Iloperidone (Monograph)
Brand name: Fanapt
Drug class: Atypical Antipsychotics
Warning
- Increased Mortality in Geriatric Patients with Dementia-related Psychosis
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Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.
-
Antipsychotic agents, including iloperidone, are not approved for the treatment of patients with dementia-related psychosis.
Introduction
Piperidinyl-benzisoxazole derivative; atypical antipsychotic agent.
Uses for Iloperidone
Schizophrenia
Treatment of schizophrenia in adults.
American Psychiatric Association (APA) and Department of Veterans Affairs/Department of Defense recommend antipsychotic medications for acute and long-term maintenance treatment of schizophrenia. Choice of antipsychotic should be based on patient preference, past response to therapy, concurrent medical conditions, and medication-specific factors (e.g., adverse effect profile, available formulations, potential drug interactions, receptor binding profiles, pharmacokinetic considerations).
Bipolar Disorder
Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
APA recommends lithium or valproate plus an antipsychotic for first-line treatment of severe manic or mixed episodes; for patients with less severe symptoms, monotherapy with lithium, valproate, or an antipsychotic may be appropriate. Selection of a specific treatment is based on clinical factors (e.g., illness severity, associated features, patient preference, side effect profile of the medication). Recommended agents for maintenance treatment include lithium and valproate. Role of iloperidone not addressed.
Department of Veterans Affairs/Department of Defense recommends lithium or quetiapine monotherapy for first-line treatment of acute mania associated with bipolar disorder; recommended alternative agents include olanzapine, paliperidone, or risperidone. If none of these agents are suitable based on patient preference or characteristics, other alternatives include aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, valproate, or ziprasidone. In patients with breakthrough episodes or unsatisfactory response to initial treatment, lithium or valproate in combination with an antipsychotic (haloperidol, asenapine, quetiapine, olanzapine, or risperidone) is recommended. Recommended agents for maintenance therapy include lithium or quetiapine; alternatives include olanzapine, paliperidone, or risperidone.
Iloperidone Dosage and Administration
General
Pretreatment Screening
-
Assess fasting plasma glucose before or soon after initiation of iloperidone.
-
Obtain fasting lipid profile before or soon after initiation of iloperidone.
-
Obtain body weight at baseline.
-
For patients with diseases, conditions, or medications that may exacerbate fall risk, complete fall risk assessment when initiating iloperidone.
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In patients at risk for significant electrolyte disturbances, obtain serum potassium and magnesium concentrations at baseline.
Patient Monitoring
-
Assess fasting plasma glucose periodically during long-term treatment.
-
Monitor fasting lipid profile periodically during treatment.
-
Monitor body weight frequently during treatment.
-
Monitor orthostatic vital signs in patients who are vulnerable to hypotension (e.g., elderly patients, patients with dehydration or hypovolemia, patients taking concomitant antihypertensive medications), patients with known cardiovascular disease (e.g., history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease.
-
For patients with diseases, conditions, or medications that may exacerbate fall risk, complete fall risk assessment recurrently during long-term therapy.
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For patients with pre-existing low WBC or a history of drug-induced leukopenia/neutropenia, monitor CBC frequently during the first few months of therapy.
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Monitor patients with clinically significant neutropenia for fever or other signs/symptoms of infection.
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In patients at risk for significant electrolyte disturbances, monitor serum potassium and magnesium concentrations periodically.
Dispensing and Administration Precautions
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To avoid medication errors, the Institute for Safe Medication Practices (ISMP) recommends that prescribers communicate both the brand and generic names for iloperidone (Fanapt) on the prescription order form.
Other General Considerations
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Titrate iloperidone dosage gradually when initiating therapy to avoid orthostatic hypotension; if iloperidone is discontinued for >3 days, follow the initiation titration schedule when restarting therapy.
Administration
Oral Administration
Administer tablets orally twice daily without regard to meals.
Dosage
Adults
Schizophrenia
Oral
Initial dosage is 1 mg twice daily. May titrate to recommended target dosage range of 6–12 mg twice daily with dosage adjustments not exceeding 2 mg twice daily (e.g., 2, 4, 6, 8, 10, and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7, respectively).
Bipolar Disorder
Oral
Initial dosage is 1 mg twice daily. May titrate to recommended target dosage of 12 mg twice daily with dosage adjustments not exceeding 3 mg twice daily (e.g., 3, 6, 9, and 12 mg twice daily on days 2, 3, 4, and 5, respectively).
Dosage Modifications for Drug Interactions
Reduce iloperidone dosage by 50% if administered concomitantly with strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) or strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole). May resume previous iloperidone dosage upon discontinuance of the strong CYP2D6 or CYP3A4 inhibitor.
Also reduce iloperidone dosage by 50% when given in combination with both a CYP2D6 and CYP3A4 inhibitor.
Special Populations
Hepatic Impairment
Mild hepatic impairment: Dosage adjustment not necessary.
Moderate hepatic impairment: Dosage reduction may be required if clinically indicated.
Severe hepatic impairment: Use not recommended.
Renal Impairment
No dosage recommendations at this time.
Geriatric Patients
No dosage recommendations at this time.
Pharmacogenomic Considerations in Dosing
Reduce dosage by 50% in CYP2D6 poor metabolizers.
Schizophrenia: initiate at 1 mg orally twice daily; titrate up to 2, 4, and 6 mg twice daily on days 2, 3, and 4 of therapy, respectively. Recommended dosage range: 3–6 mg twice daily.
Bipolar disorder: initiate at 1 mg orally twice daily; titrate up to 3 and 6 mg twice daily on days 2 and 3 of therapy, respectively. Recommended dosage: 6 mg twice daily.
Cautions for Iloperidone
Contraindications
-
Known hypersensitivity to the product; anaphylaxis, angioedema, and other hypersensitivity reactions reported.
Warnings/Precautions
Warnings
Increased Mortality in Geriatric Patients with Dementia-related Psychosis
Increased risk of death with use of antipsychotic agents in geriatric patients with dementia-related psychosis (see Boxed Warning).
Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.
Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).
Antipsychotic agents, including iloperidone, are not approved for treatment of dementia-related psychosis.
Other Warnings and Precautions
Cerebrovascular Adverse Reactions, including Stroke, in Geriatric Patients with Dementia-related Psychosis
Increased incidence of adverse cerebrovascular events (cerebrovascular accidents and TIAs), including fatalities, observed in geriatric patients with dementia-related psychosis treated with certain atypical antipsychotic agents (aripiprazole, olanzapine, risperidone) in placebo-controlled studies. Iloperidone is not approved for the treatment of patients with dementia-related psychosis.
Prolongation of QT Interval
Corrected QT (QTc) interval prolonged by 9 msec at total iloperidone daily dosage of 24 mg. CYP2D6 or CYP3A4 inhibition increases this effect; under conditions of both CYP2D6 and CYP3A4 inhibition, mean QTc interval (corrected using Fridericia’s formula) was prolonged by about 19 msec at a dosage of 12 mg twice daily. No cases of torsades de pointes or other severe cardiac arrhythmias reported during premarketing clinical trials.
Factors that may increase the risk of torsades de pointes and/or sudden death in association with drugs that prolong the QTc interval include bradycardia, hypokalemia or hypomagnesemia, concomitant use of other drugs that prolong the QTc interval, presence of congenital prolongation of the QT interval, recent acute MI, and/or uncompensated heart failure.
Avoid concomitant use of other drugs known to prolong the QTc interval. Also avoid use in patients with a known genetic susceptibility to congenital QT-interval prolongation or a history of cardiac arrhythmias.
Use with caution in patients concurrently receiving drugs that inhibit iloperidone’s metabolism and in patients with reduced CYP2D6 activity.
Hypokalemia and/or hypomagnesemia may increase the risk of QT-interval prolongation and cardiac arrhythmias. Manufacturer recommends baseline and periodic monitoring of serum potassium and magnesium in patients at risk for disturbances of these electrolytes.
Avoid use of iloperidone in patients with a history of clinically important cardiovascular illness (e.g., QT-interval prolongation, recent acute MI, uncompensated heart failure, cardiac arrhythmia).
Discontinue iloperidone therapy in patients with persistent QTc interval measurements >500 msec. Further evaluation, including cardiac monitoring, is recommended in patients with symptoms suggestive of cardiac arrhythmias (e.g., dizziness, palpitations, syncope).
Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and autonomic instability (e.g., irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia), reported with antipsychotic agents, including iloperidone. Other signs of NMS include elevated CPK, myoglobinuria, and acute renal failure.
Immediately discontinue therapy and provide intensive symptomatic treatment and monitoring if NMS occurs.
Tardive Dyskinesia
Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported with use of antipsychotic agents. Risk of developing tardive dyskinesia and the likelihood that it will become irreversible increase with duration of treatment and cumulative dose; however, it may also develop after relatively brief treatment periods at low doses. It may also occur after treatment discontinuation.
Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.
Consider discontinuance of iloperidone if signs and symptoms of tardive dyskinesia appear. However, some patients may require treatment despite presence of the syndrome.
Metabolic Changes
Atypical antipsychotic agents associated with metabolic changes, including hyperglycemia and diabetes mellitus, dyslipidemia, and weight gain. While all atypical antipsychotics produce some metabolic changes, each drug has its own specific risk profile.
Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents, including iloperidone. Assess fasting plasma glucose before or soon after initiation of antipsychotic therapy, and monitor periodically during long-term treatment.
Undesirable changes in lipid parameters observed in patients treated with atypical antipsychotics. Obtain a fasting lipid profile before or soon after initiating iloperidone, and monitor periodically during iloperidone treatment.
Weight gain observed with atypical antipsychotic therapy, including iloperidone. Monitor weight at baseline and frequently thereafter in patients treated with iloperidone.
Orthostatic Hypotension and Syncope
Risk of orthostatic hypotension associated with dizziness, tachycardia, and syncope, because of iloperidone’s α1-adrenergic blocking activity.
Increased incidence of orthostatic hypotension and syncope expected with more rapid dosage titration.
Monitor orthostatic vital signs in patients vulnerable to hypotension (e.g., elderly patients, patients with dehydration or hypovolemia, patients taking concomitant antihypertensive medications), patients with known cardiovascular disease (e.g., history of MI, ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease.
Falls
May cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.
In patients with diseases, conditions or other drugs that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic therapy and repeat such testing periodically during long-term therapy.
Seizures
May cause seizures; risk greatest in patients with history of seizures or conditions that lower the seizure threshold.
Conditions that lower the seizure threshold may be more prevalent in older patients.
Leukopenia, Neutropenia, and Agranulocytosis
Leukopenia and neutropenia temporally related to antipsychotic agents reported during clinical trial and/or postmarketing experience. Agranulocytosis (including fatal cases) also reported.
Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia. Monitor CBC frequently during the first few months of therapy in patients with such risk factors. Discontinue iloperidone at the first sign of a decline in WBC count in the absence of other causative factors.
Carefully monitor patients with neutropenia for signs and symptoms of infection (e.g., fever) and treat promptly if they occur. Discontinue iloperidone if severe neutropenia (ANC <1000/mm3) occurs; monitor WBC until recovery occurs.
Hyperprolactinemia
May cause elevated serum prolactin concentrations, which may cause clinical disturbances (e.g., galactorrhea, amenorrhea, gynecomastia, impotence). Chronic hyperprolactinemia associated with hypogonadism may lead to decreased bone density in both females and males.
If contemplating iloperidone therapy in a patient with previously detected breast cancer, consider that approximately one-third of human breast cancers are prolactin-dependent in vitro.
Body Temperature Regulation
Antipsychotic agents may disrupt ability to regulate core body temperature.
Use appropriate caution in patients who will be experiencing conditions that may contribute to an elevation in core body temperature (e.g., strenuous exercise, extreme heat, concomitant use of agents with anticholinergic activity, dehydration).
Dysphagia
Esophageal dysmotility and aspiration associated with the use of antipsychotic agents.
Aspiration pneumonia is a common cause of morbidity and mortality in geriatric patients. Use with caution in patients at risk for aspiration.
Priapism
Priapism reported in patients receiving drugs with α-adrenergic blocking activity, including iloperidone. Severe priapism may require surgical intervention.
Cognitive and Motor Impairment
Judgment, thinking, or motor skills may be impaired. Somnolence (including sedation) reported.
Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with iloperidone does not affect them adversely.
Intraoperative Floppy Iris Syndrome (IFIS)
IFIS observed during cataract surgery in some patients on or previously treated with α1-adrenergic blockers. Stopping α1-adrenergic blocker therapy prior to cataract surgery does not appear to provide benefit. Patient’s surgeon should be prepared for possible modifications to their surgical technique, such as utilization of iris hooks, iris dilator rings, or viscoelastic substances. Initiation of iloperidone not recommended in patients for whom cataract or glaucoma surgery is scheduled.
Specific Populations
Pregnancy
Limited available data with iloperidone in pregnant women not sufficient to inform a drug-associated risk for major birth defects and miscarriage. The drug was not teratogenic in animal studies; however, other adverse effects (e.g., prolonged duration of pregnancy and parturition; increased still births and early intrauterine deaths; developmental delays; decreased postpartum pup survival) were observed in some animal studies.
Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester. Symptoms have varied in severity; some infants recovered within hours to days without specific treatment while others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms; if such symptoms occur, manage appropriately.
National Pregnancy Registry for Atypical Antipsychotics: 866-961-2388 and [Web].
Lactation
Iloperidone distributes into milk in rats; not known whether iloperidone and/or its metabolites distribute into human milk. Effects of the drug on nursing infants and on milk production also not known.
Women receiving iloperidone should not breast-feed because of the potential for serious adverse reactions in breastfed infants.
Pediatric Use
Safety and efficacy not established.
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.
Geriatric patients with dementia-related psychosis treated with iloperidone are at an increased risk of death; increased incidence of cerebrovascular events also observed with certain atypical antipsychotic agents. Iloperidone is not approved for the treatment of patients with dementia-related psychosis.
Hepatic Impairment
In mild hepatic impairment (Child Pugh class A), pharmacokinetic profiles of iloperidone and its P88 and P95 metabolites (total or unbound) not substantially altered. In moderate hepatic impairment (Child Pugh class B), exposure to the P88 metabolite substantially higher (by 2-fold) and more variable compared with healthy individuals.
Dosage adjustment not necessary in patients with mild hepatic impairment. Dosage adjustment may be necessary in patients with moderate hepatic impairment if clinically indicated.
Not studied in patients with severe hepatic impairment (Child Pugh class C); use not recommended.
Renal Impairment
Renal impairment (creatinine clearance <30 mL/minute) has minimal effect on peak plasma concentrations of iloperidone and its P88 and P95 metabolites. AUC increased by 24% for iloperidone, decreased by 6% for P88, and increased by 52% for P95 in individuals with renal impairment.
Pharmacogenomic Considerations
Systemic exposure of iloperidone and the P88 metabolite increased by 47 and 85%, respectively, in CYP2D6 poor metabolizers compared to normal metabolizers. Systemic exposure of the P95 metabolite decreased by 85% in poor CYP2D6 metabolizers compared to normal metabolizers.
Common Adverse Effects
Adverse effects occurring in clinical trials in ≥5% of patients receiving short-term iloperidone therapy for schizophrenia and at a frequency at least twice that reported among patients receiving placebo include dizziness, fatigue, dry mouth, nasal congestion, tachycardia, orthostatic hypotension, somnolence, weight gain.
Adverse effects occurring in clinical trials in ≥5% of patients receiving short-term iloperidone therapy for bipolar mania and at a frequency at least twice that reported among patients receiving placebo include tachycardia, dizziness, dry mouth, increased hepatic enzymes, nasal congestion, weight gain, hypotension, somnolence.
Drug Interactions
Metabolized principally by CYP3A4 and CYP2D6.
Not a substrate or inhibitor of CYP 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, or 2E1; also not a substrate of CYP2C19, and not an inducer of CYP 1A2, 2C8, 2C9, 2C19, 3A4, or 3A5.
Iloperidone and its active metabolite P88 are not substrates of P-glycoprotein (P-gp). Iloperidone is a weak P-gp inhibitor.
Drugs Affecting Hepatic Microsomal Enzymes
Strong CYP2D6 inhibitors: Potential increased plasma concentrations of iloperidone and its P88 metabolite. Reduce iloperidone dosage by 50% if used concomitantly with a strong inhibitor of CYP2D6; may resume previous iloperidone dosage upon discontinuance of the CYP2D6 inhibitor.
Strong CYP3A4 inhibitors: Potential increased plasma concentrations of iloperidone and its metabolites. Reduce iloperidone dosage by 50% if used concomitantly with a strong inhibitor of CYP3A4; may resume previous iloperidone dosage upon discontinuance of the CYP3A4 inhibitor.
Combination of CYP2D6 and CYP3A4 inhibitors: Potential increased plasma concentrations of iloperidone and its P88 metabolite; increases not substantially greater than those observed with CYP2D6 or CYP3A4 inhibitors alone. Potential for increased QT interval prolongation. Reduce iloperidone dosage by 50% when given in combination with both a CYP2D6 and CYP3A4 inhibitor; may resume previous iloperidone dosage upon discontinuance of the CYP2D6 and CYP3A4 inhibitors.
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP2D6 or 3A4: Pharmacokinetic interactions unlikely.
Drugs that Prolong QT Interval
Potential additive effect on QT-interval prolongation; avoid concomitant use of other drugs known to prolong the QTc interval.
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Alcohol |
Avoid concomitant use |
|
Antiarrhythmics, class IA and III (e.g., amiodarone, procainamide, quinidine, sotalol) |
Increased risk of QT-interval prolongation |
Avoid concomitant use |
Anticholinergic agents |
Possible disruption of body temperature regulation |
Use with caution |
Antipsychotic agents that prolong QT interval (e.g., chlorpromazine, thioridazine) |
Increased risk of QT-interval prolongation |
Avoid concomitant use |
Dextromethorphan |
17% increase in total exposure and 26% increase in peak plasma concentrations of dextromethorphan during concurrent administration |
|
Fluoxetine |
Approximate 2- to 3-fold increase in AUC of iloperidone and its P88 metabolite and 50% decrease in AUC of its P95 metabolite during concurrent administration in CYP2D6 extensive metabolizers Single dose of iloperidone did not affect fluoxetine pharmacokinetics |
Use with caution and reduce iloperidone dosage by 50% during concurrent administration; resume previous iloperidone dosage upon discontinuance of fluoxetine Reduce iloperidone dosage by 50% if given concurrently with both fluoxetine (a CYP2D6 inhibitor) and a CYP3A4 inhibitor |
Hypotensive agents |
Possible additive hypotensive effects; may result in symptomatic hypotension |
Avoid concomitant use with α1-adrenergic blockers; adjust dosage of medications affecting BP as needed |
Ketoconazole |
Concomitant administration of ketoconazole and iloperidone increased AUC of iloperidone and its P88 and P95 metabolites by 57, 55, and 35%, respectively |
Use with caution and reduce iloperidone dosage by 50% during concurrent administration; resume previous iloperidone dosage upon discontinuance of ketoconazole Reduce iloperidone dosage by 50% if given concurrently with both a CYP2D6 inhibitor and ketoconazole (a CYP3A4 inhibitor) |
Methadone |
Increased risk of QT-interval prolongation |
Avoid concomitant use |
Midazolam |
Steady-state iloperidone increased total exposure of midazolam by <50%; peak midazolam concentrations not affected |
|
Moxifloxacin |
Increased risk of QT-interval prolongation |
Avoid concomitant use |
Paroxetine |
Approximate 1.6-fold increase in mean steady-state peak plasma concentrations of iloperidone and its P88 metabolite and 50% decrease in mean steady-state peak plasma concentrations of its P95 metabolite during concurrent administration |
Use with caution and reduce iloperidone dosage by 50% during concurrent administration; resume previous iloperidone dosage upon discontinuance of paroxetine Reduce iloperidone dosage by 50% if given concurrently with both paroxetine (a CYP2D6 inhibitor) and a CYP3A4 inhibitor |
Pentamidine |
Increased risk of QT-interval prolongation |
Avoid concomitant use |
Smoking |
Pharmacokinetic interaction unlikely |
Iloperidone Pharmacokinetics
Absorption
Bioavailability
Well absorbed following oral administration; peak plasma concentrations achieved within 2–4 hours. Steady-state concentrations of iloperidone and its 2 main metabolites, P88 and P95, attained within 3–4 days.
Food
Standard high-fat meal did not substantially affect peak plasma concentrations or AUCs of iloperidone, P88, or P95; however, time to reach peak plasma concentrations was delayed by 1, 2, and 6 hours, respectively.
Special Populations
In patients with mild hepatic impairment, the pharmacokinetic profiles of iloperidone, P88, and P95 (total or unbound) were not substantially altered in a single-dose study; however, exposure to P88 (unbound) was increased 2-fold and more variable in patients with moderate hepatic impairment compared with healthy individuals. Not studied in patients with severe hepatic impairment.
Renal impairment (Clcr <30 mL/minute) minimally affected peak plasma concentrations of iloperidone, P88, and P95 in a single-dose study. AUCs increased by 24% for iloperidone, decreased by 6% for P88, and increased by 52% for P95.
CYP2D6 poor metabolizers have higher exposure to iloperidone compared with extensive metabolizers.
Distribution
Extent
Iloperidone distributes into milk in rats; not known whether iloperidone and its metabolites distribute into human milk.
Plasma Protein Binding
Iloperidone and its metabolites are approximately 97 and 92% protein bound, respectively.
Elimination
Metabolism
Metabolized mainly by carbonyl reduction, hydroxylation (mediated by CYP2D6), and O-demethylation (mediated by CYP3A4) to P95 and P88; these metabolites undergo further oxidation and/or conjugation with glucuronic acid.
Elimination Route
Radiolabeled drug is mostly eliminated in urine (about 58 and 45% in extensive and poor metabolizers of CYP2D6, respectively), with feces accounting for about 20% (extensive metabolizers) to 22% (poor metabolizers).
Half-life
Mean elimination half-lives for iloperidone, P88, and P95 are 18, 26, and 23 hours, respectively, in extensive metabolizers of CYP2D6 and 33, 37, and 31 hours, respectively, in poor metabolizers.
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C); protect from light and moisture.
Actions
-
Exact mechanism of action of iloperidone in schizophrenia is unknown; efficacy may be mediated through a combination of antagonist activity at central dopamine type 2 (D2) and serotonin type 2 (5-hydroxytryptamine [5-HT2]) receptors.
-
Functions as an antagonist and exhibits high affinity for 5-HT2A, D2 and D3, and α1-adrenergic receptors. Demonstrates moderate affinity for D4 and 5-HT6 and 5-HT7 receptors and low affinity for 5-HT1A, D1, and histamine H1 receptors. Possesses no appreciable affinity for muscarinic cholinergic receptors.
-
Iloperidone has 2 main metabolites, P88 and P95; the affinity of P88 is generally equal to or less than that of iloperidone while P95 only demonstrates affinity for 5-HT2A and α1A-, α1B-, α1D-, and α2C-adrenergic receptors.
Advice to Patients
-
Advise patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. Inform patients and caregivers that iloperidone is not approved for treating geriatric patients with dementia-related psychosis.
-
Advise patients to immediately inform their clinician if they feel faint, lose consciousness, or have heart palpitations. Counsel patients not to take iloperidone with other drugs that prolong the QT interval. Instruct patients to inform clinicians that they are taking iloperidone before any new drug is taken.
-
Inform patients and caregivers about the risk of neuroleptic malignant syndrome (NMS), a rare but potentially life-threatening syndrome. Advise patients to contact their clinician or report to the emergency room if they experience signs or symptoms of NMS.
-
Advise patients on the signs and symptoms of tardive dyskinesia and instruct them to contact their clinician if these abnormal movements occur.
-
Inform patients about the risk of metabolic changes with iloperidone (including weight gain) and the need for specific monitoring for such changes during therapy (e.g., blood glucose, lipids, weight). Inform patients about the symptoms of hyperglycemia and diabetes mellitus.
-
Inform patients about the risk of orthostatic hypotension and syncope, especially when initiating or reinitiating treatment or increasing the dosage.
-
Advise patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia that they should have their CBC monitored while taking iloperidone.
-
Caution patients about performing activities requiring mental alertness, such as driving or operating hazardous machinery, while taking iloperidone until they gain experience with the drug’s effects.
-
Instruct patients to tell their ophthalmologist about their use of iloperidone before cataract surgery or other procedures involving the eyes, even if the patient is no longer taking iloperidone.
-
Advise patients to avoid alcohol during iloperidone therapy.
-
Advise patients to avoid overheating or dehydration.
-
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.
-
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Inform patients about the benefits and risks of taking antipsychotics during pregnancy, including that third trimester use of iloperidone may cause extrapyramidal and/or withdrawal symptoms in neonates, and about the pregnancy exposure registry. Advise patients not to breast-feed during iloperidone therapy.
-
Advise patients of other important precautionary information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
1 mg |
Fanapt |
Vanda |
2 mg |
Fanapt |
Vanda |
||
4 mg |
Fanapt |
Vanda |
||
6 mg |
Fanapt |
Vanda |
||
8 mg |
Fanapt |
Vanda |
||
10 mg |
Fanapt |
Vanda |
||
12 mg |
Fanapt |
Vanda |
||
Titration Pack |
2 Tablets, Iloperidone 1 mg (Fanapt) 2 Tablets, Iloperidone 2 mg (Fanapt) 2 Tablets, Iloperidone 4 mg (Fanapt) 2 Tablets, Iloperidone 6 mg (Fanapt) |
Fanapt Titration Pack |
Vanda |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions May 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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