Fluoxetine and Olanzapine

Olanzapine and fluoxetine capsules are indicated for the treatment of: Acute depressive episodes in Bipolar I Disorder. Treatment resistant depression (Major Depressive Disorder in patient who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode). Olanzapine and fluoxetine capsules combine olanzapine, an atypical antipsychotic and fluoxetine, a selective serotonin reuptake inhibitor, indicated for treatment of: Acute Depressive Episodes Associated with Bipolar I Disorder. Treatment Resistant Depression

The mechanism of action of olanzapine and fluoxetine in the listed indications, is unclear. However, the combined effect of olanzapine and fluoxetine at the monoaminergic neural systems (serotonin, norepinephrine, and dopamine) could be responsible for the pharmacological effect.

Adult Starting Dose: 6 mg olanzapine with 25 mg fluoxetine (6 mg/25 mg, once daily in the evening). Adult Maximum Dose: 12 mg/50 mg once daily. Pediatric Bipolar Depression Starting Dose: 3 mg/25 mg once daily (for ages 10 to 17 years). Pediatric Bipolar Depression Maximum Dose: 12 mg/50 mg. Starting dose in patients predisposed to hypotensive reactions, hepatic impairment, or with potential for slowed metabolism: 3 mg/25 mg to 6 mg/25 mg. Escalate dose cautiously

Monoamine Oxidase Inhibitors (MAOI): Because of the risk of serotonin syndrome, do not use MAOIs intended to treat psychiatric disorders with olanzapine and fluoxetine capsules or within 5 weeks of stopping treatment with olanzapine and fluoxetine capsules. Do not use olanzapine and fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start olanzapine and fluoxetine capsules in a patient who is being treated with linezolid or intravenous methylene blue. Pimozid e: Do not use. Risk of QT interval prolongation. Thioridazine: Do not use. Do not use thioridazine within 5 weeks of discontinuing olanzapine and fluoxetine capsules

Boxed warning: Suicidal Thoughts and Behaviors — Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24, there was a reduction in risk with antidepressant use in patients aged 65 and older. Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue if DRESS is suspected. Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. Hyperglycemia and Diabetes Mellitus: In some cases extreme and associated with ketoacidosis or hyperosmolar coma or death.

The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Increased Mortality in Elderly Patients with Dementia-Related Psychosis Neuroleptic Malignant syndrome (NMS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Hyperglycemia Dyslipidemia Weight Gain Serotonin Syndrome Angle-Closure Glaucoma Allergic Reactions and Rash Activation of Mania/Hypomania Tardive Dyskinesia Orthostatic Hypotension Falls Leukopenia, Neutropenia, and Agranulocytosis Dysphagia Seizures Increased Risk of Bleeding Hyponatremia Potential for Cognitive and Motor Impairment Body Temperature Dysregulation QT Prolongation Anticholinergic (antimuscarinic) Effects Hyperprolactinemia Discontinuation Adverse Reactions Sexual Dysfunction Most common adverse reactions (≥5% and at least twice that for placebo) in adults: sedation, weight increased, appetite increased, dry mouth, fatigue, edema, tremor, disturbance in attention, blurred vision.

The risks of using olanzapine and fluoxetine capsules in combination with other drugs have not been extensively evaluated in systematic studies. The drug-drug interactions sections of fluoxetine and olanzapine are applicable to olanzapine and fluoxetine capsules. As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status. Monoamine Oxidase Inhibitor (MAOI): Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway.

Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° to 30°C (59° to 86°F). Protect from light and moisture.