What are the indications, dosing regimen, contraindications, precautions, and monitoring parameters for Latuda (lurasidone)?

Latuda (Lurasidone) Medication Profile

Indications

Lurasidone is FDA-approved for treating bipolar I depression in adults and pediatric patients (10-17 years) as monotherapy, and as adjunctive therapy with lithium or valproate in adults. 1

• The drug is also approved for schizophrenia in adults, though this is not the primary focus of the expanded question 1, 2
• Efficacy in bipolar depression has been demonstrated in well-designed 6-week trials showing significant improvement in depressive symptoms 3, 4

Dosing Regimen

Administration Requirements

Lurasidone must be taken with food (at least 350 calories) as this substantially increases absorption. 1

Bipolar Depression Dosing

For adults with bipolar depression:

• Starting dose: 20 mg once daily 1
• Recommended dose range: 20-120 mg once daily 1
• The optimal therapeutic dose is 40-60 mg daily, which provides the best balance of efficacy and tolerability 5
• No initial titration is required 1, 2

For pediatric patients (10-17 years) with bipolar depression:

• Starting dose: 20 mg once daily 1
• Recommended dose range: 20-80 mg once daily 1

Dose Adjustments

Renal impairment (moderate to severe):

• Starting dose: 20 mg daily 1
• Maximum dose: 80 mg daily 1

Hepatic impairment:

• Moderate impairment: Starting dose 20 mg daily, maximum 80 mg daily 1
• Severe impairment: Starting dose 20 mg daily, maximum 40 mg daily 1

Drug interactions:

• With moderate CYP3A4 inhibitors (e.g., diltiazem): Reduce dose to half the original level; starting dose 20 mg daily, maximum 80 mg daily 1
• With moderate CYP3A4 inducers: May need to increase lurasidone dose 1

Contraindications

Absolute contraindications include: 1

• Known hypersensitivity to lurasidone or any formulation components
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole)
• Concomitant use with strong CYP3A4 inducers (e.g., rifampin)

Precautions and Warnings

Black Box Warnings

Two critical black box warnings apply: 1

1. Increased mortality in elderly patients with dementia-related psychosis - lurasidone is not approved for this population
2. Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients - requires close monitoring for clinical worsening

Major Precautions

Cerebrovascular events: Increased incidence of stroke and transient ischemic attacks in elderly patients with dementia-related psychosis 1

Neuroleptic malignant syndrome: Requires immediate discontinuation and close monitoring if suspected 1

Tardive dyskinesia: Consider discontinuation if clinically appropriate 1

Metabolic changes: 1

• Monitor for hyperglycemia and diabetes mellitus
• Monitor for dyslipidemia
• Monitor for weight gain (though lurasidone has a favorable metabolic profile compared to other atypicals) 2, 6

Hyperprolactinemia: Prolactin elevations may occur, particularly in both males and females at doses of 50-100 mg daily 5

Hematologic effects: Perform complete blood counts in patients with pre-existing low WBC or history of leukopenia/neutropenia; consider discontinuation if clinically significant WBC decline occurs 1

Orthostatic hypotension and syncope: Monitor heart rate and blood pressure, especially in patients with cardiovascular or cerebrovascular disease 1

Monitoring Parameters

Baseline Assessment

• Complete blood count (if history of leukopenia/neutropenia) 1
• Metabolic parameters: weight, fasting glucose, lipid panel 1
• Blood pressure and heart rate 1
• Prolactin levels (consider in symptomatic patients) 5

Ongoing Monitoring

Mental status: 1

• Monitor for worsening depression and emergence of suicidal thoughts, especially in first few months
• Assess for extrapyramidal symptoms and akathisia
• Monitor for manic switch

Metabolic monitoring: 1, 5

• Weight: Minimal weight gain expected (0.38 kg at 40 mg dose), but monitor regularly
• Blood glucose: Increases may occur at doses >70 mg (3.16 mg/dL increase at 100 mg)
• Lipid panel: Minimal changes expected
• Prolactin: Monitor if symptoms develop (3.21-5.61 ng/mL increase in males, 5.33-6.64 ng/mL increase in females at therapeutic doses)

Cardiovascular: Blood pressure and heart rate monitoring, particularly in patients with known cardiovascular disease 1

Movement disorders: Regular assessment for tardive dyskinesia, akathisia, and parkinsonism 1, 4

Common Adverse Effects

Most frequently reported adverse events (≥5% and twice placebo rate): 1, 4

In adults with bipolar depression:

• Akathisia
• Extrapyramidal symptoms
• Somnolence
• Nausea
• Headache

In pediatric patients (10-17 years) with bipolar depression:

• Nausea
• Weight increase
• Insomnia

The discontinuation rate due to adverse events is low (5.9-6.6%), similar to placebo (6.5%). 4

Clinical Advantages

Lurasidone offers several advantages over other atypical antipsychotics: 2, 6

• Highly favorable metabolic profile with minimal weight gain
• No clinically meaningful alterations in glucose or lipids at therapeutic doses
• No QTc prolongation
• Once-daily dosing regimen
• May be particularly helpful for patients with schizophrenia or bipolar disorder who are overweight or have metabolic syndrome, diabetes, or cardiovascular comorbidities

Common Pitfalls to Avoid

Administration without food: This is a critical error as food substantially increases absorption; patients must take lurasidone with at least 350 calories 1

Combining with strong CYP3A4 inhibitors or inducers: This is contraindicated and can lead to dangerous drug levels or treatment failure 1

Failure to reduce dose with moderate CYP3A4 inhibitors: When used with drugs like diltiazem, the lurasidone dose must be reduced to half 1

Inadequate monitoring in elderly patients: Avoid use in elderly patients with dementia due to increased mortality risk 1

Ignoring renal or hepatic impairment: Dose adjustments are mandatory in moderate to severe impairment 1

Rapid dose escalation: While no titration is required, starting at 40-60 mg provides optimal efficacy with better tolerability than higher doses 5