INDICATION AND USES:
LATUDA is an atypical antipsychotic indicated for the treatment of:
- Schizophrenia in adults and adolescents (13 to 17 years) ( 1, 14.1)
- Depressive episode associated with Bipolar I Disorder (bipolar depression) in adults and pediatric patients (10 to 17 years) as monotherapy (1, 14.2)
- Depressive episode associated with Bipolar I Disorder (bipolar depression) in adults as adjunctive therapy with lithium or valproate (1, 14.2)
DOSAGE AND ADMINISTRATION
LATUDA should be taken with food (at least 350 calories). Administration with food substantially increases the absorption of LATUDA (2.3, 12.3).
| Indication | Starting Dose | Recommended Dose |
| Schizophrenia – adults (2.1) | 40 mg per day | 40 mg to 160 mg per day |
| Schizophrenia – adolescents (13 to 17 years) (2.1) | 40 mg per day | 40 mg to 80 mg per day |
| Bipolar Depression – adults (2.2) | 20 mg per day | 20 mg to 120 mg per day |
| Bipolar Depression – pediatric patients (10 to 17 years) (2.2) | 20 mg per day | 20 mg to 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 (2.4, 8.6).
- 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 (2.5, 8.7).
- 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 (2.6, 7.1).
- Concomitant Use of a Moderate CYP3A4 Inducer: It may be necessary to increase the dose of LATUDA (2.6, 7.1).
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥ 5% and at least twice the rate for placebo) were (6.1):
- Adult patients with schizophrenia: somnolence, akathisia, extrapyramidal symptoms, and nausea
- Adolescent patients (13-17 years) with schizophrenia: somnolence, nausea, akathisia, EPS (non-akathisia), rhinitis (80mg only), and vomiting
- Adult patients with bipolar depression: akathisia, extrapyramidal symptoms, and somnolence
- Pediatric patients (10-17 years) with bipolar depression: nausea, weight increase, and insomnia.
CONTRAINDICATIONS:
- Known hypersensitivity to LATUDA or any components in the formulation (4).
- Concomitant use with a strong CYP3A4 inhibitor (e.g., ketoconazole) (2.6, 4, 7.1).
- Concomitant use with a strong CYP3A4 inducer (e.g., rifampin) (2.6, 4, 7.1).
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) (5.3).
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring (5.4).
- Tardive Dyskinesia: Discontinue if clinically appropriate (5.5).
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain (5.6).
- Hyperprolactinemia: Prolactin elevations may occur (5.7).
- 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 LATUDA if a clinically significant decline in WBC occurs in the absence of other causative factors (5.8).
- Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope (5.9).
DRUG INTERACTIONS:
| Strong CYP3A4 Inhibitors | |
| Clinical Impact: | Concomitant use of LATUDA with strong CYP3A4 inhibitors increased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. |
| Intervention: | LATUDA should not be used concomitantly with strong CYP3A4 inhibitors [see Contraindications (4)]. |
| Examples: | Ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil |
| Moderate CYP3A4 Inhibitors | |
| Clinical Impact: | Concomitant use of LATUDA with moderate CYP3A4 inhibitors increased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. |
| Intervention: | LATUDA dose should be reduced to half of the original level when used concomitantly with moderate inhibitors of CYP3A4 [see Dosage and Administration (2.6)]. |
| Examples: | Diltiazem, atazanavir, erythromycin, fluconazole, verapamil |
| Strong CYP3A4 Inducers | |
| Clinical Impact: | Concomitant use of LATUDA with strong CYP3A4 inducers decreased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. |
| Intervention: | LATUDA should not be used concomitantly with strong CYP3A4 inducers [see Contraindications (4)]. |
| Examples: | Rifampin, avasimibe, St John’s wort, phenytoin, carbamazepine |
| Moderate CYP3A4 Inducers | |
| Clinical Impact: | Concomitant use of LATUDA with moderate CYP3A4 inducers decreased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. |
| Intervention: | LATUDA dose should be increased when used concomitantly with moderate inducers of CYP3A4 [see Dosage and Administration (2.6)]. |
| Examples: | Bosentin, efavirenz, etravirine, modafinil, nafcillin |
OVERDOSE:
In premarketing clinical studies, accidental or intentional overdosage of LATUDA was identified in one patient who ingested an estimated 560 mg of LATUDA. This patient recovered without sequelae. This patient resumed LATUDA treatment for an additional two months.
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. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with an acute overdose of LATUDA.
Similarly, the alpha-blocking properties of bretylium might be additive to those of LATUDA, resulting in problematic hypotension.
Hypotension and circulatory collapse should be treated with appropriate measures. Epinephrine and dopamine should not be used, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of LATUDA-induced alpha blockade. In case of severe extrapyramidal symptoms, anticholinergic medication should be administered.
Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.
The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.
- Uses
-
INDICATION AND USES:
LATUDA is an atypical antipsychotic indicated for the treatment of:
- Schizophrenia in adults and adolescents (13 to 17 years) ( 1, 14.1)
- Depressive episode associated with Bipolar I Disorder (bipolar depression) in adults and pediatric patients (10 to 17 years) as monotherapy (1, 14.2)
- Depressive episode associated with Bipolar I Disorder (bipolar depression) in adults as adjunctive therapy with lithium or valproate (1, 14.2)
DOSAGE AND ADMINISTRATION
LATUDA should be taken with food (at least 350 calories). Administration with food substantially increases the absorption of LATUDA (2.3, 12.3).
Indication Starting Dose Recommended Dose Schizophrenia – adults (2.1) 40 mg per day 40 mg to 160 mg per day Schizophrenia – adolescents (13 to 17 years) (2.1) 40 mg per day 40 mg to 80 mg per day Bipolar Depression – adults (2.2) 20 mg per day 20 mg to 120 mg per day Bipolar Depression – pediatric patients (10 to 17 years) (2.2) 20 mg per day 20 mg to 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 (2.4, 8.6).
- 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 (2.5, 8.7).
- 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 (2.6, 7.1).
- Concomitant Use of a Moderate CYP3A4 Inducer: It may be necessary to increase the dose of LATUDA (2.6, 7.1).
- Side Effects
-
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥ 5% and at least twice the rate for placebo) were (6.1):
- Adult patients with schizophrenia: somnolence, akathisia, extrapyramidal symptoms, and nausea
- Adolescent patients (13-17 years) with schizophrenia: somnolence, nausea, akathisia, EPS (non-akathisia), rhinitis (80mg only), and vomiting
- Adult patients with bipolar depression: akathisia, extrapyramidal symptoms, and somnolence
- Pediatric patients (10-17 years) with bipolar depression: nausea, weight increase, and insomnia.
- Precautions
-
CONTRAINDICATIONS:
- Known hypersensitivity to LATUDA or any components in the formulation (4).
- Concomitant use with a strong CYP3A4 inhibitor (e.g., ketoconazole) (2.6, 4, 7.1).
- Concomitant use with a strong CYP3A4 inducer (e.g., rifampin) (2.6, 4, 7.1).
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) (5.3).
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring (5.4).
- Tardive Dyskinesia: Discontinue if clinically appropriate (5.5).
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain (5.6).
- Hyperprolactinemia: Prolactin elevations may occur (5.7).
- 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 LATUDA if a clinically significant decline in WBC occurs in the absence of other causative factors (5.8).
- Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope (5.9).
- Interactions
-
DRUG INTERACTIONS:
Strong CYP3A4 Inhibitors Clinical Impact: Concomitant use of LATUDA with strong CYP3A4 inhibitors increased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. Intervention: LATUDA should not be used concomitantly with strong CYP3A4 inhibitors [see Contraindications (4)]. Examples: Ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil Moderate CYP3A4 Inhibitors Clinical Impact: Concomitant use of LATUDA with moderate CYP3A4 inhibitors increased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. Intervention: LATUDA dose should be reduced to half of the original level when used concomitantly with moderate inhibitors of CYP3A4 [see Dosage and Administration (2.6)]. Examples: Diltiazem, atazanavir, erythromycin, fluconazole, verapamil Strong CYP3A4 Inducers Clinical Impact: Concomitant use of LATUDA with strong CYP3A4 inducers decreased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. Intervention: LATUDA should not be used concomitantly with strong CYP3A4 inducers [see Contraindications (4)]. Examples: Rifampin, avasimibe, St John’s wort, phenytoin, carbamazepine Moderate CYP3A4 Inducers Clinical Impact: Concomitant use of LATUDA with moderate CYP3A4 inducers decreased the exposure of lurasidone compared to the use of LATUDA alone [see Clinical Pharmacology (12.3)]. Intervention: LATUDA dose should be increased when used concomitantly with moderate inducers of CYP3A4 [see Dosage and Administration (2.6)]. Examples: Bosentin, efavirenz, etravirine, modafinil, nafcillin - Overdose
-
OVERDOSE:
In premarketing clinical studies, accidental or intentional overdosage of LATUDA was identified in one patient who ingested an estimated 560 mg of LATUDA. This patient recovered without sequelae. This patient resumed LATUDA treatment for an additional two months.
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. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with an acute overdose of LATUDA.
Similarly, the alpha-blocking properties of bretylium might be additive to those of LATUDA, resulting in problematic hypotension.
Hypotension and circulatory collapse should be treated with appropriate measures. Epinephrine and dopamine should not be used, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of LATUDA-induced alpha blockade. In case of severe extrapyramidal symptoms, anticholinergic medication should be administered.Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.
The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.