What is the typical dosing regimen for Latuda (lurasidone) in an adult patient with bipolar depression, considering their past medical history and potential renal or hepatic impairment?

Latuda Dosing for Bipolar Depression

Primary Dosing Recommendation

For adult patients with bipolar depression, start Latuda at 20 mg once daily with food (at least 350 calories), and titrate to a target range of 20-120 mg/day based on clinical response and tolerability. 1

Standard Dosing Algorithm

Adults with Bipolar Depression

• Starting dose: 20 mg once daily 1, 2
• Therapeutic range: 20-120 mg/day 1, 2
• Titration: Initial dose titration is not required; the starting dose of 20 mg/day can be maintained or increased based on clinical response 1, 3
• Administration requirement: Must be taken with food containing at least 350 calories to ensure adequate absorption 1, 4

Pediatric Patients (10-17 years) with Bipolar Depression

• Starting dose: 20 mg once daily 1
• Therapeutic range: 20-80 mg/day (lower maximum than adults) 1
• Administration: Same food requirement as adults (at least 350 calories) 1

Dose Adjustments for Renal Impairment

In patients with moderate to severe renal impairment, reduce both the starting and maximum doses by approximately 30-35%. 1

• Starting dose: 20 mg/day 1
• Maximum dose: 80 mg/day (reduced from 120 mg/day) 1
• Rationale: Lurasidone has an apparent volume of distribution of 6173 L and is approximately 99% protein-bound, requiring dose adjustment in renal dysfunction 5

Dose Adjustments for Hepatic Impairment

Moderate Hepatic Impairment (Child-Pugh B)

• Starting dose: 20 mg/day 1
• Maximum dose: 80 mg/day 1

Severe Hepatic Impairment (Child-Pugh C)

• Starting dose: 20 mg/day 1
• Maximum dose: 40 mg/day (substantially reduced) 1

Drug Interaction Dose Adjustments

Concomitant Moderate CYP3A4 Inhibitors (e.g., diltiazem, erythromycin)

Reduce the Latuda dose to half of the original level when starting a moderate CYP3A4 inhibitor. 1

• Starting dose: 20 mg/day 1
• Maximum dose: 80 mg/day 1
• Rationale: Lurasidone is principally metabolized by CYP3A4, and inhibitors significantly increase plasma concentrations 5

Concomitant Strong CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin)

• Contraindicated: Do not use Latuda with strong CYP3A4 inhibitors 1

Concomitant Strong CYP3A4 Inducers (e.g., rifampin, phenytoin)

• Contraindicated: Do not use Latuda with strong CYP3A4 inducers 1

Concomitant Moderate CYP3A4 Inducers

• Dose increase may be necessary: Monitor clinical response and consider increasing the Latuda dose if therapeutic effect is inadequate 1

Monotherapy vs. Adjunctive Therapy

Monotherapy

• FDA-approved for adults and pediatric patients (10-17 years) 1
• Dose range: 20-120 mg/day in adults; 20-80 mg/day in pediatric patients 1
• Evidence: NNT for response was 5 across both dose ranges (20-60 mg/day and 80-120 mg/day) 6

Adjunctive to Lithium or Valproate

• FDA-approved for adults only 1
• Dose range: 20-120 mg/day 1, 2
• Evidence: NNT for response was 7 when used adjunctively 6
• Clinical context: The American Academy of Child and Adolescent Psychiatry recommends combining antipsychotics with mood stabilizers for optimal outcomes in bipolar disorder 7

Pharmacokinetic Considerations

• Peak plasma concentration: 1-3 hours after administration 5
• Elimination half-life: Approximately 18 hours, supporting once-daily dosing 5, 3
• Metabolism: Principally via CYP3A4 with minor metabolites 5
• Excretion: Mostly eliminated in feces 5
• Food effect: Administration with food substantially increases absorption; bioavailability is approximately doubled when taken with 350 calories compared to fasting 1, 4

Common Adverse Effects and Management

The most frequently occurring adverse events (incidence ≥5% and at least twice the rate for placebo) in adults are akathisia, extrapyramidal symptoms, and somnolence. 1, 2

• Akathisia: NNH ranged from 11-130 depending on dose and specific adverse effect 6
• Nausea: NNH was 11 for the 80-120 mg/day dose range 6
• Weight gain ≥7%: NNH was 29 for 20-60 mg/day and 5550 for 80-120 mg/day, indicating minimal weight gain risk 6
• Metabolic effects: Lurasidone has a highly favorable metabolic profile with no clinically meaningful changes in glucose, lipids, or weight compared to placebo 2, 3, 6

Pediatric-Specific Adverse Effects

• Most common in pediatric patients (10-17 years): Nausea, weight increase, and insomnia 1

Critical Safety Monitoring

Baseline Assessment

• ECG: Obtain baseline ECG, especially in patients with cardiac risk factors, as lurasidone can cause QTc prolongation 8
• Metabolic parameters: Baseline BMI, waist circumference, blood pressure, fasting glucose, and fasting lipid panel 7
• Complete blood count: In patients with pre-existing low WBC or history of leukopenia/neutropenia 1

Ongoing Monitoring

• Metabolic monitoring: BMI monthly for 3 months then quarterly; blood pressure, glucose, and lipids at 3 months then yearly 7
• Movement disorders: Assess for extrapyramidal symptoms and tardive dyskinesia at each visit 1
• Prolactin: Monitor for signs of hyperprolactinemia (galactorrhea, amenorrhea, gynecomastia) 1

Common Pitfalls to Avoid

• Administering without food: This reduces absorption by approximately 50%, leading to subtherapeutic levels and treatment failure 1, 4
• Combining with strong CYP3A4 inhibitors or inducers: This is contraindicated and can lead to toxicity or treatment failure 1
• Using as monotherapy in patients requiring mood stabilization: The American Academy of Child and Adolescent Psychiatry recommends combining with lithium or valproate for optimal maintenance therapy 7
• Premature discontinuation: A 6-8 week trial at adequate doses is required before concluding ineffectiveness 7
• Overlooking renal or hepatic impairment: Failure to adjust doses appropriately can lead to adverse effects or toxicity 1

Clinical Efficacy Data

• Response rate (≥50% reduction in MADRS): Lurasidone reduced depressive symptoms significantly more than placebo, with NNT of 5-7 depending on monotherapy vs. adjunctive use 2, 6
• Remission rate (MADRS ≤12): NNT for remission was 6-7 across dose ranges 6
• Likelihood to be helped or harmed (LHH): Substantially >1, indicating benefits are more likely than harms, with a more favorable profile than quetiapine or olanzapine-fluoxetine combination 6