Dosing and uses of Latuda (lurasidone)
Adult dosage forms and strengths
tablet
- 20mg
- 40mg
- 80mg
- 120mg
Schizophrenia
40 mg PO qDay 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 qDay initially; may increase dose if needed, not to exceed 120 mg/day
Dosing Modifications
CYP3A4 inhibitors or inducers
- Concomitant use with strong CYP3A4 inhibitor: Do not coadminister
- Concomitant use with strong CYP3A4 inducer: Do not coadminister
- Concomitant use with moderate CYP3A4 inhibitor: Reduce dose to 50% of original dose, not to exceed 80 mg/day; starting dose is 20 mg/day
- Concomitant use with moderate CYP3A4 inducer: It may be necessary to increase lurasidone 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
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
Administration
Take with food (at least 350 calories)
Food substantially increases absorption; increases AUC ~2-fold and Cmax ~3-fold
Initial dose titration not required
Pediatric dosage forms and strengths
Safety and efficacy not established
Latuda (lurasidone) adverse (side) effects
>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%)
Warnings
Black box warnings
Not indicated for dementia-related psychosis
Increased risk of mortality in elderly patients with dementia-related psychosis; placebo-controlled trials with other atypical antipsychotics (ie, risperidone, aripiprazole, olanzapine) showed higher incidence of cerebrovascular adverse reactions (eg, CVA, TIA), including fatalities, compared with placebo
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants
Contraindications
Hypersensitivity
Concurrent administration of strong CYP3A4 inhibitors (eg, ketoconazole)
Concurrent administration of strong CYP3A4 inducers (eg, rifampin)
Cautions
Possibility of suicide attempt inherent to psychotic illness; close supervision required when therapy is initiated, dosage is changed, or drug is discontinued
Antidepressant treatment can increase the risk of developing a manic or hypomanic episode, particularly in patients with bipolar disorder
Patients with Parkinson’s disease or dementia with Lewy bodies are reported to have an increased sensitivity to antipsychotic medication
Concurrent administration of moderate CYP3A4 inhibitors: Lurasidone dosage not to exceed 40 mg/day
Orthostatic hypotension and syncope reported, possibly due to its alpha-1receptor antagonism
Risk of neuroleptic malignant syndrome
Esophageal dysmotility and aspiration may occur
Hyperprolactinemia reported
History of seizures; use with caution (drug may lower seizure threshold)
May cause leukopenia, neutropenia, and agranulocytosis
May disrupt body temperature regulation
May lead to cognitive and motor impairment
Incidence of cerebrovascular effects (eg, transient ischemic attacks, stroke) may increase
Esophageal dysmotility or aspiration may occur
May cause metabolic changes (eg, hyperglycemia, dyslipidemia, weight gain)
May increase QT interval: In trials, QT prolongation did not exceed 500 msec beyond baseline, even in patients determined to be at increased cardiac risk; additionally, in separate trial, QTc did not increase by >60 msec from baseline or exceed 500 msec with supratherapeutic doses (ie, 120 mg/day, 600 mg/day)
Extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia may occur; risk of tardive dyskinesia may increase in the elderly; risk of dystonia may increase with high doses
Acute overdose: If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry theoretical hazard of additive QT-prolonging effects when given to patient with acute lurasidone overdose
Pregnancy and lactation
Pregnancy category: B
Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for extrapyramidal symptoms (EPS) or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization
Lactation: Unknown whether drug is distributed in breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Latuda (lurasidone)
Mechanism of action
Atypical antipsychotic; precise mechanism is unknown; efficacy suggested to involve mediation of central dopamine type 2 and serotonin type 2 (5HT-2A) receptor antagonism
Absorption
Bioavailability: 9-19%
Peak plasma time: 1-3 hr
Distribution
Protein bound: 99%
Vd: 6173 L
Metabolism
Metabolized by CYP3A4; biotransformation pathways are oxidative N-dealkylation, hydroxylation of norbornane ring, and S-oxidation
Metabolites: 2 active (ID-14283, ID-14326) and 2 inactive (ID-20219, ID-20220)
Elimination
Half-life: 18 hr
Clearance: 3902 mL/min
Excretion: Feces (80%), urine (9%)
