Lurasidone

Indications

Lurasidone is used for: Psychotic Disorder, Schizophrenia, bipolar depression.

Adult Dose

Schizophrenia 40 mg PO once daily initially; may increase to 80 mg/day if needed; not to exceed 160 mg/day Bipolar Depression Indicated for major depressive episodes associated with bipolar I disorder; may be used as either monotherapy or adjunctive therapy with lithium or valproate 20 mg PO once daily initially; may increase dose if needed, not to exceed 120 mg/day Hepatic impairment Mild (Child-Pugh class A): Dosage adjustment may not be necessary; use caution Moderate (Child-Pugh class B): 20 mg/day initially; not to exceed 80 mg/day Severe (Child-Pugh class C): 20 mg/day initially; not to exceed 40 mg/day

Child Dose

Safety and efficacy not established

Renal Dose

Renal impairment CrCl 50 mL/min or greater: Dosage adjustment not required CrCl <50 mL/min: 20 mg/day initially; not to exceed 80 mg/day

Administration

Should be taken with food

Contra Indications

Hypersensitivity. Concurrent administration of strong CYP3A4 inhibitors (eg, Ketoconazole). Concurrent administration of strong CYP3A4 inducers (eg, Rifampin). Dementia-related psychosis.

Precautions

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants Cerebrovascular adverse reactions in elderly patients with dementia-related psychosis: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack). Neuroleptic malignant syndrome: Manage with immediate discontinuation and close monitoring. Tardive dyskinesia: Discontinue if clinically appropriate. Metabolic changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. Hyperglycemia and diabetes mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. Weight Gain: Gain in body weight has been observed. Monitor weight. Hyperprolactinemia: Prolactin elevations may occur. Leukopenia, neutropenia and agranulocytosis: Perform complete blood counts (CBC) in patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia or neutropenia. Consider discontinuing Lurasidone if a clinically significant decline in WBC occurs in the absence of other causative factors. Orthostatic hypotension and syncope: Dizziness, tachycardia or bradycardia, and syncope may occur, especially early in treatment. In patients with known cardiovascularor cerebrovascular disease, and in antipsychotic-naïve patients, consider a lower starting dose and slower titration. Lactation: Unknown whether drug is distributed in breast milk; use caution

Pregnancy-Lactation

Pregnancy Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for extrapyramidal symptoms (EPS) and/or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lurasidone during pregnancy National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-andresearchprograms/pregnancyregistry Lactation Unknown whether drug is distributed in breast milk Lurasidone is present in rat milk Consider development and health benefits of breastfeeding along with mother’s clinical need for drug and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Interactions

Adverse Effects

Side effects of Lurasidone : >10% Somnolence, dose related (22%), Akathisia, dose related (15%), Fasting glucose increased (10-14%), Nausea (12%), Parkinsonism (11%) 1-10% Vomiting (8%), Dyspepsia (8%), Anxiety (8%), Agitation (6%), Anxiety (6%), Dystonia (5%), Dizziness (5%), Fatigue (4%), Back pain (4%), Restlessness (3%), Salivary hypersecretion (2%)

Mechanism of Action

The mechanism of action of Lurasidone in the treatment of schizophrenia and bipolar depression is unknown. However, its efficacy in schizophrenia and bipolar depression could be mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.