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Revision as of 18:44, 4 August 2014

Lurasidone
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Disclaimer

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Black Box Warning

WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; AND SUICIDAL THOUGHTS AND BEHAVIORS
See full prescribing information for complete Boxed Warning.
* Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
  • LATUDA is not approved for use in patients with dementia-related psychosis.
  • Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.
  • In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

Overview

Lurasidone is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Schizophrenia

  • LATUDA is indicated for the treatment of patients with schizophrenia.
  • The efficacy of LATUDA in schizophrenia was established in five 6-week controlled studies of adult patients with schizophrenia.
  • The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Depressive Episodes Associated with Bipolar I Disorder

  • Monotherapy: LATUDA is indicated as monotherapy for the treatment of patients with major depressive episodes associated with bipolar I disorder (bipolar depression). The efficacy of LATUDA was established in a 6-week monotherapy study in adult patients with bipolar depression.
  • Adjunctive Therapy with Lithium or Valproate: LATUDA is indicated as adjunctive therapy with either lithium or valproate for the treatment of patients with major depressive episodes associated with bipolar I disorder (bipolar depression). The efficacy of LATUDA as adjunctive therapy was established in a 6-week study in adult patients with bipolar depression who were treated with lithium or valproate.
  • The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
  • The efficacy of LATUDA in the treatment of mania associated withbipolar disorder has not been established.

Dosing Information

Schizophrenia
  • The recommended starting dose of LATUDA is 40 mg once daily. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 40 mg per day to 160 mg per day [see Clinical Studies (14.1)]. The maximum recommended dose is 160 mg per day.
Depressive Episodes Associated with Bipolar I Disorder
  • The recommended starting dose of LATUDA is 20 mg given once daily as monotherapy or as adjunctive therapy with lithium or valproate. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 20 mg per day to 120 mg per day as monotherapy or as adjunctive therapy with lithium or valproate. The maximum recommended dose, as monotherapy or as adjunctive therapy with lithium or valproate, is 120 mg per day. In the monotherapy study, the higher dose range (80 mg to 120 mg per day) did not provide additional efficacy, on average, compared to the lower dose range (20 to 60 mg per day)
Dose Modifications in Special Populations
  • Renal Impairment
  • Dose adjustment is recommended in moderate (creatinine clearance: 30 to <50 mL/min) and severe renal impairment (creatinine clearance <30 mL/min) patients. The recommended starting dose is 20 mg per day. The dose in these patients should not exceed 80 mg per day.
  • Hepatic Impairment
  • Dose adjustment is recommended in moderate (Child-Pugh Score = 7 to 9) and severe hepatic impairment (Child-Pugh Score = 10 to 15) patients. The recommended starting dose is 20 mg per day. The dose in moderate hepatic impairment patients should not exceed 80 mg per day and the dose in severe hepatic impairment patients should not exceed 40 mg/day.
Dose Modifications Due to Drug Interactions
  • Concomitant Use with CYP3A4 Inhibitors
  • LATUDA should not be used concomitantly with a strong CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.)
  • If LATUDA is being prescribed and a moderate CYP3A4 inhibitor (e.g. diltiazem, atazanavir, erythromycin, fluconazole, verapamil etc.) is added to the therapy, the LATUDA dose should be reduced to half of the original dose level. Similarly, if a moderate CYP3A4 inhibitor is being prescribed and LATUDA is added to the therapy, the recommended starting dose of LATUDA is 20 mg per day, and the maximum recommended dose of LATUDA is 80 mg per day.
  • Grapefruit and grapefruit juice should be avoided in patients taking LATUDA, since these may inhibit CYP3A4 and alter LATUDA concentrations.
  • Concomitant Use with CYP3A4 Inducers
  • LATUDA should not be used concomitantly with a strong CYP3A4 inducer (e.g., rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine, etc.) . If LATUDA is used concomitantly with a moderate CYP3A4 inducer, it may be necessary to increase the LATUDA dose after chronic treatment (7 days or more) with the CYP3A4 inducer.

DOSAGE FORMS AND STRENGTHS

  • LATUDA tablets are available in the following shape and color (Table 1) with respective one-sided debossing:
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Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Bipolar disorder, depressed phase

  • initial, 20 mg ORALLY once daily as monotherapy or adjunctive therapy with lithium or valproate; give with food (at least 350 Calories); initial dose titration not required; MAX 120 mg once daily; long-term usefulness beyond 6 weeks should be periodically re-evaluated [1]

Schizophrenia

  • initial, 40 mg ORALLY once daily with food (at least 350 Calories); initial dose titration not required; MAX 160 mg once daily [1]

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lurasidone in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Lurasidone in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

  • safety and effectiveness not established in pediatric patients [1].

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lurasidone in pediatric patients.

Contraindications

  • Known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone.
  • Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.).
  • StrongCYP3A4 inducers (e.g., rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine, etc.).

Warnings

WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; AND SUICIDAL THOUGHTS AND BEHAVIORS
See full prescribing information for complete Boxed Warning.
* Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
  • LATUDA is not approved for use in patients with dementia-related psychosis.
  • Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.
  • In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.
File:Latudawarning.png
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Increased Mortality in Elderly Patients with Dementia-Related Psychosis

  • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6- to 1.7-times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. LATUDA is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning].

Suicidal Thoughts and Behaviors in Adolescents and Young Adults

  • Patients withmajor depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
  • Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
  • The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk of differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 2.
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  • No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
  • It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
  • All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
  • The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
  • Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
  • Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidal thoughts and behaviors, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for LATUDA should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.

Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis

  • In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks), including fatalities, compared to placebo-treated subjects. LATUDA is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome

  • A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including LATUDA.
  • Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure,tachycardia, diaphoresis, andcardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
  • The diagnostic evaluation of patients with this syndrome is complicated. It is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
  • The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.
  • If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. If reintroduced, the patient should be carefully monitored, since recurrences of NMS have been reported.

Tardive Dyskinesia

  • Tardive dyskinesia is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements that can develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to causetardive dyskinesia is unknown.
  • The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
  • There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
  • Given these considerations, LATUDA should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
  • If signs and symptoms of tardive dyskinesia appear in a patient on LATUDA, drug discontinuation should be considered. However, some patients may require treatment with LATUDA despite the presence of the syndrome.

Metabolic Changes

  • Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.
Hyperglycemia and Diabetes Mellitus
  • Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Because LATUDA was not marketed at the time these studies were performed, it is not known if LATUDA is associated with this increased risk.
  • Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria' polyphagia, and weakness. Patients who develop symptoms ofhyperglycemiaduring treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
Schizophrenia
  • Pooled data from short-term, placebo-controlled schizophrenia studies are presented in Table 3
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  • In the uncontrolled, longer-term schizophrenia studies (primarily open-label extension studies), LATUDA was associated with a mean change in glucose of +1.8 mg/dL at week 24 (n=355), +0.8 mg/dL at week 36 (n=299) and +2.3 mg/dL at week 52 (n=307).
Bipolar Depression
  • Monotherapy
  • Data from the short-term, flexible-dose, placebo-controlled monotherapy bipolar depression study are presented in Table 4.
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  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who received LATUDA as monotherapy in the short-term study and continued in the longer-term study, had a mean change in glucose of +1.2 mg/dL at week 24 (n=129).
  • Adjunctive Therapy with Lithium or Valproate
  • Data from the short-term, flexible-dosed, placebo-controlled adjunctive therapy bipolar depression studies are presented in Table 5.
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  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who received LATUDA as adjunctive therapy with either lithium or valproate in the short-term study and continued in the longer-term study, had a mean change in glucose of +1.7 mg/dL at week 24 (n=88).
Dyslipidemia
Schizophrenia
  • Pooled data from short-term, placebo-controlled schizophrenia studies are presented in Table 6.
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  • In the uncontrolled, longer-term schizophrenia studies (primarily open-label extension studies), LATUDA was associated with a mean change in total cholesterol and triglycerides of -3.8 (n=356) and -15.1 (n=357) mg/dL at week 24, -3.1 (n=303) and -4.8 (n=303) mg/dL at week 36 and -2.5 (n=307) and -6.9 (n=307) mg/dL at week 52, respectively.
Bipolar Depression
  • Monotherapy

Data from the short-term, flexible-dosed, placebo-controlled, monotherapy bipolar depression study are presented in Table 7

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  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who received LATUDA as monotherapy in the short-term and continued in the longer-term study had a mean change in total cholesterol and triglycerides of -0.5 (n=130) and -1.0 (n=130) mg/dL at week 24, respectively.
  • Adjunctive Therapy with Lithium or Valproate
  • Data from the short-term, flexible-dosed, placebo-controlled, adjunctive therapy bipolar depression studies are presented in Table 8.
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  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who received LATUDA, as adjunctive therapy with either lithium or valproate in the short-term study and continued in the longer-term study, had a mean change in total cholesterol and triglycerides of -0.9 (n=88) and +5.3 (n=88) mg/dL at week 24, respectively.
Weight Gain
  • Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Schizophrenia
  • Pooled data from short-term, placebo-controlled schizophrenia studies are presented in Table 9. The mean weight gain was +0.43 kg for LATUDA-treated patients compared to -0.02 kg for placebo-treated patients. Change in weight from baseline for olanzapine was +4.15 kg and for quetiapine extended-release was +2.09 kg in Studies 3 and 5 , respectively. The proportion of patients with a ≥ 7% increase in body weight (at Endpoint) was 4.8% for LATUDA-treated patients versus 3.3% for placebo-treated patients.
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  • In the uncontrolled, longer-term schizophrenia studies (primarily open-label extension studies), LATUDA was associated with a mean change in weight of -0.69 kg at week 24 (n=755), -0.59 kg at week 36 (n=443) and -0.73 kg at week 52 (n=377).
Bipolar Depression
  • Monotherapy
  • Data from the short-term, flexible-dosed, placebo-controlled monotherapy bipolar depression study are presented in Table 10. The mean weight gain was +0.29 kg for LATUDA-treated patients compared to -0.04 kg for placebo-treated patients. The proportion of patients with a ≥ 7% increase in body weight (at Endpoint) was 2.4% for LATUDA-treated patients versus 0.7% for placebo-treated patients.
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  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who received LATUDA as monotherapy in the short-term and continued in the longer-term study had a mean change in weight of -0.02 kg at week 24 (n=130).
Adjunctive Therapy with Lithium or Valproate
  • Data from the short-term, flexible-dosed, placebo-controlled adjunctive therapy bipolar depression studies are presented in Table 11. The mean weight gain was +0.11 kg for LATUDA-treated patients compared to +0.16 kg for placebo-treated patients. The proportion of patients with a ≥ 7% increase in body weight (at Endpoint) was 3.1% for LATUDA-treated patients versus 0.3% for placebo-treated patients.
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  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who were treated with LATUDA, as adjunctive therapy with either lithium or valproate in the short-term and continued in the longer-term study, had a mean change in weight of +1.28 kg at week 24 (n=86).

Hyperprolactinemia

  • As with other drugs that antagonize dopamine D2 receptors, LATUDA elevates prolactin levels.
  • Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotrophin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea,amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating compounds. Long-standing hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone density in both female and male patients.
  • Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of these drugs is considered in a patient with previously detected breast cancer. As is common with compounds which increase prolactin release, an increase in mammary gland neoplasia was observed in a LATUDA carcinogenicity study conducted in rats and mice . Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans, but the available evidence is too limited to be conclusive.
Schizophrenia
  • In short-term, placebo-controlled schizophrenia studies, the median change from baseline to endpoint in prolactin levels for LATUDA-treated patients was +0.4 ng/mL and was -1.9 ng/mL in the placebo-treated patients. The median change from baseline to endpoint for males was +0.5 ng/mL and for females was -0.2 ng/mL. Median changes for prolactin by dose are shown in Table 12.
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  • The proportion of patients with prolactin elevations ≥ 5× upper limit of normal (ULN) was 2.8% for LATUDA-treated patients versus 1.0% for placebo-treated patients. The proportion of female patients with prolactin elevations ≥ 5x ULN was 5.7% for LATUDA-treated patients versus 2.0% for placebo-treated female patients. The proportion of male patients with prolactin elevations ≥ 5x ULN was 1.6% versus 0.6% for placebo-treated male patients.
  • In the uncontrolled longer-term schizophrenia studies (primarily open-label extension studies), LATUDA was associated with a median change in prolactin of -0.9 ng/mL at week 24 (n=357), -5.3ng/mL at week 36 (n=190) and -2.2 ng/mL at week 52 (n=307).
Bipolar Depression
  • Monotherapy
  • The median change from baseline to endpoint in prolactin levels, in the short-term, flexible-dosed, placebo-controlled monotherapy bipolar depression study, was +1.7 ng/mL and +3.5 ng/mL with LATUDA 20 to 60 mg/day and 80 to 120 mg/day, respectively compared to +0.3 ng/mL with placebo-treated patients. The median change from baseline to endpoint for males was +1.5 ng/mL and for females was +3.1 ng/mL. Median changes for prolactin by dose range are shown in Table 13.
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  • The proportion of patients with prolactin elevations ≥ 5x upper limit of normal (ULN) was 0.4% for LATUDA-treated patients versus 0.0% for placebo-treated patients. The proportion of female patients with prolactin elevations ≥ 5x ULN was 0.6% for LATUDA-treated patients versus 0% for placebo-treated female patients. The proportion of male patients with prolactin elevations ≥ 5x ULN was 0% versus 0% for placebo-treated male patients.
  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who were treated with LATUDA as monotherapy in the short-term and continued in the longer-term study, had a median change in prolactin of -1.15 ng/mL at week 24 (n=130).
  • Adjunctive Therapy with Lithium or Valproate
  • The median change from baseline to endpoint in prolactin levels, in the short-term, flexible-dosed, placebo-controlled adjunctive therapy bipolar depression studies was +2.8 ng/mL with LATUDA 20 to 120 mg/day compared to 0.0 ng/mL with placebo-treated patients. The median change from baseline to endpoint for males was +2.4 ng/mL and for females was +3.2 ng/mL. Median changes for prolactin across the dose range are shown in Table 14
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  • The proportion of patients with prolactin elevations ≥ 5x upper limit of normal (ULN) was 0.0% for LATUDA-treated patients versus 0.0% for placebo-treated patients. The proportion of female patients with prolactin elevations ≥ 5x ULN was 0% for LATUDA-treated patients versus 0% for placebo-treated female patients. The proportion of male patients with prolactin elevations ≥ 5x ULN was 0% versus 0% for placebo-treated male patients.
  • In the uncontrolled, open-label, longer-term bipolar depression study, patients who were treated with LATUDA, as adjunctive therapy with either lithium or valproate, in the short-term and continued in the longer-term study, had a median change in prolactin of -2.9 ng/mL at week 24 (n=88).

Leukopenia, Neutropenia and Agranulocytosis

  • Leukopenia/neutropenia has been reported during treatment with antipsychotic agents. Agranulocytosis (including fatal cases) has been reported with other agents in the class.
  • Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and LATUDA should be discontinued at the first sign of decline in WBC, in the absence of other causative factors.
  • Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm3) should discontinue LATUDA and have their WBC followed until recovery.

Orthostatic Hypotension and Syncope

  • LATUDA may cause orthostatic hypotension and syncope, perhaps due to its α1-adrenergic receptor antagonism. Associated adverse reactions can include dizziness, lightheadedness, tachycardia, and bradycardia. Generally, these risks are greatest at the beginning of treatment and during dose escalation. Patients at increased risk of these adverse reactions or at increased risk of developing complications from hypotension include those with dehydration, hypovolemia, treatment with antihypertensive medication, history of cardiovascular disease (e.g., heart failure, myocardial infarction, ischemia, or conduction abnormalities), history of cerebrovascular disease, as well as patients who are antipsychotic-naïve. In such patients, consider using a lower starting dose and slower titration, and monitor orthostatic vital signs.
  • Orthostatic hypotension, as assessed by vital sign measurement, was defined by the following vital sign changes: ≥ 20 mm Hg decrease in systolic blood pressure and ≥ 10 bpm increase in pulse from sitting to standing or supine to standing position.
Schizophrenia
  • The incidence of orthostatic hypotension and syncope reported as adverse events from short-term, placebo-controlled schizophrenia studies was (LATUDA incidence, placebo incidence): orthostatic hypotension [0.3% (5/1508), 0.1% (1/708)] and syncope [0.1% (2/1508), 0% (0/708)].
  • In short-term schizophrenia clinical studies, orthostatic hypotension, as assessed by vital signs, occurred with a frequency of 0.8% with LATUDA 40 mg, 2.1% with LATUDA 80 mg, 1.7% with LATUDA 120 mg and 0.8% with LATUDA 160 mg compared to 0.7% with placebo.
Bipolar Depression
  • Monotherapy
  • In the short-term, flexible-dose, placebo-controlled monotherapy bipolar depression study, there were no reported adverse events of orthostatic hypotension and syncope.
  • Orthostatic hypotension, as assessed by vital signs, occurred with a frequency of 0.6% with LATUDA 20 to 60 mg and 0.6% with LATUDA 80 to 120 mg compared to 0% with placebo.
  • Adjunctive Therapy with Lithium or Valproate
  • In the short-term, flexible-dose, placebo-controlled adjunctive therapy bipolar depression therapy studies, there were no reported adverse events of orthostatic hypotension and syncope. Orthostatic hypotension, as assessed by vital signs, occurred with a frequency of 1.1% with LATUDA 20 to 120 mg compared to 0.9% with placebo

Seizures

  • As with other antipsychotic drugs, LATUDA should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold, e.g., Alzheimer's dementia. Conditions that lower the seizure threshold may be more prevalent in patients 65 years or older.
Schizophrenia
  • In short-term, placebo-controlled schizophrenia studies, seizures/convulsions occurred in 0.1% (2/1508) of patients treated with LATUDA compared to 0.1% (1/708) placebo-treated patients.
Bipolar Depression
  • Monotherapy
  • In the short-term, flexible-dose, placebo-controlled monotherapy bipolar depression study, no patient experienced seizures/convulsions.
  • Adjunctive Therapy with Lithium or Valproate
  • In the short-term, flexible-dose, placebo-controlled adjunctive therapy bipolar depression studies, no patient experienced seizures/convulsions.

Potential for Cognitive and Motor Impairment

  • LATUDA, like other antipsychotics, has the potential to impair judgment, thinking or motor skills. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with LATUDA does not affect them adversely.
  • In clinical studies with LATUDA, somnolence included: hypersomnia, hypersomnolence, sedation and somnolence.
Schizophrenia
  • In short-term, placebo-controlled schizophrenia studies, somnolence was reported by 17.0% (256/1508) of patients treated with LATUDA (15.5% LATUDA 20 mg, 15.6% LATUDA 40 mg, 15.2% LATUDA 80 mg, 26.5% LATUDA 120 mg and 8.3% LATUDA 160 mg/day) compared to 7.1% (50/708) of placebo patients.
=Bipolar Depression
  • Monotherapy
  • In the short-term, flexible-dosed, placebo-controlled monotherapy bipolar depression study, somnolence was reported by 7.3% (12/164) and 13.8% (23/167) with LATUDA 20 to 60 mg and 80 to120 mg, respectively compared to 6.5% (11/168) of placebo patients.
  • Adjunctive Therapy with Lithium or Valproate
  • In the short-term, flexible-dosed, placebo-controlled adjunctive therapy bipolar depression studies, somnolence was reported by 11.4% (41/360) of patients treated with LATUDA 20-120 mg compared to 5.1% (17/334) of placebo patients.

Body Temperature Dysregulation

  • Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing LATUDA for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Suicide

  • The possibility of a suicide attempt is inherent in psychotic illness and close supervision of high-risk patients should accompany drug therapy. Prescriptions for LATUDA should be written for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose.
Schizophrenia
  • In short-term, placebo-controlled schizophrenia studies, the incidence of treatment-emergent suicidal ideation was 0.4% (6/1508) for LATUDA-treated patients compared to 0.8% (6/708) on placebo. No suicide attempts or completed suicides were reported in these studies.
Bipolar Depression
  • Monotherapy
  • In the short-term, flexible-dose, placebo-controlled monotherapy bipolar depression study, the incidence of treatment-emergent suicidal ideation was 0.0% (0/331) with LATUDA-treated patients compared to 0.0% (0/168) with placebo-treated patients. No suicide attempts or completed suicides were reported in this study.
  • Adjunctive Therapy with Lithium or Valproate
  • In the short-term, flexible-dose, placebo-controlled adjunctive therapy bipolar depression studies, the incidence of treatment-emergent suicidal ideation was 1.1% (4/360) for LATUDA-treated patients compared to 0.3% (1/334) on placebo. No suicide attempts or completed suicides were reported in these studies.

Activation of Mania/Hypomania

  • Antidepressant treatment can increase the risk of developing a manic or hypomanic episode, particularly in patients with bipolar disorder. Monitor patients for the emergence of such episodes.
  • In the bipolar depression monotherapy and adjunctive therapy (with lithium or valproate) studies, less than 1% of subjects in the LATUDA and placebo groups developed manic or hypomanic episodes.

Dysphagia

  • Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia. LATUDA and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

Neurological Adverse Reactions in Patients with Parkinson's Disease or Dementia with Lewy Bodies

  • Patients with Parkinson's Disease or Dementia with Lewy Bodies are reported to have an increased sensitivity to antipsychotic medication. Manifestations of this increased sensitivity include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with theneuroleptic malignant syndrome.

Adverse Reactions

Clinical Trials Experience

  • Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
  • The information below is derived from an integrated clinical study database for LATUDA consisting of 3799 patients exposed to one or more doses of LATUDA for the treatment of schizophrenia and bipolar depression in placebo-controlled studies. This experience corresponds with a total experience of 1250.9 patient-years. A total of 1106 LATUDA-treated patients had at least 24 weeks and 371 LATUDA-treated patients had at least 52 weeks of exposure.
  • Adverse events during exposure to study treatment were obtained by general inquiry and voluntarily reported adverse experiences, as well as results from physical examinations, vital signs, ECGs, weights and laboratory investigations. Adverse experiences were recorded by clinical investigators using their own terminology. In order to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology.

Schizophrenia

  • The following findings are based on the short-term, placebo-controlled premarketing studies for schizophrenia in which LATUDA was administered at daily doses ranging from 20 to 160 mg (n=1508).
  • Commonly Observed Adverse Reactions:
  • The most common adverse reactions (incidence ≥ 5% and at least twice the rate of placebo) in patients treated with LATUDA were somnolence, akathisia, extrapyramidal symptoms, and nausea.
  • Adverse Reactions Associated with Discontinuation of Treatment:
  • A total of 9.5% (143/1508) LATUDA-treated patients and 9.3% (66/708) of placebo-treated patients discontinued due to adverse reactions. There were no adverse reactions associated with discontinuation in subjects treated with LATUDA that were at least 2% and at least twice the placebo rate.
  • Adverse Reactions Occurring at an Incidence of 2% or More in LATUDA-Treated Patients: :*Adverse reactions associated with the use of LATUDA (incidence of 2% or greater, rounded to the nearest percent and LATUDA incidence greater than placebo) that occurred during acute therapy (up to 6 weeks in patients with schizophrenia) are shown in Table 15.


  • Dose-Related Adverse Reactions in the Schizophrenia Studies
  • Akathisia and extrapyramidal symptoms were dose-related. The frequency of akathisia increased with dose up to 120 mg/day (5.6% for LATUDA 20 mg, 10.7% for LATUDA 40 mg, 12.3% for LATUDA 80 mg, and 22.0% for LATUDA 120 mg). Akathisia was reported by 7.4% (9/121) of patients receiving 160 mg/day. Akathisia occurred in 3.0% of subjects receiving placebo. The frequency of extrapyramidal symptoms increased with dose up to 120 mg/day (5.6% for LATUDA 20 mg, 11.5% for LATUDA 40 mg, 11.9% for LATUDA 80 mg, and 22.0% for LATUDA 120 mg).
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Lurasidone in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lurasidone in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lurasidone during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Lurasidone with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Lurasidone with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Lurasidone with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Lurasidone with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lurasidone with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lurasidone in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lurasidone in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lurasidone in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lurasidone in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Lurasidone in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Lurasidone in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Lurasidone in the drug label.

Pharmacology

There is limited information regarding Lurasidone Pharmacology in the drug label.

Mechanism of Action

Structure

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This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Lurasidone in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Lurasidone in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Lurasidone in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Lurasidone in the drug label.

How Supplied


This image is provided by the National Library of Medicine.

Storage

There is limited information regarding Lurasidone Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Lurasidone Patient Counseling Information in the drug label.

Precautions with Alcohol

  • Alcohol-Lurasidone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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