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DRUG RECORD

 

LURASIDONE

OVERVIEW
Lurasidone

 

Introduction

Lurasidone is a second generation (atypical) antipsychotic agent that is used in the treatment of schizophrenia.  Lurasidone is associated with a low rate of serum aminotransferase elevations during therapy, but has not been linked to instances of clinically apparent acute liver injury.

 

Background

Lurasidone (loo ras' i done) is a second generation antipsychotic agent which appears to act as a dopamine type 2 (D2) and serotonin (5-HT)-2A receptor antagonist in a manner similar to risperidone.  Several randomized controlled trials have shown that lurasidone improves symptoms of schizophrenia and it was approved for this indication and for depressive episodes associated with bipolar disorder in the United States in 2010.  Lurasidone is available as tablets of 20, 40, 80 and 120 mg under the brand name Latuda.  The typical maintenance dose in adults is 80 to 160 mg daily.  Common side effects include somnolence, fatigue, restlessness (akathisia), anxiety, headache, dizziness, constipation, increased appetite, weight gain, orthostatic hypotension and nasopharyngitis.  Rare, but potential severe adverse reactions (mentioned in most antipsychotic and antidepressant product labels) include tardive dyskinesia, major neurologic events, neuroleptic malignant syndrome, orthostatic hypotension, seizures, neutropenia, elevations in serum prolactin levels, and suicidal thoughts and behaviors.

 

Hepatotoxicity

Liver test abnormalities occur in 1% to 3% of patients on long term therapy with lurasidone, but similar rates have been reported with placebo therapy and with comparator agents.  The ALT elevations are usually mild, transient and often resolve even without dose modification or drug discontinuation.  There have been no published reports of clinically apparent liver injury with symptoms or jaundice attributed to lurasidone therapy. 

 

Likelihood score: E (unlikely cause of clinically apparent liver injury). 

 

Mechanism of Injury

The mechanism by which lurasidone might cause serum ALT elevations or liver injury is not known.  Lurasidone is extensively metabolized by the cytochrome P450 system (CYP 3A4) to its active metabolite and is susceptible to drug-drug interactions with agents that inhibit or induce CYP 3A4.

 

Outcome and Management

The serum aminotransferase elevations that occur on lurasidone therapy are usually self-limited and often do not require dose modification or discontinuation.  No instances of acute liver failure, chronic hepatitis or vanishing bile duct syndrome have been attributed to lurasidone.  Cross sensitivity to liver related or other hypersensitivity reactions between lurasidone and structurally related antipsychotic agents (such as iloperidone, paliperidone, risperidone and ziprasidone) have not been demonstrated, but may well occur.

 

Drug Class:  Antipsychotic Agents, Atypicals

 

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PRODUCT INFORMATION
Lurasidone


REPRESENTATIVE TRADE NAMES
Lurasidone – Latuda®


DRUG CLASS
Antipsychotic Agents


COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

 

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DRUG CAS REGISTRY NUMBER MOLECULAR FORMULA STRUCTURE
Lurasidone 367514-87-2 C28-H36-N4-O2-S Lurasidone Chemical Structure
Risperidone 106266-06-2 C23-H27-F-N4-O2 Risperidone Chemical Structure

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REFERENCES
Lurasidone

 

References updated: 15 February 2016

  1. Meyer JM. Pharmacotherapy of psychosis and mania. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 417-56.  (Textbook of pharmacology and therapeutics).

  2. Larry D. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 507-26.  (Review of hepatotoxicity of psychiatric agents does not discuss lurasidone).

  3. Nakamura M, Ogasa M, Guarino J, Phillips D, Severs J, Cucchiaro J, Loebel A. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry 2009; 70: 829-36. PubMed Citation  (Among 180 patients with an acute exacerbation of schizophrenia treated with lurasidone [80 mg daily] or placebo for 6 weeks, adverse events included nausea, vomiting, dyspepsia, constipation, anxiety, restlessness and somnolence, and one patient stopped therapy early because of ALT and AST elevations, but few details given).

  4. Parsons B, Allison DB, Loebel A, Williams K, Giller E, Romano S, Siu C. Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophr Res 2009; 110:103-10. PubMed Citation  (Analysis of weight gain in 21 placebo controlled trials [~3300 patients]; average monthly weight gain in pounds was +0.1 with placebo, +0.8 olanzapine, 0.6 risperidone, -0.3 ziprasidone; a 5% increase in weight occurred after one year in 13% of placebo, 39% haloperidol, 20% ziprasidone, 45% risperidone and 60% olanzapine treated subjects).

  5. Lurasidone (Latuda) for schizophrenia. Med Lett Drugs Ther 2011; 53: 13-4. PubMed Citation  (Brief review of efficacy and safety of lurasidone shortly after its approval in the US; common side effects are restlessness [akathisia], extrapyramidal symptoms, agitation, nausea and somnolence: no mention of ALT elevations or liver injury).

  6. Potkin SG, Ogasa M, Cucchiaro J, Loebel A. Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder. Schizophr Res 2011; 132: 101-7. PubMed Citation  (Among 301 patients with schizophrenia treated with lurasidone [120 mg once daily] or ziprasidone [80 mg twice daily], there were no on-treatment laboratory abnormalities).

  7. Meltzer HY, Cucchiaro J, Silva R, Ogasa M, Phillips D, Xu J, Kalali AH, et al. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry 2011; 168: 957-67. PubMed Citation  (Among 478 patients with acute schizophrenia treated with lurasidone [40 or 120 mg daily] or olanzapine or placebo for 6 weeks, side effects attributed to lurasidone included restlessness, anxiety, agitation, nausea and somnolence; no mention of ALT elevations or hepatotoxicity).

  8. Citrome L, Cucchiaro J, Sarma K, Phillips D, Silva R, Tsuchiya S, Loebel A. Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month, double-blind, active-controlled study. Int Clin Psychopharmacol 2012; 27: 165-76. PubMed Citation  (Among 629 adults with schizophrenia treated with lurasidone [40 to 120 mg daily] or risperidone [2 to 6 mg daily] for 12 months, “there were no clinically significant changes from baseline to month 12 in liver enzymes”).

  9. Stahl SM, Cucchiaro J, Simonelli D, Hsu J, Pikalov A, Loebel A. Effectiveness of lurasidone for patients with schizophrenia following 6 weeks of acute treatment with lurasidone, olanzapine, or placebo: a 6-month, open-label, extension study. J Clin Psychiatry 2013; 74: 507-15. PubMed Citation  (Among 113 patients enrolled in an open label extension study of lurasidone, the most common adverse events were restlessness, insomnia, somnolence, nausea, headache and weight gain; no mention of ALT elevations or hepatotoxicity).

  10. Nasrallah HA, Silva R, Phillips D, Cucchiaro J, Hsu J, Xu J, Loebel A. Lurasidone for the treatment of acutely psychotic patients with schizophrenia: a 6-week, randomized, placebo-controlled study. J Psychiatr Res 2013; 47: 670-7. PubMed Citation  (Among 496 patients with an acute exacerbation of schizophrenia treated with lurasidone [40, 80 or 120 mg daily] or placebo for 6 weeks, common adverse events were restlessness, headaches, somnolence, nausea, sedation and weight gain; no mention of ALT elevations or hepatotoxicity).

  11. Loebel A, Cucchiaro J, Sarma K, Xu L, Hsu C, Kalali AH, Pikalov A, Potkin SG. Efficacy and safety of lurasidone 80 mg/day and 160 mg/day in the treatment of schizophrenia: a randomized, double-blind, placebo- and active-controlled trial. Schizophr Res 2013; 145: 101-9. PubMed Citation  (Among 486 adults with schizophrenia treated with lurasidone [80 or 160 mg daily] or quetiapine [600 mg daily] or placebo for 6 weeks, symptom scores were improved by both agents compared to placebo, while adverse events with lurasidone included restlessness, nausea, dizziness, somnolence and weight gain, but “no other clinically relevant differences were noted for any other laboratory values” in comparison to the placebo group).

  12. Drugs for psychiatric disorders. Treat Guidel Med Lett 2013; 11 (130): 53-64; PubMed Citation  (Concise review of safety, efficacy and role of drugs for psychiatric disorders mentions that lurasidone is a second generation antipsychotic agent whose adverse side effects include akathisia, nausea, agitation and somnolence; no mention of ALT elevations or hepatotoxicity).

  13. Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014; 171: 160-8. PubMed Citation  (Among 505 patients with major depression and bipolar illness treated with lurasidone [20-60 mg or 80-120 mg daily] or placebo for 6 weeks, symptoms of depression improved with lurasidone therapy, while common side effects were nausea, headache, restlessness and somnolence and “there were no notable differences in laboratory measures” between treatment groups).

  14. Musil R, Obermeier M, Russ P, Hamerle M. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf 2015; 14: 73-96. PubMed Citation  (Extensive systematic review of the literature on the problem of weight gain during therapy with antipsychotic agents mentions that weight gain of 7% or more occurs in 1-14% of patients on lurasidone and averages -1 to +1.3 kilogram, rates being lower than with most other atypical antipsychotics).

  15. Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology 2015; 148: 1340-52. PubMed Citation  (Among 899 patients with drug induced liver injury seen over a ten year period at 8 US medical centers, one case was attributed to olanzapine, but none to lurasidone or other antipsychotic medications).

  16. Suppes T, Silva R, Cucchiaro J, Mao Y, Targum S, Streicher C, Pikalov A, et al. Lurasidone for the treatment of major depressive disorder with mixed features: A randomized, double-blind, placebo-controlled study. Am J Psychiatry 2015 Nov 10: [Epub ahead of print] PubMed Citation  (Among 209 adults with major depressive disorder with mixed features treated with lurasidone [20-60 mg daily] or placebo for 6 weeks, symptoms [including mania] improved more with lurasidone, while common adverse events were nausea [6.4%], somnolence [5.5%] and akathisia [3.7%]; no mention of ALT elevations or hepatotoxicity).

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OTHER REFERENCE LINKS
Lurasidone
  1. PubMed logoRecent References on Lurasidone

  2. Clinical Trials logoTrials on Lurasidone

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