What is the recommended dosage and treatment guidelines for Latuda (lurasidone) in patients with schizophrenia or bipolar depression?

Latuda (Lurasidone) Dosing and Treatment Guidelines

Schizophrenia Treatment

For schizophrenia, start lurasidone at 40 mg once daily with food (at least 350 calories), with a therapeutic range of 40-160 mg/day; no initial titration is required. 1

Dosing Algorithm for Schizophrenia

• Starting dose: 40 mg once daily with food (at least 350 calories required for adequate absorption) 1
• Therapeutic range: 40-160 mg/day, with efficacy established across this entire range 1, 2
• Dose titration: No initial titration required; adjust based on clinical response and tolerability 1
• Optimal efficacy dose: 80-160 mg/day provides superior symptom control compared to 40 mg, with 160 mg recommended as the most efficacious dose for acute schizophrenia 2
• Maximum dose: 160 mg/day 1

Critical Administration Requirements

• Must be taken with food containing at least 350 calories - administration with food increases absorption 2-fold (AUC) and peak concentration 3-fold (Cmax) 1
• Once-daily dosing, typically administered in the evening due to potential somnolence 3, 4
• Peak plasma concentrations occur in 1-3 hours, with elimination half-life of 18 hours 5

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Bipolar Depression Treatment

For bipolar depression, start lurasidone at 20 mg once daily with food, with a therapeutic range of 20-120 mg/day as monotherapy or adjunctive therapy with lithium or valproate. 1

Dosing Algorithm for Bipolar Depression

Adults

• Starting dose: 20 mg once daily (monotherapy or adjunctive with lithium/valproate) 1
• Therapeutic range: 20-120 mg/day 1
• No initial titration required 1
• Maximum dose: 120 mg/day 1
• Important note: In monotherapy studies, higher doses (80-120 mg/day) did not provide additional efficacy compared to lower doses (20-60 mg/day) 1

Pediatric Patients (10-17 years)

• Starting dose: 20 mg once daily as monotherapy 1
• Dose adjustment: May increase after one week based on clinical response 1
• Therapeutic range: 20-80 mg/day 1
• Maximum dose: 80 mg/day 1
• Clinical note: At study completion, 67% of patients received 20-40 mg once daily 1
• Lurasidone is NOT approved for mania in bipolar disorder 1

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Dose Modifications for Special Populations

Renal Impairment

• Moderate impairment (CrCl 30-50 mL/min): Start at 20 mg/day, maximum 80 mg/day 1
• Severe impairment (CrCl <30 mL/min): Start at 20 mg/day, maximum 80 mg/day 1

Hepatic Impairment

• Moderate impairment (Child-Pugh 7-9): Start at 20 mg/day, maximum 80 mg/day 1
• Severe impairment (Child-Pugh 10-15): Start at 20 mg/day, maximum 40 mg/day 1

Drug Interactions with CYP3A4 Inhibitors/Inducers

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, voriconazole): CONTRAINDICATED - do not use lurasidone 1
• Moderate CYP3A4 inhibitors (diltiazem, atazanavir, erythromycin, fluconazole, verapamil):
  • If adding inhibitor to existing lurasidone: Reduce lurasidone dose to half the original level 1
  • If adding lurasidone to existing inhibitor: Start at 20 mg/day, maximum 80 mg/day 1

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Safety Profile and Monitoring

Common Adverse Effects

• Most frequent: Somnolence, akathisia, nausea, and parkinsonism 3, 4
• Dose-dependent akathisia: Significantly increased at 160 mg dose 2
• Extrapyramidal symptoms: Higher rates of akathisia and parkinsonism compared to some other atypicals, particularly at 80-120 mg doses 2, 4
• Hyperprolactinemia: Higher rates observed compared to other atypical antipsychotics 4

Metabolic Advantages

• Minimal weight gain - principal advantage over olanzapine, quetiapine, and risperidone 3, 6
• No clinically meaningful alterations in glucose, lipids, or ECG QTc interval 3
• Lower long-term weight gain risk compared to active comparators in 12-month studies 6

Critical Monitoring Parameters

• Monitor for akathisia, nausea, somnolence, and extrapyramidal symptoms, especially when dosing at 80-120 mg 2
• Promptly adjust dose or discontinue if adverse reactions worsen 2
• Assess for hyperprolactinemia-related symptoms 4

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Duration of Treatment and Long-Term Considerations

• Short-term efficacy established: 6 weeks for schizophrenia 1, 3
• Long-term use: Physicians should periodically re-evaluate usefulness beyond 6 weeks for individual patients 1
• Relapse prevention: Lurasidone 40-80 mg/day demonstrated superiority over placebo (NNT=9 for relapse prevention) 6
• 12-month data available: Noninferior to quetiapine XR for relapse prevention, superior for avoiding hospitalization (NNT=8) and achieving remission (NNT=7) 6

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Common Pitfalls to Avoid

• Administering without food: Results in 50% reduction in absorption - always require at least 350 calories 1
• Starting at 40 mg for bipolar depression: Correct starting dose is 20 mg for bipolar depression, not 40 mg 1
• Using in mania: Lurasidone is NOT approved for acute mania in bipolar disorder 1
• Combining with strong CYP3A4 inhibitors: This is contraindicated and can lead to dangerous drug levels 1
• Underdosing in schizophrenia: 40 mg may be subtherapeutic; 80-160 mg provides superior efficacy 2
• Overlooking dose adjustments: Renal and hepatic impairment require mandatory dose reductions 1