Pharmacologic class: Atypical antipsychotic (benzisothiazol derivative)
Active ingredient: Lurasidone 40 mg, 80 mg; tabs.
Pharmacology: The mechanism of action of lurasidone, as with other drugs having efficacy in schizophrenia, is unknown. It has been suggested that the efficacy of lurasidone in schizophrenia is mediated through a combination of central dopamine Type 2 and serotonin Type 2 (5-HT2A) receptor antagonism.
Clinical trials: The efficacy of lurasidone was established in four short-term (six-week), placebo-controlled studies in adults who met DSM-IV criteria for schizophrenia. One study included an active-control arm (olanzapine) to assess assay sensitivity. The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale derived (BPRSd), and Clinical Global Impression severity scale (CGI-S) were used for assessing psychiatric signs and symptoms. The endpoint associated with each instrument was change from baseline in the total score to the end of Week 6.
In a six-week, placebo-controlled trial involving two fixed doses of lurasidone (40 or 120 mg/day), both doses of lurasidone at endpoint were superior to placebo on the BPRSd total score and the CGI-S, as was lurasidone 80 mg/day in another six-week placebo-controlled trial.
In a six-week, placebo- and active-controlled trial involving two fixed doses of lurasidone (40 or 120 mg/day) and an active control (olanzapine), both lurasidone doses and the active control at endpoint were superior to placebo on the PANSS total score and the CGI-S.
In a six-week, placebo-controlled trial involving three fixed doses of lurasidone (40, 80, or 120 mg/day), only the 80-mg/day dose of lurasidone at endpoint was superior to placebo on the PANSS total score and the CGI-S.
Thus, the efficacy of lurasidone at doses of 40, 80, and 120 mg/day was established in two studies for each dose. However, the 120-mg dose did not appear to add additional benefit over the 40-mg dose.
Adults: Take with food (≥350 calories). 40 mg once daily. Maximum 80 mg/day. Moderate-to-severe renal or hepatic impairment, concomitant moderate CYP3A4 inhibitors: maximum 40 mg/day.
Children: Not recommended.
Contraindications: Concomitant strong CYP3A4 inhibitors (e.g., ketoconazole) and inducers (e.g., rifampin).
Warnings/Precautions: Elderly (not for psychosis related to dementia); increased risk of death. Discontinue if neuroleptic malignant syndrome (NMS) occurs; consider discontinuing if tardive dyskinesia occurs. Cardio- or cerebrovascular disease. Pre-existing low WBCs or history of leukopenia/neutropenia; monitor complete blood counts during first few months of therapy; discontinue if WBCs decline. Moderate-to-severe hepatic or renal impairment. Diabetes risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia, dyslipidemia, weight gain, hyperprolactinemia. History of seizures. Exposure to extreme heat. Dysphagia. Write prescription for smallest practical amount. Pregnancy (Cat. B). Nursing mothers.
Interactions: See Adults and Contraindications. Additive central nervous system (CNS) effects with alcohol, other CNS depressants.
Adverse reactions: Somnolence, akathisia, nausea, parkinsonism, agitation; orthostatic hypotension, syncope, hyperglycemia, dyslipidemia, weight gain, hyperprolactinemia, leukopenia/neutropenia, possible NMS, tardive dyskinesia.
How supplied: Tabs — 28 (4 blister cards, 7 tabs), 30, 90, 500
For more information, call 800.739.0565 or visit www.Latuda.com.