LURATA 40

Indications

• Schizophrenia
• Bipolar disorder (depressive episodes)

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines based on indication and patient condition.

Mechanism of action

Lurasidone acts as an antagonist at central dopamine type 2 (D2) and serotonin type 2 (5-HT2A) receptors. This dual action is believed to improve cognitive function and alleviate negative symptoms associated with psychoses while reducing the risk of extrapyramidal side effects. Additionally, lurasidone exhibits partial agonist activity at 5-HT1A receptors and antagonistic effects at alpha2A-adrenergic receptors, contributing to its therapeutic effects.

Pharmacodynamics

Lurasidone has a high affinity for D2 and 5-HT2A receptors, which are critical in regulating mood and psychotic symptoms. It also binds with moderate affinity to alpha-2C adrenergic receptors and shows partial agonism at 5-HT1A receptors. Its negligible affinity for histamine (H1) and muscarinic (M1) receptors minimizes sedation and anticholinergic side effects, making it a favorable option among antipsychotics.

Pharmacokinetics

Lurasidone is absorbed well after oral administration, with peak plasma concentrations typically reached within 1 to 3 hours. It has a bioavailability that is influenced by food intake, with increased absorption when taken with food. The drug is extensively metabolized in the liver, primarily via the CYP3A4 enzyme, and has a half-life ranging from 18 to 26 hours, allowing for once-daily dosing. It is excreted mainly through feces and urine as metabolites.

Interactions

• posaconazole+lurasidone: Severe (increases exposure)
• cobicistat+lurasidone: Severe (increases exposure)
• grapefruit juice+lurasidone: Severe (increases exposure)
• idelalisib+lurasidone: Severe (increases exposure)
• clarithromycin+lurasidone: Severe (increases exposure)
• rifampicin+lurasidone: Severe (decreases exposure)
• cenobamate+lurasidone: Moderate (decreases exposure)
• dabrafenib+lurasidone: Moderate (decreases exposure)
• stjohn’s wort+lurasidone: Moderate (decreases exposure)
• bosentan+lurasidone: Moderate (decreases exposure)

Pregnancy

The safety of lurasidone in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether lurasidone is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Indications

• Schizophrenia
• Bipolar disorder (depressive episodes)

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines for paediatric patients.

Adults: Refer to the BNF for specific dosing recommendations based on individual patient needs and conditions.

Mechanism of action

Lurasidone acts as an antagonist at dopamine D2 receptors and serotonin 5-HT2A receptors. It also exhibits partial agonist activity at serotonin 5-HT1A receptors. This multifaceted mechanism helps to balance the dopaminergic and serotonergic activity in the brain, which is beneficial in treating psychotic and mood disorders.

Pharmacodynamics

The pharmacodynamic properties of lurasidone include its ability to reduce the symptoms of psychosis and stabilize mood. It has a lower propensity to cause extrapyramidal side effects compared to first-generation antipsychotics, making it more tolerable for long-term use. It may also improve cognitive function in patients with schizophrenia.

Pharmacokinetics

Lurasidone is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 3 hours post-dose. It has a bioavailability of about 65%, and its plasma protein binding is high (approximately 99%). The drug undergoes extensive hepatic metabolism, primarily via the cytochrome P450 system (CYP3A4), and has a relatively long half-life, allowing for once-daily dosing. Excretion occurs mainly through feces and urine.

Contra-indications

• Hypersensitivity to lurasidone or any component of the formulation
• Severe hepatic impairment
• Concurrent use of strong CYP3A4 inhibitors

Adverse effects

• Somnolence
• Akathisia
• Nausea
• Vomiting
• Extrapyramidal symptoms
• Weight gain
• Hyperglycemia
• Increased cholesterol levels
• Prolactin elevation
• Neuroleptic malignant syndrome

Interactions

• Increased risk of lurasidone toxicity with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)
• Reduced efficacy of lurasidone when used with strong CYP3A4 inducers (e.g., rifampicin, carbamazepine)
• Additive effects with other central nervous system depressants

Precautions

• Monitor for signs of suicidality and worsening of depression
• Caution in patients with a history of seizures
• Caution in elderly patients with dementia-related psychosis
• Use with caution in patients with a history of cardiovascular disease

Pregnancy

Use with caution. Limited human data available; potential risks versus benefits should be considered.

Breast-feeding

Lurasidone is excreted in breast milk; breastfeeding is not recommended during treatment.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Lurasidone 40 mg tablet
• Lurasidone 80 mg tablet
• Lurasidone 120 mg tablet

Mechanism of action

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. Lurasidone is a benzisothiazol-derivative antipsychotic agent and has been referred to as an atypical or second-generation antipsychotic agent. Lurasidone has also been described as an azapirone-derivative. Although the exact mechanism of action of lurasidone and other antipsychotic agents in schizophrenia is unknown, it has been suggested that the efficacy of lurasidone is mediated through a combination of antagonist activity at central dopamine type 2 (D2) and serotonin type 2 (5-hydroxytryptamine [5-HT2A]) receptors. Lurasidone is an antagonist that exhibits high affinity for D2, 5-HT2A, and 5-HT7 receptors and moderate affinity for a2C-adrenergic receptors in vitro. The drug acts as a partial agonist at 5-HT1A receptors and is an antagonist at alpha2A-adrenergic receptors in vitro. Lurasidone exhibits weak affinity for alpha1-adrenergic receptors and little or no affinity for histamine (H1) receptors and muscarinic (M1) receptors.

Pharmacodynamics

Lurasidone is a benzothiazol derivative that is an antagonist and binds with high affinity to Dopamine-2 (D2) (Ki = 0.994 nM), 5-HT2A (Ki = 0.47 nM) receptors, and 5-HT7 receptors (Ki = 0.495 nM). It also binds with moderate affinity to alpha-2C adrenergic receptors (Ki = 10.8 nM) and is a partial agonist at 5-HT1A receptors (Ki = 6.38 nM). Its actions on histaminergic and muscarinic receptors are negligible.