Fanapt (iloperidone)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Iloperidone is considered an atypical antipsychotic agent.
Iloperidone is a piperidinyl-benzisoxazole derivative; the drug has been referred to as an atypical antipsychotic agent. Although the exact mechanism of action of iloperidone is unknown, it has been suggested that the efficacy of iloperidone is mediated through a combination of antagonist activity at central dopamine type 2 (D2) and serotonin type 2 (5-hydroxytryptamine (5-HT2)) receptors.
Iloperidone acts as an antagonist with high binding affinity for 5-HT2A, D2 and D3, and alpha1-adrenergic receptors. The drug has moderate affinity for D4, 5-HT6, and 5-HT7 receptors and low affinity for 5-HT1A, D1, and histamine H1 receptors. Iloperidone possesses no appreciable affinity for muscarinic cholinergic receptors.
Iloperidone has 2 main metabolites, P88 and P95; the affinity of the P88 metabolite is generally equal to or less than that of the parent compound while the P95 metabolite demonstrates affinity for 5-HT2A and alpha1A-, alpha1B-, alpha1D-, and alpha2C-adrenergic receptors.
Iloperidone is well absorbed following oral administration of the tablets, with peak plasma concentrations occurring within 2-4 hours. Steady-state plasma concentrations of iloperidone and its two main metabolites, P88 and P95, are reached within 3-4 days. Administration with a high-fat meal did not significantly impact maximum plasma concentrations or AUC of iloperidone or its metabolites; time to maximum concentration was delayed by 1, 2, and 6 hours for iloperidone, P88, and P95, respectively.
At therapeutic concentrations, iloperidone and its metabolites (P88 and P95) are approximately 97 and 92% bound to plasma proteins, respectively. Iloperidone is primarily metabolized by carbonyl reduction, cytochrome P-450 (CYP) isoenzyme 2D6-mediated hydroxylation, and CYP3A4-mediated O-demethylation; P88 and P95 undergo further oxidation and/or conjugation with glucuronic acid. The P88 metabolite penetrates the CNS and is thought to contribute to the drug's antipsychotic activity whereas the P95 metabolite does not readily penetrate the CNS and primarily contributes to the adverse effect profile of the drug.
The mean elimination half-lives of 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 of CYP2D6. The majority of radiolabeled iloperidone was recovered in the urine (mean of 58.2 and 45.1% in extensive and poor metabolizers of CYP2D6, respectively), with feces accounting for 19.9% (extensive metabolizers) and 22.1% (poor metabolizers) of the radiolabeled dose.
USES: This medication is used to treat certain mental/mood disorders (such as schizophrenia, bipolar disorder). Iloperidone belongs to a class of drugs known as atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain.
Generic name: iloperidone
Pronunciation: (EYE-loe-PER-i-done)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Fanapt
Indications
The following indications are listed for Fanapt:
- Mixed Bipolar I Disorder
- Schizophrenia
Also known as: Dementia Praecox, Parergasia.
Dosing
If iloperidone is used concomitantly with a strong cytochrome P-450 (CYP) 2D6 inhibitor (e.g., fluoxetine, paroxetine), reduce the dosage of iloperidone by 50%. If the strong CYP2D6 inhibitor is discontinued, increase the dosage of iloperidone to the previous dosage.
If iloperidone is used concomitantly with a strong CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin), reduce the dosage of iloperidone by 50%. If the strong CYP3A4 inhibitor is discontinued, increase the dosage of iloperidone to the previous dosage.
If iloperidone is used concomitantly with strong CYP2D6 and strong CYP3A4 inhibitors, reduce the dosage of iloperidone by 50%. If both CYP2D6 and CYP3A4 inhibitors are discontinued, increase the dosage of iloperidone to the previous dosage.
Iloperidone is commercially available as tablets, which are administered orally twice daily without regard to meals.
Store iloperidone tablets at 25degreesC (excursions permitted between 15-30degreesC); protect the tablets from exposure to light and moisture.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Iloperidone is metabolized principally by cytochrome P-450 (CYP) isoenzymes 3A4 and 2D6.
Iloperidone is not a substrate or inhibitor of CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, or 2E1; it is also not a substrate of CYP2C19, and not an inducer of CYP isoenzymes 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.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to the product; anaphylaxis, angioedema, and other hypersensitivity reactions reported.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in clinical trials in 5% or more 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, and weight gain.
Adverse effects occurring in clinical trials in 5% or more 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, and somnolence.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness of iloperidone in pediatric patients have not been established.
A pregnancy exposure registry has been established to monitor pregnancy outcomes in women exposed to iloperidone during pregnancy. For more information, clinicians may contact the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 or visit https://womensmentalhealth.org/research/pregnancyregistry/.
Limited data are available regarding use of iloperidone in pregnant women and are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. The drug was not teratogenic when administered orally to pregnant rats during organogenesis at dosages up to 26 times the maximum recommended human dosage (MRHD) of 24 mg daily on a mg/m2 basis. However, iloperidone prolonged the duration of pregnancy and parturition, increased still births and early intrauterine deaths, increased the incidence of developmental delays, and decreased postpartum pup survival. Iloperidone was not teratogenic when administered orally to pregnant rabbits during organogenesis at dosages up to 20 times the MRHD on a mg/m2 basis. However, the drug increased early intrauterine deaths and decreased fetal viability at term at the highest dosage, which also was a maternally toxic dosage.
Neonates exposed to antipsychotic agents during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Symptoms reported to date have included agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. The symptoms have varied in severity; some neonates recovered within hours to days without specific treatment while others have required prolonged hospitalization. Neonates should be monitored for extrapyramidal and/or withdrawal symptoms and managed appropriately if symptoms occur.
Iloperidone is distributed into milk in rats. It is not known whether iloperidone and/or its metabolites distribute into milk in humans. The effects of the drug on breastfed infants or on milk production also are not known. Because of the potential for serious adverse reactions in breastfed infants, the manufacturer recommends that women receiving iloperidone not breast-feed.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Clinical trial experience with iloperidone in patients with schizophrenia who are 65 years of age or older is insufficient to determine whether they respond differently than younger adults. In premarketing clinical studies in patients with schizophrenia, 0.5% of 3210 iloperidone-treated patients were 65 years of age or older and no patients were 75 years of age or older. Of the 206 patients with bipolar mania treated with iloperidone in a clinical trial, 2 patients (0.1%) were 65 years of age and there were no patients older than 65 years of age.
Geriatric patients with dementia-related psychosis treated with iloperidone are at an increased risk of death compared with those receiving placebo. In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and transient ischemic attacks), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with certain atypical antipsychotic agents (aripiprazole, olanzapine, risperidone) in placebo-controlled studies. The manufacturer states that iloperidone is not approved for the treatment of patients with dementia-related psychosis.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.