In severe hepatic impairment, Lurasidone should start at what dose and how should it be titrated?

• A. Start at 25 mg/day, increase by 25-50 mg/day
• B. Start at 50 mg/day, increase by 10 mg/day
• C. Start at 5 mg/day, no increase
• D. Start at 75 mg/day, increase by 25 mg/day

Answer: (A)

The key idea is that severe liver impairment increases lurasidone exposure because the drug is cleared more slowly by the damaged liver. Because of this, it’s important to start with a low amount and increase the dose only gradually, allowing the body to adjust and limiting the risk of intolerable side effects. Lurasidone is metabolized by CYP3A4, so when hepatic function is poor, even small increases in dose can lead to disproportionately higher blood levels and more pronounced effects such as sedation, movement disorders, or other adverse effects. Taking it with food helps absorption, but the main safety and efficacy balance in severe hepatic impairment comes from reducing the starting amount and using slow, careful titration to reach a therapeutic level while monitoring tolerability. This approach avoids the risk of overshooting the target exposure that would come with a higher initial dose or rapid titration, while still aiming for clinical benefit.