Lurasidone

Lurasidone is an Antipsychotic agent belonging to Serotonin-dopamine antagonist class.

Lurasidone is an atypical antipsychotic used to treat schizophrenia and depressive episodes associated with bipolar I disorder.

Lurasidone is readily absorbed and quickly reaches maximal concentrations (Cmax) within 1-4 hours. When taken with food, there is a two-fold increase in exposure and time to maximal concentration is increased by 0.5-1.5 hours. Lurasidone has Volume of distribution of about 6,173 L. Lurasidone is metabolized by CYP3A4 in which its major active metabolite is referred to as ID-14283 (25% of parent exposure). Its two non-active metabolites are referred to as ID-20219 and ID-20220.It is excreted in Urine (9%) and 80% in feces.

Lurasidone shows side effects like Dizziness, feeling unsteady, or having trouble keeping your balance, anxiety, weakness, tiredness, restlessness, uncontrollable shaking of a part of the body, slow movements or shuffling walk, nausea, vomiting, etc.

Lurasidone is available in the form of Oral Tablets.

Lurasidone is available in India, US, Italy, Canada, UK, Switzerland, Denmark, Thailand, and Singapore.

Lurasidone belongs to Serotonin-dopamine antagonist class and acts as Antipsychotic Agent.

Lurasidone is an atypical antipsychotic that is D2 and 5-HT2A (mixed serotonin and dopamine activity) to improve cognition. It is thought that antagonism of serotonin receptors can improve negative symptoms of psychoses and reduce the extrapyramidal side effects that are often associated with typical antipsychotics.

The Onset of action of Lurasidone is not clinically established.

The Time to peak plasma concentration of Lurasidone is approximately 1 to 3 hours.

Lurasidone is available in the form of Oral Tablets.

Lurasidone tablet is taken orally, usually once daily.

Lurasidone is an antipsychotic medicine. It is used for the treatment of schizophrenia (a mental condition in which a person is unable to differentiate between the real-world and imaginary world) and episodes of depression in bipolar disorder (a mental condition with extreme mood swings with an emotional high or low).

Lurasidone is an Antipsychotic agent belonging to Serotonin-dopamine antagonist class.

The mechanism of action of Lurasidone in the treatment of schizophrenia and bipolar depression is unknown. However, its efficacy in schizophrenia and bipolar depression could be mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.

Lurasidone is approved for use in the following clinical indications

• Bipolar major depression
• Major depressive disorder with mixed features
• Schizophrenia

• Bipolar major depression

Adult Dose:

Bipolar major depression, acute, with mixed features (off label) or without (labeled use) (monotherapy or in combination with antimanic therapy)

Oral: Initial: 20 mg once daily in the evening within 30 minutes of food (≥350 calories); may increase daily dose based on response and tolerability in increments of 20 mg every ≥2 days to a maximum dose of 120 mg/day.

Maintenance treatment for depressive episodes (off-label use)

Oral: Continue dose and combination regimen that was used to achieve control of the acute episode. Maximum dose: 120 mg/day.

Pediatric Dose:

Children ≥10 years and Adolescents <18 years: Monotherapy: Oral: Initial: 20 mg once daily; may increase dose after 1 week based on response and tolerability; reported range: 20 to 80 mg/day; in the largest double-blind placebo-controlled trial (n=175 treatment group), the majority of patients (67%) responded to a dose of 20 or 40 mg once daily; the modal daily dose was 20 mg in 52.3% of patients and 40 mg in 26.2% of patients.

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.

• Major depressive disorder with mixed features (off-label use)

Adult Oral Dose: 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.

• Schizophrenia

Adult Oral Dose: 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.

Lurasidone is available in various strengths as 20 mg; 40 mg; 60 mg; 80 mg; 120 mg.

• Dosage Adjustment in Kidney Patient

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl <50 mL/minute: Initial: 20 mg daily; maximum: 80 mg/day.

• Dosage Adjustment in Hepatic impairment Patient

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Initial: 20 mg daily; maximum: 80 mg/day.

Severe impairment (Child-Pugh class C): Initial: 20 mg daily; maximum: 40 mg/day.

Lurasidone is contraindicated in patients with

• 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).

• 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.

• Falls

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

• Orthostatic hypotension

May cause orthostatic hypotension and syncope; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of dehydration or hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (myocardial infarction, heart failure, or ischemic disease).

• Cardiovascular disease

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

• Hepatic impairment

Use with caution in patients with hepatic disease or impairment; dosage reduction is recommended in moderate to severe impairment.

• Renal impairment

Use with caution in patients with renal disease; dosage reduction is recommended in moderate to severe impairment.

• Seizures

Use with caution in patients at risk of seizures, including those with a history of seizures or conditions that lower the seizure threshold such as Alzheimer disease. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

• Strong CYP3A4 inhibitors

CYP3A4 is an enzyme in the body that is responsible for the breakdown of toxins and medicines so that they can get removed from the body. CYP3A4 inhibitors are a class of medicines that can inhibit the activity of the CYP3A4 enzyme. Lurasidone is not recommended for use if you are receiving treatment with strong CYP3A4 inhibitors such as Ketoconazole, Clarithromycin, Voriconazole, etc., due to the increased risk of serious side effects.

• Strong CYP3A4 Inducers

CYP3A4 is an enzyme in the body that is responsible for the breakdown of toxins and medicines so that they can get removed from the body. CYP3A4 inducers are medicine that may increase the activity of the CYP3A4 enzyme. Lurasidone is not recommended for use if you are receiving treatment with strong CYP3A4 inducers such as Rifampin, Phenytoin, Carbamazepine, etc., as it may worsen your condition.

Consumption of alcohol is not recommended during treatment with Lurasidone due to the increased risk of side effects such as dizziness, difficulty in concentration, impaired judgment, etc.

Lurasidone was excreted in milk of rats during lactation. It is not known whether Lurasidone or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the risk of drug discontinuation to the mother.

There are no adequate and well controlled studies of Lurasidone use in pregnant women. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Lurasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Common

Increase in fasting plasma glucose, increased serum cholesterol, increased serum triglycerides, Nausea, Viral infection, Akathisia, drowsiness, extrapyramidal reaction, insomnia, parkinsonism, Hypertension, orthostatic hypotension, tachycardia, Pruritus, skin rash, Increased serum prolactin, weight gain, Abdominal pain, decreased appetite, diarrhea, dyspepsia, sialorrhea, upper abdominal pain, vomiting, xerostomia, Urinary tract infection, Influenza, Agitation, anxiety, dizziness, dystonia, fatigue, restlessness, Back pain, dyskinesia, increased creatine phosphokinase in blood specimen, Blurred vision , Increased serum creatinine, Nasopharyngitis, oropharyngeal pain, rhinitis.

• Rare

• Lithium: It is not necessary to adjust the Lurasidone dose when used concomitantly with lithium.
• Valproate: It is not necessary to adjust the Lurasidone dose when used concomitantly with valproate. A dedicated drug-drug interaction study has not been conducted with valproate and Lurasidone. Based on pharmacokinetic data from the bipolar depression studies valproate levels were not affected by lurasidone, and lurasidone concentrations were not affected by valproate.
• Abametapir: The serum concentration of Lurasidone can be increased when it is combined with Abametapir.
• Acetophenazine: The risk or severity of CNS depression can be increased when Acetophenazine is combined with Lurasidone.
• Benoxaprofen: The risk or severity of hypertension can be increased when Benoxaprofen is combined with Lurasidone.
• Iopamidol: Agents with Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of Iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs.
• 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.
• Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patients closely for evidence of CNS depression.
• 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.
• Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania).
• 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.
• Zuclopenthixol: Agents with Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased.
• Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects.

The common side effects of Lurasidone include the following

Common side effects

Dizziness, feeling unsteady, or having trouble keeping your balance, anxiety, weakness, tiredness, restlessness, uncontrollable shaking of a part of the body, slow movements or shuffling walk, nausea, vomiting, appetite changes, increased saliva, breast enlargement or discharge, late or missed menstrual period, decreased sexual ability.

Rare side effects

Seizures, swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs, hoarseness, difficulty swallowing or breathing, shortness of breath, abnormal heartbeat, sore throat, fever, cough, chills, and other signs of infection, fever, sweating, confusion, fast or irregular heartbeat, and severe muscle stiffness, unusual movements of your face or body that you cannot control, falling.

• Pregnancy

Pregnancy Category B

There are no adequate and well controlled studies of Lurasidone use in pregnant women. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Lurasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

Lurasidone was excreted in the milk of rats during lactation. It is not known whether Lurasidone or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the risk of drug discontinuation to the mother.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

Clinical studies with Lurasidone did not include enough patients aged 65 and older to determine whether or not they respond differently from younger patients. In elderly patients with psychosis (65 to 85), Lurasidone concentrations (20 mg/day) were similar to those in young subjects. It is unknown whether dose adjustment is necessary on the basis of age alone. Elderly patients with dementia-related psychosis treated with Lurasidone are at an increased risk of death compared to placebo. Lurasidone is not approved for the treatment of patients with dementia-related psychosis.

• Pharmacodynamic

Lurasidone is an atypical antipsychotic that is a D2 and 5-HT2A (mixed serotonin and dopamine activity) to improve cognition. It is thought that antagonism of serotonin receptors can improve negative symptoms of psychoses and reduce the extrapyramidal side effects that are often associated with typical antipsychotics.

• Pharmacokinetics

Absorption

Lurasidone is readily absorbed and quickly reaches maximal concentrations (Cmax) within 1-4 hours. When taken with food, there is a two-fold increase in exposure and time to maximal concentration is increased by 0.5-1.5 hours.

Distribution

Lurasidone has Volume of distribution of about 6,173 L.

Metabolism and Excretion

Lurasidone is metabolized by CYP3A4 in which its major active metabolite is referred to as ID-14283 (25% of parent exposure). Its two minor metabolites are referred to as ID14326 and ID11614 which make up 3% and 1% of parent exposure respectively. Its two non-active metabolites are referred to as ID-20219 and ID-20220.It is excreted in Urine (9%) and 80% in feces.

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• https://www.practo.com/medicine-info/lurasidone-1613-api#:~:text=It is used for the,an emotional high or low).