Drugs Details

Drugs Info of Fanapt
Drugs Details
  • Drugs Type  : FDA
  • Date : 10th Feb 2015 01:49 am
  • Brand Name : Fanapt
  • Generic Name :  iloperidone (Pronunciation: EYE loe PER i done
Descriptions

o off-white finely crystalline powder. It is practically insoluble in water, very slightly soluble in 0.1 N HCl and freely soluble in chloroform, ethanol, methanol, and acetonitrile.

FANAPT tablets are intended for oral administration only. Each round, uncoated tablet contains 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, or 12 mg of iloperidone. Inactive ingredients are: lactose monohydrate, microcrystalline cellulose, hydroxypropylmethylcellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and purified water (removed during processing). The tablets are white, round, flat, beveled-edged and identified with a logo “ ” debossed on one side and tablet strength “1”, “2”, “4”, “6”, “8”, “10”, or “12” debossed on the other side.

What are the possible side effects of iloperidone (Fanapt)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking this medication and call your doctor at once if you have a serious side effect such as:

  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
  • very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;
  • twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or...

Read All Potential Side Effects and See Pictures of Fanapt »

What are the precautions when taking iloperidone tablets (Fanapt)?

See also Warning section.

Before taking iloperidone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, heart problems (such as past heart attack, chest pain, abnormal heartbeat), stroke, diabetes (including family history), obesity, low blood pressure, seizures, low white blood cell count, loss of too much body water (dehydration), breast cancer, dementia (such as Alzheimer's Disease), trouble swallowing.

Iloperidone may cause a condition that affects the heart rhythm...

Read All Potential Precautions of Fanapt »


This monograph has been modified to include the generic and brand name in many instances.

Indications

FANAPT® tablets are indicated for the treatment of adults with schizophrenia. Efficacy was established in two short-term (4-and 6-week) placebo-and active-controlled studies of adult patients with schizophrenia [see Clinical Studies].

When deciding among the alternative treatments available for this condition, the prescriber should consider the finding that FANAPT is associated with prolongation of the QTc interval [see WARNINGS AND PRECAUTIONS]. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointes-type 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 FANAPT 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 FANAPT. 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 [see DOSAGE AND ADMINISTRATION and Clinical Studies].

The effectiveness of FANAPT in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use FANAPT for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see DOSAGE AND ADMINISTRATION].

Dosage Administration

Usual Dose

FANAPT must be titrated slowly from a low starting dose to avoid orthostatic hypotension due to its alpha-adrenergic blocking properties. The recommended starting dose for FANAPT tablets is 1 mg twice daily. Dose increases to reach the target range of 6-12 mg twice daily (12_24 mg/day) may be made with daily dosage adjustments not to exceed 2 mg twice daily (4 mg/day). The maximum recommended dose is 12 mg twice daily (24 mg/day). FANAPT doses above 24 mg/day have not been systematically evaluated in the clinical trials. Efficacy was demonstrated with FANAPT in a dose range of 6 to 12 mg twice daily. Prescribers should be mindful of the fact that patients need to be titrated to an effective dose of FANAPT. 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 similar titration. Prescribers should also be aware that some adverse effects associated with FANAPT use are dose related.

FANAPT can be administered without regard to meals.

Dosage In Special Populations

Dosage adjustments are not routinely indicated on the basis of age, gender, race, or renal impairment status [see Use in Specific Populations].

Dosage adjustment for patients taking FANAPT concomitantly with potential CYP2D6 inhibitors

FANAPT dose should be reduced by one-half when administered concomitantly with strong CYP2D6 inhibitors such as fluoxetine or paroxetine. When the CYP2D6 inhibitor is withdrawn from the combination therapy, FANAPT dose should then be increased to where it was before [see DRUG INTERACTIONS].

Dosage adjustment for patients taking FANAPT concomitantly with potential CYP3A4 inhibitors

FANAPT dose should be reduced by one-half when administered concomitantly with strong CYP3A4 inhibitors such as ketoconazole or clarithromycin. When the CYP3A4 inhibitor is withdrawn from the combination therapy, FANAPT dose should be increased to where it was before [see DRUG INTERACTIONS].

Dosage adjustment for patients taking FANAPT who are poor metabolizers of CYP2D6

FANAPT dose should be reduced by one-half for poor metabolizers of CYP2D6 [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

No dose adjustment to FANAPT is needed in patients with mild hepatic impairment. Exercise caution when administering it to patients with moderate hepatic impairment. FANAPT is not recommended for patients with severe hepatic impairment [see Use In Specific Populations].

Maintenance Treatment

Although there is no body of evidence available to answer the question of how long the patient treated with FANAPT should be maintained, it is generally recommended that responding patients be continued beyond the acute response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation Of Treatment In Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that the initiation titration schedule be followed whenever patients have had an interval off FANAPT of more than 3 days.

Switching From Other Antipsychotics

There are no specific data to address how patients with schizophrenia can be switched from other antipsychotics to FANAPT or how FANAPT can be used concomitantly with other antipsychotics. Although immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

How Supplied

Dosage Forms And Strengths

FANAPT tablets are available in the following strengths: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg. The tablets are white, round, flat, beveled-edged and identified with a logo debossed on one side and tablet strength “1”, “2”, “4”, “6”, “8”, “10”, or “12” debossed on the other side. “

Storage And Handling

FANAPT tablets are white, round and identified with a logo debossed on one side and tablet strength “1”, “2”, “4”, “6”, “8”, “10”, or “12” debossed on the other side. Tablets are supplied in the following strengths and package configurations:

 

Package Configuration Tablet Strength (mg) NDC Code
Bottles of 60 1 mg 0078-0595-20
Bottles of 60 2 mg 0078-0596-20
Bottles of 60 4 mg 0078-0597-20
Bottles of 60 6 mg 0078-0598-20
Bottles of 60 8 mg 0078-0599-20
Bottles of 60 10 mg 0078-0600-20
Bottles of 60 12 mg 0078-0601-20
Titration Pack 2x1 mg, 2x2 mg, 2x4 mg, 2x6 mg (Total of 8 tablets) 0078-0602-08
Storage

Store FANAPT tablets at controlled room temperature, 25°C (77°F); excursions permitted to 15°_ 30 °C (59° _ 86°F) [See USP Controlled Room Temperature]. Protect FANAPT tablets from exposure to light and moisture.

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, NJ 07936. April 2014


This monograph has been modified to include the generic and brand name in many instances.

 

Side Effects

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The information below is derived from a clinical trial database for FANAPT consisting of 2070 patients exposed to FANAPT at doses of 10 mg/day or greater, for the treatment of schizophrenia. Of these, 806 received FANAPT for at least 6 months, with 463 exposed to FANAPT for at least 12 months. All of these patients who received FANAPT were participating in multiple-dose clinical trials. The conditions and duration of treatment with FANAPT varied greatly and included (in overlapping categories), open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and flexible-dose studies, and short-term and longer-term exposure.

Adverse reactions during exposure were obtained by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions, reactions were grouped in standardized categories using MedDRA terminology.

The stated frequencies of adverse reactions represent the proportions of individuals who experienced a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

The information presented in these sections was derived from pooled data from -4 placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies in patients who received FANAPT at daily doses within a range of 10 to 24 mg (n=874).

Adverse Reactions Occurring at an Incidence of 2% or More among FANAPT-Treated Patients and More Frequent than Placebo

Table 7 enumerates the pooled incidences of treatment-emergent adverse reactions that were spontaneously reported in four placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies, listing those reactions that occurred in 2% or more of patients treated with FANAPT in any of the dose groups, and for which the incidence in FANAPT-treated patients in any dose group was greater than the incidence in patients treated with placebo.

Table 7: Percentage of Treatment-Emergent Adverse Reactions in Short-Term, Fixed-or Flexible-Dose, Placebo-Controlled Trials in Adult Patients*

Body System or Organ Class Dictionary-derived Term Placebo % (N=587) FANAPT 10-16 mg/day % (N=483) FANAPT 20-24 mg/day % (N=391)
Body as a Whole
Arthralgia 2 3 3
  Fatigue 3 4 6
  Musculoskeletal Stiffness 1 1 3
  Weight Increased 1 1 9
Cardiac Disorders
  Tachycardia 1 3 12
Eye Disorders
  Vision Blurred 2 3 1
Gastrointestinal Disorders
  Nausea 8 7 10
  Dry Mouth 1 8 10
  Diarrhea 4 5 7
  Abdominal Discomfort 1 1 3
Infections
  Nasopharyngitis 3 4 3
  Upper Respiratory Tract Infection 1 2 3
Nervous System Disorders
  Dizziness 7 10 20
  Somnolence 5 9 15
  Extrapyramidal Disorder 4 5 4
  Tremor  2 3 3
  Lethargy 1 3 1
Reproductive System
  Ejaculation Failure < 1 2 2
Respiratory
  Nasal Congestion 2 5 8
  Dyspnea < 1 2 2
Skin
  Rash 2 3 2
Vascular Disorders
  Orthostatic Hypotension 1 3 5
  Hypotension < 1 < 1 3
* Table includes adverse reactions that were reported in 2% or more of patients in any of the FANAPT dose groups and which occurred at greater incidence than in the placebo group. Figures rounded to the nearest integer.
Dose-Related Adverse Reactions in Clinical Trials

Based on the pooled data from 4 placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies, adverse reactions that occurred with a greater than 2% incidence in the patients treated with FANAPT, and for which the incidence in patients treated with FANAPT 20-24 mg/day were twice than the incidence in patients treated with FANAPT 10-16 mg/day were: abdominal discomfort, dizziness, hypotension, musculoskeletal stiffness, tachycardia, and weight increased.

Common and Drug-Related Adverse Reactions in Clinical Trials

Based on the pooled data from 4 placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies, the following adverse reactions occurred in ≥ 5% incidence in the patients treated with FANAPT and at least twice the placebo rate for at least 1 dose: dizziness, dry mouth, fatigue, nasal congestion, somnolence, tachycardia, orthostatic hypotension, and weight increased. Dizziness, tachycardia, and weight increased were at least twice as common on 20-24 mg/day as on 10-16 mg/day.

Extrapyramidal Symptoms (EPS) in Clinical Trials

Pooled data from the 4 placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies provided information regarding treatment-emergent EPS. Adverse event data collected from those trials showed the following rates of EPS-related adverse events as shown in Table 8.

Table 8: Percentage of EPS Compared to Placebo

Adverse Event Term Placebo (%)
(N=587)
FANAPT 10-16 mg/day (%)
(N=483)
FANAPT 20-24 mg/day (%)
(N=391)
All EPS events 11.6 13.5 15.1
Akathisia 2.7 1.7 2.3
Bradykinesia 0 0.6 0.5
Dyskinesia 1.5 1.7 1.0
Dystonia 0.7 1.0 0.8
Parkinsonism 0 0.2 0.3
Tremor 1.9 2.5 3.1
Adverse Reactions Associated with Discontinuation of Treatment in Clinical Trials

Based on the pooled data from 4 placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies, there was no difference in the incidence of discontinuation due to adverse events between FANAPT-treated (5%) and placebo-treated (5%) patients. The types of adverse events that led to discontinuation were similar for the FANAPT-and placebo-treated patients.

Demographic Differences in Adverse Reactions in Clinical Trials

An examination of population subgroups in the 4 placebo-controlled, 4-or 6-week, fixed-or flexible-dose studies did not reveal any evidence of differences in safety on the basis of age, gender or race [see WARNINGS AND PRECAUTIONS].

Laboratory Test Abnormalities in Clinical Trials

There were no differences between FANAPT and placebo in the incidence of discontinuation due to changes in hematology, urinalysis, or serum chemistry.

In short-term placebo-controlled trials (4-to 6-weeks), there were 1.0% (13/1342) iloperidone-treated patients with hematocrit at least one time below the extended normal range during post-randomization treatment, compared to 0.3% (2/585) on placebo. The extended normal range for lowered hematocrit was defined in each of these trials as the value 15% below the normal range for the centralized laboratory that was used in the trial.

Other Reactions During the Pre-marketing Evaluation of FANAPT

The following is a list of MedDRA terms that reflect treatment-emergent adverse reactions in patients treated with FANAPT at multiple doses ≥ 4 mg/day during any phase of a trial with the database of 3210 FANAPT-treated patients. All reported reactions are included except those already listed in Table 7, or other parts of the ADVERSE REACTIONS section, those considered in the WARNINGS AND PRECAUTIONS, those reaction terms which were so general as to be uninformative, reactions reported in fewer than 3 patients and which were neither serious nor life-threatening, reactions that are otherwise common as background reactions, and reactions considered unlikely to be drug related. It is important to emphasize that, although the reactions reported occurred during treatment with FANAPT, they were not necessarily caused by it.

Reactions are further categorized by MedDRA system organ class and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring in at least 1/100 patients (only those not listed in Table 7 appear in this listing); InFrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

Blood and Lymphatic Disorders: InFrequent – anemia, iron deficiency anemia; Rare – leukopenia

Cardiac Disorders: Frequent – palpitations; Rare – arrhythmia, atrioventricular block first degree, cardiac failure (including congestive and acute)

Ear and Labyrinth Disorders: InFrequent – vertigo, tinnitus

Endocrine Disorders: InFrequent – hypothyroidism

Eye Disorders: Frequent -conjunctivitis (including allergic); InFrequent – dry eye, blepharitis, eyelid edema, eye swelling, lenticular opacities, cataract, hyperemia (including conjunctival)

Gastrointestinal Disorders: InFrequent – gastritis, salivary hypersecretion, fecal incontinence, mouth ulceration; Rare aphthous stomatitis, duodenal ulcer, hiatus hernia, hyperchlorhydria, lip ulceration, reflux esophagitis, stomatitis

General Disorders and Administrative Site Conditions: InFrequent – edema (general, pitting, due to cardiac disease), difficulty in walking, thirst; Rare -hyperthermia

Hepatobiliary Disorders: InFrequent – cholelithiasis

Investigations: Frequent: weight decreased; InFrequent – hemoglobin decreased, neutrophil count increased, hematocrit decreased

Metabolism and Nutrition Disorders: InFrequent – increased appetite, dehydration, hypokalemia, fluid retention

Musculoskeletal and Connective Tissue Disorders: Frequent – myalgia, muscle spasms; Rare – torticollis

Nervous System Disorders: InFrequent – paresthesia, psychomotor hyperactivity, restlessness, amnesia, nystagmus; Rare – restless legs syndrome

Psychiatric Disorders: Frequent – restlessness, aggression, delusion; InFrequent – hostility, libido decreased, paranoia, anorgasmia, confusional state, mania, catatonia, mood swings, panic attack, obsessive-compulsive disorder, bulimia nervosa, delirium, polydipsia psychogenic, impulse-control disorder, major depression

Renal and Urinary Disorders: Frequent – urinary incontinence; InFrequent – dysuria, pollakiuria, enuresis, nephrolithiasis; Rare – urinary retention, renal failure acute

Reproductive System and Breast Disorders: Frequent – erectile dysfunction; InFrequent – testicular pain, amenorrhea, breast pain; Rare – menstruation irregular, gynecomastia, menorrhagia, metrorrhagia, postmenopausal hemorrhage, prostatitis.

Respiratory, Thoracic and Mediastinal Disorders: InFrequent – epistaxis, asthma, rhinorrhea, sinus congestion, nasal dryness; Rare – dry throat, sleep apnea syndrome, dyspnea exertional

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of FANAPT-: retrograde ejaculation. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Read the Fanapt (iloperidone tablets) Side Effects Center for a complete guide to possible side effects

Interactions

Given the primary CNS effects of FANAPT, caution should be used when it is taken in combination with other centrally acting drugs and alcohol. Due to its -alpha1-adrenergic receptor antagonism, FANAPT has the potential to enhance the effect of certain antihypertensive agents.

Potential For Other Drugs To Affect FANAPT

Iloperidone is not a substrate for CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1 enzymes. This suggests that an interaction of iloperidone with inhibitors or inducers of these enzymes, or other factors, like smoking, is unlikely.

Both CYP3A4 and CYP2D6 are responsible for iloperidone metabolism. Inhibitors of CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g., fluoxetine, paroxetine) can inhibit iloperidone elimination and cause increased blood levels.

Ketoconazole

Co-administration of ketoconazole (200 mg twice daily for 4 days), a potent inhibitor of CYP3A4, with a 3 mg single dose of iloperidone to 19 healthy volunteers, ages 18-45 years, increased the area under the curve (AUC) of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively. Iloperidone doses should be reduced by about one-half when administered with ketoconazole or other strong inhibitors of CYP3A4 (e.g., itraconazole). Weaker inhibitors (e.g., erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level.

Fluoxetine

Coadministration of fluoxetine (20 mg twice daily for 21 days), a potent inhibitor of CYP2D6, with a single 3 mg dose of iloperidone to 23 healthy volunteers, ages 29-44 years, who were classified as CYP2D6 extensive metabolizers, increased the AUC of iloperidone and its metabolite P88, by about 2-to 3-fold, and decreased the AUC of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with fluoxetine. When fluoxetine is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level. Other strong inhibitors of CYP2D6 would be expected to have similar effects and would need appropriate dose reductions. When the CYP2D6 inhibitor is withdrawn from the combination therapy, iloperidone dose could then be increased to the previous level.

Paroxetine

Coadministration of paroxetine (20 mg/day for 5-8 days), a potent inhibitor of CYP2D6, with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18-65 years resulted in increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6 fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. Iloperidone doses should be reduced by one-half when administered with paroxetine. When paroxetine is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level. Other strong inhibitors of CYP2D6 would be expected to have similar effects and would need appropriate dose reductions. When the CYP2D6 inhibitor is withdrawn from the combination therapy, iloperidone dose could then be increased to previous levels.

Paroxetine and Ketoconazole

Coadministration of paroxetine (20 mg once daily for 10 days), a CYP2D6 inhibitor, and ketoconazole (200 mg twice daily) with multiple doses of iloperidone (8 or 12 mg twice daily) to patients with schizophrenia ages 18-65 years resulted in a 1.4 fold increase in steady-state concentrations of iloperidone and its metabolite P88 and a 1.4 fold decrease in the P95 in the presence of paroxetine. So giving iloperidone with inhibitors of both of its metabolic pathways did not add to the effect of either inhibitor given alone. Iloperidone doses should therefore be reduced by about one-half if administered concomitantly with both a CYP2D6 and CYP3A4 inhibitor.

Potential For FANAPT To Affect Other Drugs

In vitro studies in human liver microsomes showed that iloperidone does not substantially inhibit the metabolism of drugs metabolized by the following cytochrome P450 isozymes: CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, or CYP2E1. Furthermore, in vitro studies in human liver microsomes showed that iloperidone does not have enzyme inducing properties, specifically for the following cytochrome P450 isozymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.

Dextromethorphan

A study in healthy volunteers showed that changes in the pharmacokinetics of dextromethorphan (80 mg dose) when a 3 mg dose of iloperidone was co-administered resulted in a 17% increase in total exposure and a 26% increase in the maximum plasma concentrations (Cmax )of dextromethorphan. Thus, an interaction between iloperidone and other CYP2D6 substrates is unlikely.

Fluoxetine

A single 3 mg dose of iloperidone had no effect on the pharmacokinetics of fluoxetine (20 mg twice daily).

Midazolam (a sensitive CYP 3A4 substrate)

A study in patients with schizophrenia showed a less than 50% increase in midazolam total exposure at iloperidone steady state (14 days of oral dosing at up to 10 mg iloperidone twice daily) and no effect on midazolam Cmax. Thus, an interaction between iloperidone and other CYP3A4 substrates is unlikely.

Drugs That Prolong The QT Interval

FANAPT should not be used with any other drugs that prolong the QT interval [see WARNINGS AND PRECAUTIONS].

Drug Abuse And Dependence

Controlled Substance

FANAPT is not a controlled substance.

Abuse

FANAPT has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this experience the extent to which a CNS active drug, FANAPT, will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of FANAPT misuse or abuse (e.g. development of tolerance, increases in dose, drug-seeking behavior).

Read the Fanapt Drug Interactions Center for a complete guide to possible interactions

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This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Increased Risks In Elderly Patients With Dementia-Related Psychosis

Increased Mortality

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. FANAPT is not approved for the treatment of patients with dementia-related psychosis [see BOXED WARNING].

Cerebrovascular Adverse Events, Including Stroke

In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse events (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated patients. FANAPT is not approved for the treatment of patients with dementia-related psychosis [see BOXED WARNING].

QT Prolongation

In an open-label QTc study in patients with schizophrenia or schizoaffective disorder (n=160), FANAPT was associated with QTc prolongation of 9 msec at an iloperidone dose of 12 mg twice daily. The effect of FANAPT on the QT interval was augmented by the presence of CYP450 2D6 or 3A4 metabolic inhibition (paroxetine 20 mg once daily and ketoconazole 200 mg twice daily, respectively). Under conditions of metabolic inhibition for both 2D6 and 3A4, FANAPT 12 mg twice daily was associated with a mean QTcF increase from baseline of about 19 msec.

No cases of torsade de pointes or other severe cardiac arrhythmias were observed during the pre-marketing clinical program.

The use of FANAPT should be avoided in combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone). FANAPT should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Certain circumstances may increase the risk of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval; (5) recent acute myocardial infarction; and/or (6) uncompensated heart failure.

Caution is warranted when prescribing FANAPT with drugs that inhibit FANAPT metabolism [see DRUG INTERACTIONS], and in patients with reduced activity of CYP2D6 [see CLINICAL PHARMACOLOGY].

It is recommended that patients being considered for FANAPT treatment who are at risk for significant electrolyte disturbances have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QT prolongation and arrhythmia. FANAPT should be avoided in patients with histories of significant cardiovascular illness, e.g., QT prolongation, recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia. FANAPT should be discontinued in patients who are found to have persistent QTc measurements > 500 msec.

If patients taking FANAPT experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, or syncope, the prescriber should initiate further evaluation, including cardiac monitoring.

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including FANAPT. Clinical manifestations include hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases in which the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.

The management of this syndrome should include: (1) immediate discontinuation of the antipsychotic drugs and other drugs not essential to concurrent therapy, (2) intensive symptomatic treatment and medical monitoring, and (3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

Tardive Dyskinesia

Tardive dyskinesia is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, which may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely on prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic administered increases. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, FANAPT should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on FANAPT, drug discontinuation should be considered. However, some patients may require treatment with FANAPT despite the presence of the syndrome.

Metabolic Changes

Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain [see PATIENT INFORMATION]. While all atypical antipsychotic drugs have been shown to produce some metabolic changes, each drug in the class has its own specific risk profile.

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including FANAPT. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics included in these studies. Because FANAPT was not marketed at the time these studies were performed, it is not known if FANAPT is associated with this increased risk.

Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.

Data from a 4-week, fixed-dose study in adult subjects with schizophrenia, in which fasting blood samples were drawn, are presented in Table 1.

Table 1: Change in Fasting Glucose

  Placebo FANAPT- 24 mg/day
Mean Change from Baseline(mg/dL)
n=114 n=228
Serum Glucose Change from Baseline -0.5 6.6
  Proportion of Patients with Shifts
Serum Glucose Normal to High ( < 100 mg/dL to ≥ 126 mg/dL) 2.5 % (2/80) 10.7 % (18/169)

Pooled analyses of glucose data from clinical studies including longer term trials are shown in Table 2.

Table 2: Change in Glucose

Mean Change from Baseline (mg/dL)
  3-6 months 6-12 months > 12 months
FANAPT 10-16 mg/day 1.8 (N=773) 5.4 (N=723) 5.4 (N=425)
FANAPT 20-24 mg/day -3.6 (N=34) -9.0 (N=31) -18.0 (N=20)
Dyslipidemia

Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.

Data from a placebo-controlled, 4-week, fixed-dose study, in which fasting blood samples were drawn, in adult subjects with schizophrenia are presented in Table 3.

Table 3: Change in Fasting Lipids

  Placebo FANAPT-24 mg/day
Mean Change from Baseline (mg/dL)
Cholesterol n= 114 n=228
Change from baseline -2.17 8.18
LDL n=109 n=217
Change from baseline -1.41 9.03
HDL n= 114 n=228
Change from baseline -3.35 0.55
Triglycerides n= 114 n=228
Change from baseline 16.47 -0.83
  Proportion of Patients with Shifts
Cholesterol
Normal to High ( < 200 mg/dL to ≥ 240 mg/dL) 1.4 % (1/72) 3.6% (5/141)
LDL
Normal to High ( < 100 mg/dL to ≥ 160 mg/dL) 2.4% (1/42) 1.1% (1/90)
HDL
Normal to Low ( ≥ 40 mg/dL to < 40 mg/dL) 23.8% (19/80) 12.1% (20/166)
Triglycerides
Normal to High ( < 150 mg/dL to ≥ 200 mg/dL) 8.3% (6/72) 10.1% (15/148)

Pooled analyses of cholesterol and triglyceride data from clinical studies including longer term trials are shown in Tables 4 and 5.

Table 4: Change in Cholesterol

Mean Change from Baseline (mg/dL)
  3-6 months 6-12 months > 12 months
FANAPT 10-16 mg/day -3.9 (N=783) -3.9 (N=726) -7.7 (N=428)
FANAPT 20-24 mg/day -19.4 (N=34) -23.2 (N=31) -19.4 (N=20)

Table 5: Change in Triglycerides

  3-6 months 6-12 months > 12 months
FANAPT 10-16 mg/day -8.9 (N=783) -8.9 (N=726) -17.7 (N=428)
FANAPT 20-24 mg/day -26.6 (N=34) -35.4 (N=31) -17.7 (N=20)
Weight Gain

Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended. Across all short-and long-term studies, the overall mean change from baseline at endpoint was 2.1 kg. Changes in body weight (kg) and the proportion of subjects with ≥ 7% gain in body weight from 4 placebo-controlled, 4 or 6-week, fixed-or flexible-dose studies in adult subjects are presented in Table 6.

Table 6: Change in Body Weight

  Placebo
n=576
FANAPT 10-16 mg/day
n=481
FANAPT 20-24 mg/day
n=391
Weight (kg) Change from Baseline -0.1 2.0 2.7
Weight Gain ≥ 7% increase from Baseline 4% 12% 18%

Seizures

In short-term placebo-controlled trials (4-to 6-weeks), seizures occurred in 0.1% (1/1344) of patients treated with FANAPT compared to 0.3% (2/587) on placebo. As with other antipsychotics, FANAPT should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g., Alzheimer's dementia. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

Orthostatic Hypotension And Syncope

FANAPT can induce orthostatic hypotension associated with dizziness, tachycardia, and syncope. This reflects its alpha1adrenergic antagonist properties. In double-blind placebo-controlled short-term studies, where the dose was increased slowly, as recommended above, syncope was reported in 0.4% (5/1344) of patients treated with FANAPT, compared with 0.2% (1/587) on placebo. Orthostatic hypotension was reported in 5% of patients given 20-24 mg/day, 3% of patients given 10-16 mg/day, and 1% of patients given placebo. More rapid titration would be expected to increase the rate of orthostatic hypotension and syncope.

FANAPT should be used with caution in patients with known cardiovascular disease (e.g., heart failure, history of myocardial infarction, ischemia, or conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications). Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to hypotension.

Leukopenia, Neutropenia And Agranulocytosis

In clinical trial and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents. Agranulocytosis (including fatal cases) has also been reported.

Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored Frequently during the first few months of therapy and should discontinue FANAPT at the first sign of a decline in WBC in the absence of other causative factors.

Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm³) should discontinue FANAPT and have their WBC followed until recovery.

Hyperprolactinemia

As with other drugs that antagonize dopamine D2 receptors, FANAPT elevates prolactin levels.

Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadalsteroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.

Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with previously detected breast cancer. Mammary gland proliferative changes and increases in serum prolactin were seen in mice and rats treated with FANAPT [see Nonclinical Toxicology]. Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans; the available evidence is considered too limited to be conclusive at this time.

In a short-term placebo-controlled trial (4-weeks), the mean change from baseline to endpoint in plasma prolactin levels for the FANAPT 24 mg/day-treated group was an increase of 2.6 ng/mL compared to a decrease of 6.3 ng/mL in the placebo-group. In this trial, elevated plasma prolactin levels were observed in 26% of adults treated with FANAPT compared to 12% in the placebo group. In the short-term trials, FANAPT was associated with modest levels of prolactin elevation compared to greater prolactin elevations observed with some other antipsychotic agents. In pooled analysis from clinical studies including longer term trials, in 3210 adults treated with iloperidone, gynecomastia was reported in 2 male subjects (0.1%) compared to 0% in placebo-treated patients, and galactorrhea was reported in 8 female subjects (0.2%) compared to 3 female subjects (0.5%) in placebo-treated patients.

Body Temperature Regulation

Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing FANAPT for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Dysphagia

Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia. FANAPT and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia [see BOXED WARNING].

Suicide

The possibility of a suicide attempt is inherent in psychotic illness, and close supervision of high-risk patients should accompany drug therapy. Prescriptions for FANAPT should be written for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose.

Priapism

Three cases of priapism were reported in the pre-marketing FANAPT program. Drugs with alpha-adrenergic blocking effects have been reported to induce priapism. FANAPT shares this pharmacologic activity. Severe priapism may require surgical intervention.

Potential For Cognitive And Motor Impairment

FANAPT, like other antipsychotics, has the potential to impair judgment, thinking or motor skills. In short-term, placebo-controlled trials, somnolence (including sedation) was reported in 11.9% (104/874) of adult patients treated with FANAPT at doses of 10 mg/day or greater versus 5.3% (31/587) treated with placebo. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that therapy with FANAPT does not affect them adversely.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Lifetime carcinogenicity studies were conducted in CD-1 mice and Sprague Dawley rats. Iloperidone was administered orally at doses of 2.5, 5.0 and 10 mg/kg/day to CD-1 mice and 4, 8, and 16 mg/kg/day to Sprague Dawley rats (0.5, 1.0 and 2.0 times and 1.6, 3.2 and 6.5 times, respectively, the --MRHD-of 24 mg/day on a mg/m² basis). There was an increased incidence of malignant mammary gland tumors in female mice treated with the lowest dose (2.5 mg/kg/day) only. There were no treatment-related increases in neoplasia in rats.

The carcinogenic potential of the iloperidone metabolite P95, which is a major circulating metabolite of iloperidone in humans but is not present at significant amounts in mice or rats, was assessed in a lifetime carcinogenicity study in Wistar rats at oral doses of 25, 75 and 200 mg/kg/day in males and 50, 150, and 250 (reduced from 400) mg/kg/day in females.

Drug-related neoplastic changes occurred in males, in the pituitary gland (pars distalis adenoma) at all doses and in the pancreas (islet cell adenoma) at the high dose. Plasma levels of P95 (AUC) in males at the tested doses (25, 75, and 200 mg/kg/day) were approximately 0.4, 3, and 23 times, respectively, the human exposure to P95 at the MRHD of iloperidone.

An increase in mammary, pituitary and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be mediated by prolonged dopamine D2 antagonism and hyperprolactinemia. Increases in serum prolactin were seen in mice and rats treated with iloperidone. The relevance of these tumor findings in rodents in terms of human risk is unknown.

Mutagenesis

Iloperidone was negative in the Ames test and in the in vivo mouse bone marrow and rat liver micronucleus tests. Iloperidone induced chromosomal aberrations in Chinese Hamster Ovary (CHO) cells in vitro at concentrations which also caused some cytotoxicity.

The iloperidone metabolite P95 was negative in the Ames test, the V79 chromosome aberration test, and an in vivo mouse bone marrow micronucleus test.

Impairment of Fertility

Iloperidone decreased fertility at 12 and 36 mg/kg in a study in which both male and female rats were treated. The no-effect dose was 4 mg/kg, which is 1.6 times the-MRHD of 24 mg/day on a mg/m² basis.

Use In Specific Populations

Pregnancy

Pregnancy Category C

FANAPT caused developmental toxicity, but was not teratogenic, in rats and rabbits.

In an embryo-fetal development study, pregnant rats were given 4, 16, or 64 mg/kg/day (1.6, 6.5, and 26 times the maximum recommended human dose (MRHD) of 24 mg/day on a mg/m² basis) of iloperidone orally during the period of organogenesis. The highest dose caused increased early intrauterine deaths, decreased fetal weight and length, decreased fetal skeletal ossification, and an increased incidence of minor fetal skeletal anomalies and variations; this dose also caused decreased maternal food consumption and weight gain.

In an embryo-fetal development study, pregnant rabbits were given 4, 10, or 25 mg/kg/day (3, 8, and 20 times the MRHD on a mg/m² basis) of iloperidone during the period of organogenesis. The highest dose caused increased early intrauterine deaths and decreased fetal viability at term; this dose also caused maternal toxicity.

In additional studies in which rats were given iloperidone at doses similar to the above beginning from either preconception or from day 17 of gestation and continuing through weaning, adverse reproductive effects included prolonged pregnancy and parturition, increased stillbirth rates, increased incidence of fetal visceral variations, decreased fetal and pup weights, and decreased post-partum pup survival. There were no drug effects on the neurobehavioral or reproductive development of the surviving pups. No-effect doses ranged from 4 to 12 mg/kg except for the increase in stillbirth rates which occurred at the lowest dose tested of 4 mg/kg, which is 1.6 times the MRHD on a mg/m² basis. Maternal toxicity was seen at the higher doses in these studies.

The iloperidone metabolite P95, which is a major circulating metabolite of iloperidone in humans but is not present in significant amounts in rats, was given to pregnant rats during the period of organogenesis at oral doses of 20, 80, or 200 mg/kg/day. No teratogenic effects were seen. Delayed skeletal ossification occurred at all doses. No significant maternal toxicity was produced. Plasma levels of P95 (AUC) at the highest dose tested were 2 times those in humans receiving the MRHD of iloperidone.

There are no adequate and well-controlled studies in pregnant women.

Non-teratogenic Effects

Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

FANAPT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor And Delivery

The effect of FANAPT on labor and delivery in humans is unknown.

Nursing Mothers

FANAPT was excreted in milk of rats during lactation. It is not known whether FANAPT or its metabolites are excreted in human milk. It is recommended that women receiving FANAPT should not breast-feed.

Pediatric Use

Safety and effectiveness in pediatric and adolescent patients have not been established.

Geriatric Use

Clinical Studies of FANAPT in the treatment of schizophrenia did not include sufficient numbers of patients aged 65 years and over to determine whether or not they respond differently than younger adult patients. Of the 3210 patients treated with FANAPT in premarketing trials, 25 (0.5%) were ≥ 65 years old and there were no patients ≥ 75 years old.

Studies of elderly patients with psychosis associated with Alzheimer's disease have suggested that there may be a different tolerability profile (i.e., increased risk in mortality and cerebrovascular events including stroke) in this population compared to younger patients with schizophrenia [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. The safety and efficacy of FANAPT in the treatment of patients with psychosis associated with Alzheimer's disease has not been established. If the prescriber elects to treat such patients with FANAPT, vigilance should be exercised.

Renal Impairment

Because FANAPT is highly metabolized, with less than 1% of the drug excreted unchanged, renal impairment alone is unlikely to have a significant impact on the pharmacokinetics of FANAPT. Renal impairment (creatinine clearance < 30 mL/min) had minimal effect on Cmax of iloperidone (given in a single dose of 3 mg) and its metabolites P88 and P95 in any of the 3 analytes measured. AUC0–∞ was increased by 24%, decreased by 6%, and increased by 52% for iloperidone, P88 and P95, respectively, in subjects with renal impairment.

Hepatic Impairment

No dose adjustment to FANAPT is needed in patients with mild hepatic impairment. Exercise caution when administering it to patients with moderate hepatic impairment. FANAPT is not recommended for patients with severe hepatic impairment [see Dosage in Special Populations].

In adult subjects with mild hepatic impairment no relevant difference in pharmacokinetics of iloperidone, P88 or P95 (total or unbound) was observed compared to healthy adult controls. In subjects with moderate hepatic impairment a higher (2-fold) and more variable free exposure to the active metabolites P88 was observed compared to healthy controls, whereas exposure to iloperidone and P95 was generally similar (less than 50% change compared to control). Since a study in severe liver impaired subjects has not been conducted, FANAPT is not recommended for patients with severe hepatic impairment.

Smoking Status

Based on in vitro studies utilizing human liver enzymes, FANAPT is not a substrate for CYP1A2; smoking should therefore not have an effect on the pharmacokinetics of FANAPT.
This monograph has been modified to include the generic and brand name in many instances.

OverDose

Human Experience

In pre-marketing trials involving over 3210 patients, accidental or intentional overdose of FANAPT was documented in 8 patients ranging from 48 mg to 576 mg taken at once and 292 mg taken over a -3-day period. No fatalities were reported from these cases. The largest confirmed single ingestion of FANAPT was 576 mg; no adverse physical effects were noted for this patient. The next largest confirmed ingestion of FANAPT was 438 mg over a -4-day period; extrapyramidal symptoms and a QTc interval of 507 msec were reported for this patient with no cardiac sequelae. This patient resumed FANAPT treatment for an additional 11 months. In general, reported signs and symptoms were those resulting from an exaggeration of the known pharmacological effects (e.g., drowsiness and sedation, tachycardia and hypotension) of FANAPT.

Management Of Overdose

There is no specific antidote for FANAPT. Therefore appropriate supportive measures should be instituted. In case of acute overdose, the physician should establish and maintain an airway and ensure adequate oxygenation and ventilation. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizures or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous ECG monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide and quinidine should not be used, as they have the potential for QT-prolonging effects that might be additive to those of FANAPT. Similarly, it is reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of FANAPT, resulting in problematic hypotension. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of FANAPT-induced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision should continue until the patient recovers.

ContrainDications

FANAPT is contraindicated in individuals with a known hypersensitivity reaction to the product. Reactions have included pruritus and urticaria.


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism Of Action

The mechanism of action of FANAPT, as with other drugs having efficacy in schizophrenia, is unknown. However it is proposed that the efficacy of FANAPT is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonisms.

Pharmacodynamics

FANAPT exhibits high (nM) affinity binding to serotonin 5-HT2Adopamine D2 and D3 receptors, and norepinephrine NEα1 receptors (Ki values of 5.6, 6.3, 7.1, and 0.36 nM, respectively). FANAPT has moderate affinity for dopamine D4, and serotonin 5-HT6 and 5-HT7receptors (Ki values of 25, 43, and 22, nM respectively), and low affinity for the serotonin 5-HT1A, dopamine D1, and histamine H1 receptors (Ki values of 168, 216 and 437 nM, respectively). FANAPT has no appreciable affinity (Ki > 1000 nM) for cholinergic muscarinic receptors. FANAPT functions as an antagonist at the dopamine D2, D3, serotonin 5-HT1A and norepinephrine α1/α2C receptors. The affinity of the FANAPT metabolite P88 is generally equal or less than that of the parent compound. In contrast, the metabolite P95 only shows affinity for 5-HT2A (Ki value of 3.91) and the NEα1A, NEα1B, NEα1D, and NEα2C receptors (Ki values of 4.7, 2.7, 8.8 and 4.7 nM respectively).

Pharmacokinetics

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. Steady-state concentrations are attained within 3 -4 days of dosing. Iloperidone accumulation is predictable from single-dose pharmacokinetics. The pharmacokinetics of iloperidone is more than dose proportional. Elimination of iloperidone is mainly through hepatic metabolism involving 2 P450 isozymes, CYP2D6 and CYP3A4.

Absorption

Iloperidone is well absorbed after administration of the tablet with peak plasma concentrations occurring within 2 to 4 hours; while the relative bioavailability of the tablet formulation compared to oral solution is 96%. Administration of iloperidone with a standard high-fat meal did not significantly affect the Cmax or AUC of iloperidone, P88, or P95, but delayed Tmax by 1 hour for iloperidone, 2 hours for P88 and 6 hours for P95. FANAPT can be administered without regard to meals.

Distribution

Iloperidone has an apparent clearance (clearance / bioavailability) of 47 to 102 L/h, with an apparent volume of distribution of 1340-2800 L. At therapeutic concentrations, the unbound fraction of iloperidone in plasma is ~3% and of each metabolite (P88 and P95) it is ~8%.

Metabolism and Elimination

Iloperidone is metabolized primarily by 3 biotransformation pathways: carbonyl reduction, hydroxylation (mediated by CYP2D6) and O-demethylation (mediated by CYP3A4). There are 2 predominant iloperidone metabolites, P95 and P88. The iloperidone metabolite P95 represents 47.9% of the AUC of iloperidone and its metabolites in plasma at steady-state for extensive metabolizers (EM) and 25% for poor metabolizers (PM). The active metabolite P88 accounts for 19.5% and 34.0% of total plasma exposure in EM and PM, respectively.

Approximately 7% -10% of Caucasians and 3% -8% of black/African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are intermediate, extensive or ultrarapid metabolizers. Coadministration of FANAPT with known strong inhibitors of CYP2D6 like fluoxetine results in a 2.3-fold increase in iloperidone plasma exposure, and therefore one-half of the FANAPT dose should be administered.

Similarly, PMs of CYP2D6 have higher exposure to iloperidone compared with EMs and PMs should have their dose reduced by one-half. Laboratory tests are available to identify CYP2D6 PMs.

The bulk of the radioactive materials were recovered in the urine (mean 58.2% and 45.1% in EM and PM, respectively), with feces accounting for 19.9% (EM) to 22.1% (PM) of the dosed radioactivity.

Transporter Interaction: Iloperidone and P88 are not substrates of P-gp and iloperidone is a weak P-gp inhibitor.

Clinical Studies

The efficacy of FANAPT in the treatment of schizophrenia was supported by 2 placebo-and active-controlled short-term (4-and 6-week) trials. Both trials enrolled patients who met the DSM-III/IV criteria for schizophrenia.

Two instruments were used for assessing psychiatric signs and symptoms in these studies. The Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) are both multi-item inventories of general psychopathology usually used to evaluate the effects of drug treatment in schizophrenia.

A 6-week, placebo-controlled trial (n=706) involved 2flexible dose ranges of FANAPT (12-16 mg/day or 20-24 mg/day) compared to placebo and an active control (risperidone). For the 12-16 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on Days 1 and 2, 2 mg twice daily on Days 3 and 4, 4 mg twice daily on Days 5 and 6, and 6 mg twice daily on Day 7. For the 20 _24 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on Day 1, 2 mg twice daily on Day 2, 4 mg twice daily on Day 3, 6 mg twice daily on Days 4 and 5, 8 mg twice daily on Day 6, and 10 mg twice daily on Day 7. The primary endpoint was change from baseline on the BPRS total score at the end of treatment (Day 42). Both the 12-16 mg/day and the 20-24 mg/day dose ranges of FANAPT were superior to placebo on the BPRS total score. The active control antipsychotic drug appeared to be superior to FANAPT in this trial within the first 2 weeks, a finding that may in part be explained by the more rapid titration that was possible for that drug. In patients in this study who remained on treatment for at least 2 weeks, iloperidone appeared to have had comparable efficacy to the active control.

A 4-week, placebo-controlled trial (n=604) involved one fixed dose of FANAPT (24 mg/day) compared to placebo and an active control (ziprasidone). The titration schedule for this study was similar to that for the 6-week study. This study involved titration of FANAPT starting at 1 mg twice daily on Day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on Days 2, 3, 4, 5, 6, and 7. The primary endpoint was change from baseline on the PANSS total score at the end of treatment (Day 28). The 24 mg/day FANAPT dose was superior to placebo in the PANSS total score. FANAPT appeared to have similar efficacy to the active control drug which also needed a slow titration to the target dose.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Mechanism Of Action

The mechanism of action of FANAPT, as with other drugs having efficacy in schizophrenia, is unknown. However it is proposed that the efficacy of FANAPT is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonisms.

Pharmacodynamics

FANAPT exhibits high (nM) affinity binding to serotonin 5-HT2Adopamine D2 and D3 receptors, and norepinephrine NEα1 receptors (Ki values of 5.6, 6.3, 7.1, and 0.36 nM, respectively). FANAPT has moderate affinity for dopamine D4, and serotonin 5-HT6 and 5-HT7receptors (Ki values of 25, 43, and 22, nM respectively), and low affinity for the serotonin 5-HT1A, dopamine D1, and histamine H1 receptors (Ki values of 168, 216 and 437 nM, respectively). FANAPT has no appreciable affinity (Ki > 1000 nM) for cholinergic muscarinic receptors. FANAPT functions as an antagonist at the dopamine D2, D3, serotonin 5-HT1A and norepinephrine α1/α2C receptors. The affinity of the FANAPT metabolite P88 is generally equal or less than that of the parent compound. In contrast, the metabolite P95 only shows affinity for 5-HT2A (Ki value of 3.91) and the NEα1A, NEα1B, NEα1D, and NEα2C receptors (Ki values of 4.7, 2.7, 8.8 and 4.7 nM respectively).

Pharmacokinetics

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. Steady-state concentrations are attained within 3 -4 days of dosing. Iloperidone accumulation is predictable from single-dose pharmacokinetics. The pharmacokinetics of iloperidone is more than dose proportional. Elimination of iloperidone is mainly through hepatic metabolism involving 2 P450 isozymes, CYP2D6 and CYP3A4.

Absorption

Iloperidone is well absorbed after administration of the tablet with peak plasma concentrations occurring within 2 to 4 hours; while the relative bioavailability of the tablet formulation compared to oral solution is 96%. Administration of iloperidone with a standard high-fat meal did not significantly affect the Cmax or AUC of iloperidone, P88, or P95, but delayed Tmax by 1 hour for iloperidone, 2 hours for P88 and 6 hours for P95. FANAPT can be administered without regard to meals.

Distribution

Iloperidone has an apparent clearance (clearance / bioavailability) of 47 to 102 L/h, with an apparent volume of distribution of 1340-2800 L. At therapeutic concentrations, the unbound fraction of iloperidone in plasma is ~3% and of each metabolite (P88 and P95) it is ~8%.

Metabolism and Elimination

Iloperidone is metabolized primarily by 3 biotransformation pathways: carbonyl reduction, hydroxylation (mediated by CYP2D6) and O-demethylation (mediated by CYP3A4). There are 2 predominant iloperidone metabolites, P95 and P88. The iloperidone metabolite P95 represents 47.9% of the AUC of iloperidone and its metabolites in plasma at steady-state for extensive metabolizers (EM) and 25% for poor metabolizers (PM). The active metabolite P88 accounts for 19.5% and 34.0% of total plasma exposure in EM and PM, respectively.

Approximately 7% -10% of Caucasians and 3% -8% of black/African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are intermediate, extensive or ultrarapid metabolizers. Coadministration of FANAPT with known strong inhibitors of CYP2D6 like fluoxetine results in a 2.3-fold increase in iloperidone plasma exposure, and therefore one-half of the FANAPT dose should be administered.

Similarly, PMs of CYP2D6 have higher exposure to iloperidone compared with EMs and PMs should have their dose reduced by one-half. Laboratory tests are available to identify CYP2D6 PMs.

The bulk of the radioactive materials were recovered in the urine (mean 58.2% and 45.1% in EM and PM, respectively), with feces accounting for 19.9% (EM) to 22.1% (PM) of the dosed radioactivity.

Transporter Interaction: Iloperidone and P88 are not substrates of P-gp and iloperidone is a weak P-gp inhibitor.

Clinical Studies

The efficacy of FANAPT in the treatment of schizophrenia was supported by 2 placebo-and active-controlled short-term (4-and 6-week) trials. Both trials enrolled patients who met the DSM-III/IV criteria for schizophrenia.

Two instruments were used for assessing psychiatric signs and symptoms in these studies. The Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) are both multi-item inventories of general psychopathology usually used to evaluate the effects of drug treatment in schizophrenia.

A 6-week, placebo-controlled trial (n=706) involved 2flexible dose ranges of FANAPT (12-16 mg/day or 20-24 mg/day) compared to placebo and an active control (risperidone). For the 12-16 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on Days 1 and 2, 2 mg twice daily on Days 3 and 4, 4 mg twice daily on Days 5 and 6, and 6 mg twice daily on Day 7. For the 20 _24 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on Day 1, 2 mg twice daily on Day 2, 4 mg twice daily on Day 3, 6 mg twice daily on Days 4 and 5, 8 mg twice daily on Day 6, and 10 mg twice daily on Day 7. The primary endpoint was change from baseline on the BPRS total score at the end of treatment (Day 42). Both the 12-16 mg/day and the 20-24 mg/day dose ranges of FANAPT were superior to placebo on the BPRS total score. The active control antipsychotic drug appeared to be superior to FANAPT in this trial within the first 2 weeks, a finding that may in part be explained by the more rapid titration that was possible for that drug. In patients in this study who remained on treatment for at least 2 weeks, iloperidone appeared to have had comparable efficacy to the active control.

A 4-week, placebo-controlled trial (n=604) involved one fixed dose of FANAPT (24 mg/day) compared to placebo and an active control (ziprasidone). The titration schedule for this study was similar to that for the 6-week study. This study involved titration of FANAPT starting at 1 mg twice daily on Day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on Days 2, 3, 4, 5, 6, and 7. The primary endpoint was change from baseline on the PANSS total score at the end of treatment (Day 28). The 24 mg/day FANAPT dose was superior to placebo in the PANSS total score. FANAPT appeared to have similar efficacy to the active control drug which also needed a slow titration to the target dose.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ILOPERIDONE - ORAL

 

(EYE-loe-PER-i-done)

 

COMMON BRAND NAME(S): Fanapt

 

WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.

If you are using iloperidone in combination with other medication to treat depression, also carefully read the drug information for the other medication.

 

USES: This medication is used to treat certain mental/mood disorders (such as schizophrenia). Iloperidone helps you to think more clearly, feel less nervous, and take part in everyday life. It may also help to decrease hallucinations (hearing/seeing things that are not there). Iloperidone is a psychiatric medication that belongs to the class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain.

 

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used in combination with other medication to treat depression.

 

HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually 2 times a day. Dosage is based on your medical condition, other drugs you are taking, and your response to treatment.

To reduce your risk of side effects from low blood pressure (such as dizziness, fainting, fast heartbeat), your doctor will start you on a low dose and gradually increase your dose until you are taking the best dose for you. It may take 1 to 2 weeks before you are taking your full dose. Follow your doctor's directions carefully.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. If you miss or stop taking this medication for more than 3 days, do not restart taking this medication at the same dose without calling your doctor first. Your doctor may direct you to restart at a low dose and gradually increase the dose.

Continue taking this medication exactly as prescribed, even if you are feeling better and thinking more clearly. Do not increase your dose or take this drug more often than prescribed. Your symptoms will not improve any faster, and your risk of side effects will increase. Do not stop taking this medication without consulting your doctor.

Tell your doctor if your condition does not improve or if it worsens. It may take several weeks before you feel the full benefit of this medication.

Consumer Overview Side Effect

SIDE EFFECTS: See also How to Use section.

Drowsiness, dizziness, dry mouth, tiredness, stuffy nose, and weight gain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

This medication may cause a serious drop in blood pressure, especially when starting or increasing the dose. To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but serious side effects occur: drooling/trouble swallowing, signs of infection (such as persistent cough, fever), shaking (tremor), muscle spasms.

Infrequently, this medication may cause face/muscle twitching and uncontrollable movements (tardive dyskinesia). In some cases, this condition may be permanent. Tell your doctor immediately if you develop any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements.

This drug may rarely make your blood sugar level rise, which can cause or worsen diabetes. Weight gain from this drug may increase the risk of this side effect. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst and urination. If you already have diabetes, be sure to check your blood sugar level regularly.

In rare cases, iloperidone may increase your level of a certain substance made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.

Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and seek immediate medical attention, or permanent problems could occur.

Seek immediate medical attention if any of these rare but very serious side effects occur: fainting, slow heartbeat, seizures, severe dizziness, chest pain.

This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, change in the amount of urine.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Fanapt (iloperidone tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: See also Warning section.

Before taking iloperidone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, heart problems (such as past heart attack, chest pain, abnormal heartbeat), stroke, diabetes (including family history), obesity, low blood pressure, seizures, low white blood cell count, loss of too much body water (dehydration), breast cancer, dementia (such as Alzheimer's Disease), trouble swallowing.

Iloperidone may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using iloperidone, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using iloperidone safely.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication may decrease your ability to sweat, making you more likely to get heat stroke. Avoid activities that may cause you to overheat (such as doing strenuous work/exercise in hot weather, using hot tubs). When the weather is hot, drink plenty of fluids and dress lightly. If you become overheated, promptly seek cooler shelter and stop exercising. Seek immediate medical attention if you develop a fever, mental/mood changes, headache, or dizziness.

Older adults may be more sensitive to the side effects of this drug, especially QT prolongation (see above).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Do not stop taking this medication unless directed by your doctor. Babies born to mothers who have used this drug during the last 3 months of pregnancy may infrequently develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn anytime during their first month, tell the doctor right away.

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: alpha blockers (such as prazosin), anticholinergic/antispasmodic drugs (such as atropine, dicyclomine, scopolamine).

Other medications can affect the removal of iloperidone from your body, which may affect how iloperidone works. Examples include azole antifungals (such as ketoconazole, itraconazole), HIV drugs (such as ritonavir), macrolide antibiotics (such as clarithromycin), antidepressants (such as fluoxetine, paroxetine, nefazodone), among others.

Many drugs besides iloperidone may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using iloperidone, report all medications you are currently using to your doctor or pharmacist.

Tell your doctor or pharmacist if you are taking other products that cause dizziness or drowsiness, including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause dizziness or drowsiness. Ask your pharmacist about using those products safely.

This document does not contain all possible drug interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as EKG, blood sugar level, potassium/magnesium blood levels, blood pressure, weight, blood cholesterol/triglyceride levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised July 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Fanapt

Generic Name: iloperidone (Pronunciation: EYE loe PER i done)

  • What is iloperidone (Fanapt)?
  • What are the possible side effects of iloperidone (Fanapt)?
  • What is the most important information I should know about iloperidone (Fanapt)?
  • What should I discuss with my healthcare provider before taking iloperidone (Fanapt)?
  • How should I take iloperidone (Fanapt)?
  • What happens if I miss a dose (Fanapt)?
  • What happens if I overdose (Fanapt)?
  • What should I avoid while taking iloperidone (Fanapt)?
  • What other drugs will affect iloperidone (Fanapt)?
  • Where can I get more information?

What is iloperidone (Fanapt)?

Iloperidone is an antipsychotic medication. It works by changing the effects of chemicals in the brain.

Iloperidone is used to treat schizophrenia.

Iloperidone may also be used for purposes not listed in this medication guide.

Fanapt 1 mg

round, white, imprinted with LOGO, 1

What are the possible side effects of iloperidone (Fanapt)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop taking this medication and call your doctor at once if you have a serious side effect such as:

  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
  • very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;
  • twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs;
  • high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss);
  • thoughts about suicide or hurting yourself;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • seizure (convulsions);
  • urinating less than usual or not at all;
  • trouble swallowing; or
  • penis erection that is painful or lasts 4 hours or longer.

Less serious side effects may include:

  • dizziness, drowsiness, tired feeling;
  • dry mouth, stuffy nose;
  • breast swelling or discharge;
  • weight gain; or
  • changes in menstrual periods.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Fanapt (iloperidone tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about iloperidone (Fanapt)?

Iloperidone is not for use in psychotic conditions related to dementia. Iloperidone may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

Before you take iloperidone, tell your doctor about all your medical conditions.

While you are taking iloperidone, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking iloperidone.

Iloperidone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid drinking alcohol. It can increase some of the side effects of iloperidone.

Stop using iloperidone and call your doctor at once if you have very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, restless muscle movements in your face or neck, tremor (uncontrolled shaking), trouble swallowing, or feeling like you might pass out.

If you have stopped taking iloperidone for any reason, talk with your doctor before you start taking it again. You may need to restart the medication at a lower dose.

Side Effects Centers
  • Fanapt

Patient Detailed How Take

What should I discuss with my healthcare provider before taking iloperidone (Fanapt)?

Iloperidone is not for use in psychotic conditions related to dementia. Iloperidone may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

You should not use this medication if you are allergic to iloperidone.

To make sure you can safely take iloperidone, tell your doctor if you have any of these other conditions:

  • kidney or liver disease;
  • a personal or family history of Long QT syndrome;
  • seizures or epilepsy;
  • heart disease, heart rhythm problems;
  • high blood pressure, high cholesterol;
  • a history of low white blood cell (WBC) counts;
  • a history of heart attack or stroke;
  • an electrolyte imbalance, such as low potassium or magnesium levels in your blood;
  • a history of breast cancer;
  • diabetes (iloperidone may raise your blood sugar);
  • trouble swallowing; or
  • a history of suicidal thoughts.

FDA pregnancy category C. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Taking antipsychotic medication during the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant while taking iloperidone, do not stop taking it without your doctor's advice.

Do not start or stop taking iloperidone during pregnancy without your doctor's advice. The benefit of controlling your schizophrenia may outweigh any risks posed by taking iloperidone.

It is not known whether iloperidone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking iloperidone.

Older adults may be more likely to have side effects from this medicine.

How should I take iloperidone (Fanapt)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Iloperidone can be taken with or without food.

Your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

Iloperidone may cause you to have high blood sugar (hyperglycemia). Talk to your doctor if you have any signs of hyperglycemia such as increased thirst or urination, excessive hunger, or weakness. If you are diabetic, check your blood sugar levels on a regular basis while you are taking iloperidone.

If you have stopped taking iloperidone for any reason, talk with your doctor before you start taking it again. You may need to restart the medication at a lower dose.

Store at room temperature away from moisture, light, and heat.

Side Effects Centers
  • Fanapt

Patient Detailed Avoid Taking

What happens if I miss a dose (Fanapt)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Fanapt)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include drowsiness, fast heart rate, and feeling light-headed.

What should I avoid while taking iloperidone (Fanapt)?

While you are taking iloperidone, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking iloperidone.

Iloperidone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can increase certain side effects of iloperidone.

What other drugs will affect iloperidone (Fanapt)?

Before using iloperidone, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by iloperidone.

Tell your doctor about all other medicines you use, especially:

  • arsenic trioxide (Trisenox);
  • tacrolimus (Prograf);
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), levofloxacin (Levaquin), moxifloxacin (Avelox), or pentamidine (NebuPent, Pentam);
  • an antidepressant such as amitriptylline (Elavil, Vanatrip, Limbitrol), clomipramine (Anafranil), or desipramine (Norpramin);
  • anti-malaria medications such as chloroquine (Aralen) or mefloquine (Lariam);
  • heart rhythm medicine such as amiodarone (Cordarone, Pacerone), dofetilide (Tikosyn), disopyramide (Norpace), dronedarone (Multaq), ibutilide (Corvert), procainamide (Procan, Pronestyl), propafenone (Rythmol), quinidine (Quin-G), or sotalol (Betapace);
  • medicine to prevent or treat nausea and vomiting such as dolasetron (Anzemet), droperidol (Inapsine), or ondansetron (Zofran);
  • other medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), clozapine (FazaClo, Clozaril), haloperidol (Haldol), pimozide (Orap), thioridazine (Mellaril), or ziprasidone (Geodon);
  • migraine headache medicine such as sumatriptan (Imitrex, Treximet) or zolmitriptan (Zomig); or
  • narcotic medication such as methadone (Methadose, Diskets, Dolophine).

This list is not complete and other drugs may interact with iloperidone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about iloperidone.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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