Overview
11 DESCRIPTION Lurasidone hydrochloride is an atypical antipsychotic belonging to the chemical class of benzisothiazol derivatives. Its chemical name is (3a R ,4 S ,7 R ,7a S )-2-{(1 R ,2 R )-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl] cyclohexylmethyl}hexahydro-4,7-methano-2 H -isoindole-1,3-dione hydrochloride.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of lurasidone in the treatment of schizophrenia and bipolar depression is unclear. However, its efficacy in schizophrenia and bipolar depression could be mediated through a combination of central dopamine D 2 and serotonin Type 2 (5HT 2A ) receptor antagonism. 12.2 Pharmacodynamics Lurasidone is an antagonist with high affinity binding at the dopamine D 2 receptors (Ki of 1 nM) and the serotonin 5-HT 2A (Ki of 0.5 nM) and 5-HT 7 (Ki of 0.5 nM) receptors. It also binds with moderate affinity to the human α 2 C adrenergic receptors (Ki of 11 nM), is a partial agonist at serotonin 5-HT 1A (Ki of 6.4 nM) receptors, and is an antagonist at the α 2A adrenergic receptors (Ki of 41 nM).
Indications
- 1 INDICATIONS AND USAGE Lurasidone hydrochloride tablets are indicated for: • Treatment of adult and adolescent patients (13 to 17 years) with schizophrenia [see Clinical Studies ( 14.1 )] . • Monotherapy treatment of adult and pediatric patients (10 to 17 years) with major depressive episode associated with bipolar I disorder (bipolar depression) [see Clinical Studies ( 14.2 )]. • Adjunctive treatment with lithium or valproate in adult patients with major depressive episode associated with bipolar I disorder (bipolar depression) [see Clinical Studies ( 14.2 )].
Common Doses
- 40 mg
- 160 mg
- 80 mg
- 20 mg
Dosage
2 DOSAGE AND ADMINISTRATION Lurasidone hydrochloride tablets should be taken with food (at least 350 calories). Administration with food substantially increases the absorption of lurasidone hydrochloride tablets ( 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.
Black Box Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Lurasidone hydrochloride is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 )].
Contraindications
- 4 CONTRAINDICATIONS • Known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone [see Adverse Reactions ( 6.1 )]. • Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. • Strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. John’s wort, phenytoin, carbamazepine, etc.) [see Drug Interactions ( 7.1 )]. • Known hypersensitivity to lurasidone hydrochloride tablets or any components in the formulation ( 4 ).
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: • Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Suicidal Thoughts and Behaviors [see Boxed Warning and Warnings and Precautions ( 5.2 )] • Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-related Psychosis [see Warnings and Precautions ( 5.3 )] • Neuroleptic Malignant Syndrome [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS 7.1 Drugs Having Clinically Important Interactions with Lurasidone Hydrochloride Table 34: Clinically Important Drug Interactions with Lurasidone Hydrochloride Strong CYP3A4 Inhibitors Clinical Impact: Concomitant use of lurasidone hydrochloride with strong CYP3A4 inhibitors increased the exposure of lurasidone compared to the use of lurasidone hydrochloride alone [see Clinical Pharmacology ( 12.3 )]. Intervention: Lurasidone hydrochloride should not be used concomitantly with strong CYP3A4 inhibitors [see Contraindications ( 4 )].