What is Latuda (lurasidone)?

What is Latuda (Lurasidone)?

Latuda (lurasidone hydrochloride) is an atypical second-generation antipsychotic medication FDA-approved for treating schizophrenia and bipolar depression, with a notably favorable metabolic profile compared to other antipsychotics. 1

Drug Classification and Mechanism

• Lurasidone belongs to the benzisothiazol derivative chemical class of atypical antipsychotics 1
• Its mechanism of action involves high-affinity antagonism at dopamine D2 receptors (Ki of 1 nM) and serotonin 5-HT2A receptors (Ki of 0.5 nM), which mediates its efficacy in treating psychotic symptoms and bipolar depression 1
• Lurasidone has distinctive 5-HT7 receptor antagonism (Ki of 0.5 nM) and partial agonism at 5-HT1A receptors (Ki of 6.4 nM), which may contribute to its antidepressant effects 1, 2
• Unlike many other antipsychotics, lurasidone exhibits little or no affinity for histamine H1 and muscarinic M1 receptors (IC50 >1,000 nM), which explains its low risk of sedation and anticholinergic side effects 1

FDA-Approved Indications

• Schizophrenia in adults at doses of 40-160 mg once daily 1, 3
• Bipolar depression (depressive episodes associated with bipolar I disorder) at doses of 20-120 mg once daily 1, 4
• The medication is classified as a second-generation antipsychotic and is mentioned alongside other atypicals like aripiprazole, olanzapine, quetiapine, and risperidone in treatment guidelines 5

Dosing and Administration

• Lurasidone must be taken with food (at least 350 calories) as food increases absorption by 2-3 times compared to fasting conditions 1
• For schizophrenia, the recommended starting dose is 40 mg once daily with no initial titration required, with a dose range of 40-160 mg/day 1, 3
• Steady-state concentrations are reached within 7 days of starting treatment 1
• Peak plasma concentrations occur in 1-3 hours after administration, with a mean elimination half-life of 18 hours 1, 2

Pharmacokinetic Profile

• Lurasidone is highly protein-bound (~99%) and has an apparent volume of distribution of 6173 L 1
• The drug is primarily metabolized by CYP3A4, so it should not be coadministered with strong CYP3A4 inhibitors or inducers 1, 2
• Approximately 9-19% of an administered dose is absorbed, with most elimination occurring through feces 1
• Lurasidone does not significantly inhibit or induce CYP450 hepatic enzymes, minimizing drug-drug interactions 2

Safety and Tolerability Profile

• Lurasidone has a highly favorable metabolic profile with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or ECG QTc interval 3, 4
• The maximum mean QTc prolongation was 7.5 ms at 120 mg dose and 4.6 ms at 600 mg dose, with no post-baseline QT prolongations exceeding 500 msec reported in clinical trials 1
• The most common adverse events are somnolence, akathisia, nausea, and parkinsonism 3
• The risk of akathisia may exceed that of other modern antipsychotics 4
• Lurasidone is not a controlled substance and has shown no tendency for drug-seeking behavior in clinical studies 1

Clinical Efficacy Evidence

• Short-term efficacy in schizophrenia is supported by five 6-week, fixed-dose, randomized, placebo-controlled trials, yielding relatively modest symptomatic improvements 3, 4
• Lurasidone shows unusual efficacy in acute bipolar depression even without psychotic features 4
• Long-term data includes a 12-month double-blind safety study comparing lurasidone with risperidone, demonstrating sustained tolerability 3

Important Clinical Considerations

• In overdose situations, no specific antidotes exist; supportive care with cardiovascular monitoring is essential 1
• Epinephrine and dopamine should not be used in lurasidone-induced hypotension due to potential worsening from beta stimulation in the setting of alpha blockade 1
• The medication is available as oral tablets in 20 mg, 40 mg, 60 mg, 80 mg, and 120 mg strengths 1