Lurasidone

What is Lurasidone?

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Chemical structure of Lurasidone

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Ball-and-stick model of Lurasidone

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Skeletal formula of Lurasidone

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Skeletal formula of related compounds

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Image of Latuda (Lurasidone) bottles

• Lurasidone (Latuda) is an atypical antipsychotic used to treat schizophrenia and bipolar disorder.

What are the uses of this medicine?

Lurasidone (Latuda) is a prescription medicine used:

• To treat people 13 years of age or older with schizophrenia.
• Alone to treat people 10 years of age and older with depressive episodes that happen with Bipolar I Disorder (bipolar depression).
• With the medicine lithium or valproate to treat adults with depressive episodes that happen with Bipolar I Disorder (bipolar depression).

How does this medicine work?

• Lurasidone (loo ras' i done) is a second generation antipsychotic agent which appears to act as a dopamine type 2 (D2) and serotonin (5-HT)-2A receptor antagonist in a manner similar to risperidone.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are allergic to lurasidone hydrochloride or any of the ingredients in Latuda.
• are taking certain other medicines called CYP3A4 inhibitors or inducers including ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, rifampin, avasimibe, St. John's wort, phenytoin, or carbamazepine.

What drug interactions can this medicine cause?

• Latuda should not be used concomitantly with strong CYP3A4 inhibitors (eg:Ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil).
• Latuda dose should be reduced to half of the original level when used concomitantly with moderate inhibitors of CYP3A4 (eg:Diltiazem, atazanavir, erythromycin, fluconazole, verapamil)
• Latuda should not be used concomitantly with strong CYP3A4 inducers (eg:Rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine)
• Latuda dose should be increased when used concomitantly with moderate inducers of CYP3A4 (eg:Bosentan, efavirenz, etravirine, modafinil, nafcillin)
• No dosage adjustment of Latuda is required when administered concomitantly with lithium, valproate, or substrates of P-gp or CYP3A4.

Is this medicine FDA approved?

• Several randomized controlled trials have shown that lurasidone improves symptoms of schizophrenia and it was approved for this indication and for depressive episodes associated with bipolar disorder in the United States in 2010.

How should this medicine be used?

Recommended dosage:

Schizophrenia Adults:

• The recommended starting dose of Latuda is 40 mg once daily.
• The maximum recommended dose is 160 mg per day.

Adolescents (13 – 17 years):

• The recommended starting dose of Latuda is 40 mg once daily.
• The maximum recommended dose is 80 mg per day.

Depressive Episodes Associated with Bipolar I Disorder: Adults:

• The recommended starting dose of Latuda is 20 mg given once daily as monotherapy or as adjunctive therapy with lithium or valproate. Initial dose titration is not required.
• The maximum recommended dose, as monotherapy or as adjunctive therapy with lithium or valproate, is 120 mg per day.

Pediatric Patients (10 – 17 years)

• The recommended starting dose of Latuda is 20 mg given once daily as monotherapy. Initial dose titration is not required. The dose may be increased after one week based on clinical response.
• The maximum recommended dose is 80 mg per day.

Moderate and Severe Renal Impairment:

• Recommended starting dose is 20 mg per day, and the maximum recommended dose is 80 mg per day.

Moderate and Severe Hepatic Impairment:

• Recommended starting dose is 20 mg per day.
• The maximum recommended dose is 80 mg per day in moderate hepatic impairment and 40 mg per day in severe hepatic impairment.

Concomitant Use of a Moderate CYP3A4 inhibitor (e.g., diltiazem):

• Latuda dose should be reduced to half of the original dose level.
• Recommended starting dose is 20 mg per day.
• Maximum recommended dose is 80 mg per day.

Concomitant Use of a Moderate CYP3A4 Inducer:

• It may be necessary to increase the dose of Latuda.

Administration:

• Take Latuda by mouth, with food (at least 350 calories).
• If you take too much Latuda, call your healthcare provider or poison control center or go to the nearest hospital emergency room right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 20 mg, 40 mg, 60 mg, 80 mg and 120 mg

This medicine is available in fallowing brand namesː

• Latuda

What side effects can this medication cause?

The most common side effects of this medicine include: In Adults with schizophrenia:

• sleepiness or drowsiness
• restlessness and feeling like you need to move around (akathisia)
• difficulty moving, slow movements, muscle stiffness, or tremor
• nausea

In Children 13 to 17 years of age with schizophrenia:

• sleepiness or drowsiness
• nausea
• restlessness and feeling like you need to move around (akathisia)
• difficulty moving, slow movements, muscle stiffness, or tremor
• runny nose
• vomiting

In Adults with bipolar depression:

• restlessness and feeling like you need to move around (akathisia)
• difficulty moving, slow movements, muscle stiffness, or tremor
• sleepiness or drowsiness

In Children 10 to 17 years of age with bipolar depression:

• nausea
• weight gain
• problems sleeping (insomnia)

Latuda may cause serious side effects, including:

• Increased risk of death in elderly people with dementia-related psychosis
• Increased risk of suicidal thoughts or actions in children and young adults
• tardive dyskinesia
• hyperglycemia
• increased fat levels (cholesterol and triglycerides)
• weight gain
• hyperprolactinemia
• Low white blood cell count
• orthostatic hypotension
• Falls
• Seizures (convulsions)
• Problems controlling your body temperature so that you feel too warm
• Mania or hypomania

What special precautions should I follow?

• Do not drive, operate heavy machinery, or do other dangerous activities until you know how Latuda affects you. Latuda may make you drowsy.
• Avoid eating grapefruit or drinking grapefruit juice during treatment with Latuda. Grapefruit and grapefruit juice may affect the amount of Latuda in your blood.
• Do not become too hot or dehydrated during treatment with Latuda:
• Do not exercise too much.
• In hot weather, stay inside in a cool place if possible.
• Stay out of the sun.
• Do not wear too much clothing or heavy clothing.
• Drink plenty of water.
• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Latuda is not approved for the treatment of patients with dementia-related psychosis.
• Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) may oocur with Latuda. Latuda is not approved for the treatment of patients with dementia-related psychosis.
• A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including Latuda. If NMS is suspected, immediately discontinue Latuda and provide intensive symptomatic treatment and monitoring.
• Tardive dyskinesia is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements that can develop in patients treated with antipsychotic drugs. If signs and symptoms of tardive dyskinesia appear in a patient on Latuda, drug discontinuation should be considered.
• Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain
• Leukopenia/neutropenia has been reported during treatment with antipsychotic agents. Perform complete blood counts (CBC) in patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia or neutropenia. Consider discontinuing Latuda if a clinically significant decline in WBC occurs in the absence of other causative factors.
• Latuda may cause orthostatic hypotension and syncope, perhaps due to its α1-adrenergic receptor antagonism. Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
• Latuda may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• arrhythmias
• Hypotension
• obtundation
• seizures

Management of overdosage:

• No specific antidotes for Latuda are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement. If an overdose occurs, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org).
• Cardiovascular monitoring should commence immediately, including continuous electrocardiographic monitoring for possible arrhythmias.
• Hypotension and circulatory collapse should be treated with appropriate measures.
• Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.

Can this medicine be used in pregnancy?

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Latuda during pregnancy. For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388.
• There are no studies of Latuda use in pregnant women.
• The limited available data are not sufficient to inform a drug-associated risk of birth defects or miscarriage.

Can this medicine be used in children?

Schizophrenia:

• The safety and effectiveness of Latuda 40-mg/day and 80-mg/day for the treatment of schizophrenia in adolescents (13 to 17 years) was established.
• The safety and effectiveness of Latuda has not been established in pediatric patients less than 13 years of age with schizophrenia.

Bipolar Depression:

• The safety and effectiveness of Latuda 20 to 80 mg/day for the treatment of bipolar depression in pediatric patients (10 to 17 years) was established.
• The safety and effectiveness of Latuda has not been established in pediatric patients less than 10 years of age with bipolar depression.

• The effectiveness of Latuda in pediatric patients for the treatment of irritability associated with autistic disorder has not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: lurasidone hydrochloride
• Inactive ingredients: mannitol, pregelatinized starch, croscarmellose sodium, hypromellose, magnesium stearate, Opadry® and carnauba wax. Additionally, the 80 mg tablet contains yellow ferric oxide and FD&C Blue No. 2 Aluminum Lake

Who manufactures and distributes this medicine?

• Manufactured for: Sunovion Pharmaceuticals Inc. Marlborough, MA USA

Latuda is a registered trademark of Sumitomo Dainippon Pharma Co. Ltd.; Sunovion

What should I know about storage and disposal of this medication?

• Store Latuda tablets at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Latuda and all medicines out of the reach of children.

Antipsychotic agents

First Generation

• Phenothiazines
  • Chlorpromazine, Fluphenazine, Perphenazine, Prochlorperazine, Thioridazine, Trifluoperazine

• Other
  • Haloperidol, Lithium, Loxapine, Molindone, Pimozide

Second Generation (Atypicals)

• Aripiprazole, Asenapine, Brexpiprazole, Cariprazine, Clozapine, Iloperidone, Lurasidone, Olanzapine, Paliperidone, Pimavanserin, Quetiapine, Risperidone, Ziprasidone

• Dailymed label info on Lurasidone
• FDA Lurasidone

Pharmacodynamics