Can a patient take Latuda (lurasidone) 80 mg twice daily?

Latuda Cannot Be Dosed at 80 mg Twice Daily

Latuda (lurasidone) must not be taken at 80 mg twice daily—the maximum approved dose is 120 mg once daily for schizophrenia and 80 mg once daily for bipolar depression in pediatric patients, always administered as a single daily dose with food. 1

FDA-Approved Dosing Regimen

The FDA label explicitly states that lurasidone is administered once daily, not in divided doses:

• Schizophrenia (adults): Starting dose 40 mg once daily; effective range 40-160 mg once daily; maximum 160 mg once daily 1
• Bipolar I depression (adults): Starting dose 20 mg once daily; effective range 20-120 mg once daily; maximum 120 mg once daily (monotherapy or adjunctive) 1
• Bipolar I depression (pediatric 10-17 years): Starting dose 20 mg once daily; effective range 20-80 mg once daily; maximum 80 mg once daily 1

Critical administration requirement: Lurasidone must be taken with food (at least 350 calories) because food increases absorption approximately 2-fold for AUC and 3-fold for Cmax 1, 2, 3. All clinical trials demonstrating efficacy used once-daily dosing with food 1.

Why Twice-Daily Dosing Is Not Appropriate

No initial dose titration is required for lurasidone, and the pharmacokinetic profile supports once-daily administration 1, 4, 2. The drug has:

• Rapid absorption with linear pharmacokinetics 5
• A half-life that supports once-daily dosing 4
• Clinical trial data exclusively using once-daily regimens 1, 6

Doses above 80 mg/day do not confer added benefit in many contexts and may increase adverse effects such as somnolence and akathisia 6, 2. In the bipolar depression monotherapy study, higher doses (80-120 mg/day) did not provide additional efficacy compared to lower doses (20-60 mg/day) 1.

Correct Dosing Strategy

If a patient requires 160 mg total daily dose for schizophrenia:

• Administer 160 mg once daily with food (≥350 calories), not split into two 80 mg doses 1
• No titration needed—can start at target dose 1, 4
• Monitor for somnolence and akathisia, which are dose-related 6, 2, 3

Dose Modifications Required in Special Populations

Renal impairment (moderate to severe):

• Starting dose 20 mg once daily; maximum 80 mg once daily 1

Hepatic impairment:

• Moderate (Child-Pugh 7-9): Starting dose 20 mg once daily; maximum 80 mg once daily 1
• Severe (Child-Pugh 10-15): Starting dose 20 mg once daily; maximum 40 mg once daily 1

Concomitant moderate CYP3A4 inhibitors (diltiazem, erythromycin, fluconazole):

• Reduce dose to half of original level, or start at 20 mg once daily with maximum 80 mg once daily 1

Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir):

• Contraindicated—do not use lurasidone 1, 2

Common Pitfalls to Avoid

• Never split the daily dose into twice-daily administration—this deviates from all evidence-based dosing and FDA approval 1, 4, 6
• Never administer without food—bioavailability is substantially reduced, compromising efficacy 1, 2, 3
• Never exceed 160 mg/day for schizophrenia or 120 mg/day for bipolar depression in adults—higher doses increase adverse effects without added benefit 1, 6
• Never use with strong CYP3A4 inhibitors or inducers—contraindicated due to significant drug interactions 1, 2

Tolerability Profile

Lurasidone demonstrates minimal weight gain and no clinically meaningful alterations in glucose, lipids, or QTc interval compared to placebo 4, 6, 2, 3. The most common adverse events are:

• Somnolence (dose-related) 6, 2, 3
• Akathisia (dose-related) 4, 6, 2, 3
• Nausea 4, 3
• Parkinsonism 4, 3

These effects are typically early in treatment and may be more pronounced at higher doses 6, 3.