Fluoxetine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS 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.

Monitor for symptoms of hyperglycemia.

Perform fasting blood glucose testing before beginning, and periodically during treatment.

Dyslipidemia : Appropriate clinical monitoring is recommended, including fasting blood lipid testing before beginning, and periodically during, treatment Weight gain : Consider potential consequences of weight gain.

Monitor weight regularly Serotonin Syndrome : Serotonin syndrome has been reported with SSRIs and SNRIs, including olanzapine and fluoxetine capsules, both when taken alone, but especially when co-administered with other serotonergic agents.

If such symptoms occur, discontinue olanzapine and fluoxetine capsules and serotonergic agents and initiate supportive treatment.

If concomitant use of olanzapine and fluoxetine capsules with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases Angle-Closure Glaucoma : Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants Allergic Reactions and Rash : Discontinue upon appearance of rash or allergic phenomena Activation of Mania/Hypomania : Screen for Bipolar Disorder and monitor for activation of mania/hypomania Tardive Dyskinesia : Discontinue if clinically appropriate Orthostatic Hypotension : Can be associated with bradycardia and syncope.

Risk is increased during initial dose titration.

Use caution in patients with cardiovascular disease or cerebrovascular disease, and those conditions that could affect hemodynamic responses Leukopenia, Neutropenia, and Agranulocytosis : Has been reported with antipsychotics, including olanzapine and fluoxetine capsules.

Patients with a history of a clinically significant low white blood cell count (WBC) or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy.

Consider discontinuing olanzapine and fluoxetine capsules at the first sign of a clinically significant decline in WBC in the absence of other causative factors Seizures : Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold Increased Risk of Bleeding : SSRIs increase the risk of bleeding.

Use with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding Hyponatremia : Can occur in association with syndrome of inappropriate antidiuretic hormone (SIADH).

Consider discontinuing olanzapine and fluoxetine capsules if symptomatic hyponatremia occurs (SIADH) Potential for Cognitive and Motor Impairment : Has potential to impair judgment, thinking, and motor skills.

Caution patients about operating machinery QT Prolongation : QT prolongation and ventricular arrhythmia including Torsade de Pointes have been reported with fluoxetine.

Use with caution in conditions that predispose to arrhythmias or increased fluoxetine exposure.

Use cautiously in patients with risk factors for QT prolongation ( 4.2 , 5.20 ) Anticholinergic (antimuscarinic) Effects : Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, history of paralytic ileus or related conditions Hyperprolactinemia : May elevate prolactin levels Long Elimination Half-Life of Fluoxetine : Changes in dose will not be fully reflected in plasma for several weeks Sexual Dysfunction: Olanzapine and fluoxetine capsules use may cause symptoms of sexual dysfunction 5.1 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients with Major Depressive Disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.

Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.

Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with Major Depressive Disorder (MDD) and other psychiatric disorders.

Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, Obsessive Compulsive Disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.

The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients.

There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied.

There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD.

The risk differences (drug versus placebo), however, were relatively stable within age strata and across indications.