Olanzapine and Samidorphan l-malate

LYBALVI is indicated for the treatment of: Schizophrenia in adults Bipolar I disorder in adults Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate Maintenance monotherapy treatment LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, indicated for the treatment of: Schizophrenia in adults. Bipolar I disorder in adults. Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate Maintenance monotherapy treatment

The mechanism of action of olanzapine is unclear, however, its efficacy in the treatment of schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT 2 ) antagonism. The mechanism of action of samidorphan could be mediated through opioid receptor antagonism.

Indication Recommended Starting Dose (olanzapine/samidorphan) Recommended Dose (olanzapine/samidorphan) Schizophrenia 5 mg/10 mg or 10 mg/10 mg 10 mg/10 mg 15 mg/10 mg 20 mg/10 mg Bipolar I disorder (manic or mixed episodes) 10 mg/10 mg or 15 mg/10 mg 5 mg/10 mg 10 mg/10 mg 15 mg/10 mg 20 mg/10 mg Bipolar I disorder adjunct to lithium or valproate 10 mg/10 mg 10 mg/10 mg 15 mg/10 mg 20 mg/10 mg See the full prescribing information for the recommended titration and maximum recommended dosage. Administer LYBALVI once daily with or without food. Do not divide tablets or combine strengths. Recommended starting dosage is 5 mg/10 mg once daily in patients who have a predisposition to hypotensive reactions, have potential for slower metabolism of olanzapine, or may be more pharmacodynamically sensitive to olanzapine.

LYBALVI is contraindicated in patients: who are using opioids. who are undergoing acute opioid withdrawal. If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products. Patients using opioids. Patients undergoing acute opioid withdrawal. If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for those products.

Boxed warning (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. LYBALVI is not approved for the treatment of patients with dementia-related psychosis. Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities). Precipitation of Opioid Withdrawal in Patients Who are Dependent on Opioids: LYBALVI can precipitate opioid withdrawal in patients who are dependent on opioids.

The following adverse reactions are discussed in detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-related Psychosis Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis Precipitation of Opioid Withdrawal in Patients Who Are Dependent on Opioids Vulnerability to Life-Threatening Opioid Overdose Neuroleptic Malignant Syndrome Drug Reaction with Eosinophilia and Systemic Symptoms Metabolic Changes Tardive Dyskinesia Orthostatic Hypotension and Syncope Falls Leukopenia, Neutropenia, and Agranulocytosis Dysphagia Seizures Potential for Cognitive and Motor Impairment Body Temperature Regulation Anticholinergic (Antimuscarinic) Effects Hyperprolactinemia Risks Associated with Combination Treatment with Lithium or Valproate Most common adverse reactions (incidence ≥5% and at least twice placebo): Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache.

Strong CYP3A4 Inducers: Not recommended. Strong CYP1A2 Inhibitors: Consider dosage reduction of olanzapine component of LYBALVI. CYP1A2 Inducer: Consider dosage increase of the olanzapine component of LYBALVI. CNS Acting Drugs: May potentiate orthostatic hypotension. Anticholinergic Drugs: Can increase risk for severe gastrointestinal adverse reactions. Antihypertensive Agents: Monitor blood pressure. Levodopa and Dopamine Agonists: Not recommended.

Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F). Keep tightly closed and protect from moisture.