FLUOXETINE- fluoxetine hydrochloride_capsule

Although the exact mechanism of fluoxetine is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Studies at clinically relevant doses in man have demonstrated that fluoxetine blocks the uptake of serotonin into human platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine. 1 in vitro Systemic Bioavailability in vitro 1 R S S S R S R S S S R [see Drug Interactions (7. 7) [see Warnings and Precautions (5. 14) Liver Disease [see Dosage and Administration (2. 7 Use in Specific Populations (8.

Fluoxetine capsules are indicated for the treatment of: Acute and maintenance treatment of Major Depressive Disorder [see Clinical Studies (14. 1) Acute and maintenance treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD) [see Clinical Studies (14. 2) Acute and maintenance treatment of binge-eating and vomiting behaviors in patients with moderate to severe Bulimia Nervosa [see Clinical Studies (14. 3) Acute treatment of Panic Disorder, with or without agoraphobia [see Clinical Studies (14. 4) Fluoxetine capsules and Olanzapine in Combination are indicated for the treatment of: Acute treatment of depressive episodes associated with Bipolar I Disorder. Treatment resistant depression (Major Depressive Disorder in patients, who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode). Fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder or the treatment of treatment resistant depression. registered Fluoxetine capsules are 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 Fluoxetine capsules and olanzapine in combination for treatment of: Acute Depressive Episodes Associated with Bipolar I Disorder ( 1 Treatment Resistant Depression ( 1.

Indication Adult Pediatric MDD ( 2. 1 20 mg/day in am (initial dose) 10 to 20 mg/day OCD ( 2. 2 20 mg/day in am (initial dose) 10 mg/day Bulimia Nervosa 2. 3 60 mg/day in am Panic Disorder ( 2. 4 10 mg/day (initial dose) Depressive Episodes 2. 5 Oral in combination with Oral in combination with olanzapine: 2. 6 Oral in combination with 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 Fluoxetine capsules and olanzapine in combination: Dosage adjustments should be made with the individual components according to efficacy and tolerability ( 2. 6 Fluoxetine monotherapy is not indicated for the treatment of Depressive Episodes associated with Bipolar I Disorder or treatment resistant depression ( 2. 6 Safety of the coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in adults ( 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 Initial Treatment [see Clinical Studies (14. 1) [see Clinical Studies (14. 1) [see Warnings and Precautions (5. 2) Drug Interactions (7. 7) Initial Treatment [see Clinical Studies (14. 2) [see Clinical Studies (14. 2) Initial Treatment [see Clinical Studies (14. 3) Initial Treatment [see Clinical Studies (14. 4) When using fluoxetine capsules and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax Adult Children and adolescents (10 to 17 years of age ) Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine capsules and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability. Table 1: Approximate Dose Correspondence Between Symbyax 1 1 For Symbyax (mg/day) Use in Combination Olanzapine (mg/day) Fluoxetine (mg/day) 3 mg olanzapine/25 mg fluoxetine 2. 5 20 6 mg olanzapine/25 mg fluoxetine 5 20 12 mg olanzapine/25 mg fluoxetine 10+2. 5 20 6 mg olanzapine/50 mg fluoxetine 5 40+10 12 mg olanzapine/50 mg fluoxetine 10+2. 5 40+10 When using fluoxetine capsules and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax. Administer fluoxetine in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Adjust dosage, if indicated, according to efficacy and tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 20 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 18 mg and fluoxetine 25 to 50 mg. Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Table 1 demonstrates the appropriate individual component doses of fluoxetine capsules and olanzapine versus Symbyax. Periodically re-examine the need for continued pharmacotherapy. Safety of coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Fluoxetine capsules monotherapy is not indicated for the treatment of treatment resistant depression (Major Depressive Disorder in patients who do not respond to 2 antidepressants of adequate dose and duration in the current episode). Geriatric [see Use in Specific Populations (8. 5) [see Clinical Pharmacology (12. 4) Use in Specific Populations (8. 6) [see Clinical Pharmacology (12. 4) Warnings and Precautions (5. 12) [see Warnings and Precautions (5. 16) Drug Interactions (7. 7) Symptoms associated with discontinuation of fluoxetine, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5. At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with fluoxetine capsules. Conversely, at least 5 weeks should be allowed after stopping fluoxetine capsules before starting an MAOI intended to treat psychiatric disorders [ see Contraindications (4. 1) Do not start fluoxetine capsules in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4. 2) [see Warnings and Precautions (5.

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 [see Boxed Warning Warnings and Precautions (5. 1) Serotonin Syndrome [see Warnings and Precautions (5. 2) Allergic Reactions and Rash [see Warnings and Precautions (5. 3) Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania [see Warnings and Precautions (5. 4) Seizures [see Warnings and Precautions (5. 5) Altered Appetite and Weight [see Warnings and Precautions (5. 6) Increased Risk of Bleeding [see Warnings and Precautions (5. 7) Angle-Closure Glaucoma [see Warnings and Precautions (5. 8) Hyponatremia [see Warnings and Precautions (5. 9) Anxiety and Insomnia [see Warnings and Precautions (5. 10) QT Prolongation [see Warnings and Precautions (5. 11) Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5. 13) Discontinuation Adverse Reactions [see Warnings and Precautions (5. 15) Sexual Dysfunction [see Warnings and Precautions (5. 17) When using fluoxetine and olanzapine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax. Most common adverse reactions (>=5% and at least twice that for placebo) associated with: (6. gov/medwatch Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice. Table 3: Most Common Treatment-Emergent Adverse Reactions: Incidence in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials 1,2 Percentage of Patients Reporting Event Major Depressive OCD Bulimia Panic Disorder 1 2 3 Body System/ Adverse Reaction Fluoxetine Placebo Fluoxetine Placebo Fluoxetine Placebo Fluoxetine Placebo Body as a Whole Asthenia 9 5 15 11 21 9 7 7 Flu syndrome 3 4 10 7 8 3 5 5 Cardiovascular System Vasodilatation 3 2 5 -- 2 1 1 -- Digestive System Nausea 21 9 26 13 29 11 12 7 Diarrhea 12 8 18 13 8 6 9 4 Anorexia 11 2 17 10 8 4 4 1 Dry mouth 10 7 12 3 9 6 4 4 Dyspepsia 7 5 10 4 10 6 6 2 Nervous System Insomnia 16 9 28 22 33 13 10 7 Anxiety 12 7 14 7 15 9 6 2 Nervousness 14 9 14 15 11 5 8 6 Somnolence 13 6 17 7 13 5 5 2 Tremor 10 3 9 1 13 1 3 1 Libido decreased 3 -- 11 2 5 1 1 2 Abnormal dreams 1 1 5 2 5 3 1 1 Respiratory System Pharyngitis 3 3 11 9 10 5 3 3 Sinusitis 1 4 5 2 6 4 2 3 Yawn -- -- 7 -- 11 -- 1 -- Skin and Appendages Sweating 8 3 7 -- 8 3 2 2 Rash 4 3 6 3 4 4 2 2 Urogenital System Impotence 3 2 -- -- -- 7 -- 1 -- Abnormal ejaculation 3 -- -- 7 -- 7 -- 2 1 Table 4: Treatment-Emergent Adverse Reactions: Incidence in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials 1,2 Percentage of Patients Reporting Event Major Depressive Disorder, OCD, 1 2 Body System/Adverse Reaction Fluoxetine Placebo Body as a Whole Headache 21 19 Asthenia 11 6 Flu syndrome 5 4 Fever 2 1 Cardiovascular System Vasodilatation 2 1 Digestive System Nausea 22 9 Diarrhea 11 7 Anorexia 10 3 Dry mouth 9 6 Dyspepsia 8 4 Constipation 5 4 Flatulence 3 2 Vomiting 3 2 Metabolic and Nutritional Disorders Weight loss 2 1 Nervous System Insomnia 19 10 Nervousness 13 8 Anxiety 12 6 Somnolence 12 5 Dizziness 9 6 Tremor 9 2 Libido decreased 4 1 Thinking abnormal 2 1 Respiratory System Yawn 3 -- Skin and Appendages Sweating 7 3 Rash 4 3 Pruritus 3 2 Special Senses Abnormal vision 2 1 Associated with discontinuation in Major Depressive Disorder, OCD, bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials) Table 5: Most Common Adverse Reactions Associated with Discontinuation in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials 1 1 Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Combined Major Depressive Disorder OCD Bulimia Panic Disorder Anxiety (1%) -- Anxiety (2%) -- Anxiety (2%) -- -- -- Insomnia (2%) -- -- Nervousness (1%) -- -- Nervousness (1%) -- -- Rash (1%) -- -- Other adverse reactions in pediatric patients (children and adolescents) Following is a list of treatment-emergent adverse reactions reported by patients treated with fluoxetine in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo. Frequent: Infrequent: Rare: Frequent: Infrequent: 1 Digestive System Infrequent: Rare: Hemic and Lymphatic System Infrequent: Rare: Investigations em dash Frequent: c 3 Nervous System Frequent: Infrequent: 1 1 Rare: Respiratory System Rare: Skin and Appendages Infrequent: Rare: Special Senses Frequent: Infrequent: Urogenital System em dash Frequent: Infrequent: 2 1 2 3 The following adverse reactions have been identified during post approval use of fluoxetine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or evaluate a causal relationship to drug exposure. Voluntary reports of adverse reactions temporally associated with fluoxetine that have been received since market introduction and that may have no causal relationship with the drug include the following: anosmia, aplastic anemia, atrial fibrillation 1 1 1 1 1 1 1 1.

When using fluoxetine capsules and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax. Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with fluoxetine capsules or within 5 weeks of stopping treatment with fluoxetine capsules. Do not use fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start fluoxetine capsules 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. 8) Thioridazine: Do not use. Risk of QT interval prolongation and elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing fluoxetine (4. 8) When using fluoxetine capsules and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax (4) The use of MAOIs intended to treat psychiatric disorders with fluoxetine capsules or within 5 weeks of stopping treatment with fluoxetine capsules is contraindicated because of an increased risk of serotonin syndrome. The use of fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2. 9) Warnings and Precautions (5. 2) [see Dosage and Administration (2. 10) Warnings and Precautions (5. 2) The use of fluoxetine capsules is contraindicated with the following: Pimozide [see Warnings and Precautions (5. 11) Drug Interactions (7. 8) Thioridazine [see Warnings and Precautions (5. 8) Pimozide and thioridazine prolong the QT interval. Fluoxetine capsules can increase the levels of pimozide and thioridazine through inhibition of CYP2D6. Fluoxetine capsules can also prolong the QT interval.

When using fluoxetine and olanzapine in combination, also refer to the Use in Specific Populations section of the package insert for Symbyax. Pregnancy: 8. 1 Pediatric Use: (8. 4) Hepatic Impairment: (8. 6) Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth. org/clinical-and-research­programs/pregnancyregistry/antidepressants/. Risk Summary [see Warnings and Precautions (5. 7) (see Data) (see Data) (see Clinical Considerations). In rats and rabbits treated with fluoxetine during the period of organogenesis, there was no evidence of developmental effects at doses up to 1. 9 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m 2 2 The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. [see Warnings and Precautions (5. 7) Neonates exposed to fluoxetine and other SSRI or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of SSRIs and SNRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5. 2) Data Human Data em dash Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1 to 2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data 2 2 2 2 Risk Summary Data from published literature report the presence of fluoxetine and norfluoxetine in human milk (see Data). (see Clinical Considerations). Clinical Considerations Infants exposed to fluoxetine should be monitored for agitation, irritability, poor feeding, and poor weight gain. Data A study of 19 nursing mothers on fluoxetine with daily doses of 10-60 mg showed that fluoxetine was detectable in 30% of nursing infant sera (range: 1 to 84 ng/mL) whereas norfluoxetine was found in 85% (range: <1 to 265 ng/mL). Use of fluoxetine in children - [see Clinical Studies (14. 1) The efficacy of fluoxetine for the treatment of OCD was demonstrated in one 13-week placebo-controlled clinical trial with 103 pediatric outpatients ages 7 to <18 [see Clinical Studies (14. 2) The safety and effectiveness in pediatric patients <8 years of age in Major Depressive Disorder and <7 years of age in OCD have not been established. Fluoxetine pharmacokinetics were evaluated in 21 pediatric patients (ages 6 to <=18) with Major Depressive Disorder or OCD [see Clinical Pharmacology (12. 3) The acute adverse reaction profiles observed in the 3 studies (N=418 randomized; 228 fluoxetine-treated, 190 placebo-treated) were generally similar to that observed in adult studies with fluoxetine. The longer-term adverse reaction profile observed in the 19-week Major Depressive Disorder study (N=219 randomized; 109 fluoxetine-treated, 110 placebo-treated) was also similar to that observed in adult trials with fluoxetine [see Adverse Reactions (6. 1) Manic reaction, including mania and hypomania, was reported in 6 (1 mania, 5 hypomania) out of 228 (2. 6%) fluoxetine-treated patients and in 0 out of 190 (0%) placebo-treated patients. Mania/hypomania led to the discontinuation of 4 (1. 8%) fluoxetine-treated patients from the acute phases of the 3 studies combined. Consequently, regular monitoring for the occurrence of mania/hypomania is recommended. As with other SSRIs, decreased weight gain has been observed in association with the use of fluoxetine in children and adolescent patients. After 19 weeks of treatment in a clinical trial, pediatric subjects treated with fluoxetine gained an average of 1. 1 cm less in height and 1. 1 kg less in weight than subjects treated with placebo. In addition, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels. The safety of fluoxetine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than several months in duration. In particular, there are no studies that directly evaluate the longer-term effects of fluoxetine on the growth, development and maturation of children and adolescent patients. Therefore, height and weight should be monitored periodically in pediatric patients receiving fluoxetine [see Warnings and Precautions (5. 6) Fluoxetine is approved for use in pediatric patients with MDD and OCD [see Box Warning Warnings and Precautions (5. 1) Animal Data These fluoxetine toxicities in juvenile rats have not been observed in adult animals. Plasma exposures (AUC) to fluoxetine in juvenile rats receiving 3, 10, or 30 mg/kg/day doses in this study are approximately 0. 2, 1 to 2, and 5 to 10 times, respectively, the average exposure in pediatric patients receiving the MRHD of 20 mg/day. Rat exposures to the major metabolite, norfluoxetine, are approximately 0. 8, 1 to 8, and 3 to 20 times, respectively, the pediatric exposure at the MRHD. A specific effect on bone development was reported in juvenile mice administered fluoxetine by the intraperitoneal route to 4 week old mice for 4 weeks at doses 0. 5 and 2 times the oral MRHD of 20 mg/day on mg/m 2 Use of fluoxetine in combination with olanzapine in children and adolescents: U. fluoxetine clinical trials included 687 patients >=65 years of age and 93 patients >=75 years of age. The efficacy in geriatric patients has been established [see Clinical Studies (14. 1) [see Clinical Pharmacology (12. 4) [see Warnings and Precautions (5. 9) In subjects with cirrhosis of the liver, the clearances of fluoxetine and its active metabolite, norfluoxetine, were decreased, thus increasing the elimination half-lives of these substances. A lower or less frequent dose of fluoxetine should be used in patients with cirrhosis. Caution is advised when using fluoxetine in patients with diseases or conditions that could affect its metabolism [see Dosage and Administration (2. 7 Clinical Pharmacology (12.

As with all drugs, the potential for interaction by a variety of mechanisms (e. , pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc. ) is a possibility. Monoamine Oxidase Inhibitors (MAOIs): (2. 2 Drugs Metabolized by CYP2D6: (7. 7) Tricyclic Antidepressants (TCAs): (5. 7) CNS Acting Drugs: (7. 2) Benzodiazepines: (7. 7) Antipsychotics: (7. 7) Anticonvulsants: (7. 7) Serotonergic Drugs: (2. 2) Drugs that Interfere with Hemostasis (e. , NSAIDs, Aspirin, Warfarin): (7. 4) Drugs Tightly Bound to Plasma Proteins: (7. 7) Olanzapine: (7. 7) Drugs that Prolong the QT Interval: 4. 8 [See Dosage and Administration (2. 10 Contraindications (4. 1) Warnings and Precautions (5. 2) Caution is advised if the concomitant administration of fluoxetine and such drugs is required. 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 [see Clinical Pharmacology (12. 3) The concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) with fluoxetine increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of fluoxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5. 2) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SNRIs or SSRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when fluoxetine is initiated or discontinued [see Warnings and Precautions (5. 7) There are no clinical studies establishing the benefit of the combined use of ECT and fluoxetine. There have been rare reports of prolonged seizures in patients on fluoxetine receiving ECT treatment. Drugs Tightly Bound to Plasma Proteins em dash [see Clinical Pharmacology (12. 3) Pimozide em dash [see Contraindications (4. 2) Warnings and Precautions (5. 11) Drug Interactions (7. 8) [see Contraindications (4. 8) max [see Contraindications (4. 2 em dash [see Warnings and Precautions (5. 2) Clinical Pharmacology (12. 3) em dash [see Clinical Pharmacology (12. 3) Lithium em dash [see Warnings and Precautions (5. em dash [see Clinical Pharmacology (12. 3) em dash in vivo in vitro em dash Symbyax. Do not use fluoxetine in combination with thioridazine or pimozide. Use fluoxetine with caution in combination with other drugs that cause QT prolongation. These include: specific antipsychotics (e. , ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e. , erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e. , quinidine, procainamide); Class III antiarrhythmics (e. , amiodarone, sotalol); and others (e. , pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). Fluoxetine is primarily metabolized by CYP2D6. Concomitant treatment with CYP2D6 inhibitors can increase the concentration of fluoxetine. Concomitant use of other highly protein-bound drugs can increase the concentration of fluoxetine [see Contraindications (4. 7) Clinical Pharmacology (12.

OVERDOSAGE
The following have been reported with fluoxetine overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, torsade de pointes, and cardiac arrest. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other pro-serotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a fluoxetine overdose. Consider contacting a Poison Center (1-800-221-2222) or a medical toxicologist for additional overdosage management recommendations.
NONCLINICAL TOXICOLOGY
Carcinogenicity 2 Mutagenicity in vivo Impairment of Fertility em dash 2 [see Use in Specific Populations (8. 4) Phospholipids are increased in some tissues of mice, rats, and dogs given fluoxetine chronically. This effect is reversible after cessation of fluoxetine treatment. Phospholipid accumulation in animals has been observed with many cationic amphiphilic drugs, including fenfluramine, imipramine, and ranitidine. The significance of this effect in humans is unknown.
CLINICAL STUDIES
Efficacy for fluoxetine was established for the: Acute and maintenance treatment of Major Depressive Disorder in adults, and children and adolescents (8 to 18 years) in 7 short-term and 2 long-term, placebo-controlled trials [see Clinical Studies (14. 1) Acute treatment of obsessions and compulsions in adults, and children and adolescents (7 to 17 years) with Obsessive Compulsive Disorder (OCD) in 3 short-term placebo-controlled trials [see Clinical Studies (14. 2) Acute and maintenance treatment of binge-eating and vomiting behaviors in adult patients with moderate to severe Bulimia Nervosa in 3 short-term and 1 long-term, placebo-controlled trials [see Clinical Studies (14. 3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients in 2 short-term, placebo-controlled trials [see Clinical Studies (14. 4) Efficacy for fluoxetine and olanzapine in combination was established for the: Acute treatment of depressive episodes in Bipolar I Disorder in adults, and children and adolescents (10 to 17 years) in 3 short-term, placebo-controlled trials. Acute and maintenance treatment of treatment resistant depression in adults (18 to 85 years) in 3 short-term, placebo-controlled trials and 1 randomized withdrawal study with an active control. When using fluoxetine and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax. Daily Dosing. em dash Adult Table 6 Outcome Classification (%) on CGI Improvement Scale for Completers in Pool of Two OCD Studies Fluoxetine Outcome Classification Placebo 20 mg 40 mg 60 mg Worse 8% 0% 0% 0% No change 64% 41% 33% 29% Minimally improved 17% 23% 28% 24% Much improved 8% 28% 27% 28% Very much improved 3% 8% 12% 19% Exploratory analyses for age and gender effects on outcome did not suggest any differential responsiveness on the basis of age or sex. Subgroup analyses on outcome did not suggest any differential responsiveness on the basis of age or gender. The effectiveness of fluoxetine for the treatment of bulimia was demonstrated in two 8-week and one 16-week, multicenter, parallel group studies of adult outpatients meeting DSM-III-R criteria for bulimia. Patients in the 8-week studies received either 20 or 60 mg/day of fluoxetine or placebo in the morning. Patients in the 16-week study received a fixed fluoxetine dose of 60 mg/day (once a day) or placebo. Patients in these 3 studies had moderate to severe bulimia with median binge-eating and vomiting frequencies ranging from 7 to 10 per week and 5 to 9 per week, respectively. In these 3 studies, fluoxetine 60 mg, but not 20 mg, was statistically significantly superior to placebo in reducing the number of binge-eating and vomiting episodes per week. The statistically significantly superior effect of 60 mg versus placebo was present as early as Week 1 and persisted throughout each study. The fluoxetine-related reduction in bulimic episodes appeared to be independent of baseline depression as assessed by the Hamilton Depression Rating Scale. In each of these 3 studies, the treatment effect, as measured by differences between fluoxetine 60 mg and placebo on median reduction from baseline in frequency of bulimic behaviors at endpoint, ranged from 1 to 2 episodes per week for binge-eating and 2 to 4 episodes per week for vomiting. The size of the effect was related to baseline frequency, with greater reductions seen in patients with higher baseline frequencies. Although some patients achieved freedom from binge-eating and purging as a result of treatment, for the majority, the benefit was a partial reduction in the frequency of binge-eating and purging. The effectiveness of fluoxetine in the treatment of Panic Disorder was demonstrated in 2 double-blind, randomized, placebo-controlled, multicenter studies of adult outpatients who had a primary diagnosis of Panic Disorder (DSM-IV), with or without agoraphobia.
Medication Guide
Fluoxetine Capsules, USP for oral use What is the most important information I should know about fluoxetine capsules? 1. Suicidal thoughts or actions: Fluoxetine capsules and other antidepressant medicines may increase suicidal thoughts or actions first few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice: New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when fluoxetine capsules are started or when the dose is changed. Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting on dangerous impulses acting aggressive or violent thoughts about suicide or dying new or worse depression new or worse anxiety or panic attacks feeling agitated, restless, angry or irritable trouble sleeping an increase in activity or talking more than what is normal for you other unusual changes in behavior or mood Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Fluoxetine capsules may be associated with these serious side effects: 2. Serotonin Syndrome. This condition can be life-threatening and may include: agitation, hallucinations, coma or other changes in mental status coordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressure sweating or fever nausea, vomiting, or diarrhea muscle rigidity dizziness flushing tremor seizures 3. Severe allergic reactions: trouble breathing swelling of the face, tongue, eyes or mouth rash, itchy welts (hives) or blisters, alone or with fever or joint pain 4. Abnormal bleeding: registered registered 5. Visual problems: eye pain changes in vision swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Seizures or convulsions 7. Manic episodes: greatly increased energy severe trouble sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual 8. Changes in appetite or weight. Low salt (sodium) levels in the blood. headache weakness or feeling unsteady confusion, problems concentrating or thinking or memory problems 10. Changes in the electrical activity of your heart (QT prolongation and ventricular arrhythmia including Torsades de Pointes). This condition can be life threatening. The symptoms may include: fast, slow, or irregular heartbeat shortness of breath dizziness or fainting 11. Sexual problems (dysfunction). Symptoms in males may include: Delayed ejaculation or inability to have an ejaculation Decreased sex drive Problems getting or keeping an erection Symptoms in females may include: Decreased sex drive Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with fluoxetine capsules. There may be treatments your healthcare provider can suggest. without first talking to your healthcare provider. anxiety, irritability, high or low mood, feeling restless or changes in sleep habits headache, sweating, nausea, dizziness electric shock-like sensations, shaking, confusion What are fluoxetine capsules? Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Bulimia Nervosa* Panic Disorder* Depressive episodes associated with Bipolar I Disorder, taken with olanzapine (Zyprexa) Treatment Resistant Depression (depression that has not gotten better with at least 2 other treatments), taken with olanzapine (Zyprexa)* *Not approved for use in children Who should not take fluoxetine capsules? are allergic to fluoxetine hydrochloride or any of the ingredients in fluoxetine capsules. See the end of this Medication Guide for a complete list of ingredients in fluoxetine capsules. take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 5 weeks of stopping fluoxetine capsules unless directed to do so by your physician. Do not start fluoxetine capsules if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. People who take fluoxetine capsules close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever uncontrolled muscle spasms stiff muscles rapid changes in heart rate or blood pressure confusion loss of consciousness (pass out) take Mellaril registered registered take the antipsychotic medicine pimozide (Orap registered What should I tell my healthcare provider before taking fluoxetine capsules? Ask if you are not sure. Are taking certain drugs or treatments such as: Triptans used to treat migraine headache Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, buspirone, SSRIs, SNRIs, MAOIs or antipsychotics Amphetamines Tramadol, fentanyl, meperidine, methadone, or other opioids Over-the-counter supplements such as tryptophan or St. John’s Wort Electroconvulsive therapy (ECT) have liver problems have kidney problems have heart problems have or had seizures or convulsions have bipolar disorder or mania have low sodium levels in your blood have a history of a stroke have high blood pressure have or had bleeding problems are pregnant or plan to become pregnant. Taking fluoxetine capsules late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy. If you become pregnant while taking fluoxetine capsules, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185 or go to https://womensmentalhealth. org/clinical-and-research-programs/pregnancyregistry/antidepressants/. are breast-feeding or plan to breast-feed. Fluoxetine may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if taking fluoxetine capsules. Tell your healthcare provider about all the medicines that you take, Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762 Symbyax Sarafem How should I take fluoxetine capsules? Take fluoxetine capsules exactly as prescribed. Your healthcare provider may need to change the dose of fluoxetine capsules until it is the right dose for you. Fluoxetine capsules may be taken with or without food. If you miss a dose of fluoxetine capsules, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of fluoxetine capsules at the same time. If you take too much fluoxetine, call your healthcare provider or poison control center right away, or get emergency treatment. What should I avoid while taking fluoxetine capsules? Fluoxetine capsules can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how fluoxetine capsules affect you. Do not drink alcohol while using fluoxetine capsules. What are the possible side effects of fluoxetine capsules? Fluoxetine capsules may cause serious side effects, including: See “What is the most important information I should know about fluoxetine capsules?” Problems with blood sugar control. Feeling anxious or trouble sleeping Common possible side effects in people who take fluoxetine capsules include: unusual dreams sexual problems loss of appetite, diarrhea, indigestion, nausea or vomiting, weakness, or dry mouth flu symptoms feeling tired or fatigued change in sleep habits yawning sinus infection or sore throat tremor or shaking sweating feeling anxious or nervous hot flashes rash Other side effects in children and adolescents include: increased thirst abnormal increase in muscle movement or agitation nose bleed urinating more often heavy menstrual periods possible slowed growth rate and weight change. Your child’s height and weight should be monitored during treatment with fluoxetine capsules. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of fluoxetine capsules. For more information, ask your healthcare provider or pharmacist. CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088. How should I store fluoxetine capsules? Store fluoxetine capsules at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). Keep fluoxetine capsules away from light. Keep fluoxetine capsules bottle closed tightly. Keep fluoxetine capsules and all medicines out of the reach of children. General information about fluoxetine capsules Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use fluoxetine capsules for a condition for which it was not prescribed. Do not give fluoxetine capsules to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about fluoxetine capsules. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about fluoxetine capsules that is written for healthcare professionals. For more information about fluoxetine capsules, call Aurobindo Pharma USA, Inc. at 1-866-850-2876. What are the ingredients in fluoxetine capsules? Active ingredient: fluoxetine hydrochloride Inactive ingredients: colloidal silicon dioxide, FD&C Blue #1, gelatin, pregelatinized starch (maize), sodium lauryl sulphate, titanium dioxide and yellow iron oxide. In addition 40 mg also contains FD&C Yellow #6. The capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol, shellac and strong ammonia solution. Symbyax registered registered Mellaril registered Orap registered Coumadin registered Jantoven registered Zyprexa registered This Medication Guide has been approved by the U. Food and Drug Administration. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762.

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