Dosing & Uses
Dosage Forms & Strengths
tablet
- 20mg
- 40mg
- 60mg
- 80mg
- 120mg
Schizophrenia
Indicated for schizophrenia
40 mg PO qDay initially; not to exceed 160 mg/day
Initial dose titration is not required; shown to be effective in a dose range of 40-160 mg/day
Bipolar Depression
Monotherapy
- Indicated as monotherapy for adults with major depressive episode associated with bipolar I disorder (bipolar depression)
- 20 mg PO qDay initially; may increase dose if needed, not to exceed 120 mg/day
- In monotherapy study, higher dose range (80-120 mg/day) did not provide additional efficacy compared to the lower dose range (20-60 mg/day)
Adjunctive therapy
- Indicated as adjunctive therapy for major depressive episodes associated with bipolar I disorder with lithium or valproate
- 20 mg PO qDay initially; may increase dose if needed, not to exceed 120 mg/day
Dosage Modifications
CYP3A4 inhibitors or inducers
- Coadministration with CYP3A4 inhibitors
- Strong CYP3A4 inhibitor: Contraindicated; do not coadminister (see Contraindications)
- Moderate CYP3A4 inhibitor (eg, diltiazem, atazanavir, erythromycin, fluconazole, verapamil): Reduce dose to 50% of original dose, not to exceed 80 mg/day; starting dose is 20 mg/day
- Grapefruit and grapefruit juice: Avoid coadministration
- Coadministration with CYP3A4 inducers
- Strong CYP3A4 inducer: Contraindicated; do not coadminister (see Contraindications)
- Moderate CYP3A4 inducer (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin): It may be necessary to increase lurasidone dose after chronic treatment (ie, ≥7 days) with the inducer
Renal impairment
- Mild (CrCl ≥50 mL/min): No dosage adjustment required
- Moderate-to-severe (CrCl <50 mL/min): 20 mg/day initially; not to exceed 80 mg/day
Hepatic impairment
- Mild (Child-Pugh class A): No dosage adjustment necessary
- Moderate (Child-Pugh class B [Score 7-9]): 20 mg/day initially; not to exceed 80 mg/day
- Severe (Child-Pugh class C [Score 10-15]): 20 mg/day initially; not to exceed 40 mg/day
Dosing Considerations
Effectiveness for longer-term use (ie, >6 weeks) has not been established in controlled studies; therefore, the physician who elects to use lurasidone for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient
Dosage Forms & Strengths
tablet
- 20mg
- 40mg
- 60mg
- 80mg
- 120mg
Schizophrenia
Indicated for treatment of schizophrenia in adolescents aged 13-17 years
<13 years: Safety and efficacy not established
13-17 years
- Starting dose: 40 mg PO qDay; initial dose titration is not required
- Effective dosage range: 40-80 mg/day; not to exceed 80 mg/day
Bipolar Depression
Indicated as monotherapy for major depressive episode associated with bipolar I disorder (bipolar depression) in adolescents aged 10-17 yr
20 mg PO qDay; initial dose titration is not required
May increase dose after 1 week based on clinical response; not to exceed 80 mg qDay Effective dose range is 20-80 mg/day
Clinical studies found most patients (67%) received 20-40 mg/day
Dosage Modifications
CYP3A4 inhibitors or inducers
- Coadministration with CYP3A4 inhibitors
- Strong CYP3A4 inhibitor: Contraindicated; do not coadminister (see Contraindications)
- Moderate CYP3A4 inhibitor (eg, diltiazem, atazanavir, erythromycin, fluconazole, verapamil): Reduce dose to 50% of original dose, not to exceed 80 mg/day; starting dose is 20 mg/day
- Grapefruit and grapefruit juice: Avoid coadministration
- Coadministration with CYP3A4 inducers
- Strong CYP3A4 inducer: Contraindicated; do not coadminister (see Contraindications)
- Moderate CYP3A4 inducer (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin): It may be necessary to increase lurasidone dose after chronic treatment (ie, ≥7 days) with the inducer
Renal impairment
- Mild (CrCl ≥50 mL/min): No dosage adjustment required
- Moderate-to-severe (CrCl <50 mL/min): 20 mg/day initially; not to exceed 80 mg/day
Hepatic impairment
- Mild (Child-Pugh class A): No dosage adjustment necessary
- Moderate (Child-Pugh class B [Score 7-9]): 20 mg/day initially; not to exceed 80 mg/day
- Severe (Child-Pugh class C [Score 10-15]): 20 mg/day initially; not to exceed 40 mg/day
Dosing Considerations
Effectiveness for longer-term use (ie, >6 weeks) has not been established in controlled studies; therefore, the physician who elects to use lurasidone for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Somnolence, dose related (15-26%)
Akathisia, dose related (6-22%)
Extrapyramidal disorder, dose related (6-22%)
Parkinsonism, dose related (6-17%)
Fasting glucose increased, dose related (10-14%)
Nausea, dose related (9-13%)
Insomnia, dose-related (7-11%)
1-10%
Agitation, dose related (3-10%)
Vomiting, dose related (6-8%)
Dyspepsia, dose related (5-8%)
Anxiety, dose related (3-8%)
Elevated serum creatinine, dose related (1-7.2%)
Dystonia (5%)
Dizziness, dose related (4-6%)
Fatigue (4%)
Back pain, dose related (2-4%)
Restlessness (3%)
Salivary hypersecretion, dose related (1-4%)
Hypertension
Rash
Pruritus
CPK increased
Abdominal pain
Diarrhea
Blurred vision
Tachycardia
<1%
Anemia
AV block 1st degree
Angina pectoris
Bradycardia
Vertigo
Gastritis
Rhabdomyolysis
Cerebrovascular accident
Dysarthria
Abnormal dreams
Panic attack
Sleep disorder
Dysuria
Renal failure
Amenorrhea
Dysmenorrhea
Breast enlargement
Breast pain
Galactorrhea
Erectile dysfunction
Angioedema
Postmarketing Reports
Hypersensitivity (urticaria, throat swelling, tongue swelling, and dyspnea)
Hyponatremia
Warnings
Black Box Warnings
Increased mortality in elderly patients with dementia-related psychosis
- Not indicated for dementia-related psychosis
- 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; placebo-controlled trials with other atypical antipsychotics showed higher incidence of cerebrovascular adverse reactions (eg, CVA, TIA), including fatalities, compared with placebo
Suicidal thoughts and behaviors
- Antidepressants increased the risk of suicidal thoughts and behavior in children and young adults in short-term studies; closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors
Contraindications
Hypersensitivity
Coadministration with strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil)
Coadministration with strong CYP3A4 inducers (eg, rifampin, St. John’s wort, phenytoin, carbamazepine)
Cautions
Possibility of suicide attempt inherent to psychotic illness; close supervision required when therapy is initiated, dosage is changed, or drug is discontinued; the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use (eg, >4 months) is unknown; there is substantial evidence from placebo-controlled maintenance studies in adults with MDD that antidepressants delay the recurrence of depression
Antidepressant treatment can increase the risk of developing a manic or hypomanic episode, particularly in patients with bipolar disorder
Patients with Parkinson’s disease or dementia with Lewy bodies are reported to have an increased sensitivity to antipsychotic medication
Orthostatic hypotension and syncope reported, possibly due to its alpha-1receptor antagonism
Risk of neuroleptic malignant syndrome (NMS) reported in association with administration of antipsychotic drugs, including lurasidone; clinical manifestations of NMS (eg, hyperpyrexia, muscle rigidity, altered mental status, evidence of autonomic instability); additional symptoms (eg, elevated creatine phosphokinase, myoglobinuria [rhabdomyolysis], acute renal failure); the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment; if NMS is suspected, immediately discontinue therapy and provide intensive symptomatic treatment and monitoring
Hyperprolactinemia reported; galactorrhea, amenorrhea, gynecomastia, and impotence reported with prolactin-elevating compounds; long-standing hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone density in both female and male patients
Exercise caution in patients with a history of seizures or with conditions that lower the seizure threshold (eg, Alzheimer’s dementia); conditions that lower the seizure threshold may be more prevalent in patients ≥65 years
May cause leukopenia, neutropenia, and agranulocytosis; monitor patients with neutropenia should for fever or other signs of infection and treat promptly if symptoms occur; discontinue treatment in patients with severe neutropenia (ANC <1,000/mm³) and follow WBC until recovery
May disrupt body temperature regulation
May lead to cognitive and motor impairment; caution patients about operating hazardous machinery
Incidence of cerebrovascular effects (eg, transient ischemic attacks, stroke) may increase
Esophageal dysmotility or aspiration may occur
May increase QT interval: In trials, increase in baseline adjusted QTc intervals did not exceed mean based on individual correction method (QTcI) was 7.5 ms (120-mg dose) and 4.6 ms (600-mg dose) observed at 2-4 hours after dosing; additionally, in separate trial, QTc did not increase by >60 msec from baseline or exceed 500 msec with supratherapeutic doses (ie, 120 mg/day, 600 mg/day)
Acute overdose: If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry theoretical hazard of additive QT-prolonging effects when given to patient with acute lurasidone overdose
Motor instability, somnolence, and orthostatic hypotension reported, which may lead to falls and, consequently, fractures or other fall-related injuries; assess risk of falls when initiating treatment and recurrently for patients receiving repeated doses, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects
Metabolic changes with atypical antipsychotic use
- Hyperglycemia, some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, reported; monitor glucose control in patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics
- Monitor symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia, weakness)
- In the 6-week, placebo-controlled study of pediatric patients with bipolar depression, mean change in fasting glucose was +1.6 mg/dL for lurasidone 20-80 mg/day
- Undesirable alterations in lipids observed
- Weight gain observed; clinically monitor weight
Tardive dyskinesia
- Extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia may occur; risk of tardive dyskinesia may increase in the elderly; risk of dystonia may increase with high doses
- Risk of developing tardive dyskinesia and likelihood of it becoming irreversible may increase as the duration of treatment and total cumulative dose of antipsychotic drugs administered to the patient increase
Drug interactions overview
- Coadministration with strong (eg, ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil) and moderate CYP3A4 inhibitors increased exposure of lurasidone (see Dosage Modifications, Contraindications)
- Coadministration with strong (eg, rifampin, avasimibe, St. John’s wort, phenytoin, carbamazepine) and moderate CYP3A4 inducers decreased exposure of lurasidone (see Dosage Modifications, Contraindications)
Pregnancy & Lactation
Pregnancy
Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for extrapyramidal symptoms (EPS) and/or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lurasidone during pregnancy
National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-andresearchprograms/pregnancyregistry
Lactation
Unknown whether drug is distributed in breast milk
Lurasidone is present in rat milk
Consider development and health benefits of breastfeeding along with mother’s clinical need for drug and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Atypical antipsychotic; precise mechanism is unknown; efficacy suggested to involve mediation of central dopamine type 2 and serotonin type 2 (5HT-2A) receptor antagonism
Absorption
Bioavailability: 9-19%
Peak plasma time: 1-3 hr
Mean peak plasma concentrations and AUC were ~3x and 2x when administered with food compared to levels observed under fasting conditions
Distribution
Protein bound: 99%
Vd: 6173 L
Metabolism
Metabolized by CYP3A4; biotransformation pathways are oxidative N-dealkylation, hydroxylation of norbornane ring, and S-oxidation
Metabolites: 2 active (ID-14283, ID-14326) and 2 inactive (ID-20219, ID-20220)
Elimination
Half-life: 18 hr
Clearance: 3902 mL/min
Excretion: Feces (80%), urine (9%)
Administration
Oral Administration
Take with food (at least 350 calories)
Food substantially increases absorption; increases AUC ~2-fold and Cmax ~3-fold
Initial dose titration not required
Storage
Tablets: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
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Patient Handout
Formulary
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