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Lurasidone

Medically reviewed by Drugs.com. Last updated on July 30, 2020.

Pronunciation

(loo RAS i done)

Index Terms

  • Lurasidone HCl
  • Lurasidone Hydrochloride
  • SM-13496

Dosage Forms

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 aluminum lake]

Latuda: 120 mg

Brand Names: U.S.

  • Latuda

Pharmacologic Category

  • Second Generation (Atypical) Antipsychotic

Pharmacology

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).

Absorption

Increased in fed state.

Distribution

Vd: 6,173 L

Metabolism

Primarily via CYP3A4; two active metabolites (ID-14283 and ID-14326) and two major nonactive metabolites (ID-20219 and ID-20220) produced

Excretion

Urine (~9%); feces (~80%)

Time to Peak

1 to 3 hours; steady state concentrations achieved within 7 days

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)

Protein Binding

~99%

Special Populations: Renal Function Impairment

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).

Special Populations: 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).

Use: Labeled Indications

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.

Off Label Uses

Major depressive disorder (unipolar) with mixed features

Data from a randomized, double-blind, placebo-controlled study support the use of lurasidone in the treatment of major depressive disorder (MDD) with mixed features (hypomanic symptoms) [Suppes 2016]. Post hoc analyses of this study suggest that lurasidone might be particularly effective in patients with MDD with mixed features who present with significant irritability or moderate to severe anxiety [Swann 2017], [Tsai 2017].

Contraindications

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).

Dosing: Adult

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 (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; Shelton 2020; 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 2020; Tandon 2016).

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: Gradual dose reduction is advised to avoid withdrawal symptoms (ie, insomnia, headache, GI symptoms) unless discontinuation is due to significant adverse effects. In general, when discontinuing antipsychotic therapy for a chronic psychiatric disorder (eg, schizophrenia, bipolar disorder), decreasing the dose very gradually over weeks to months (eg, reducing the dose by 10% per month) with close monitoring is suggested to allow for detection of prodromal symptoms of disease recurrence (APA [Lehman 2004]; CPA 2005).

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 (Post 2020; Stroup 2020).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Bipolar depression:

Children ≥10 years and Adolescents ≤17 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; maximum recommended daily dose: 80 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).

Administration

Oral: Administer consistently at the same time every day with food (≥350 calories). Evening administration may help reduce adverse effects (Shelton 2020).

Dietary Considerations

Should be taken with food (≥350 calories). Avoid grapefruit and grapefruit juice.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome may be increased. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. 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). Consider therapy modification

Atazanavir: May increase the serum concentration of Lurasidone. Management: Atazanavir labeling recommends reducing the lurasidone dose as directed by the lurasidone labeling for moderate CYP3A4 inhibitors when used together with lurasidone. Consider therapy modification

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Monitor therapy

Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Avoid combination

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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. Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Lurasidone. 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. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lurasidone. Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Disopyramide: Lurasidone may enhance the QTc-prolonging effect of Disopyramide. Management: Consider alternatives to disopyramide in patients with acute lurasidone overdose. If disopyramide treatment cannot be avoided, monitor for excessive QTc interval prolongation. Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

DOPamine: May enhance the hypotensive effect of Lurasidone. Avoid combination

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. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

EPINEPHrine (Systemic): May enhance the hypotensive effect of Lurasidone. Avoid combination

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

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. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Grapefruit Juice: May increase the serum concentration of Lurasidone. Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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. 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. 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. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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. 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. Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

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. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. 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 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. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. 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. Avoid combination

Procainamide: Lurasidone may enhance the QTc-prolonging effect of Procainamide. Management: Consider alternatives to procainamide in patients with acute lurasidone overdose. If procainamide treatment cannot be avoided, monitor for excessive QTc interval prolongation. Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

QuiNIDine: Lurasidone may enhance the QTc-prolonging effect of QuiNIDine. Management: Consider alternatives to quinidine in patients with acute lurasidone overdose. If quinidine treatment cannot be avoided, monitor for excessive QTc interval prolongation. Consider therapy modification

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

St John's Wort: May decrease the serum concentration of Lurasidone. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. 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. Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Endocrine & metabolic: Increased serum triglycerides (10% to 14%), increased serum cholesterol (6% to 14%), increased serum glucose (6% to 13%; fasting)

Gastrointestinal: Nausea (7% to 17%)

Infection: Viral infection (adolescents: 10% to 11%)

Nervous system: Extrapyramidal reaction (adults: 5% to 39%; children and adolescents: 6% to 14%), drowsiness (adults: 8% to 26%; children and adolescents: 11% to 15%), akathisia (adults: 6% to 22%; adolescents: 9%), parkinsonian-like syndrome (adults: 5% to 17%; adolescents: 4%), insomnia (5% to 11%)

1% to 10%:

Cardiovascular: Tachycardia (3%), orthostatic hypotension (≤3%), hypertension (adults: ≥1%)

Dermatologic: Pruritus (adults: ≥1%), skin rash (≥1%)

Endocrine & metabolic: Weight gain (2% to 7%), increased serum prolactin (≥5 x ULN: females: ≤6%; males: ≤2%)

Gastrointestinal: Dyspepsia (adults: 6% to 11%), vomiting (6% to 9%), xerostomia (adolescents and adults: 2% to 6%), diarrhea (3% to 5%), decreased appetite (children and adolescents: 4%; adults: ≥1%), sialorrhea (adults: 1% to 4%), abdominal pain (children and adolescents: 3%; adults: ≥1%), upper abdominal pain (children and adolescents: 3%)

Genitourinary: Urinary tract infection (adults: 1% to 2%)

Infection: Influenza (adults: 2%)

Nervous system: Agitation (adults: 5% to 10%), anxiety (adults: 4% to 7%), dystonia (adults: 2% to 7%; adolescents: ≤1%), dizziness (4% to 6%), fatigue (children and adolescents: 3%), restlessness (adults: 2% to 3%)

Neuromuscular & skeletal: Back pain (adults: 3% to 4%), increased creatine phosphokinase in blood specimen (adults: ≥1%), dyskinesia (adolescents: 1%)

Ophthalmic: Blurred vision (adults: ≥1%)

Renal: Increased serum creatinine (2% to 7%)

Respiratory: Rhinitis (adolescents: 8%), nasopharyngitis (adults: 4%), oropharyngeal pain (adolescents: ≤3%)

Frequency not defined: Nervous system: Suicidal ideation, suicidal tendencies, tardive dyskinesia

<1%, postmarketing, and/or case reports: Abnormal dreams, amenorrhea, anemia, angina pectoris, angioedema, bradycardia, breast hypertrophy, cerebrovascular accident, dysarthria, dysmenorrhea, dyspnea, dysuria, erectile dysfunction, first-degree atrioventricular block, galactorrhea, gastritis, hyponatremia, mastalgia, neuroleptic malignant syndrome, panic attack, pharyngeal edema, priapism, psychomotor agitation, renal failure syndrome, rhabdomyolysis, sleep disorder, syncope, tongue edema, urticaria, vertigo

ALERT: U.S. Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Lurasidone is not approved for the treatment of patients with dementia-related psychosis.

Suicidal thoughts and behaviors:

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.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies; consider risk prior to prescribing. Closely monitor all antidepressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription.

- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

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.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Dyslipidemia: Increases in total cholesterol and triglyceride concentrations have been observed with atypical antipsychotic use; incidence varies with product. During clinical trials of lurasidone, there were no significant changes in total cholesterol or triglycerides observed. Compared to other antipsychotics, the risk of metabolic side effects like dyslipidemia with lurasidone is minimal to low (Solmi 2017).

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Incidence varies with product; compared to other antipsychotics, the risk of metabolic side effects like hyperglycemia with lurasidone is minimal to low (Solmi 2017). Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control.

• Hyperprolactinemia: Use is associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson disease or Lewy body dementia) (McKeith 2002). If NMS is suspected, discontinue lurasidone and initiate symptomatic treatment and monitoring.

• 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).

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI (ADA 2004; Lehman 2004; Marder 2004). Compared to other antipsychotics, the risk of weight gain with lurasidone is minimal to low (Solmi 2017).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiac disease, hemodynamic instability, prior myocardial infarction or ischemic heart disease.

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. (APA [Reus 2016]). Lurasidone is not approved for the treatment of dementia-related psychosis.

• 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, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA 2005; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia); electrolytes, renal and liver function (annually and as clinically indicated); personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease (baseline; repeat annually); fasting plasma glucose level/HbA1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal repeat at 2- to 5-year intervals or more frequently if clinically indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; Lehman 2004; Marder 2004); fall risk (baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk).

Pregnancy Considerations

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).

Patient Education

What is this drug used for?

• It is used to treat schizophrenia.

• It is used to treat low mood (depression) in people with bipolar disorder.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Runny nose

• Nausea

• Vomiting

• Trouble sleeping

• Anxiety

• Diarrhea

• Dry mouth

• Loss of strength and energy

• Weight gain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.

• Agitation

• Panic attacks

• Mood changes

• Behavioral changes

• Severe dizziness

• Passing out

• Fast heartbeat

• Slow heartbeat

• Abnormal heartbeat

• Tremors

• Abnormal movements

• Stiff muscles

• Enlarged breasts

• Nipple discharge

• Sexual dysfunction

• No menstrual periods

• Drooling

• Trouble focusing

• Seizures

• Trouble swallowing

• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot.

• Tardive dyskinesia like unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; or puffing cheeks.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions