INDICATION AND USES:
PROZAC® is a selective serotonin reuptake inhibitor indicated for:
- Acute and maintenance treatment of Major Depressive Disorder (MDD) (1)
- Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) (1)
- Acute and maintenance treatment of Bulimia Nervosa (1)
- Acute treatment of Panic Disorder, with or without agoraphobia (1)
DOSAGE AND ADMINISTRATION
| Indication | Adult | Pediatric |
| MDD (2.1) | 20 mg/day in am (initial dose) | 10 to 20 mg/day (initial dose) |
| OCD (2.2) | 20 mg/day in am (initial dose) | 10 to 20 mg/day (initial dose) |
| Bulimia Nervosa (2.3) | 60 mg/day in am | |
| Panic Disorder (2.4) | 10 mg/day (initial dose) | |
| Depressive Episodes Associated with Bipolar I Disorder (2.5) | Oral in combination with olanzapine: 5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) | Oral in combination with olanzapine: 2.5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) |
| Treatment Resistant Depression (2.6) | Oral in combination with olanzapine: 5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) |
PROZAC and olanzapine in combination for treatment of:
- Acute Depressive Episodes Associated with Bipolar I Disorder (1)
- Treatment Resistant Depression (1)
- A lower or less frequent dosage should be used in patients with hepatic impairment, the elderly, and for patients with concurrent disease or on multiple concomitant medications (2.7)
PROZAC and olanzapine in combination:
- Dosage adjustments should be made with the individual components according to efficacy and tolerability (2.5, 2.6)
- Fluoxetine monotherapy is not indicated for the treatment of Depressive Episodes associated with Bipolar I Disorder or treatment resistant depression (2.5, 2.6)
- Safety of the coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in adults (2.5, 2.6)
- Safety of the coadministration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in children and adolescents ages 10 to 17 (2.5)
SIDE EFFECTS:
Most common adverse reactions (≥5% and at least twice that for placebo) associated with:
Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder: abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido decreased, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawn (6.1)
PROZAC and olanzapine in combination – Also refer to the Adverse Reactions section of the package insert for Symbyax (6)
CONTRAINDICATIONS:
- Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PROZAC or within 5 weeks of stopping treatment with PROZAC. Do not use PROZAC within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start PROZAC in a patient who is being treated with linezolid or intravenous methylene blue (4.1)
- Pimozide: Do not use. Risk of QT prolongation and drug interaction (4.2, 5.11, 7.7, 7.8)
- Thioridazine: Do not use. Risk of QT interval prolongation and elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing PROZAC. Do not use thioridazine within 5 weeks of discontinuing PROZAC (4.2, 5.11, 7.7, 7.8)
- When using PROZAC and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax (4)
WARNINGS AND PRECAUTIONS:
- Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults: Monitor for clinical worsening and suicidal thinking and behavior (5.1)
- Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including PROZAC, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort). If such symptoms occur, discontinue PROZAC and initiate supportive treatment. If concomitant use of PROZAC 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 (5.2)
- Allergic Reactions and Rash: Discontinue upon appearance of rash or allergic phenomena (5.3)
- Activation of Mania/Hypomania: Screen for Bipolar Disorder and monitor for mania/hypomania (5.4)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold (5.5)
- Altered Appetite and Weight: Significant weight loss has occurred (5.6)
- Abnormal Bleeding: May 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 (5.7)
- Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.8)
- Hyponatremia: Has been reported with PROZAC in association with syndrome of inappropriate antidiuretic hormone (SIADH). Consider discontinuing if symptomatic hyponatremia occurs (5.9)
- Anxiety and Insomnia: May occur (5.10)
- QT Prolongation: QT prolongation and ventricular arrhythmia including Torsades de Pointes have been reported with PROZAC use. 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, 5.11)
- Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery (5.13)
- Long Half-Life: Changes in dose will not be fully reflected in plasma for several weeks (5.14)
- PROZAC and Olanzapine in Combination: When using PROZAC and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax (5.16)
DRUG INTERACTIONS:
- Monoamine Oxidase Inhibitors (MAOIs): (2.9, 2.10, 4.1, 5.2)
- Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.7)
- Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with PROZAC or when PROZAC has been recently discontinued (5.2, 7.7)
- CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs (7.2)
- Benzodiazepines: Diazepam – increased t½, alprazolam – further psychomotor performance decrement due to increased levels (7.7)
- Antipsychotics: Potential for elevation of haloperidol and clozapine levels (7.7)
- Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity (7.7)
- Serotonergic Drugs: (2.9, 2.10, 4.1, 5.2)
- Drugs that Interfere with Hemostasis (e.g. NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding (7.4)
- Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations (7.6, 7.7)
- Olanzapine: When used in combination with PROZAC, also refer to the Drug Interactions section of the package insert for Symbyax (7.7)
- Drugs that Prolong the QT Interval: Do not use Prozac with thioridazine or pimozide. Use with caution in combination with other drugs that prolong the QT interval (4.2, 5.11, 7.7, 7.8)
OVERDOSE:
Worldwide exposure to fluoxetine hydrochloride is estimated to be over 38 million patients (circa 1999). Of the 1578 cases of overdose involving fluoxetine hydrochloride, alone or with other drugs, reported from this population, there were 195 deaths. Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania. The remaining 206 patients had an unknown outcome. The most common signs and symptoms associated with non-fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting. The largest known ingestion of fluoxetine hydrochloride in adult patients was 8 grams in a patient who took fluoxetine alone and who subsequently recovered. However, in an adult patient who took fluoxetine alone, an ingestion as low as 520 mg has been associated with lethal outcome, but causality has not been established. Among pediatric patients (ages 3 months to 17 years), there were 156 cases of overdose involving fluoxetine alone or in combination with other drugs. Six patients died, 127 patients completely recovered, 1 patient experienced renal failure, and 22 patients had an unknown outcome. One of the six fatalities was a 9-year-old boy who had a history of OCD, Tourette’s syndrome with tics, attention deficit disorder, and fetal alcohol syndrome. He had been receiving 100 mg of fluoxetine daily for 6 months in addition to clonidine, methylphenidate, and promethazine. Mixed-drug ingestion or other methods of suicide complicated all 6 overdoses in children that resulted in fatalities. The largest ingestion in pediatric patients was 3 grams which was nonlethal. Other important adverse reactions reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as nodal rhythm, QT interval prolongation and ventricular arrhythmias, including Torsades de Pointes-type arrhythmias), hypotension, mania, neuroleptic malignant syndrome-like reactions, pyrexia, stupor, and syncope.
Management of Overdose: For current information on the management of PROZAC overdose, contact a certified poison control center (1-800- 222-1222 or www.poison.org). Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multi-drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use general supportive and symptomatic measures. Induction of emesis is not recommended. Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for fluoxetine are known. A specific caution involves patients who are taking or have recently taken fluoxetine and might ingest excessive quantities of a TCA. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation [see Drug Interactions (7.7)]. For specific information about overdosage with olanzapine and fluoxetine in combination, refer to the Overdosage section of the Symbyax package insert.
- Uses
-
INDICATION AND USES:
PROZAC® is a selective serotonin reuptake inhibitor indicated for:
- Acute and maintenance treatment of Major Depressive Disorder (MDD) (1)
- Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) (1)
- Acute and maintenance treatment of Bulimia Nervosa (1)
- Acute treatment of Panic Disorder, with or without agoraphobia (1)
DOSAGE AND ADMINISTRATION
Indication Adult Pediatric MDD (2.1) 20 mg/day in am (initial dose) 10 to 20 mg/day (initial dose) OCD (2.2) 20 mg/day in am (initial dose) 10 to 20 mg/day (initial dose) Bulimia Nervosa (2.3) 60 mg/day in am Panic Disorder (2.4) 10 mg/day (initial dose) Depressive Episodes Associated with Bipolar I Disorder (2.5) Oral in combination with olanzapine: 5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) Oral in combination with olanzapine: 2.5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) Treatment Resistant Depression (2.6) Oral in combination with olanzapine: 5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) PROZAC and olanzapine in combination for treatment of:
- Acute Depressive Episodes Associated with Bipolar I Disorder (1)
- Treatment Resistant Depression (1)
- A lower or less frequent dosage should be used in patients with hepatic impairment, the elderly, and for patients with concurrent disease or on multiple concomitant medications (2.7)
PROZAC and olanzapine in combination:
- Dosage adjustments should be made with the individual components according to efficacy and tolerability (2.5, 2.6)
- Fluoxetine monotherapy is not indicated for the treatment of Depressive Episodes associated with Bipolar I Disorder or treatment resistant depression (2.5, 2.6)
- Safety of the coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in adults (2.5, 2.6)
- Safety of the coadministration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in children and adolescents ages 10 to 17 (2.5)
- Side Effects
-
SIDE EFFECTS:
Most common adverse reactions (≥5% and at least twice that for placebo) associated with:
Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder: abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido decreased, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawn (6.1)
PROZAC and olanzapine in combination – Also refer to the Adverse Reactions section of the package insert for Symbyax (6)
- Precautions
-
CONTRAINDICATIONS:
- Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PROZAC or within 5 weeks of stopping treatment with PROZAC. Do not use PROZAC within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start PROZAC in a patient who is being treated with linezolid or intravenous methylene blue (4.1)
- Pimozide: Do not use. Risk of QT prolongation and drug interaction (4.2, 5.11, 7.7, 7.8)
- Thioridazine: Do not use. Risk of QT interval prolongation and elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing PROZAC. Do not use thioridazine within 5 weeks of discontinuing PROZAC (4.2, 5.11, 7.7, 7.8)
- When using PROZAC and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax (4)
WARNINGS AND PRECAUTIONS:
- Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults: Monitor for clinical worsening and suicidal thinking and behavior (5.1)
- Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including PROZAC, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort). If such symptoms occur, discontinue PROZAC and initiate supportive treatment. If concomitant use of PROZAC 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 (5.2)
- Allergic Reactions and Rash: Discontinue upon appearance of rash or allergic phenomena (5.3)
- Activation of Mania/Hypomania: Screen for Bipolar Disorder and monitor for mania/hypomania (5.4)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold (5.5)
- Altered Appetite and Weight: Significant weight loss has occurred (5.6)
- Abnormal Bleeding: May 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 (5.7)
- Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.8)
- Hyponatremia: Has been reported with PROZAC in association with syndrome of inappropriate antidiuretic hormone (SIADH). Consider discontinuing if symptomatic hyponatremia occurs (5.9)
- Anxiety and Insomnia: May occur (5.10)
- QT Prolongation: QT prolongation and ventricular arrhythmia including Torsades de Pointes have been reported with PROZAC use. 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, 5.11)
- Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery (5.13)
- Long Half-Life: Changes in dose will not be fully reflected in plasma for several weeks (5.14)
- PROZAC and Olanzapine in Combination: When using PROZAC and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax (5.16)
- Interactions
-
DRUG INTERACTIONS:
- Monoamine Oxidase Inhibitors (MAOIs): (2.9, 2.10, 4.1, 5.2)
- Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.7)
- Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with PROZAC or when PROZAC has been recently discontinued (5.2, 7.7)
- CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs (7.2)
- Benzodiazepines: Diazepam – increased t½, alprazolam – further psychomotor performance decrement due to increased levels (7.7)
- Antipsychotics: Potential for elevation of haloperidol and clozapine levels (7.7)
- Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity (7.7)
- Serotonergic Drugs: (2.9, 2.10, 4.1, 5.2)
- Drugs that Interfere with Hemostasis (e.g. NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding (7.4)
- Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations (7.6, 7.7)
- Olanzapine: When used in combination with PROZAC, also refer to the Drug Interactions section of the package insert for Symbyax (7.7)
- Drugs that Prolong the QT Interval: Do not use Prozac with thioridazine or pimozide. Use with caution in combination with other drugs that prolong the QT interval (4.2, 5.11, 7.7, 7.8)
- Overdose
-
OVERDOSE:
Worldwide exposure to fluoxetine hydrochloride is estimated to be over 38 million patients (circa 1999). Of the 1578 cases of overdose involving fluoxetine hydrochloride, alone or with other drugs, reported from this population, there were 195 deaths. Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania. The remaining 206 patients had an unknown outcome. The most common signs and symptoms associated with non-fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting. The largest known ingestion of fluoxetine hydrochloride in adult patients was 8 grams in a patient who took fluoxetine alone and who subsequently recovered. However, in an adult patient who took fluoxetine alone, an ingestion as low as 520 mg has been associated with lethal outcome, but causality has not been established. Among pediatric patients (ages 3 months to 17 years), there were 156 cases of overdose involving fluoxetine alone or in combination with other drugs. Six patients died, 127 patients completely recovered, 1 patient experienced renal failure, and 22 patients had an unknown outcome. One of the six fatalities was a 9-year-old boy who had a history of OCD, Tourette’s syndrome with tics, attention deficit disorder, and fetal alcohol syndrome. He had been receiving 100 mg of fluoxetine daily for 6 months in addition to clonidine, methylphenidate, and promethazine. Mixed-drug ingestion or other methods of suicide complicated all 6 overdoses in children that resulted in fatalities. The largest ingestion in pediatric patients was 3 grams which was nonlethal. Other important adverse reactions reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as nodal rhythm, QT interval prolongation and ventricular arrhythmias, including Torsades de Pointes-type arrhythmias), hypotension, mania, neuroleptic malignant syndrome-like reactions, pyrexia, stupor, and syncope.
Management of Overdose: For current information on the management of PROZAC overdose, contact a certified poison control center (1-800- 222-1222 or www.poison.org). Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multi-drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use general supportive and symptomatic measures. Induction of emesis is not recommended. Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for fluoxetine are known. A specific caution involves patients who are taking or have recently taken fluoxetine and might ingest excessive quantities of a TCA. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation [see Drug Interactions (7.7)]. For specific information about overdosage with olanzapine and fluoxetine in combination, refer to the Overdosage section of the Symbyax package insert.