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Lurasidone

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

Medically reviewed by Drugs.com on Feb 22, 2021. Written by ASHP.

Warning

    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.

  • 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.

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

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

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

    Suicidality
  • Antidepressants increased risk of suicidal thinking and behavior (suicidality) compared with placebo in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need. Lurasidone is not approved for use in pediatric patients. (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.

  • Appropriately monitor and closely observe all patients who are started on lurasidone therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process. (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Benzisothiazol-derivative; atypical or second-generation antipsychotic agent.

Uses for Lurasidone

Schizophrenia

Acute treatment of schizophrenia in adults.

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

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.

Bipolar Disorder

Treatment (alone or in combination with lithium or valproate) of major depressive episodes associated with bipolar I disorder (bipolar depression).

Appears less likely to cause weight gain and to adversely affect metabolic parameters than some other atypical antipsychotic agents (e.g., olanzapine, quetiapine). Consider as alternative therapy in patients at higher risk of metabolic abnormalities (e.g., those with diabetes mellitus or hyperlipidemia).

Manufacturer states that efficacy of lurasidone in the treatment of mania associated with bipolar disorder has not been established.

Lurasidone Dosage and Administration

General

  • Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

Administration

Oral Administration

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

Dosage

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

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

Adults

Schizophrenia
Oral

For acute treatment, recommended initial dosage is 40 mg once daily. Initial dosage titration not required. Dosages ranging from 40–160 mg daily were effective in controlled trials.

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

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. Consider antipsychotic therapy discontinuance only after ≥1 year of symptom remission or optimal response while receiving the drug. Indefinite maintenance treatment recommended if patient has experienced multiple previous psychotic episodes or 2 episodes within 5 years.

Depressive Episodes Associated with Bipolar Disorder
Oral

As monotherapy or adjunctive therapy with lithium or valproate, initially, 20 mg once daily. Initial dosage titration not required. Although dosages ranging from 20–120 mg daily were effective in controlled trials, in the monotherapy study the higher dosage range (80–120 mg daily) did not provide additional efficacy over the lower dosage range (20–60 mg daily).

Long-term (i.e., >6 weeks) efficacy not established in controlled trials. Periodically reassess need for continued therapy.

Prescribing Limits

Adults

Schizophrenia
Oral

Maximum 160 mg daily.

Depressive Episodes Associated with Bipolar Disorder
Oral

Maximum 120 mg daily, as monotherapy or adjunctive therapy with lithium or valproate.

Special Populations

Hepatic Impairment

Severe hepatic impairment (Child-Pugh score 10–15): Initially, 20 mg daily. Do not exceed 40 mg daily.

Moderate hepatic impairment (Child-Pugh score 7–9): Initially, 20 mg daily. Do not exceed 80 mg daily.

Mild hepatic impairment: Dosage adjustment does not appear necessary. (See Hepatic Impairment under Cautions.)

Renal Impairment

Moderate or severe renal impairment: Initially, 20 mg daily. Do not exceed 80 mg daily.

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

Geriatric Patients

Not known whether dosage adjustment is necessary based on age alone.

Gender or Race

Dosage adjustment not recommended based on gender or race.

Cautions for Lurasidone

Contraindications

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

  • Concurrent use of potent CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir, voriconazole) or potent CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort [Hypericum perforatum]). (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.

Antipsychotic agents, including lurasidone, are not approved for the treatment of dementia-related psychosis. (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.)

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. (See Boxed Warning and also see Pediatric Use under Cautions.) However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving lurasidone for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of the patient’s presenting symptoms.

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Sensitivity Reactions

Rash and pruritus reported frequently; angioedema reported rarely. (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. Lurasidone is not approved for the treatment of patients with dementia-related psychosis. (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.

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

Tardive Dyskinesia

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

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. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.

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. Consider discontinuance of lurasidone if signs and symptoms of tardive dyskinesia appear. However, some patients may require treatment despite presence of the syndrome.

Metabolic Changes

Atypical antipsychotic agents are associated with metabolic changes that may increase cardiovascular and cerebrovascular risk (e.g., hyperglycemia, dyslipidemia, weight gain). While all atypical antipsychotics produce some metabolic changes, each drug has its own specific risk profile. (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. 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.

Periodically 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). If manifestations of hyperglycemia occur in any lurasidone-treated patient, perform fasting blood glucose testing. (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.

Dyslipidemia

Undesirable changes in lipid parameters observed in patients treated with some atypical antipsychotics. However, clinically important effects of lurasidone on serum lipids not observed in short- and longer-term clinical studies.

Weight Gain

Weight gain observed with atypical antipsychotic therapy. Although lurasidone generally produces minimal weight gain and less weight gain compared with some other atypical antipsychotics (e.g., olanzapine, quetiapine, risperidone), manufacturer recommends monitoring of weight during lurasidone therapy. (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.

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.

Hematologic Effects

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

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

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

Orthostatic Hypotension and Syncope

Risk of orthostatic hypotension associated with dizziness, lightheadedness, tachycardia or bradycardia, and syncope, particularly early in treatment and when dosage is increased, because of lurasidone's α1-adrenergic blocking activity.

Orthostatic hypotension (0.3%) and syncope (0.1%) reported in lurasidone-treated patients in short-term schizophrenia trials; not reported in short-term bipolar depression trials.

Patients at increased risk of these adverse reactions or of developing complications from hypotension include those with dehydration, hypovolemia, a history of cardiovascular disease (e.g., heart failure, MI, ischemic heart disease, conduction abnormalities), or a history of cerebrovascular disease, and patients receiving concomitant antihypertensive therapy and those who are antipsychotic-naive. Consider a lower initial dosage and more gradual dosage titration and monitor orthostatic vital signs in such patients.

Seizures

Seizures reported in 0.1% of both lurasidone-treated patients and placebo recipients in short-term schizophrenia trials. No reports of seizures or convulsions in lurasidone-treated patients in short-term bipolar depression trials.

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.

Cognitive and Motor Impairment

Judgment, thinking, or motor skills may be impaired. Somnolence (including hypersomnia, hypersomnolence, and sedation) reported in 17 and 7.3–13.8% of lurasidone-treated patients in schizophrenia and bipolar depression (as monotherapy) clinical trials, respectively; frequency of somnolence may be dose related. (See Advice to Patients.)

Body Temperature Regulation

Antipsychotic agents may disrupt ability to regulate core body temperature.

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).

Suicide

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

Activation of Mania/Hypomania

Antidepressants can increase risk of developing manic or hypomanic episodes, particularly in patients with bipolar disorder. Monitor patients for emergence of such episodes during therapy.

Dysphagia

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

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

Neurologic Adverse Reactions in Patients with Parkinsonian Syndrome or Dementia with Lewy Bodies

Patients with parkinsonian syndrome or dementia with Lewy bodies reportedly have an increased sensitivity to antipsychotic agents. Clinical manifestations of increased sensitivity reportedly include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and features consistent with NMS.

Specific Populations

Pregnancy

Category B.

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. Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.

Lactation

Lurasidone distributes into milk in rats; not known whether lurasidone and/or its metabolites distribute into human milk. Discontinue nursing or the drug, considering risk of drug discontinuance to the woman.

Pediatric Use

Safety and effectiveness not established in pediatric patients.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressants (SSRIs and others). However, a later meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. Manufacturer states not known if dosage adjustment necessary based on age alone. (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; increased incidence of cerebrovascular events also observed with certain atypical antipsychotic agents. Lurasidone is not approved for the treatment of patients with dementia-related psychosis. (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.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Dosage adjustment recommended in patients with moderate (Child-Pugh score 7–9) or severe (Child-Pugh score 10–15) hepatic impairment. (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 <50 mL/minute). (See Renal Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Schizophrenia: Somnolence (hypersomnia, hypersomnolence, sedation), akathisia, extrapyramidal symptoms (parkinsonian symptoms, dyskinesia), nausea. Akathisia and extrapyramidal symptoms were dose related.

Bipolar depression (as monotherapy or adjunctive therapy with lithium or valproate): Somnolence (hypersomnia, hypersomnolence, sedation), akathisia, nausea, extrapyramidal symptoms (parkinsonian symptoms, dyskinesia), vomiting, diarrhea, anxiety. Nausea, somnolence, akathisia, and extrapyramidal symptoms appear to be dose related.

Interactions for Lurasidone

Metabolized principally by CYP3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction. Concomitant use contraindicated.

Moderate CYP3A4 inhibitors: Potential pharmacokinetic interaction. Reduce lurasidone dosage to 50% of original dosage when a moderate CYP3A4 inhibitor is added to therapy. In patients receiving a moderate CYP3A4 inhibitor in whom lurasidone is initiated, recommended initial lurasidone hydrochloride dosage is 20 mg daily and maximum recommended dosage is 80 mg daily.

Potent CYP3A4 inducers: Potential pharmacokinetic interaction. Concomitant use contraindicated.

Moderate CYP3A4 inducers: Potential pharmacokinetic interaction. May need to increase lurasidone dosage after chronic therapy (i.e., ≥7 days) with the CYP3A4 inducer.

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.

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Alcohol

Possible additive CNS effects

Avoid concomitant use

Anticholinergic agents

Possible disruption of body temperature regulation

Use with caution

Atazanavir

Atazanavir (moderate CYP3A4 inhibitor) may increase lurasidone exposure

When atazanavir is added to lurasidone therapy, reduce lurasidone dosage to 50% of original dosage

In patients receiving atazanavir, recommended initial lurasidone hydrochloride dosage is 20 mg daily and maximum recommended dosage is 80 mg daily

Carbamazepine

Carbamazepine (a strong CYP3A4 inducer) potentially can decrease peak serum concentrations and AUCs of lurasidone

Concomitant use contraindicated

Clarithromycin

Clarithromycin (a strong CYP3A4 inhibitor) may substantially increase lurasidone exposure

Concomitant use contraindicated

CNS agents

Possible additive CNS effects

Use with caution

Digoxin

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

Digoxin dosage adjustment not required

Diltiazem

Diltiazem (a moderate CYP3A4 inhibitor) increased peak serum concentrations and AUCs of lurasidone by about twofold

When diltiazem is added to lurasidone therapy, reduce lurasidone dosage to 50% of original dosage

In patients receiving diltiazem, recommended initial lurasidone hydrochloride dosage is 20 mg daily and maximum recommended dosage is 80 mg daily

Erythromycin

Erythromycin (a moderate CYP3A4 inhibitor) may increase lurasidone exposure

When erythromycin is added to lurasidone therapy, reduce lurasidone dosage to 50% of original dosage

In patients receiving erythromycin, recommended initial lurasidone hydrochloride dosage is 20 mg daily and maximum recommended dosage is 80 mg daily

Fluconazole

Fluconazole (a moderate CYP3A4 inhibitor) may increase lurasidone exposure

When fluconazole is added to lurasidone therapy, reduce lurasidone dosage to 50% of original dosage

In patients receiving fluconazole, recommended initial lurasidone hydrochloride dosage is 20 mg daily and maximum recommended dosage is 80 mg daily

Grapefruit

Possible increased peak serum concentrations and AUCs of lurasidone

Avoid concomitant use

Hypotensive agents

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

Consider use of lower initial lurasidone dosage and more gradual titration; monitor orthostatic vital signs

Ketoconazole

Increased peak serum concentrations and AUCs of lurasidone by 6.8 and 9.3 times, respectively

Concomitant use contraindicated

Lithium

Decreased peak serum lurasidone concentrations by 8% and increased lurasidone AUCs by 7%; no evidence of additive CNS toxicity

No clinically important change in lithium exposure

Dosage adjustment of lurasidone and lithium not required

Midazolam

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

Midazolam dosage adjustment not required

Oral contraceptives

Peak plasma concentrations and AUCs of oral contraceptives not substantially affected

Sex hormone binding globulin concentrations not substantially affected

Oral contraceptive dosage adjustment not required

Phenytoin

Phenytoin (potent CYP3A4 inducer) potentially can decrease peak serum concentrations and AUCs of lurasidone

Concomitant use contraindicated

Rifampin

Rifampin (potent CYP3A4 inducer) decreased peak serum concentrations and AUCs of lurasidone by approximately 85 and 82%, respectively

Concomitant use contraindicated

Ritonavir

Ritonavir (potent CYP3A4 inhibitor) may substantially increase lurasidone exposure

Concomitant use contraindicated

Smoking

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

St. John's wort (Hypericum perforatum)

St. John's wort (potent CYP3A4 inducer) potentially can decrease peak serum concentrations and AUCs of lurasidone

Concomitant use contraindicated

Valproate

No clinically important change in lurasidone or valproate serum concentrations

Dosage adjustment of lurasidone and valproate not required

Verapamil

Verapamil (moderate CYP3A4 inhibitor) may increase lurasidone exposure

When verapamil is added to lurasidone therapy, reduce lurasidone dosage to 50% of original dosage

In patients receiving verapamil, recommended initial lurasidone hydrochloride dosage is 20 mg daily and maximum recommended dosage is 80 mg daily

Voriconazole

Voriconazole (potent CYP3A4 inhibitor) may substantially increase lurasidone exposure

Concomitant use contraindicated

Lurasidone Pharmacokinetics

Absorption

Bioavailability

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

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

Steady-state concentrations of lurasidone achieved within 7 days.

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. Exposure not affected as meal size increased from 350 to 1000 calories and was independent of fat content.

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.

Mean AUCs were 1.5, 1.7, and 3 times higher in individuals with mild (Child-Pugh score 5–6), moderate (Child-Pugh score 7–9), and severe hepatic impairment (Child-Pugh score 10–15), respectively, compared with healthy individuals. 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.

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

Distribution

Extent

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

Plasma Protein Binding

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

Elimination

Metabolism

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

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.

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.

Half-life

Averages 18 hours.

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Actions

  • Exact mechanism of action in schizophrenia and bipolar depression 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.

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

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

Advice to Patients

  • Importance of providing a copy of written patient information (medication guide) each time lurasidone is dispensed. Importance of advising patients to read the patient information before taking lurasidone and each time the prescription is refilled.

  • Importance of advising patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. Inform patients and caregivers that lurasidone is not approved for treating geriatric patients with dementia-related psychosis.

  • Risk of suicidality and activation of mania or hypomania; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, manic or hypomanic symptoms, irritability, agitation, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk and also see Activation of Mania/Hypomania under Cautions.)

  • 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.

  • Importance of informing patients and caregivers about the risk of metabolic changes (e.g., hyperglycemia and diabetes mellitus, dyslipidemia, weight gain, cardiovascular reactions) and the need for specific monitoring for such changes. Importance of patients and caregivers being aware of the symptoms of hyperglycemia and diabetes mellitus (e.g., increased thirst, increased urination, increased appetite, weakness). Importance of informing patients who are diagnosed with diabetes or those with risk factors for diabetes (e.g., obesity, family history of diabetes) that they should have their blood glucose monitored at the beginning of and periodically during lurasidone therapy; patients who develop symptoms of hyperglycemia during therapy should have their blood glucose assessed.

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

  • Risk of leukopenia/neutropenia. 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.

  • Risk of somnolence (i.e., sleepiness, drowsiness). 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.

  • Importance of avoiding eating grapefruit or drinking grapefruit juice during lurasidone therapy, since they can affect lurasidone concentrations in the blood.

  • Importance of avoiding alcohol during lurasidone therapy.

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

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

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

  • Importance of avoiding overheating and dehydration.

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Lurasidone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film coated

20 mg

Latuda

Sunovion

40 mg

Latuda

Sunovion

60 mg

Latuda

Sunovion

80 mg

Latuda

Sunovion

120 mg

Latuda

Sunovion

AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 2, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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