Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Lurasidone is not approved for the treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.
Note: Take with a meal (≥350 calories) for adequate absorption.
Bipolar major depression:
Note: Not effective for treating acute bipolar mania or hypomania (WFSBP [Grunze 2017]).
Bipolar major depression, acute, with mixed features (off label) or without (labeled use) (monotherapy or in combination with antimanic therapy): Oral: Initial: 20 mg once daily in the evening within 30 minutes of food (≥350 calories); may increase daily dose based on response and tolerability in increments of 20 mg every ≥2 days to a maximum dose of 120 mg/day (Calabrese 2017; Loebel 2014a; Loebel 2014b; McIntyre 2015; Shelton 2021; manufacturer's labeling).
Maintenance treatment for depressive episodes (off-label use): Oral: Continue dose and combination regimen that was used to achieve control of the acute episode (CANMAT/ISBD [Yatham 2018]). Maximum dose: 120 mg/day.
Major depressive disorder (unipolar) with mixed features (monotherapy) (off-label use): Oral: Initial: 20 mg once daily in the evening within 30 minutes of food (≥350 calories) for 7 days; may subsequently increase daily dose based on response and tolerability by 20 mg every 2 to 7 days up to 60 mg/day (Suppes 2016).
Schizophrenia: Oral: Initial: 40 mg once daily in the evening within 30 minutes of food (≥350 calories); may increase daily dose based on response and tolerability in increments of 40 mg every ≥3 days to a maximum dose of 160 mg/day; usual dose: 40 to 80 mg/day (Loebel 2016; Stroup 2022; Tandon 2016; manufacturer’s labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Discontinuation of therapy: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (APA [Keepers 2020]; Lambert 2007; Moncrieff 2020; Post 2021).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Cerovecki 2013; Remington 2005; Takeuchi 2017). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Stroup 2022).
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Initial: 20 mg daily; maximum: 80 mg/day
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 20 mg daily; maximum: 80 mg/day.
Severe impairment (Child-Pugh class C): Initial: 20 mg daily; maximum: 40 mg/day.
(For additional information see "Lurasidone: Pediatric drug information")
Bipolar depression:
Children ≥10 years and Adolescents <18 years: Monotherapy: Oral: Initial: 20 mg once daily; may increase dose after 1 week based on response and tolerability; reported range: 20 to 80 mg/day; in the largest double-blind placebo-controlled trial (n=175 treatment group), the majority of patients (67%) responded to a dose of 20 or 40 mg once daily; the modal daily dose was 20 mg in 52.3% of patients and 40 mg in 26.2% of patients (DelBello 2017).
Adolescents ≥18 years: Monotherapy or as adjunct to lithium or divalproex: Oral: Initial: 20 mg once daily in the evening; may increase dose further based on response and tolerability in 20 mg increments every 2 to 7 days up to 120 mg/day (Chapel 2016; Loebel 2014a; Loebel 2014b).
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 40 mg once daily; may increase dose further based on response and tolerability; age-dependent maximum recommended daily dose: for ages <18 years: 80 mg/day; for ages ≥18 years: 160 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Discontinuation of therapy: Children and Adolescents: American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), National Institute for Health and Care Excellence (NICE), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (AACAP [McClellan 2007]; APA [Lehman 2004]; Cerovecki 2013; CPA 2005; NICE 2013; WFSBP [Hasan 2012]); risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months and the APA guidelines recommend reducing the dose by 10% each month (APA [Lehman 2004]; CPA 2005). Continuing antiparkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Cerovecki 2013). When switching antipsychotics, three strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited and results are conflicting (Cerovecki 2013; Remington 2005).
CrCl ≥50 mL/minute: Children ≥10 years and Adolescents: Oral: No dosage adjustment necessary.
CrCl <50 mL/minute:
Bipolar depression: Children ≥10 years and Adolescents: Oral: Higher drug exposure occurs in patients with CrCl <50 mL/minute; based on adult information, reduce initial dose; do not exceed an initial dose of 20 mg daily; maximum daily dose: 80 mg/day. Note: For patients ≤17 years of age, manufacturer-recommended renal impairment dose does not reflect a change from recommended dose for this indication; use caution.
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 20 mg daily; maximum daily dose: 80 mg/day.
Mild impairment: Children ≥10 years and Adolescents: Oral: No dosage adjustment necessary.
Moderate impairment:
Bipolar depression: Children ≥10 years and Adolescents: Oral: Higher drug exposure occurs in patients with moderate to severe hepatic impairment; based on adult information, reduce initial dose; do not exceed an initial dose of 20 mg daily; maximum daily dose: 80 mg/day. Note: For patients ≤17 years of age, manufacturer-recommended hepatic impairment dose does not reflect a change from recommended dose for this indication; use caution.
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 20 mg daily; maximum daily dose: 80 mg/day.
Severe impairment:
Bipolar depression: Children ≥10 years to Adolescents: Oral: Higher drug exposure occurs in patients with moderate to severe hepatic impairment; based on adult information, reduce initial dose; do not exceed an initial dose of 20 mg daily; maximum daily dose: 40 mg/day. Note: For patients ≤17 years of age, manufacturer-recommended hepatic impairment dose does not reflect a change from recommended dose for this indication; use caution.
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 20 mg daily; maximum daily dose: 40 mg/day.
Refer to adult dosing. Dosages in the lower range of recommended adult dosing are generally sufficient with low-onset schizophrenia or psychosis. Titrate dosage slowly and monitor carefully (Howard 2000).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Latuda: 20 mg, 40 mg, 60 mg
Latuda: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Latuda: 120 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Latuda: 20 mg, 40 mg, 60 mg
Latuda: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Latuda: 120 mg
Generic: 20 mg, 40 mg, 60 mg, 80 mg, 120 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/200603s035lbl.pdf#page=62, must be dispensed with this medication.
Oral: Administer consistently at the same time every day with food (≥350 calories). Evening administration may help reduce adverse effects (Shelton 2020). The manufacturer recommends not to split, crush, or cut the tablets because the effects of splitting or crushing the tablets has not been evaluated in clinical and pharmacokinetic studies (Sunovion Pharmaceuticals written communication 2022).
Oral: Administer with food (≥350 calories). The manufacturer recommends to not split, crush, or cut the tablets because the effects of splitting or crushing the tablets has not been evaluated in clinical and pharmacokinetic studies (Sunovion Pharmaceuticals written communication 2022).
Bipolar major depression: Treatment of depressive episodes associated with bipolar I disorder, both as monotherapy (children ≥10 years of age, adolescents, and adults) and as an adjunct to lithium or divalproex (adults).
Schizophrenia: Treatment of schizophrenia in adults and adolescents.
Bipolar disorder, mixed depressive episodes; Major depressive disorder (unipolar) with mixed features
Latuda may be confused with Lantus
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of cerebrovascular accidents (stroke) and a greater rate of cognitive decline and mortality in patients with dementia. Antipsychotics may be appropriate for schizophrenia, bipolar disorder, other mental health conditions or short-term use as antiemetic during chemotherapy but should be given in the lowest effective dose for the shortest duration possible. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2019]).
Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Compared to other antipsychotics, lurasidone is usually associated with a minimal to low risk for dyslipidemia in adults (data are too limited in pediatric patients), however, significant increased serum triglycerides and decreased HDL cholesterol have been observed in some trials (Ref). In addition, data from short-term and long-term trials (≥12 months) in adults suggest lurasidone may even lead to improvements in metabolic parameters in patients switched from certain antipsychotics associated with a high risk of metabolic syndrome to lurasidone (Ref).
Mechanism: The mechanism of antipsychotics effect on lipids is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; in general, metabolic alterations from antipsychotics (data do not include lurasidone) can develop in as short as 3 months after initiation (Ref).
Risk factors:
• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population primarily due to cardiovascular disease (Ref).
• Specific antipsychotic: Lurasidone is usually considered to have minimal to low risk for causing lipid abnormalities in adults (Ref).
Lurasidone is associated with extrapyramidal reaction (extrapyramidal symptoms [EPS]), also known as drug-induced movement disorders, in adult and pediatric patients. Antipsychotics can cause four main EPS: Acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia. Of these, akathisia and drug-induced parkinsonism are commonly associated with lurasidone, followed less frequently by dystonia and rarely by tardive dyskinesia (Ref). EPS presenting as dysphagia, esophageal dysmotility, or aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).
Mechanism:
EPS: Dose-related (Ref); due to antagonism of dopaminergic D2 receptors in nigrostriatal pathway (Ref).
Akathisia: Mechanism not completely understood, but possibly associated with an imbalance between the dopamine and serotonin/noradrenergic neurotransmitter system (Ref); however, since lurasidone displays strong antagonism at 5-HT2A receptors and is associated with akathisia, it has been suggested that the mechanism is multifactorial (Ref).
Tardive dyskinesia: Time-related (delayed); results from chronic exposure to D2 receptor-antagonists leading to up-regulation of these receptors over time (Ref). EPS-associated esophageal dysfunction has been attributed to drug-induced parkinsonism and tardive dyskinesia (Ref).
Onset:
Antipsychotics in general:
Dystonia: Rapid; in the majority of cases, dystonia occurs usually within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).
Parkinsonism: Varied; may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).
Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases, and within 3 months in 90% of cases (Ref).
Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine antagonist, and almost never before 3 months, with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization, and then a chronic waxing and waning of symptoms (Ref).
Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref)
Risk factors:
Antipsychotics in general:
EPS (in general):
• Prior history of EPS (Ref)
• Higher doses (Ref)
• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)
• Specific antipsychotic: Overall, lurasidone is associated with a moderate risk for EPS (Ref). Some data have observed a very high relative risk for akathisia (4.48) with lurasidone therapy (Ref).
Dystonia:
• Younger adult males (Ref)
Parkinsonism:
• Females (Ref)
• Older patients (Ref)
• Higher antipsychotic potency at antagonizing D2 receptors (Ref).
Akathisia:
• Higher antipsychotic dosages (Ref)
• Polypharmacy (Ref)
• Mood disorders (Ref)
• Females (Ref)
• Older patients (Ref)
Tardive dyskinesia:
• Age >55 years (Ref)
• Cognitive impairment (Ref)
• Concomitant treatment with anticholinergic medications (Ref)
• Diabetes (Ref)
• Diagnosis of schizophrenia or affective disorders (Ref)
• Females (Ref)
• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)
• History of extrapyramidal symptoms (Ref)
• Substance misuse or dependence (Ref)
• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Ref), newer studies have challenged this assertion (Ref).
Esophageal dysfunction (associated with EPS):
• Increasing age (≥40 years) (Ref)
Anemia, thrombocytopenia, leukopenia, and neutropenia have been reported rarely with lurasidone (Ref).
Mechanism: Dose-related (potentially) (Ref); mechanism is unclear (Ref).
Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure; however, the onset may be insidious (Ref). In case reports with lurasidone, anemia has been reported from 2 to 10 months after initiation of treatment (Ref).
Risk factors:
Antipsychotics in general:
• History of antipsychotic-induced neutropenia (Ref)
• Older adults (Ref)
• History of drug-induced leukopenia/neutropenia or low white blood cell count/absolute neutrophil count
Antipsychotics are associated with hyperglycemia in pediatric and adult patients, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Lurasidone is associated with a minimal to low risk of causing hyperglycemia and diabetes in adults (data are too limited in pediatric patients); however, significant increase in fasting plasma glucose, elevated glycosylated hemoglobin, and increase in serum insulin have been observed in some trials (Ref). In addition, data from short-term and long-term trials (≤12 months) in adults suggest lurasidone may even lead to improvements in metabolic parameters in patients switched from certain antipsychotics associated with a high risk of metabolic syndrome to lurasidone (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; new-onset diabetes has been observed within first 3 months to a median onset of 3.9 years with antipsychotics (data do not include lurasidone) (Ref).
Risk factors:
Antipsychotics in general:
• African American race (Ref)
• Males (Ref)
• Younger adults (Ref)
• Patients with preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)
• Exposure to other agents that also increase the risk of hyperglycemia (Ref)
• Specific antipsychotic: Lurasidone is usually considered to have a minimal to low risk for causing glycemic abnormalities in adults (Ref).
Lurasidone may cause mild to moderate, dose-dependent increased serum prolactin and, in some patients, hyperprolactinemia which may lead to gynecomastia, galactorrhea not associated with childbirth, amenorrhea, sexual disorder, acne, hirsutism, and infertility (Ref). Although long-term effects of antipsychotic-induced elevated prolactin levels have not been fully evaluated, some studies have also suggested a possible association between hyperprolactinemia and an increased risk for breast and/or pituitary tumors and osteopenia/osteoporosis in both men and women (Ref).
Mechanism: Dose-dependent; antagonism of dopamine D2 receptors in the tuberoinfundibular dopaminergic pathway which causes disinhibition of prolactin release resulting in hyperprolactinemia (Ref).
Onset: Varied; in general, onset of antipsychotic-induced hyperprolactinemia is typically within a few days or weeks following initiation or a dosage increase and usually persists throughout treatment (although partial tolerance may develop). Onset may also arise after long-term stable use (Ref).
Risk factors:
• Specific typical antipsychotic: Lurasidone is usually considered to have an intermediate effect on serum prolactin (Ref), although some authors consider it to have a low propensity for increasing serum prolactin or causing hyperprolactinemia (Ref)
• Higher doses, particularly in women of reproductive age and younger patients (Ref)
• Females, particularly of reproductive age (although both males and females are affected) (Ref)
Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature (Ref). In addition, an increased incidence of cerebrovascular effects (eg, cerebrovascular accident, transient ischemic attacks), including fatalities, have been reported in placebo-controlled trials (trials did not include lurasidone) in older adults with dementia-related psychosis (Ref). Of note, lurasidone is not approved for the treatment of dementia-related psychosis.
Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).
Risk factors:
Antipsychotics in general:
• Higher antipsychotic dosage (Ref)
• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)
• Older adults
All antipsychotics have been associated with neuroleptic malignant syndrome (NMS), although the incidence is less with second-generation (atypical) antipsychotics compared to first-generation (typical) antipsychotics (Ref). There are a few published case reports of NMS with lurasidone (Ref).
Mechanism: Non–dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).
Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). However, there are many cases of NMS occurring months after stable antipsychotic therapy (Ref).
Risk factors:
Antipsychotics in general:
• Males (twice as likely to develop NMS compared to females) (Ref)
• Dehydration (Ref)
• High-dose antipsychotic treatment (Ref)
• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)
• Catatonia (Ref)
• Polypharmacy (Ref)
• Pharmacokinetic interactions (Ref)
• IM administration (Ref)
• Rapid dosage escalation (Ref)
• Psychomotor agitation (Ref)
Sedating effects (eg, drowsiness) may occur in children, adolescents, and adults treated with lurasidone, and lead to nonadherence or discontinuation. Individual patient experience can vary depending on the person’s sensitivity toward sedation and the dose used. Sedation is typically transient with therapy (Ref).
Mechanism: Sedation: Dose-related (Ref); sedation from antipsychotics is believed to be due to H1 antagonism leading to potential CNS depressant effects; however, lurasidone displays little to no affinity for histamine H1 receptors suggesting a lower risk for sedation and CNS depressant effect (Ref).
Risk factors:
• Children and adolescents (Ref)
• Higher doses and concurrent use of somnolence-prone agents (Ref)
• Specific antipsychotic (lurasidone is generally considered to be mildly to moderately sedating at usual therapeutic doses in comparison with other antipsychotics) (Ref).
Antipsychotics may impair the body’s ability to regulate core body temperature, which may cause a potentially life-threatening heat stroke during predisposing conditions such as heat wave or strenuous exercise. Conversely, some antipsychotics have been associated with hypothermia; however, there are no published case reports with lurasidone to date (Ref).
Mechanism: Non–dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism may cause a decrease in body temperature. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect, by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref).
Risk factors:
Antipsychotics in general:
Heat stroke:
• Psychiatric illness (regardless of medication) (Ref)
• Strenuous exercise (Ref)
• Heat exposure (Ref)
• Dehydration (Ref)
• Concomitant medication possessing anticholinergic effects (Ref).
Hypothermia:
• In general, predisposing risk factors include advanced age, a cerebrovascular accident or preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis, benzodiazepine use, polypharmacy, alcohol intoxication, immobility, kidney, or liver failure (Ref)
• Schizophrenia (regardless of antipsychotic use) (Ref)
Antipsychotics are associated with weight gain, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class in adult and pediatric patients (Ref). Lurasidone is associated with a minimal to low risk of causing metabolic abnormalities and weight gain, but some short-term, placebo-controlled trials in adults have observed significant weight gain (increase of >7% from baseline) (Ref). However, some long-term (≤1 year) primarily observational data in adults has observed a decrease in weight, weight circumference, and/or BMI in lurasidone-treated patients (Ref). In addition, data from short-term and long-term trials (≤12 months) in adults suggest lurasidone may even lead to improvements in metabolic parameters in patients switched from certain antipsychotics associated with a high risk of metabolic syndrome to lurasidone (Ref).
Mechanism: Multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref). Of note, lurasidone exhibits weak affinity for 5-HT2C receptors (which is often implicated as a proposed mechanism) and no appreciable affinity for histamine H1 or muscarinic M1 receptors (Ref).
Risk factors:
Antipsychotics in general:
• Family history of obesity (Ref)
• Parental BMI (Ref)
• Children and adolescents (Ref)
• Rapid weight gain in the initial period: Younger age, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)
• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)
• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref)
• Specific antipsychotic: In adults, lurasidone is considered to have a minimal or low risk for weight gain (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Increase in fasting plasma glucose (2% to 13% (table 1)), increased serum cholesterol (6% to 14%), increased serum triglycerides (6% to 14%) (table 2)
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
6% |
4% |
Adults |
80 mg to 120 mg/day |
Bipolar depression |
141 |
141 |
Shift to fasting serum glucose ≥126 mg/dL |
|
2% |
4% |
Adults |
20 mg to 60 mg/day |
Bipolar depression |
138 |
141 |
Shift to fasting serum glucose ≥126 mg/dL |
|
13% |
8% |
Adults |
40 mg/day |
Schizophrenia |
449 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
12% |
8% |
Adults |
20 mg/day |
Schizophrenia |
60 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
10% |
8% |
Adults |
120 mg/day |
Schizophrenia |
260 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
7% |
8% |
Adults |
80 mg/day |
Schizophrenia |
472 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
6% |
8% |
Adults |
160 mg/day |
Schizophrenia |
108 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
10% |
5% |
Adults |
20 mg to 60 mg/day |
Bipolar depression |
119 |
126 |
Shift to triglycerides ≥200 mg/dL |
|
10% |
5% |
Adults |
80 mg to 120 mg/day |
Bipolar depression |
122 |
126 |
Shift to triglycerides ≥200 mg/dL |
|
14% |
10% |
Adults |
20 mg/day |
Schizophrenia |
49 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
11% |
10% |
Adults |
40 mg/day |
Schizophrenia |
379 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
11% |
10% |
Adults |
120 mg/day |
Schizophrenia |
209 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
7% |
10% |
Adults |
160 mg/day |
Schizophrenia |
100 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
6% |
10% |
Adults |
80 mg/day |
Schizophrenia |
400 |
526 |
Shift to triglycerides ≥200 mg/dL |
Gastrointestinal: Nausea (7% to 17%)
Infection: Viral infection (adolescents: 10% to 11%)
Nervous system: Akathisia (adolescents: 9%; adults: 6% to 22%), drowsiness (children and adolescents: 11% to 15%; adults: 7% to 26%) (table 3), extrapyramidal reaction (children and adolescents: 6% to 14%; adults: 5% to 39%), insomnia (5% to 11%), parkinsonism (adolescents: 4%; adults: 5% to 17%)
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
11% |
6% |
Children and adolescents |
20 mg to 80 mg/day |
Bipolar depression |
175 |
172 |
|
15% |
7% |
Adolescents |
40 mg/day |
Schizophrenia |
110 |
112 |
|
13% |
7% |
Adolescents |
80 mg/day |
Schizophrenia |
104 |
112 |
|
14% |
7% |
Adults |
80 mg to 120 mg/day |
Bipolar depression |
167 |
168 |
|
7% |
7% |
Adults |
20 mg to 60 mg/day |
Bipolar depression |
164 |
168 |
|
26% |
7% |
Adults |
120 mg/day |
Schizophrenia |
291 |
708 |
|
16% |
7% |
Adults |
40 mg/day |
Schizophrenia |
487 |
708 |
|
15% |
7% |
Adults |
20 mg/day |
Schizophrenia |
71 |
708 |
|
15% |
7% |
Adults |
80 mg/day |
Schizophrenia |
538 |
708 |
|
8% |
7% |
Adults |
160 mg/day |
Schizophrenia |
121 |
708 |
1% to 10%:
Cardiovascular: Hypertension (adults: ≥1%), orthostatic hypotension (≤3%), tachycardia (3%)
Dermatologic: Pruritus (adults: ≥1%), skin rash (≥1%)
Endocrine & metabolic: Increased serum prolactin (≥5 x ULN: females: ≤6%; males: ≤2%) (table 4), weight gain (2% to 7%) (table 5)
|
Drug (Lurasidone) |
Placebo |
Population |
Indication |
Comments |
|---|---|---|---|---|
|
0.5% |
1% |
Adolescents |
Schizophrenia |
≥5x ULN |
|
1% |
0% |
Adolescent females |
Schizophrenia |
≥5x ULN |
|
0% |
2% |
Adolescent males |
Schizophrenia |
≥5x ULN |
|
0.4% |
0% |
Adults |
Bipolar depression |
≥5x ULN |
|
3% |
1% |
Adults |
Schizophrenia |
≥5x ULN |
|
0.6% |
0% |
Adult females |
Bipolar depression |
≥5x ULN |
|
6% |
2% |
Adult females |
Schizophrenia |
≥5x ULN |
|
2% |
0.6% |
Adult males |
Schizophrenia |
≥5x ULN |
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
7% |
2% |
Children and adolescents |
20 mg to 80 mg/day |
Bipolar depression |
175 |
172 |
N/A |
|
4% |
5% |
Children and adolescents |
20 mg to 80 mg/day |
Bipolar depression |
N/A |
N/A |
≥7% increase in body weight |
|
3% |
5% |
Adolescents |
N/A |
Schizophrenia |
N/A |
N/A |
≥7% increase in body weight |
|
2% |
0.7% |
Adults |
N/A |
Bipolar depression |
N/A |
N/A |
≥7% increase in body weight |
|
5% |
3% |
Adults |
N/A |
Schizophrenia |
N/A |
N/A |
≥7% increase in body weight |
Gastrointestinal: Abdominal pain (children and adolescents: 3%; adults: ≥1%), decreased appetite (children and adolescents: 4%; adults: ≥1%), diarrhea (3% to 5%), dyspepsia (adults: 6% to 11%), sialorrhea (adults: 1% to 4%), upper abdominal pain (children and adolescents: 3%), vomiting (6% to 9%), xerostomia (adolescents and adults: 2% to 6%)
Genitourinary: Urinary tract infection (adults: 1% to 2%)
Infection: Influenza (adults: 2%)
Nervous system: Agitation (adults: 5% to 10%), anxiety (adults: 4% to 7%), dizziness (4% to 6%), dystonia (adolescents: ≤1%; adults: 2% to 7%), fatigue (children and adolescents: 3%), restlessness (adults: 2% to 3%)
Neuromuscular & skeletal: Back pain (adults: 3% to 4%), dyskinesia (adolescents: 1%), increased creatine phosphokinase in blood specimen (adults: ≥1%)
Ophthalmic: Blurred vision (adults: ≥1%)
Renal: Increased serum creatinine (2% to 7%)
Respiratory: Nasopharyngitis (adults: 4%), oropharyngeal pain (adolescents: ≤3%), rhinitis (adolescents: 8%)
<1%:
Cardiovascular: Angina pectoris, bradycardia, cerebrovascular accident, first degree atrioventricular block, syncope
Endocrine & metabolic: Amenorrhea, galactorrhea not associated with childbirth
Gastrointestinal: Gastritis
Genitourinary: Breast hypertrophy, dysmenorrhea, dysuria, erectile dysfunction, mastalgia, priapism
Hematologic & oncologic: Anemia
Hypersensitivity: Angioedema
Nervous system: Abnormal dreams, dysarthria, panic attack, psychomotor agitation, sleep disorder, vertigo
Neuromuscular & skeletal: Rhabdomyolysis
Renal: Renal failure syndrome
Frequency not defined: Nervous system: Suicidal ideation, suicidal tendencies, tardive dyskinesia
Postmarketing:
Cardiovascular: Pedal edema (Su 2021)
Dermatologic: Urticaria
Endocrine & metabolic: Decreased HDL cholesterol (Jena 2020), hyponatremia
Gastrointestinal: Hyperinsulinism (Jena 2020)
Hematologic & oncologic: Elevated glycosylated hemoglobin (Correll 2016), leukopenia (Rafi 2018), neutropenia (Sood 2017), thrombocytopenia (Rafi 2018)
Hypersensitivity: Tongue edema
Nervous system: Neuroleptic malignant syndrome (Lee 2017)
Respiratory: Dyspnea, pharyngeal edema
Hypersensitivity to lurasidone or any component of the formulation (including angioedema); concomitant use with strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil) and inducers (eg, rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine).
Concerns related to adverse effects:
• Altered cardiac conduction: Antipsychotics may alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics (Haddad 2002). Relative to other antipsychotics, lurasidone has minimal effects on the QTc interval and therefore, risk for arrhythmias is low.
• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.
• Orthostatic hypotension: May cause orthostatic hypotension and syncope; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of dehydration or hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (myocardial infarction, heart failure, or ischemic disease).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe cardiac disease, hemodynamic instability, prior myocardial infarction or ischemic heart disease.
• Hepatic impairment: Use with caution in patients with hepatic disease or impairment; dosage reduction is recommended in moderate to severe impairment.
• Renal impairment: Use with caution in patients with renal disease; dosage reduction is recommended in moderate to severe impairment.
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures or conditions that lower the seizure threshold such as Alzheimer disease. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Pediatric psychiatric disorders are frequently serious mental disorders which present with variable symptoms that do not always match adult diagnostic criteria. Conduct a thorough diagnostic evaluation and carefully consider risks of psychotropic medication before initiation in pediatric patients with schizophrenia or bipolar disorder. Medication therapy for pediatric patients with these disorders is indicated as part of a total treatment program that frequently includes educational, psychological, and social interventions. Long-term usefulness of lurasidone should be periodically reevaluated in patients receiving the drug for extended periods of time. Although other second-generation antipsychotics have shown efficacy in the management of autism, efficacy data for lurasidone is lacking (Loebel 2016; McClellan 2017); in a 6-week double-blind, placebo-controlled trial of 150 children and adolescents (age range: 6 to 17 years; n=49 lurasidone 20 mg treatment group, n=51 lurasidone 60 mg treatment group, and n=50 placebo), once daily lurasidone was not shown to be more effective than placebo in treatment of moderate to severe irritability associated with autistic disorder (Loebel 2016).
Substrate of BCRP/ABCG2, CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor therapy
Amphetamines: Antipsychotic Agents may enhance the adverse/toxic effect of Amphetamines. Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
Antipsychotic Agents: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of Lurasidone. Management: Decrease lurasidone dose 50% if adding atazanavir. Start lurasidone 20 mg daily and increase to no more than 80 mg daily in patients already taking atazanavir. Use of ritonavir- or cobicistat-boosted atazanavir with lurasidone is contraindicated. Risk D: Consider therapy modification
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Lurasidone. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lurasidone. Risk X: Avoid combination
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Lurasidone. Risk X: Avoid combination
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Itraconazole: May increase the serum concentration of Lurasidone. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Lurasidone. Risk X: Avoid combination
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Administration with food (≥350 calories) increased Cmax and AUC of lurasidone ~3 times and 2 times, respectively, compared to administration under fasting conditions. Lurasidone exposure was not affected by the fat content of the meal. Management: Administer with food (≥350 calories).
Lurasidone serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.
Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization. Lurasidone may cause hyperprolactinemia, which may decrease reproductive function in both males and females.
The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited and routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to a typical antipsychotic that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008).
Health care providers are encouraged to enroll women 18 to 45 years of age exposed to lurasidone during pregnancy in the Atypical Antipsychotics Pregnancy Registry (866-961-2388 or http://www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry).
It is not known if lurasidone is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother.
Should be taken with food (≥350 calories). Avoid grapefruit and grapefruit juice.
|
Frequency of Antipsychotic Monitoringa,b | ||
|---|---|---|
|
Monitoring parameter |
Frequency of monitoring |
Comments |
|
Adherence |
Every visit |
|
|
Blood chemistries (electrolytes, renal function, liver function, TSH) |
Annually |
|
|
CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia. |
|
Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high risk.c |
|
|
Fall risk |
Every visit |
|
|
Fasting plasma glucose/A1C |
12 weeks after initiation and dose change; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
|
Lipid panel |
12 weeks after initiation and dose change; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
|
Mental status and alertness |
Every visit |
|
|
Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease. |
|
Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function. |
|
Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high risk.d |
|
|
Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change. |
|
|
Weight/Height/BMI |
8 and 12 weeks after initiation and dose change; quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit. |
|
a For all monitoring parameters, it is appropriate to check at baseline and when clinically relevant (based on symptoms or suspected ADRs) in addition to the timeline. b ADA 2004b; APA [Keepers 2020]; de Hert 2011; Gugger 2011; manufacturer’s labeling. c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. d Risk factors for tardive dyskinesia include >55 years of age, female sex, White or African ethnicity, presence of a mood disorder, intellectual disability, CNS injury, or past or current EPS. | ||
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 15 to 40 ng/mL (SI: 30.45 to 81.2 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations; however, therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 120 ng/mL (SI: 243.6 nmol/L) (Hiemke 2018).
Lurasidone is a benzoisothiazol-derivative atypical antipsychotic with mixed serotonin-dopamine antagonist activity. It exhibits high affinity for D2, 5-HT2A, and 5-HT7 receptors; moderate affinity for alpha2C-adrenergic receptors; and is a partial agonist for 5-HT1A receptors. Lurasidone has no significant affinity for muscarinic M1 and histamine H1 receptors. The addition of serotonin antagonism to dopamine antagonism (classic neuroleptic mechanism) is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects as compared to typical antipsychotics (Huttunen 1995).
Note: Lurasidone exposure in pediatric patients 10 to 17 years was observed to be generally similar to adult data.
Onset of action:
Bipolar disorder, depressive episode: Initial effects may be observed within 1 week of treatment with continued improvements through 6 weeks (Cruz 2010).
Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption: Increased in fed state.
Distribution: Vd: 6,173 L.
Protein binding: ~99%.
Metabolism: Primarily via CYP3A4; two active metabolites (ID-14283 and ID-14326) and two major nonactive metabolites (ID-20219 and ID-20220) produced.
Bioavailability: 9% to 19%.
Half-life elimination: 18 to 40 hours; Main active metabolite, ID-14283 (exo-hydroxy metabolite), exhibits a half-life of 7.5 to 10 hours (Citrome 2011).
Time to peak: 1 to 3 hours; steady state concentrations achieved within 7 days.
Excretion: Urine (~9%); feces (~80%).
Altered kidney function: In patients with mild, moderate, or severe renal impairment, mean Cmax increased by 40%, 92%, and 54%, respectively, and mean AUC0-∞ increased by 53%, 91%, and 2 times, respectively, compared with healthy matched subjects (Citrome 2011).
Hepatic function impairment: Mean AUC0-last was 1.5 times higher in subjects with mild hepatic impairment (Child-Pugh class A), 1.7 times higher in subjects with moderate hepatic impairment (Child-Pugh class B), and 3 times higher in subjects with severe hepatic impairment (Child-Pugh class C) compared with the values for healthy matched subjects. Mean Cmax was 1.3, 1.2, and 1.3 times higher for patients with mild, moderate, and severe hepatic impairment, respectively, compared with the values for healthy matched subjects (Citrome 2011).
Tablets (Latuda Oral)
20 mg (per each): $56.75
40 mg (per each): $56.75
60 mg (per each): $56.75
80 mg (per each): $56.75
120 mg (per each): $84.71
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