Lurasidonum

Uses

Lurasidonum Hydrochloride is an atypical antipsychotic. This is used for the treatment of: Schizophrenia, Depressive episodes associated with Bipolar I Disorder (bipolar depression), as monotherapy and as adjunctive therapy with lithium or valproate.

Lurasidonum is also used to associated treatment for these conditions: Acute Depressive Episode, Schizophrenia

How Lurasidonum works

Lurasidonum 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.

Dosage

Lurasidonum dosage

Schizophrenia-

• Starting Dose: 40 mg once daily
• Recommended Dose:40 mg to 160 mg once daily

Bipolar Depression-

• Starting Dose:20 mg once daily
• Recommended Dose:20 mg to 120 mg once daily

Lurasidonum should be taken with food. Administration with food substantially increases the absorption of Lurasidonum.

Side Effects

Somnolence, akathisia, extrapyramidal symptoms, and nausea.

Precaution

Cerebrovascular adverse reactions in elderly patients with dementia-related psychosis: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack).

Neuroleptic malignant syndrome: Manage with immediate discontinuation and close monitoring.

Tardive dyskinesia: Discontinue if clinically appropriate.

Metabolic changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain.

Hyperglycemia and diabetes mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes.

Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics.

Weight Gain: Gain in body weight has been observed. Monitor weight.

Hyperprolactinemia: Prolactin elevations may occur.

Leukopenia, neutropenia and agranulocytosis: 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 Lurasidonum if a clinically significant decline in WBC occurs in the absence of other causative factors.

Orthostatic hypotension and syncope: Dizziness, tachycardia or bradycardia, and syncope may occur, especially early in treatment. In patients with known cardiovascularor cerebrovascular disease, and in antipsychotic-naïve patients, consider a lower starting dose and slower titration.

Interaction

The Lurasidonum dose should be reduced to half of the original level when used concomitantly with moderate inhibitors of CYP3A4 (e.g., Diltiazem, Atazanavir, Erythromycin, Fluconazole, Verapamil, etc.). If Lurasidonum is used concomitantly with a moderate CYP3A4 inducer, it may be necessary to increase the Lurasidonum dose.

Grapefruit: Grapefruit and grapefruit juice should be avoided in patients taking Lurasidonum, since these may inhibit CYP3A4 and alter Lurasidonum concentrations.

Food Interaction

• Take with food. The manufacturer recommends co-administration with at least 350 calories.

[Major] GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of lurasidone.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Inhibition of hepatic CYP450 3A4 may also contribute.

The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors.

When a single 10 mg dose of lurasidone was administered with the potent CYP450 3A4 inhibitor ketoconazole (400 mg

The AUC of lurasidone's active metabolite increased by 6-fold.

Another potent CYP450 3A4 inhibitor, posaconazole, has been reported to increase lurasidone AUC by approximately 4.5-fold.

When a single 20 mg dose of lurasidone was administered with the moderate CYP450 3A4 inhibitor diltiazem (extended release formulation 240 mg

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

GENERALLY AVOID: Alcohol may potentiate some of the central nervous system and hypotensive effects of lurasidone.

Use in combination may result in increased sedation, dizziness, hypotension, and impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of lurasidone.

According to the product labeling, lurasidone mean Cmax and AUC were increased approximately 3-fold and 2-fold, respectively, when administered with food relative to under fasting conditions.

Lurasidonum AUC was not affected by meal size (in the range of 350 to 1000 calories) or fat content.

In clinical studies, lurasidone was administered with food.

MANAGEMENT: Patients treated with lurasidone should avoid consumption of grapefruit and grapefruit juice as well as alcohol.

Lurasidonum should be taken with food (at least 350 calories).

Lurasidonum Cholesterol interaction

[Moderate] Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels.

While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile.

Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

Lurasidonum Drug Interaction

Moderate: aripiprazole, zolpidem, lorazepam, buspirone, duloxetine, lamotrigine, escitalopram, lithium, fluoxetine, quetiapine, valproic acid, sertraline, cetirizineUnknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, omega-3 polyunsaturated fatty acids, cyanocobalamin, ascorbic acid, cholecalciferol, lisdexamfetamine

Lurasidonum Disease Interaction

Major: dementia, NMS, tardive dyskinesiaModerate: depression, aspiration, seizure, hematologic abnormalities, hyperglycemia/diabetes, hypotension, lipid alterations, renal impairment, weight gain, hyperprolactinemia

Volume of Distribution

6173 L

Elimination Route

Lurasidonum 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. This occurs regardless of fat or caloric content.
Bioavailability = 9-19%.

Half Life

40 mg dose= 18 hours 120 mg - 160 mg dose = 29-37 hours

Clearance

3902 mL/min

Elimination Route

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

Pregnancy & Breastfeeding use

Pregnancy Category B. Lurasidonum should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Patient should be advised not to breast-feed an infant if they are taking Lurasidonum.

Contraindication

Hypersensitivity. Concurrent administration of strong CYP3A4 inhibitors (eg, Ketoconazole). Concurrent administration of strong CYP3A4 inducers (eg, Rifampin). Dementia-related psychosis.

Special Warning

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.

Storage Condition

Protect from light and moisture, store below 30° C. Keep out of the reach of children.

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