iloperidone

Absorption: Well absorbed (96%) following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized by the liver, primarily by the CYP3A4 and CYP2D6 isoenzymes. The CYP2D6 enzyme system exhibits genetic polymorphism (7–10% of White patients and 3–8% of Black patients are considered poor metabolizers [PM]). Two major metabolites (P88 and P95) may be partially responsible for pharmacologic activity. 58% excreted in urine as metabolites in extensive metabolizers (EM) and 45% in PM; 20% eliminated in feces in EM and 22.1% in PM.

Half-Life: EMs: iloperidone: 18 hr, P88: 26 hr, P95: 23 hr; PMs: iloperidone: 33 hr, P88: 37 hr, P95: 31 hr.

Time/Action Profile ⬆ ⬇

(antipsychotic effect)

ROUTE	ONSET	PEAK	DURATION
PO	2–4 wk	2–4 hr‡	unknown

‡Blood level.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Bradycardia, recent MI, or uncompensated HF (↑ risk of serious arrhythmias);
Congenital long QT syndrome, QTc interval >500 msec, or history of cardiac arrhythmias;
Electrolyte abnormalities, especially hypomagnesemia or hypokalemia (correct prior to therapy);
Severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

Known cardiovascular disease including HF, history of MI/ischemia, conduction abnormalities, cerebrovascular disease, or other conditions known to predispose to hypotension, including dehydration, hypovolemia, and concurrent antihypertensive therapy (↑ risk of orthostatic hypotension);
Known ↓ WBC or history of drug-induced leukopenia/neutropenia;
Circumstances that may result in ↑ body temperature, including strenuous exercise, exposure to extreme heat, concurrent anticholinergic activity, or dehydration (may impair thermoregulation);
At risk for aspiration or falls;
History of breast cancer;
Moderate hepatic impairment;
Undergoing cataract or glaucoma surgery (↑ risk of intraoperative floppy iris syndrome);
OB: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri:
Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia
.

Adv. Reactions/Side Effects ⬆ ⬇

CV: orthostatic hypotension, tachycardia, palpitations, QT interval prolongation

EENT: nasal congestion, intraoperative floppy iris syndrome

Endo: hyperglycemia, hyperprolactinemia

GI: dry mouth, nausea, abdominal discomfort, diarrhea

GU: priapism, urinary incontinence

Metab: weight gain, dyslipidemia, weight loss

MS: ↓bone density, musculoskeletal stiffness

Neuro: dizziness, drowsiness, fatigue, agitation, cognitive impairment, delusions, extrapyramidal disorders, NEUROLEPTIC MALIGNANT SYNDROME, restlessness, tardive dyskinesia

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

QT interval prolonging medications, including quinidine, procainamide, amiodarone, sotalol, chlorpromazine, thioridazine, moxifloxacin, pentamidine, and methadone, may ↑ risk of QT interval prolongation; avoid concurrent use.
Strong CYP2D6 inhibitors, including fluoxetine and paroxetine, may ↑ levels and the risk of toxicity; ↓ iloperidone dose.
Strong CYP3A4 inhibitors, including ketoconazole and clarithromycin, may ↑ levels and the risk of toxicity; ↓ iloperidone dose.
Antihypertensives, including diuretics, may ↑ risk of orthostatic hypotension.
Anticholinergics may ↑ risk of impaired thermoregulation.

Route/Dosage ⬆ ⬇

Schizophrenia

PO (Adults ): 1 mg twice daily on Day 1, then 2 mg twice daily on Day 2; then ↑ by 2 mg/day every day until a target dose of 12–24 mg/day given in two divided doses is reached; retitration is required if iloperidone is discontinued >3 days. Concurrent use of strong CYP2D6 and/or CYP3A4 inhibitors:↓ dose by 50%; if inhibitor is withdrawn, ↑ iloperidone dose to previous amount. CYP2D6 PMs: 1 mg twice daily on Day 1, then 2 mg twice daily on Day 2; then ↑ by 2 mg/day every day until a target dose of 6–12 mg/day given in two divided doses is reached.

Acute Manic or Mixed Episodes Associated With Bipolar I Disorder

PO (Adults ): 1 mg twice daily on Day 1, then 3 mg twice daily on Day 2; then ↑ by 3 mg/day every day until a target dose of 12 mg twice daily is reached; retitration is required if iloperidone is discontinued >3 days.Concurrent use of strong CYP2D6 and/or CYP3A4 inhibitors:↓ dose by 50%; if inhibitor is withdrawn ↑ dose to previous amount.CYP2D6 PMs: 1 mg twice daily on Day 1, then 3 mg twice daily on Day 2; then ↑ by 3 mg/day every day until a target dose of 6 mg twice daily is reached.

Availability ⬆ ⬇

(Generic available)

Tablets: 1 mg; 2 mg; 4 mg; 6 mg; 8 mg; 10 mg; 12 mg

Assessment ⬆ ⬇

Monitor mental status (delusions, hallucinations, behavior) before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression, especially during early therapy. Restrict amount of drug available to patient.
Assess weight and BMI initially and throughout therapy. Refer as appropriate for nutritional/weight and medical management.
Obtain ECG at baseline. Monitor BP (sitting, standing, lying down) and HR before and periodically during therapy. May cause QT interval prolongation, tachycardia, hypertension, and orthostatic hypotension.
Monitor for signs and symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, nausea, weakness) during treatment.
Monitor for extrapyramidal side effects (akathisia: restlessness; dystonia: muscle spasms and twisting motions; or pseudoparkinsonism: masklike face, rigidity, tremors, drooling, shuffling gait, dysphagia). Report these symptoms; ↓ dose or discontinuation of medication may be necessary.
Monitor for tardive dyskinesia (involuntary rhythmic movement of mouth, face, and extremities). Report immediately and discontinue therapy; may be irreversible.
Monitor for development of neuroleptic malignant syndrome (fever, muscle rigidity, delirium, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, cardiac arrhythmia, pallor, tiredness). If these symptoms occur, discontinue iloperidone immediately.
Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction, changes in libido, erectile or ejaculatory dysfunction).
Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability ↑ risk. Institute prevention if indicated.

Lab Test Considerations:

Monitor fasting blood glucose at baseline, at Wk 12, and annually in all patients; monitor more frequently for patients with risk factors for diabetes mellitus; patients with diabetes should be closely monitored for worsening glucose control.
- Monitor cholesterol levels at baseline, at Wk 12, and every 5 yr thereafter.
- Monitor potassium and magnesium in patients at risk for electrolyte disturbances.
- Monitor serum prolactin prior to and periodically during therapy. May ↑ prolactin.
- Monitor CBC frequently during initial months of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. If any of these occur, discontinue therapy.

Implementation ⬆ ⬇

Do not confuse Fanapt with Xanax.
PO: Administer twice daily without regard to food. Observe patient when administering medication to ensure that medication is actually swallowed and not hoarded or cheeked.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of iloperidone to patient. Instruct patient to take medication exactly as directed. Do not share medication with others, even if they have similar symptoms; may be harmful. Keep out of children's reach. If doses are missed for >3 days, restart at initiation dose. Advise patient that appearance of tablets in stool is normal and not of concern. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Emphasize the importance of routine follow-up exams and lab tests to monitor side effects and continued participation in psychotherapy to improve coping skills.
Inform patient of the possibility of extrapyramidal symptoms, neuroleptic malignant syndrome, and tardive dyskinesia. Instruct patient to report these symptoms immediately to health care provider.
Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
Inform patient of potential for weight gain and hyperglycemia and the need for monitoring weight and blood glucose periodically during therapy.
May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Extremes in temperature should also be avoided; this drug impairs body temperature regulation.
Instruct patient to notify health care provider promptly if sore throat, fever, unusual bleeding or bruising, rash, tremors, palpitations, fainting, menstrual abnormalities, galactorrhea, or sexual dysfunction occur.
Advise patient and family to notify health care provider if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme ↑ in activity and talking, or other unusual changes in behavior or mood occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications. Caution patient to avoid concurrent use of alcohol and other CNS depressants.
Advise patient to notify health care provider of medication regimen before treatment or surgery (especially cataract surgery).
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Monitor neonates exposed to iloperidone during the 3rd trimester of pregnancy 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. Monitor breastfed infants for excessive drowsiness, lethargy, and developmental delays. Encourage women who become pregnant while taking iloperidone to enroll in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇