUC.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Iloperidone Cholesterol interaction

[Moderate] Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels.

While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile.

Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

Iloperidone Drug Interaction

Major: hydroxyzine, citalopram, clozapine, ziprasidone, haloperidol, paliperidone, lithium, thioridazine, risperidoneModerate: aripiprazole, divalproex sodium, clonazepam, lamotrigine, lurasidone, eszopiclone, molindone, thiothixeneUnknown: amphetamine / dextroamphetamine, methylphenidate, methylphenidate

Iloperidone Disease Interaction

Major: dementia, QT Prolongation, NMS, tardive dyskinesiaModerate: depression, aspiration, seizure, hematologic abnormalities, hyperglycemia/diabetes, hypotension, lipid alterations, priapism, weight gain, hyperprolactinemia

Volume of Distribution

Apparent Vd = 1340-2800 L

Elimination Route

Well absorbed from the GI tract and Cmax is reached within 2-4 hours. Steady-state concentration is achieved in 3-4 days post-administration of iloperidone. Relative bioavailability of the tablet formulation compared to oral solution is 96%. Accumulation occurs in a predictable fashion.

Half Life

The observed mean elimination half-lives for iloperidone, P88 and P95 in CYP2D6 extensive metabolizers (EM) are 18, 26 and 23 hours, respectively, and in poor metabolizers (PM) are 33, 37 and 31 hours, respectively.

Clearance

Apparent clearance (clearance/bioavilability) = 47-102 L/h.

Elimination Route

Renal (in which <1% of iloperidone is excreted unchanged).

Pregnancy & Breastfeeding use

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.

Contraindication

Hypersensitivity.

Special Warning

Renal Dose Adjustments: No adjustment recommended.

Liver Dose Adjustments-

• Mild hepatic impairment: No adjustment recommended.
• Moderate hepatic impairment: Use with caution.
• Severe hepatic impairment: Not recommended.

Innovators Monograph

You find simplified version here Iloperidone