iloperidone

Action

Unknown

Availability

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

Indications and dosages

➣ Acute treatment of schizophrenia

Adults: Initially, 1 mg P.O. daily; may increase by daily adjustments to 2 mg b.i.d., 4 mg b.i.d., 6 mg b.i.d., 8 mg b.i.d., 10 mg b.i.d., and 12 mg b.i.d. on days 2, 3, 4, 5, 6, and 7, respectively, to reach target dosage range of 6 to 12 mg P.O. b.i.d.

Dosage adjustment

• Concomitant use of strong CYP2D6 inhibitors (such as fluoxetine, paroxetine) and strong CYP3A inhibitors (such as clarithromycin, ketoconazole)

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• hepatic impairment (use not recommended)

• congenital long QTc syndrome, history of cardiac arrhythmias (avoid use)

• known cardiovascular disease, cerebrovascular disease, or conditions that predispose patient to hypotension

• seizures or conditions that lower seizure threshold (such as Alzheimer's dementia)

• history of neuroleptic malignant syndrome

• preexisting low WBC count, history of drug-induced leukopenia or neutropenia

• possibility of conditions contributing to an elevated core body temperature (strenuous exercise, exposure to extreme heat, concomitant medication with anticholinergic activity, dehydration)

• concomitant use of drugs known to prolong QTc interval, including Class 1A antiarrhythmics (such as procainamide quinidine), Class III antiarrhythmics (such as amiodarone, sotalol), antipsychotics (such as chlorpromazine, thioridazine), antibiotics (such as gatifloxacin, moxifloxacin), or other drug classes known to prolong QTc interval (avoid use)

• conditions that may increase risk of torsades de pointes or sudden death in association with use of drugs that prolong QTc interval, including bradycardia, hypokalemia, hypomagnesemia, recent acute myocardial infarction, uncompensated heart failure, and cardiac arrhythmia (avoid use)

• concomitant use of drugs that inhibit iloperidone metabolism, patients with reduced CYP2D6 activity

• concomitant use of other centrally acting drugs

• patients at risk for suicide or aspiration pneumonia

• pregnant or breastfeeding patients

• children and adolescents (safety and efficacy not established).

Administration

• Determine baseline serum potassium and magnesium levels in patients at risk for significant electrolyte imbalance before starting drug.

• Perform fasting glucose testing in patients at risk for diabetes mellitus before starting drug.

• Administer without regard to meals.

• Be aware that drug must be titrated slowly to avoid orthostatic hypotension.

• Follow initiation schedule if an interval between dosing of more than 3 days occurs.

Adverse reactions

CNS: fatigue, tardive dyskinesia, dizziness, somnolence, tremor, lethargy, extrapyramidal disorder, seizures, neuroleptic malignant syndrome

CV: hypotension, orthostatic hypotension, tachycardia, prolonged QTc interval

EENT: blurred vision, nasopharyngitis, nasal congestion

GI: nausea, diarrhea, dry mouth, abdominal discomfort, dysphagia

GU: ejaculation failure

Hematologic: leukopenia, neutropenia, agranulocytosis

Metabolic: hyperprolactinemia, hyperglycemia (with associated ketoacidosis, hyperosmolar coma, or death)

Musculoskeletal: arthralgia, stiffness

Respiratory: upper respiratory tract infection, dyspnea

Skin: rash

Other: weight gain, altered body temperature regulation, hypersensitivity (including pruritus, urticaria)

Interactions

Drug-drug. Drugs known to prolong QTc interval: increased risk of life-threatening arrhythmia

Strong CYP2D6 inhibitors (such as fluoxetine, paroxetine), strong CYP3A inhibitors (such as clarithromycin, ketoconazole): inhibited iloperidone elimination resulting in increased blood levels

Drug-diagnostic tests. Blood glucose: increased level

Prolactin: increased level

White blood cells (WBCs): decreased levels

Drug-behaviors. Alcohol use: increased CNS effects

Patient monitoring

See Discontinue drug in patient with persistent QTc measurements above 500 ms.

See Initiate further evaluation, including cardiac monitoring, if patient develops signs and symptoms of cardiac arrhythmias (such as dizziness, palpitations, or syncope).

See Monitor patient for signs and symptoms of neuroleptic malignant syndrome, such as hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac arrhythmia, elevated creatine kinase level, myoglobinuria from rhabdomyolysis, and renal failure). If such signs and symptoms occur, immediately discontinue drug and treat appropriately.

See Frequently monitor CBC with differential, especially during first few months of therapy in patient with preexisting low WBC count or history of drug-induced leukopenia or neutropenia. Discontinue drug at first sign of decline in WBC count in absence of other causative factors.

See Discontinue drug if patient develops severe neutropenia (absolute neutrophil count below 1,000/mm³) and continue to monitor WBC count until recovery.

• Periodically perform fasting glucose testing in patient at risk for diabetes mellitus; watch closely for worsening of glucose control in patient with diabetes mellitus.

• Periodically monitor serum potassium and magnesium levels; hypokalemia and hypomagnesemia may increase risk of QTc interval prolongation.

• Consider discontinuing drug if signs and symptoms of tardive dyskinesia occur (such as repetitive, involuntary, purposeless movements; grimacing; tongue protrusion; or lip smacking).

• Carefully evaluate patient for history of drug abuse; if history exists, observe patient for signs and symptoms of misuse or abuse (such as drug-seeking behavior and increases in dosage). Also evaluate patient for risk of suicide.

Patient teaching

• Instruct patient to take drug with or without food.

See Instruct patient to immediately report signs and symptoms of cardiac arrhythmias (such as dizziness, palpitations, or syncope).

See Instruct patient to immediately report signs and symptoms of neurologic malignant syndrome, such as fever, muscle rigidity, altered mental status (including catatonic signs), irregular pulse or blood pressure, rapid heartbeat, and excessive sweating.

• Tell patient to promptly report fever or other signs and symptoms of infection.

• Tell patient to promptly report signs and symptoms of tardive dyskinesia (such as repetitive, involuntary, purposeless movements; grimacing; tongue protrusion; or lip smacking).

• Tell patient to report signs and symptoms of high blood glucose level (such as weakness, or excessive thirst, hunger, or urination).

• Advise patient to move slowly on rising to avoid sudden drop in blood pressure.

• Advise patient to avoid excessive exercise, exposure to extreme heat, and dehydration.

• Caution patient to avoid driving and other hazardous activities until drug's effects on concentration and alertness are known.

• Advise patient to avoid alcohol use while taking drug.

• Advise patient to consult prescriber before taking other prescription or nonprescription drugs.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.