Initiating Lurasidone Therapy
The recommended starting dose of lurasidone is 40 mg once daily taken with food (at least 350 calories), with no initial dose titration required. 1
Dosing Recommendations
- Start with 40 mg once daily as the initial dose for most patients 1, 2
- Lurasidone must be taken with food (at least 350 calories) as food substantially increases absorption, with approximately 2-fold increase in AUC and 3-fold increase in Cmax 1
- No initial dose titration is required when starting therapy 1, 3
- The effective dose range is 40-80 mg/day, with maximum recommended dose of 80 mg/day 2, 4
- Doses above 80 mg/day do not appear to confer additional benefit and may increase adverse effects such as somnolence and akathisia 2, 4
Special Population Considerations
- Renal impairment: For moderate (CrCl 30-50 mL/min) or severe (CrCl <30 mL/min) renal impairment, start with 20 mg/day with maximum dose not exceeding 80 mg/day 1
- Hepatic impairment: For moderate (Child-Pugh score 7-9) or severe (Child-Pugh score 10-15) hepatic impairment, start with 20 mg/day with maximum dose not exceeding 80 mg/day for moderate and 40 mg/day for severe impairment 1
Drug Interaction Considerations
- Strong CYP3A4 inhibitors: Concomitant use is contraindicated (e.g., ketoconazole, clarithromycin, ritonavir) 1
- Moderate CYP3A4 inhibitors: Reduce lurasidone dose to half of the original dose (e.g., diltiazem, erythromycin, fluconazole) 1
- Strong CYP3A4 inducers: Concomitant use is contraindicated (e.g., rifampin, St. John's wort, phenytoin, carbamazepine) 1
- Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 and alter lurasidone concentrations 1
Monitoring and Follow-up
- Assess therapeutic response after 4-6 weeks of treatment at an adequate dose 5
- Monitor for common adverse effects including somnolence, akathisia, nausea, and parkinsonism, especially early in treatment 3, 6
- Lurasidone has minimal weight gain and no clinically meaningful alterations in glucose, lipids, or ECG QT interval compared to some other antipsychotics 3, 2
- If switching from another antipsychotic, consider gradual cross-titration informed by the half-life and receptor profile of each medication 5
Clinical Pearls
- Unlike some other antipsychotics, lurasidone must be taken with food (≥350 calories) to ensure proper absorption 1, 2
- The effectiveness of lurasidone for longer-term use (more than 6 weeks) has not been established in controlled studies, so periodically re-evaluate the long-term usefulness for the individual patient 1
- For patients who may have difficulty with adherence, emphasize the advantage of once-daily dosing 6
- Lurasidone may be particularly beneficial for patients at risk for metabolic complications due to its favorable metabolic profile 6
By following these guidelines for initiating lurasidone therapy, clinicians can optimize treatment outcomes while minimizing adverse effects for patients requiring antipsychotic medication.