What is the recommended starting dose of Latuda (lurasidone) for a patient who stopped it abruptly for 1 month?

Restarting Latuda After 1-Month Abrupt Discontinuation

After a 1-month abrupt discontinuation of Latuda, restart at the standard initial dose of 20 mg once daily with food, regardless of the previous dose. 1

Rationale for Starting Dose

The FDA-approved prescribing information for lurasidone clearly states that the recommended starting dose is 20 mg once daily, with no initial dose titration required 1. This applies to both treatment-naïve patients and those restarting therapy after discontinuation. The label makes no distinction for patients who previously tolerated higher doses 1.

Key principle: After a 1-month gap, the patient should be treated as if starting fresh, as any tolerance to the medication has likely dissipated 1.

Administration Requirements

• Must be taken with food (at least 350 calories) - this is non-negotiable, as food increases absorption approximately 2-fold for AUC and 3-fold for Cmax 1
• Administer once daily 1
• All clinical trials demonstrating efficacy used food co-administration 1

Dose Titration After Restart

• After restarting at 20 mg daily, the dose may be increased based on clinical response 1
• For schizophrenia: effective dose range is 40-160 mg/day, with 40-80 mg/day being the typical target 1
• For bipolar depression (adults): effective dose range is 20-120 mg/day 1
• For bipolar depression (pediatric 10-17 years): effective dose range is 20-80 mg/day 1
• No specific titration schedule is mandated by the FDA label, allowing flexibility based on tolerability 1

Critical Safety Considerations

Common early adverse effects to monitor:

• Somnolence 2, 3
• Akathisia 2, 3
• Nausea 2, 3
• Parkinsonism 2, 3

These effects are particularly common early in treatment and may necessitate slower titration 2.

Dose Modifications Based on Patient Factors

Renal impairment:

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

Hepatic impairment:

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

Drug interactions:

• Contraindicated with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir) 1
• With moderate CYP3A4 inhibitors (diltiazem, erythromycin, fluconazole): reduce dose to half 1

Why Not Resume at Previous Dose?

Abrupt discontinuation creates risk if restarting at high doses:

• The patient has lost any gradual tolerance built up during previous treatment 4
• Starting at a previously tolerated high dose (e.g., 120 mg) after a gap increases risk of acute adverse effects including sedation and movement disorders 2, 3
• The FDA label does not provide guidance for "restarting" scenarios, only for initial dosing, which reinforces treating this as a new start 1

Common Pitfalls to Avoid

• Do not restart at the previous maintenance dose - this significantly increases risk of adverse effects 1, 2
• Do not administer without food - bioavailability is dramatically reduced, potentially leading to treatment failure 1
• Do not co-prescribe with strong CYP3A4 inhibitors - this is an absolute contraindication due to risk of severe adverse effects 1
• Do not assume the patient will tolerate rapid titration - even if they previously tolerated higher doses, restart conservatively 2, 3

Monitoring During Restart

• Assess for early adverse effects (somnolence, akathisia, nausea, parkinsonism) within the first 1-2 weeks 2, 3
• Monitor for psychiatric symptom control to guide dose titration 1
• Evaluate metabolic parameters, though lurasidone has a favorable metabolic profile with minimal weight gain and no clinically meaningful alterations in glucose or lipids 2, 3, 5