Usage
- Lurasidone is prescribed for the treatment of schizophrenia in adults and adolescents aged 13 years and older, and for depressive episodes associated with bipolar I disorder (bipolar depression) in adults, both as monotherapy and adjunctive therapy with lithium or valproate. It is also used in children aged 10-17 years old to treat depressive episodes associated with bipolar I disorder.
- Pharmacological Classification: Atypical antipsychotic (second-generation antipsychotic).
- Mechanism of Action: Lurasidone is a serotonin-dopamine activity modulator (SDAM). It acts as an antagonist at serotonin 5-HT2A and dopamine D2 receptors, with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT7 receptors. It has negligible affinity for muscarinic M1 and histamine H1 receptors. This combined activity is believed to contribute to its antipsychotic and mood-stabilizing effects.
Alternate Names
- International Nonproprietary Name (INN): Lurasidone
- Brand Name: Latuda
How It Works
- Pharmacodynamics: Lurasidone’s therapeutic effects are primarily attributed to its antagonism of 5-HT2A and D2 receptors, coupled with partial agonism at 5-HT1A receptors. Its low affinity for muscarinic and histamine receptors minimizes certain side effects, like dry mouth, blurred vision, and sedation commonly seen with some other antipsychotics.
- Pharmacokinetics:
- Absorption: Lurasidone is absorbed orally and its absorption is significantly enhanced when taken with food (at least 350 calories).
- Metabolism: Primarily metabolized by CYP3A4.
- Elimination: Excreted in urine and feces.
- Mode of Action: Lurasidone binds to and blocks the 5-HT2A and D2 receptors. Its partial agonism at 5-HT1A receptors may contribute to mood stabilizing effects.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Antagonist at 5-HT2A, D2, and 5-HT7 receptors; partial agonist at 5-HT1A receptors.
- Elimination Pathways: Hepatic metabolism (primarily CYP3A4), renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Schizophrenia: Initial dose: 40 mg once daily with food. May increase based on clinical response and tolerability. Maximum dose: 160 mg/day.
- Bipolar Depression (Monotherapy or Adjunctive): Initial dose: 20 mg once daily with food. May increase based on clinical response and tolerability. Maximum dose: 120 mg/day.
Children:
- Schizophrenia (13-17 years): Initial dose: 40 mg once daily with food. May increase up to maximum dose of 80 mg/day.
- Bipolar Depression (10-17 years): Initial dose: 20 mg once daily with food. May increase up to maximum dose of 80 mg/day.
- Bipolar Depression with Adjunctive Therapy (10-17 years): Not recommended.
- Children younger than 10 years of age: Not established for Bipolar Depression and use is not recommended. Not established for Schizophrenia.
Special Cases:
- Elderly Patients: Same as adult dosing but consider renal function and potential drug interactions.
- Patients with Renal Impairment (moderate to severe): Initial dose: 20 mg/day with food. Maximum dose: 80 mg/day.
- Patients with Hepatic Dysfunction (moderate): Initial dose: 20 mg/day with food. Maximum dose: 80 mg/day.
- Patients with Hepatic Dysfunction (severe): Initial dose: 20 mg/day with food. Maximum dose: 40 mg/day.
- Patients with Comorbid Conditions: Close monitoring and dose adjustments may be necessary, particularly for patients with cardiovascular disease, diabetes, or conditions affecting seizure threshold.
Clinical Use Cases
Lurasidone’s indicated uses are limited to schizophrenia and bipolar depression. Its use is not established for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- CYP3A4 Inhibitors (Moderate): Reduce lurasidone dose to 50% of the original dose, not to exceed 80 mg/day; starting dose is 20 mg/day. Strong CYP3A4 inhibitors are contraindicated.
- CYP3A4 Inducers (Moderate): Lurasidone dose may need to be increased. Strong CYP3A4 inducers are contraindicated.
- Renal/Hepatic Impairment: As described in Special Cases.
Side Effects
Common Side Effects
- Akathisia (restlessness), Parkinsonism, nausea, somnolence, insomnia, agitation, anxiety, dizziness, dystonia.
Rare but Serious Side Effects
- Neuroleptic malignant syndrome (NMS), tardive dyskinesia, seizures, suicidal thoughts and behavior, severe allergic reactions (including angioedema), dysphagia.
Long-Term Effects
- Tardive dyskinesia, metabolic changes (weight gain, dyslipidemia, hyperglycemia), hyperprolactinemia.
Adverse Drug Reactions (ADR)
- NMS, angioedema, severe allergic reactions, QTc interval prolongation.
Contraindications
- Hypersensitivity to lurasidone.
- Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) or strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort).
Drug Interactions
- CYP3A4 Inhibitors (Moderate): Diltiazem, verapamil, erythromycin, fluconazole, atazanavir. Dosage adjustments of lurasidone are needed.
- CYP3A4 Inducers (Moderate): Efavirenz, modafinil, bosentan. Dosage adjustments of lurasidone may be necessary.
- Other Medications: QTc prolonging drugs, drugs with anticholinergic properties, CNS depressants.
- OTC Drugs and Supplements: St. John’s Wort.
- Food and Lifestyle Factors: Grapefruit and grapefruit juice (avoid concomitant use), alcohol (may increase sedation and other CNS effects).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Use only if the potential benefit justifies the potential risk to the fetus. Neonatal adverse reactions have been reported in infants exposed to antipsychotics during the third trimester.
- Breastfeeding: Lurasidone may be excreted in breast milk. Use with caution and monitor infants for potential side effects.
Drug Profile Summary
- Mechanism of Action: SDAM; antagonist at 5-HT2A, D2, and 5-HT7 receptors; partial agonist at 5-HT1A receptor.
- Side Effects: Akathisia, parkinsonism, nausea, somnolence, insomnia, NMS, tardive dyskinesia.
- Contraindications: Hypersensitivity, strong CYP3A4 inhibitors and inducers.
- Drug Interactions: CYP3A4 inhibitors and inducers, QTc prolonging drugs, alcohol, grapefruit juice.
- Pregnancy & Breastfeeding: Not established/Use with caution.
- Dosage: Schizophrenia: 40-160 mg/day; Bipolar depression: 20-120 mg/day. Adjust for renal/hepatic impairment and drug interactions.
- Monitoring Parameters: Weight, blood glucose, lipids, extrapyramidal symptoms, QTc interval, NMS.
Popular Combinations
- Lithium or valproate as adjunctive therapy in bipolar depression.
- Other antipsychotics for treatment-resistant schizophrenia, though this is not officially recommended and should be done under careful monitoring by healthcare professionals.
- Antidepressants in some cases.
Precautions
- General Precautions: Monitor for metabolic changes, extrapyramidal symptoms, neuroleptic malignant syndrome, suicidal thoughts/behavior, orthostatic hypotension.
- Specific Populations:
- Pregnant Women: Use with caution; weigh risks and benefits.
- Breastfeeding Mothers: Use with caution; monitor infants.
- Children & Elderly: Adjust dosage as needed.
- Menstruating Individuals: Monitor for hyperprolactinemia and related side effects.
- Lifestyle Considerations: Avoid alcohol, excessive heat, and activities requiring alertness until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lurasidone?
A: Adults: Schizophrenia: 40-160 mg/day; Bipolar Depression: 20-120 mg/day. Children (Schizophrenia 13-17 years): 40-80 mg/day; Children (Bipolar Depression 10-17 years): 20-80 mg/day. All doses are to be taken once daily with food (at least 350 calories).
Q2: What are the key differences between lurasidone and other atypical antipsychotics?
A: Lurasidone has a lower risk of weight gain and metabolic side effects compared to some other atypical antipsychotics. It also has a lower affinity for muscarinic and histamine receptors, which may result in fewer anticholinergic and sedative side effects. It’s however important to monitor for extrapyramidal symptoms, similar to those observed with other atypical antipsychotics.
A: Lurasidone is primarily metabolized by CYP3A4.
Q4: How should lurasidone be administered?
A: Lurasidone should be administered orally once daily with food (at least 350 calories). Administration with food significantly increases its absorption.
Q5: What are the most common side effects of lurasidone?
A: Common side effects include akathisia (restlessness), parkinsonism, nausea, somnolence, insomnia, agitation, anxiety, and dizziness.
Q6: What are the contraindications for lurasidone use?
A: Lurasidone is contraindicated in patients with hypersensitivity to the drug and in those concomitantly taking strong CYP3A4 inhibitors or inducers.
Q7: Does lurasidone have any specific monitoring requirements?
A: Patients on lurasidone should be monitored for metabolic changes (weight, glucose, lipids), extrapyramidal symptoms (EPS), emergence of suicidal ideation, and other potential adverse effects.
Q8: Can lurasidone be used during pregnancy?
A: Lurasidone’s safety during pregnancy has not been fully established. Use only if the potential benefit outweighs the potential risk to the fetus.
Q9: Can lurasidone be used during breastfeeding?
A: Lurasidone may be excreted in breast milk. Use with caution and monitor the infant for potential side effects. Discuss the risks and benefits with the patient and consider alternate treatment options if appropriate.
Q10: What should be done in case of a missed dose of lurasidone?
A: The patient should take the missed dose as soon as they remember. However, if it is close to the time for the next dose, they should skip the missed dose and take the next scheduled dose. Patients should not double the dose to make up for a missed dose.
