Lurasidone Hydrochloride

Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: monohydrochloride (3aR,4S,7R,7aS)-4,3(2H)-dione, 2 - [[(1R,2R) - 2 - [[4 - (1,2 - benzisothiazol - 3 - yl) - 1 - piperazinyl]methyl]cyclohexyl]methyl]hexahydro - ,7 - Methano - 1H - isoindole - 1
Molecular Formula: C28H36N4O2S•HCl
CAS Number: 367514-88-3
Brands: Latuda

Warning(s)

  • Increased Mortality in Geriatric Patients with Dementia-related Psychosis
  • Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.1 28 39 73 75

  • Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.1 39 73

  • Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).1 73

  • Observational studies suggest that conventional or first-generation antipsychotic agents also may increase mortality in such patients.1 28 39

  • Antipsychotic agents, including lurasidone, are not approved for the treatment of dementia-related psychosis.1 39 73

Introduction

benzisothiazol-derivative; atypical or second-generation antipsychotic agent.1 2 8 9

Uses for Lurasidone Hydrochloride

Schizophrenia

Acute treatment of schizophrenia in adults.1 2 4 5 8

Slideshow: Prescription Drug Addiction - Are You at Risk?

American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for management of the acute phase of schizophrenia (including first psychotic episodes).28

Patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.28 70 71 72

Lurasidone Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer tablets orally once daily, usually in the morning or evening.1 9 Take with food (containing at least 350 calories).1 (See Food under Pharmacokinetics.)

Dosage

Available as lurasidone hydrochloride; dosage expressed in terms of the hydrochloride salt.1

If used with a moderate CYP3A4 inhibitor, dosage adjustment may be required.1 (See Contraindications under Cautions and also see Interactions.)

Adults

Schizophrenia
Oral

For acute treatment, recommended initial dosage is 40 mg once daily.1 Initial dosage titration not required.1 9 Although dosages ranging from 40–120 mg daily were effective in controlled trials,1 the highest dosage (120 mg daily) did not provide additional therapeutic benefit but was associated with a dose-related increase in certain adverse effects.1 Maximum recommended dosage is 80 mg daily.1

Long-term (i.e., >6 weeks) efficacy of lurasidone not systematically evaluated in controlled trials.1 In responsive patients, continue drug therapy beyond the acute response and as long as clinically necessary and tolerated; periodically reassess need for continued therapy.1 28

In patients with remitted first or multiple episodes, APA recommends either indefinite maintenance therapy or gradual discontinuance of the antipsychotic with close follow-up and a plan to reinstitute treatment upon symptom recurrence.28 Consider antipsychotic therapy discontinuance only after ≥1 year of symptom remission or optimal response while receiving the drug.28 Indefinite maintenance treatment recommended if patient has experienced multiple previous psychotic episodes or 2 episodes within 5 years.28

Prescribing Limits

Adults

Schizophrenia
Oral

Maximum 80 mg daily.1

Special Populations

Hepatic Impairment

Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment: Do not exceed 40 mg daily.1

Mild hepatic impairment (Child-Pugh class A): Dosage adjustment does not appear necessary.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Moderate or severe renal impairment: Do not exceed 40 mg daily.1

Mild renal impairment: Dosage adjustment does not appear necessary.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustment not required.1

Gender or Race

Dosage adjustment not recommended based on gender or race.1

Cautions for Lurasidone Hydrochloride

Contraindications

  • Known hypersensitivity to lurasidone hydrochloride or any components in the formulation.1 Angioedema reported.1

  • Concurrent administration of strong CYP3A4 inhibitors (e.g., ketoconazole) or strong CYP3A4 inducers (e.g., rifampin).1 (See Interactions.)

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis.1 28 39 73 75

Antipsychotic agents, including lurasidone, are not approved for the treatment of dementia-related psychosis.1 39 73 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning, see Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis under Cautions, and see Dysphagia under Cautions.)

Sensitivity Reactions

Rash and pruritus reported frequently; angioedema reported rarely.1 (See Contraindications under Cautions.)

Other Warnings and Precautions

Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis

Increased incidence of adverse cerebrovascular events (cerebrovascular accidents and TIAs), including fatalities, observed in geriatric patients with dementia-related psychosis treated with certain atypical antipsychotic agents (aripiprazole, olanzapine, risperidone) in placebo-controlled studies.1 28 Lurasidone is not approved for the treatment of dementia-related psychosis.1 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents, including lurasidone.1

Immediately discontinue therapy and initiate supportive and symptomatic treatment if NMS occurs.1 Careful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.1

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported with use of antipsychotic agents, including lurasidone.1

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.1 In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.1

APA recommends assessing patients receiving atypical antipsychotic agents for abnormal involuntary movements every 12 months; for patients at increased risk for tardive dyskinesia, assess every 6 months.28 Consider discontinuance of lurasidone if signs and symptoms of tardive dyskinesia appear.1 However, some patients may require treatment despite presence of the syndrome.1

Metabolic Changes

Atypical antipsychotic agents are associated with metabolic changes that may increase cardiovascular and cerebrovascular risk (e.g., hyperglycemia, dyslipidemia, weight gain).1 While all atypical antipsychotics produce some metabolic changes, each drug has its own specific risk profile.1 (See Hyperglycemia and Diabetes Mellitus, see Dyslipidemia, and also see Weight Gain under Cautions.)

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents.1 11 12 14 15 16 17 18 20 21 22 23 25 31 40 41 42 46 65 In short-term clinical trials, clinically important differences between lurasidone and placebo in mean change from baseline to end point in serum glucose concentrations not observed.1

Closely monitor patients with an established diagnosis of diabetes mellitus for worsening of glucose control and perform fasting blood glucose testing at baseline and periodically in patients with risk factors for diabetes (e.g., obesity, family history of diabetes).1 11 12 14 15 16 17 18 19 20 21 22 23 31 83 If manifestations of hyperglycemia occur in any lurasidone-treated patient, perform fasting blood glucose testing.1 11 12 14 15 16 17 18 19 20 21 22 23 31 83 (See Advice to Patients.)

Some patients who developed hyperglycemia while receiving an atypical antipsychotic have required continuance of antidiabetic treatment despite discontinuance of the suspect drug; in other patients, hyperglycemia resolved with discontinuance of the antipsychotic.1 11 12 14 15 16 17 18 19 20 21 22 23 31 46 83

Dyslipidemia

Undesirable changes in lipid parameters observed in patients treated with some atypical antipsychotics.1 9 In clinical studies, clinically important effects of lurasidone on serum lipids not observed.1

Weight Gain

Weight gain observed with atypical antipsychotic therapy.1 9 Although lurasidone generally produces minimal weight gain compared with some other atypical antipsychotic agents (e.g., olanzapine),1 2 9 82 manufacturer recommends clinical monitoring of weight during lurasidone therapy.1 (See Hyperglycemia and Diabetes Mellitus under Cautions)

Hyperprolactinemia

May cause elevated serum prolactin concentrations, which may persist during chronic administration and cause clinical disturbances (e.g., galactorrhea, amenorrhea, gynecomastia, impotence); chronic hyperprolactinemia associated with hypogonadism may lead to decreased bone density in both females and males.1 2 4

If contemplating lurasidone therapy in a patient with previously detected breast cancer, consider that approximately one-third of human breast cancers are prolactin-dependent in vitro.1

Hematologic Effects

Leukopenia and neutropenia temporally related to antipsychotic agents, including lurasidone, reported during clinical trial and/or postmarketing experience.1 31 78 Agranulocytosis (including fatal cases) also reported with other antipsychotic agents.1

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia.1 78 Monitor CBC frequently during the first few months of therapy in patients with such risk factors.1 Discontinue lurasidone at the first sign of a decline in WBC count in the absence of other causative factors.1

Carefully monitor patients with neutropenia for signs and symptoms of infection (e.g., fever) and treat promptly if they occur.1 Discontinue lurasidone if severe neutropenia (ANC <1000/mm3) occurs; monitor WBC until recovery occurs.1

Orthostatic Hypotension and Syncope

Risk of orthostatic hypotension associated with dizziness, tachycardia or bradycardia, and syncope, particularly early in treatment, because of lurasidone's α1-adrenergic blocking activity.1 In short-term, placebo-controlled clinical trials, orthostatic hypotension and syncope reported in 0.4 and <0.1% of lurasidone-treated patients, respectively.1

Use with caution in patients with known cardiovascular disease (e.g., heart failure, history of MI or ischemic heart disease, conduction abnormalities), cerebrovascular disease, or conditions that would predispose patients to develop hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy) and in antipsychotic-naive patients.1 Consider monitoring orthostatic vital signs in patients who are susceptible to hypotension.1

Seizures

Seizures reported in <0.1% of lurasidone-treated patients compared with 0.2% of placebo recipients in short-term clinical trials.1 Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold (e.g., dementia of the Alzheimer’s type); conditions that lower seizure threshold may be more prevalent in patients ≥65 years of age.1

Cognitive and Motor Impairment

Judgment, thinking, or motor skills may be impaired.1 Somnolence (including hypersomnia, hypersomnolence, and sedation) reported in about 22% of lurasidone-treated patients in clinical trials; frequency of somnolence is dose-related.1 (See Advice to Patients.)

Body Temperature Regulation

Antipsychotic agents may disrupt ability to regulate core body temperature.1

Use appropriate caution in patients who will be experiencing conditions that may contribute to an elevation in core body temperature (e.g., strenuous exercise, extreme heat, concomitant use of agents with anticholinergic activity, dehydration).1

Suicide

Attendant risk with psychotic illnesses; closely supervise high-risk patients.1 Prescribe in the smallest quantity consistent with good patient management to reduce risk of overdosage.1

Dysphagia

Esophageal dysmotility and aspiration associated with the use of antipsychotic agents.1

Aspiration pneumonia is a common cause of morbidity and mortality in geriatric patients, particularly in those with advanced Alzheimer's dementia.1 Lurasidone is not approved for the treatment of patients with dementia-related psychosis and should not be used in patients at risk for aspiration pneumonia.1 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Concomitant Illnesses

Limited experience with lurasidone in patients with certain concomitant diseases.1

Not adequately evaluated in patients with a recent history of MI or unstable cardiovascular disease.1 (See Orthostatic Hypotension and Syncope under Cautions.)

Specific Populations

Pregnancy

Category B.1

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms.1 79 80 81 Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.1 79 80 81

Lactation

Lurasidone distributes into milk in rats; not known whether lurasidone and/or its metabolites distribute into human milk.1 Manufacturer generally recommends avoiding breast-feeding; consider only if potential benefit justifies potential risk to child.1

Pediatric Use

Safety and effectiveness not established in pediatric patients.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.1 (See Geriatric Patients under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Geriatric patients with dementia-related psychosis treated with either conventional or atypical antipsychotic agents are at an increased risk of death;1 39 73 75 increased incidence of cerebrovascular events also observed with certain atypical antipsychotic agents.1 Lurasidone is not approved for the treatment of dementia-related psychosis.1 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning and also see Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis under Cautions and Dysphagia under Cautions.)

Hepatic Impairment

Dosage adjustment recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1 (See Hepatic Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustment recommended in patients with moderate or severe renal impairment (Clcr 10 to less than 50 mL/minute).1 (See Renal Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Somnolence (including hypersomnia, hypersomnolence, and sedation),1 2 4 akathisia,1 2 4 nausea,1 2 4 parkinsonism,1 agitation.1

Interactions for Lurasidone Hydrochloride

Metabolized principally by CYP3A4.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction with moderate or strong CYP3A4 inhibitors and strong CYP3A4 inducers.1 Avoid concurrent use of strong CYP3A4 inhibitors or strong CYP3A4 inducers.1 Do not exceed lurasidone dosage of 40 mg daily if used concomitantly with moderate CYP3A4 inhibitors.1 (See Specific Drugs under Interactions.)

Lurasidone is not a substrate of CYP isoenzymes 1A1, 1A2, 2A6, 4A11, 2B6, 2C8, 2C9, 2C19, 2D6, or 2E1; clinically important pharmacokinetic interactions with lurasidone and drugs that are inhibitors or inducers of these enzymes unlikely.1

Specific Drugs

Drug

Interaction

Comments

Alcohol

Possible additive CNS effects1

Avoid concomitant use1

Anticholinergic agents

Possible disruption of body temperature regulation1

Use with caution1

CNS agents

Possible additive CNS effects1

Use with caution1

Digoxin

Increased peak plasma concentrations and AUCs of digoxin by about 9 and 13%, respectively1

Digoxin dosage adjustment not required1

Diltiazem

Increased peak serum concentrations and AUCs of lurasidone by about twofold1

Do not exceed a lurasidone dosage of 40 mg daily1

Hypotensive agents

Possible additive hypotensive effects; may result in orthostatic hypotension and syncope1

Use concomitantly with caution; consider monitoring orthostatic vital signs1

Ketoconazole

Increased peak serum concentrations and AUCs of lurasidone by 6.9 and 9 times, respectively1

Concomitant use contraindicated1

Lithium

Decreased lurasidone peak serum concentrations by 10% and increased lurasidone AUCs by 1.1 times1

Lurasidone dosage adjustment not required1

Midazolam

Increased peak plasma concentrations and AUCs of midazolam by approximately 21 and 44%, respectively1

Midazolam dosage adjustment not required1

Oral contraceptives

Peak plasma concentrations and AUCs of oral contraceptives not substantially affected

Sex hormone binding globulin concentrations not substantially affected1

Oral contraceptive dosage adjustment is not required1

Rifampin

Decreased peak serum concentrations and AUCs of lurasidone by approximately 86 and 80%, respectively1

Concomitant use contraindicated1

Smoking

Lurasidone is not a substrate for CYP1A2 in vitro; smoking unlikely to alter lurasidone pharmacokinetics1

Lurasidone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak serum concentrations achieved within about 1–3 hours.1 9

Approximately 9–19% of an orally administered dose is absorbed.1

Steady-state concentrations of lurasidone achieved within 7 days.1

Food

Mean peak serum concentrations and AUCs of lurasidone increased by about threefold and twofold, respectively, when administered with food compared with values obtained under fasting conditions.1 Exposure not affected as meal size increased from 350 to 1000 calories and was independent of fat content.1

Special Populations

In patients with mild, moderate, and severe renal impairment, mean peak serum concentrations of lurasidone increased by 40, 92, and 54%, respectively, and mean AUCs increased by 53%, 91%, and twofold, respectively, compared with healthy individuals.1

Mean AUCs were 1.5, 1.7, and 3 times higher in individuals with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe hepatic impairment (Child-Pugh class C), respectively, compared with healthy individuals.1 Mean peak serum concentrations were 1.3, 1.2, and 1.3 times higher for patients with mild, moderate, and severe hepatic impairment, respectively, compared with healthy individuals.1

In geriatric patients with psychosis, serum lurasidone concentrations were similar to those observed in younger adults.1

Distribution

Extent

Lurasidone distributes into milk in rats; not known whether the drug and/or its metabolites distribute into human milk.1

Plasma Protein Binding

Highly bound (99.8%), including to albumin and α1-acid glycoprotein.1 9

Elimination

Metabolism

Metabolized mainly via CYP3A4.1 Major biotransformation pathways are oxidative N-dealkylation, hydroxylation of norbornane ring, and S-oxidation.1

Metabolized into 2 active metabolites (ID-14283 and ID-14326) and 2 major inactive metabolites (ID-20219 and ID-20220); pharmacologic activity primarily due to parent drug.1

Elimination Route

Following administration of a single radiolabeled dose, about 89% of the dose was recovered; approximately 80% recovered in feces and 9% in urine.1

Half-life

Averages 18 hours.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Exact mechanism of action of lurasidone and other antipsychotic agents in schizophrenia unknown; efficacy may be mediated through a combination of antagonist activity at central dopamine type 2 (D2) and serotonin type 2 (5-hydroxytryptamine [5-HT2A]) receptors.1 7 9

  • Exhibits high affinity for D2, 5-HT2A, and 5-HT7 receptors and moderate affinity for α2C-adrenergic receptors in vitro.1 6 7 9 Acts as a partial agonist at 5-HT1A receptors and is an antagonist at α2A-adrenergic receptors in vitro.1 6 7 9

  • Exhibits weak affinity for α1-adrenergic receptors and little or no affinity for histamine (H1) receptors and muscarinic (M1) receptors.1 6 7 9

Advice to Patients

  • Importance of advising patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.1 28 39 73 Patients and caregivers also should be informed that lurasidone is not approved for treating geriatric patients with dementia-related psychosis.1 73

  • Importance of informing patients and caregivers about the risk of NMS, which can cause high fever, stiff muscles, sweating, fast or irregular heart beat, change in BP, confusion, and kidney damage.1

  • Importance of patients being aware of the symptoms of hyperglycemia and diabetes mellitus (e.g., increased thirst, increased urination, increased appetite, weakness).1 Importance of informing patients who are diagnosed with diabetes, those with risk factors for diabetes, and those who develop hyperglycemia symptoms during treatment that they should have their blood glucose monitored at the beginning of and periodically during lurasidone treatment.1

  • Risk of orthostatic hypotension, especially when initiating or reinitiating treatment or increasing the dosage.1

  • Risk of leukopenia/neutropenia.1 Importance of advising patients with a preexisting low WBC count or history of drug-induced leukopenia/neutropenia that their CBC count should be monitored during lurasidone therapy.1

  • Risk of somnolence (i.e., sleepiness, drowsiness).1 Importance of advising patients to exercise caution when performing activities requiring mental alertness (e.g., driving or operating hazardous machinery) until they gain experience with the drug’s effects.1

  • Importance of avoiding alcohol during lurasidone therapy.1

  • Importance of informing patients in whom chronic lurasidone use is contemplated of risk of tardive dyskinesia.1 67 Importance of advising patients to report any muscle movements that cannot be stopped to a healthcare professional.67

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (see Interactions) and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, diabetes mellitus, seizures).1

    Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 81 Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Pregnancy under Cautions).1 81 Importance of advising patients not to stop taking lurasidone if they become pregnant without consulting their clinician; abruptly stopping antipsychotic agents may cause complications.81 Importance of advising patients not to breast-feed during lurasidone therapy.1

  • Importance of avoiding overheating and dehydration.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Lurasidone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

40 mg

Latuda

Sunovion

80 mg

Latuda

Sunovion

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Latuda 80MG Tablets (SUNOVION PHARMACEUTICALS): 30/$535.98 or 90/$1,559.90

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 28, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sunovion Pharmaceuticals Inc. Latuda (lurasidone hydrochloride) tablets prescribing information. Marlborough, MA; 2010 Oct.

2. Nakamura M, Ogasa M, Guarino J et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2009; 70:829-36. [PubMed 19497249]

3. Meyer JM, Cucchiaro J, Pikalov A et al. Differential metabolic profiles of lurasidone and olanzapine: data from a 6-week, double-blind, placebo-controlled schizophrenia trial [abstract]. Presented at the 163rd Annual American Psychiatric Association Meeting. New Orleans, LA: 2010 May 22-26. Abstract NR6-19.

4. Cucchiaro J, Pikalov A, Ogasa M et al. Safety of lurasidone: pooled analysis of five placebo-controlled trials in patients with schizophrenia. Presented at the163rd Annual American Psychiatric Association Meeting. New Orleans, LA: 2010 May 22-26. Abstract NR6-20.

5. Meltzer H, Cucchiaro J, Silva R et al. Lurasidone in the treatment of acute schizophrenia: results of the double-blind placebo-controlled PEARL 2 trial [abstract]. Presented at the 163rd Annual American Psychiatric Association Meeting. New Orleans, LA: 2010 May 22-26. Abstract NR6-15.

6. Ishiyama T, Loebel A, Cucchiaro J et al. Comparative receptor binding profile of lurasidone and other first and second generation antipsychotics [abstract]. Presented at the 163rd Annual American Psychiatric Association Meeting. New Orleans, LA: 2010 May 22-26. Abstract NR6-40.

7. Ishibashi T, Horisawa T, Tokuda K et al. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther. 2010; 334:171-81. [PubMed 20404009]

8. Citrome L. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. Int J Clin Pract. 2011; 65:189-210. [PubMed 21129135]

9. Meyer JM, Loebel AD, Schweizer E. Lurasidone: a new drug in development for schizophrenia. Expert Opin Investig Drugs. 2009; 18:1715-26. [PubMed 19780705]

11. Eli Lilly and Company. Zyprexa (olanzapine) tablets and Zyprexa Zydis (olanzapine) orally disintegrating tablets prescribing information. Indianapolis, IN; 2004 Sep 22.

12. Eli Lilly and Company. Lilly announces FDA notification of class labeling for atypical antipsychotics regarding hyperglycemia and diabetes. Indianapolis, IN; 2003 Sep 17. Press release.

13. Dixon L, Perkins D, Calmes C. Guideline watch (September 2009): practice guideline for the treatment of patients with schizophrenia. American Psychiatric Association. Arlington, VA; 2009 Sep. From the American Psychiatric Association website.

14. Novartis Pharmaceuticals. Clozaril (clozapine) prescribing information. East Hanover, NJ; 2003 Dec.

15. AstraZeneca Pharmaceuticals. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2004 Jul.

16. Janssen Pharmaceutica. Risperdal (risperidone) tablets and oral solution prescribing information. Titusville, NJ; 2003 Oct.

17. Pfizer Inc. Geodon (ziprasidone) prescribing information. New York, NY; 2004 Aug.

18. Lewis-Hall F. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Princeton, NJ: Bristol-Myers Squibb Company; 2004 Mar 25. From FDA website.

19. Bess AL, Cunningham SR. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 Apr 1. From the FDA website.

20. Eisenberg P. Dear health care professional letter regarding safety data on Zyprexa (olanzapine) – hyperglycemia and diabetes. Indianapolis, IN: Eli Lilly and Company; 2004 Mar 1. From the FDA website.

21. Macfadden W. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Wilmington, DE: AstraZeneca Pharmaceuticals; 2004 Apr 22. From the FDA website.

22. Mahmoud RA. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Titusville, NJ: Janssen Pharmaceutica, Inc; 2004. From the FDA website.

23. Clary CM. Dear health care practitioner letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. New York NY: Pfizer Global Pharmaceuticals; 2004 Aug. From the FDA website.

24. Cunningham F, Lambert B, Miller DR et al. Antipsychotic induced diabetes in veteran schizophrenic patients. In: Abstracts of the 1st International Conference on Therapeutic Risk Management and 19th International Conference on Pharmacoepidemiology, Philadelphia, PA, 2003 Aug 21-24. Pharmacoepidemiol Drug Saf. 2003; 12(Suppl 1): S154-5.

25. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. [PubMed 14747245]

26. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics. Drugs. 2004; 64:701-23. [PubMed 15025545]

27. Citrome LL, Jaffe AB. Relationship of atypical antipsychotics with development of diabetes mellitus. Ann Pharmacother. 2003; 37:1849-57. [IDIS 510453] [PubMed 14632602]

28. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004; 161(2 Suppl):1-56.

29. Sumiyoshi T, Roy A, Anil AE et al. A comparison of incidence of diabetes mellitus between atypical antipsychotic drugs. J Clin Psychopharmacol. 2004; 24:345-8. [IDIS 515736] [PubMed 15118492]

30. Expert Group. ’Schizophrenia and Diabetes 2003’ expert consensus meeting, Dublin, 3–4 October 2003: consensus summary. Br J Psychiatry. 2004; 47(Suppl):S112-4.

31. Schering-Plough. Saphris (asenapine maleate) sublingual tablets prescribing information. Kenilworth, NJ; 2009 Aug.

32. Holt RI. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2086-7. [IDIS 524618] [PubMed 15277449]

33. Citrome L, Volavka J. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2087-8. [IDIS 524619] [PubMed 15277450]

34. Isaac MT, Isaac MB. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2088. [IDIS 524620] [PubMed 15277451]

35. Boehm G, Racoosin JA, Laughren TP et al. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2088-9. [IDIS 524621] [PubMed 15277452]

36. Barrett EJ. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to Holt, Citrome and Volevka, Isaac and Isaac, and Boehm et al. Diabetes Care. 2004; 27:2089-90.

37. Fuller MA, Shermock KM, Secic M et al. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2002; 23:1037-43.

38. Koller EA, Cross JT, Doraiswamy PM et al. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy. 2003; 23:735-44. [IDIS 498493] [PubMed 12820816]

39. US Food and Drug Administration. Information for Healthcare Professionals: Conventional antipsychotics. Rockville, MD; 2008 Jun 16. From the FDA website: .

40. Ananth J, Johnson KM, Levander EM et al. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004; 65:724. [IDIS 516345] [PubMed 15163265]

41. Torrey EF, Swalwell CI. Fatal olanzapine-induced ketoacidosis. Am J Psychiatry. 2003; 160:2241. [IDIS 516756] [PubMed 14638601]

42. Wehring HJ, Kelly DL, Love RC et al. Deaths from diabetic ketoacidosis after long-term clozapine treatment. Am J Psychiatry. 2003; 160:2241-2. [IDIS 516757] [PubMed 14638600]

43. Koro CE, Fedder DO, L’Italien GJ et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. Br Med J. 2002; 325:243.

44. Citrome LL. Efficacy should drive atypical antipsychotic treatment. Br Med J. 2003; 326:283.

45. Anon. Which atypical antipsychotic for schizophrenia?. Drug Ther Bull. 2004; 42:57-60. [PubMed 15310154]

46. Anon. Atypical antipsychotics and hyperglycaemia. Aust Adv Drug React Bull. 2004; 23:11-2.

47. Sussman N. The implications of weight changes with antipsychotic treatment. J Clin Psychopharmacol. 2003; 23 (Suppl 1):S21-6.

48. Gianfrancesco F, Grogg A, Mahmoud R et al. Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Clin Ther. 2003; 25:1150-71. [IDIS 497269] [PubMed 12809963]

49. Bushe C, Leonard B. Association between atypical antipsychotic agents and type 2 diabetes: review of prospective clinical data. Br J Psychiatry Suppl. 2004; 47:S87-93. [PubMed 15056600]

50. Cavazzoni P, Mukhopadhyay N, Carlson C et al. Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications. Br J Psychiatry Suppl. 2004; 47:s94-101. [PubMed 15056601]

51. Gianfrancesco FD, Grogg AL, Mahmoud RA et al. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002; 63:920-30. [IDIS 488480] [PubMed 12416602]

52. Etminan M, Streiner DL, Rochon PA. Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults. Pharmacotherapy. 2003; 23:1411-5. [IDIS 510498] [PubMed 14620387]

53. Leslie DL, Rosenheck RA. Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications. Am J Psychiatry. 2004; 161:1709-11. [IDIS 522186] [PubMed 15337666]

54. Sernyak MJ, Leslie DL, Alarcon RD et al. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002; 159:561-6. [IDIS 494206] [PubMed 11925293]

55. Geller WK, MacFadden W. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388. [IDIS 513919] [PubMed 12562601]

56. Gianfrancesco FD. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388-9; author reply 389. [IDIS 513920] [PubMed 12562599]

57. Lamberti JS, Crilly JF, Maharaj K. Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs. J Clin Psychiatry. 2004; 65:702-6. [IDIS 516341] [PubMed 15163259]

58. Lee DW, Fowler RB. Olanzapine/risperidone and diabetes risk. J Clin Psychiatry. 2003; 64:847-8; author reply 848. [IDIS 500324] [PubMed 12934988]

59. Reviewer comments (personal observations).

60. AstraZeneca. Wayne, PA: Personal communication.

61. Eli Lilly and Company. Indianapolis, IN: Personal communication.

62. Novartis Pharmaceuticals Corporation. East Hanover, NJ: Personal communication.

63. Janssen Pharmaceuticals. Titusville, NJ: Personal communication.

64. Citrome LL. The increase in risk of diabetes mellitus from exposure to second generation antipsychotic agents. Drugs Today (Barc). 2004; 40:445-64. [PubMed 15319799]

65. Citrome L, Jaffe A, Levine J et al. Relationship between antipsychotic medication treatment and new cases of diabetes among psychiatric inpatients. Psychiatr Serv. 2004; 55:1006-13. [PubMed 15345760]

67. Food and Drug Administration. Patient information sheet: aripiprazole (marketed as Abilify). 2006 Sep 6.

68. American Psychiatric Association. DSM-IV: diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:273-86.

70. Volavka J, Citrome L. Oral antipsychotics for the treatment of schizophrenia: heterogeneity in efficacy and tolerability should drive decision-making. Expert Opin Pharmacother. 2009; 10:1917-28. [PubMed 19558339]

71. Lieberman JA. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. J Clin Psychiatry. 1996; 57(Suppl 11):68-71. [IDIS 376650] [PubMed 8941173]

72. Lahti AC, Tamminga CA. Recent developments in the neuropharmacology of schizophrenia. Am J Health-Syst Pharm. 1995; 52(Suppl 1):S5-8. [IDIS 341484] [PubMed 7749964]

73. US Food and Drug Administration. Public health advisory: Deaths with antipsychotics in elderly patients with behavioral disturbances. Rockville, MD; 2005 Apr 11. From the FDA website: ().

74. McIntyre RS. Pharmacology and efficacy of asenapine for manic and mixed states in adults with bipolar disorder. Expert Rev Neurother. 2010; 10:645-9. [PubMed 20420486]

75. Banerjee S. The use of antipsychotic medication for people with dementia: time for action. A report for the Minister of State for Care Services. United Kingdom Department of Health. From the website: .

76. Ortho-McNeil-Janssen Pharmaceuticals. Invega (paliperidone) extended-release tablets prescribing information. Titusville, NJ; 2009 Jul.

78. Qureshi SU, Rubin E. Risperidone- and aripiprazole-induced leukopenia: a case report. Prim Care Companion J Clin Psychiatry. 2008; 10:482-3. [PubMed 19287562]

79. Sexson WR, Barak Y. Withdrawal emergent syndrome in an infant associated with maternal haloperidol therapy. J Perinatol. 1989; 9:170-2. [PubMed 2738729]

80. Coppola D, Russo LJ, Kwarta RF Jr. et al. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf. 2007; 30:247-64. [PubMed 17343431]

81. US Food and Drug Administration. FDA drug safety communication: Antipsychotic drug labels updated in use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns.. Rockville, MD; 2010 Feb 22. From the FDA website: .

82. Citrome L. Lurasidone for schizophrenia: a brief review of a new second-generation antipsychotic. Clin Schizophr Relat Psychoses. 2011; 4:251-7. [PubMed 21177242]

83. Vanda Pharmaceuticals Inc. Fanapt (iloperidone) tablets prescribing information. Rockville, MD; 2011 Mar.

84. Sunovion Pharmaceuticals, Marlborough, MA: Personal communication.

Hide
(web2)