(loo RAS i done)
Psychiatric issues: Treatment of schizophrenia; monotherapy or adjunctive therapy of depressive episodes associated with bipolar I disorder
Hypersensitivity to lurasidone or any component of the formulation; concomitant use with strong CYP3A4 inhibitors (eg, ketoconazole) and inducers (eg, rifampin)
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.
Suicidality and antidepressant drugs:Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years; there was a reduction in risk with antidepressant use in patients 65 years and older.
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the health care provider.
Depressive episodes associated with bipolar I disorder (monotherapy or as an adjunct to lithium or valproic acid): Oral: Initial: 20 mg once daily; titration is not required; maximum recommended dose: 120 mg daily. Note: Doses ≥80 mg daily during monotherapy studies did not provide additional efficacy compared to lower doses (eg, 20-60 mg daily).
Schizophrenia: Oral: Initial: 40 mg once daily; titration is not required; maximum recommended dose: 160 mg daily
Concomitant CYP3A4 inhibitors/inducers:
CYP3A4 inhibitors:
Concomitant administration with a strong CYP3A4 inhibitor (eg, ketoconazole) is contraindicated.
Concomitant administration with a moderate CYP3A4 inhibitor (eg, diltiazem):
US labeling: Initial dose: 20 mg once daily; do not exceed 80 mg daily of lurasidone
Canadian labeling: Do not exceed 40 mg daily of lurasidone
CYP3A4 inducers:
Concomitant administration with a strong CYP3A4 inducer (eg, rifampin) is contraindicated.
Concomitant administration with a moderate CYP3A4 inducer: Lurasidone dose may need to be increased when combined with a moderate CYP3A4 inducer for ≥7 days.
Refer to adult dosing.
US labeling:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Initial: 20 mg daily; maximum: 80 mg daily
Canadian labeling:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Maximum: 40 mg daily
US labeling:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 20 mg daily; maximum: 80 mg daily
Severe impairment (Child-Pugh class C): Initial: 20 mg daily; maximum: 40 mg daily
Canadian labeling:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate and severe impairment (Child-Pugh class B and C): Maximum: 40 mg daily
Administer with food ( ≥350 calories).
Should be taken with food ( ≥350 calories).
Store at controlled room temperature of 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
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
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
Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. 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 using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Lurasidone. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lurasidone. Management: U.S. labeling: start at 20 mg/day and limit to max of 80 mg/day with moderate CYP3A4 inhibitor. Canadian labeling: limit to max of 40 mg/day with moderate CYP3A4 inhibitor; avoid concomitant 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. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Dimethindene: 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 (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
EPINEPHrine (Systemic): May enhance the hypotensive effect of Lurasidone. Avoid combination
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Grapefruit Juice: May increase the serum concentration of Lurasidone. Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. 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
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. 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: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. 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
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. 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 [INT]: Antipsychotic Agents may diminish the therapeutic effect of Piribedil [INT]. Piribedil [INT] 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
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
St Johns Wort: May decrease the serum concentration of Lurasidone. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy
Tetrahydrocannabinol: 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. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification
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).
Frequencies reported for schizophrenia unless otherwise noted.
10%:
Central nervous system: Drowsiness (dose-related: 8% to 27%; depressive episodes, monotherapy: 11%), extrapyramidal reaction (dose-related: 14% to 26%; depressive episodes, monotherapy: 7%), akathisia (dose-related: 6% to 22%; depressive episodes, monotherapy: 8% to 11%), parkinsonian-like syndrome (6% to 17%; depressive episodes, monotherapy: 8%)
Endocrine & metabolic: Increased serum triglycerides (10% to 14%), increased serum glucose (fasting, 10% to 14%), increased serum cholesterol (6% to 14%)
Gastrointestinal: Nausea (dose-related; 10%; depressive episodes, monotherapy: 14%)
1% to 10%:
Cardiovascular: Orthostatic hypotension (1% to 2%), tachycardia
Central nervous system: Insomnia (10%), agitation (5%), anxiety (5%; depressive episodes, monotherapy: 4%), dizziness (4%), dystonia ( ≤7%; depressive episodes, monotherapy: ≤2%), restlessness (1% to 3%)
Dermatologic: Pruritus, skin rash
Endocrine & metabolic: Increased serum prolactin ( ≥5 x ULN: females: 8%; males: ≤2%), weight gain ( ≥7% increase in baseline body weight: 2% to 6%)
Gastrointestinal: Vomiting (8%; depressive episodes, monotherapy: 4%), dyspepsia (6%), xerostomia (depressive episodes, monotherapy: 5%), diarrhea ( ≥1%; depressive episodes, monotherapy: 4%), sialorrhea (2%), abdominal pain, decreased appetite
Genitourinary: Urinary tract infection (depressive episodes, monotherapy: 2%)
Infection: Influenza (depressive episodes, monotherapy: 2%)
Neuromuscular & skeletal: Back pain (3%; depressive episodes, monotherapy: 2%), increased creatine phosphokinase
Ophthalmic: Blurred vision
Renal: Increased serum creatinine (3% to 7%; depressive episodes, monotherapy: 2% to 4%)
Respiratory: Nasopharyngitis (depressive episodes, monotherapy: 4%)
<1% (Limited to important or life-threatening): Amenorrhea, anemia, angina pectoris, angioedema, atrioventricular block, breast hypertrophy, cerebrovascular accident, gastritis, dysmenorrhea, erectile dysfunction, galactorrhea, hypomania, leukopenia, mania, neuroleptic malignant syndrome, panic attack, renal failure, rhabdomyolysis, seizure, suicidal ideation, tardive dyskinesia, venous thromboembolism
In patients with mild, moderate, or severe renal impairment, mean Cmax increased by 40%, 92%, and 54%, respectively, and mean AUC0- ¢ ˆ ž increased by 53%, 91%, and 2 times, respectively, compared with healthy matched subjects.
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.
Mean AUC was 18% higher in women than in men, and correspondingly, the apparent oral clearance was lower in women. Mean Cmax was similar between women and men.
Major psychiatric warnings:
- Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder and other psychiatric disorders; consider risk prior to prescribing. Lurasidone is not approved in the US for use in children. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. [US Boxed Warning]: Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patients family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare 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. Patients treated with antidepressants (for any indication) should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes (increases or decreases). 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. Relative to other antipsychotics, lurasidone has minimal effects on the QTc interval and therefore, risk for arrhythmias is low. However, Canadian labeling recommends avoiding use of lurasidone in patients with a history of cardiac arrhythmias, situations that may increase the risk of torsade de pointes and/or sudden death due to QT prolongation including bradycardia, congenital QT prolongation, electrolyte disturbances (ie, hypokalemia or hypomagnesemia), or in combination with other QTc-prolonging agents.
- 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, pre-existing 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 <1000/mm3.
- Cerebrovascular effects: An increased incidence of cerebrovascular effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of antipsychotics for the unapproved use in elderly patients with dementia-related psychosis.
- Dyslipidemia: Increases in total cholesterol and triglyceride concentrations have been observed with atypical antipsychotic use; during clinical trials of lurasidone, there were no significant changes in total cholesterol or triglycerides observed.
- Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (eg, Alzheimer's disease).
- Extrapyramidal symptoms (EPS): May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (potentially irreversible). Risk of tardive dyskinesia may be increased in elderly patients, particularly elderly women. Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients.
- Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. 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 (NMS): Use may be associated with neuroleptic malignant syndrome; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson's disease or Lewy body dementia).
- Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (MI, heart failure, or ischemic disease).
- Sedation: Low to moderately sedating, use with caution in disorders where CNS depression is a feature; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
- 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.
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 compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. 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.
- Parkinson's disease: Use with caution in patients with Parkinson's disease.
- 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, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
B
Adverse events were not observed in animal reproduction studies. 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).
Healthcare providers are encouraged to enroll women 18-45 years of age exposed to lurasidone during pregnancy in the Atypical Antipsychotics Pregnancy Registry (866-961-2388 or http://www.womensmentalhealth.org/pregnancyregistry).
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.
Vd: 6173 L
Primarily via CYP3A4; two active metabolites (ID-14283 and ID-14326) and two major nonactive metabolites (ID-20219 and ID-20220) produced
Urine (~9%); feces (~80%)
1-3 hours; steady state concentrations achieved within 7 days
18 hours; Main active metabolite, ID-14283 (exo-hydroxy metabolite), exhibits a half-life of 7.5-10 hours
~99%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, restlessness, nausea, vomiting, insomnia, diarrhea, dry mouth, loss of strength and energy, or weight gain. Have patient report immediately to prescriber signs of infection, signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), severe dizziness, passing out, tachycardia, bradycardia, arrhythmia, behavioral changes, tremors, abnormal movements, rigidity, enlarged breasts, nipple discharge, sexual dysfunction, amenorrhea, drooling, difficulty focusing, seizures, dysphagia, difficulty speaking, angina, coughing up blood, shortness of breath, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot), or signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.