Antipsychotic with improved tolerability
Pharmacologic class: Antipsychotic (piperidinyl-benzisoxazole atypical)
Active ingredient: Iloperidone 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg; tabs.
Indication: Acute treatment of schizophrenia.
Pharmacology: Iloperidone is an atypical antipsychotic agent whose efficacy in the treatment of schizophrenia may be due to its antagonism at dopamine types 2 and 3 (D2, D3) and serotonin type 2A (5-HT2A) receptors in the central nervous system (CNS). It exhibits high affinity for these receptor subtypes, moderate affinity for D4, 5-HT6 and 5-HT7 and norepinephrine receptor sites, and low affinity for 5-HT1A, D1, and histamine H1 receptors. It acts as an antagonist at norepinephrine 1/2C receptors as well. Along with its antipsychotic effects, it can cause orthostatic hypotension, priapism, and other effects which may be attributable to its 1-adrenergic blocking activity.
Clinical trials: Two placebo- and active-controlled clinical trials were conducted to assess the efficacy of iloperidone in the treatment of schizophrenia. A six-week trial compared two doses ranges for iloperidone (12-16 mg/day and 20-24 mg/day, after titration) with placebo and an active control drug. The primary endpoint was the change from baseline on the Brief Psychiatric Rating Scale total score at the end of treatment (Day 42). Both dose ranges for iloperidone were superior to placebo. Within the first two weeks, the active control psychiatric drug appeared to be superior to iloperidone. This may be explained by the more rapid titration that was possible for that drug.
In a four-week trial, iloperidone 24 mg/day after titration was compared with placebo and an active control drug that also required an initial titration phase. The primary efficacy endpoint was the change in baseline on the Positive and Negative Syndrome Scale total score at the end of treatment (Day 28). In this study, iloperidone was superior to placebo and had similar efficacy to the active control medication.
Adults:≥18 years: 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 Day 4, 8 mg twice daily on Day 5, 10 mg twice daily on Day 6, 12 mg twice daily on Day 7; target range 6-12 mg twice daily; maximum 24 mg/day. Reduce dose by half with concomitant strong inhibitors of CYP2D6 or CYP3A4. Retitrate if therapy suspended more than three days. Reassess periodically. Children: <18 years: not recommended.
Precautions: Bradycardia, hypokalemia, hypomagnesemia, congenital QT prolongation, recent MI, uncompensated heart failure, arrhythmias: avoid (risk of torsades de pointes/sudden death). Cardio- or cerebrovascular disease. Monitor electrolytes, especially potassium and magnesium. Hepatic impairment: not recommended. Diabetes or risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia. History of breast cancer or seizures. Orthostatic hypotension. Preexisting low WBC count or history of leukopenia/neutropenia: monitor complete blood count during first few months of therapy; discontinue if WBCs decline. Exposure to extreme heat. Dehydration. Suicidal tendencies. Write prescription for the smallest practical amount. Monitor for neuroleptic malignant syndrome. Elderly (not for dementia-related psychosis). Pregnancy (Cat. C). Nursing mothers: not recommended.
Interactions: Avoid other drugs that cause QT prolongation (e.g., quinidine, amiodarone, sotalol, procainamide, chlorpromazine, thioridazine, moxifloxacin, methadone). May potentiate antihypertensives. Caution with alcohol, CNS depressants. Potentiated by inhibitors of CYP2D6 (e.g., fluoxetine, paroxetine) or CYP3A4 (e.g., clarithromycin, ketoconazole).
Adverse reactions: Dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, increased weight; QT prolongation (discontinue if QTc >500 msec persists), priapism, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, dysphagia.
How supplied: Tabs—60 Titration pack—8 (2 1 mg, 2 2 mg, 2 4 mg, 2 6 mg)
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