fluoxetine

RECENT MAJOR CHANGES Warnings and Precautions, Serotonin Syndrome ( 5.2 ) 06/2023 Warnings and Precautions ( 5.7 ) 06/2023 Warnings and Precautions, Sexual Dysfunction ( 5.15 ) 09/2021

1 INDICATIONS AND USAGE Fluoxetine is a selective serotonin reuptake inhibitor indicated for: Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years (1.1) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adults and pediatric patients aged 7 to 17 years (1.2) Acute and maintenance treatment of Bulimia Nervosa in adult patients (1.3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients (1.4) 1.1 Major Depressive Disorder Fluoxetine is indicated for the acute and maintenance treatment of Major Depressive Disorder in adult patients and in pediatric patients aged 8 to 18 years [see Clinical Studies (14.1)] . The usefulness of the drug in adult and pediatric patients receiving fluoxetine for extended periods should periodically be re-evaluated [see Dosage and Administration (2.1)] . 1.2 Obsessive Compulsive Disorder Fluoxetine is indicated for the acute and maintenance treatment of obsessions and compulsions in adult patients and in pediatric patients aged 7 to 17 years with Obsessive Compulsive Disorder (OCD) [see Clinical Studies (14.2)] . The effectiveness of fluoxetine in long-term use, i.e., for more than 13 weeks, has not been systematically evaluated in placebo-controlled trials. Therefore, the physician who elects to use fluoxetine for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see Dosage and Administration (2.2)] . 1.3 Bulimia Nervosa Fluoxetine is indicated for the acute and maintenance treatment of binge-eating and vomiting behaviors in adult patients with moderate to severe Bulimia Nervosa [see Clinical Studies (14.3)] . The physician who elects to use fluoxetine for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see Dosage and Administration (2.3)] . 1.4 Panic Disorder Fluoxetine is indicated for the acute treatment of Panic Disorder, with or without agoraphobia, in adult patients [see Clinical Studies (14.4)] . The effectiveness of fluoxetine in long-term use, i.e., for more than 12 weeks, has not been established in placebo-controlled trials. Therefore, the physician who elects to use fluoxetine for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see Dosage and Administration (2.4)] .

2 DOSAGE AND ADMINISTRATION Indication Adult Pediatric MDD (2.1) 20 mg/day in am (initial dose) 10 mg/day to 20 mg/day (initial dose) OCD (2.2) 20 mg/day in am (initial dose) 10 mg/day (initial dose) Bulimia Nervosa (2.3) 60 mg/day in am Panic Disorder (2.4) 10 mg/day (initial dose) 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) 2.1 Major Depressive Disorder Initial Treatment Adult In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 mg/day to 80 mg/day. Studies comparing fluoxetine 20 mg/day, 40 mg/day, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose. A dose increase may be considered after several weeks if insufficient clinical improvement is observed. Doses above 20 mg/day may be administered on a once-a-day (morning) or BID schedule (i.e., morning and noon) and should not exceed a maximum dose of 80 mg/day . Pediatric (Children and Adolescents) In the short-term (8 to 9 week) controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Major Depressive Disorder, patients were administered fluoxetine doses of 10 mg/day to 20 mg/day [see Clinical Studies (14.1)]. Treatment should be initiated with a dose of 10 mg/day or 20 mg/day. After 1 week at 10 mg/day, the dose should be increased to 20 mg/day. However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. A dose increase to 20 mg/day may be considered after several weeks if insufficient clinical improvement is observed. All Patients As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer. Maintenance/Continuation/Extended Treatment It is generally agreed that acute episodes of Major Depressive Disorder require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown. Daily Dosing Systematic evaluation of fluoxetine in adult patients has shown that its efficacy in Major Depressive Disorder is maintained for periods of up to 38 weeks following 12 weeks of open-label acute treatment (50 weeks total) at a dose of 20 mg/day [see Clinical Studies (14.1)] . Switching Patients to a Tricyclic Antidepressant (TCA) Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Drug Interactions (7.7)]. 2.2 Obsessive Compulsive Disorder Initial Treatment Adult In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20 mg, 40 mg, or 60 mg of fluoxetine or placebo [see Clinical Studies (14.2)]. In one of these studies, no dose-response relationship for effectiveness was demonstrated. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose. Since there was a suggestion of a possible dose-response relationship for effectiveness in the second study, a dose increase may be considered after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. Doses above 20 mg/day may be administered on a once daily (i.e., morning) or BID schedule (i.e., morning and noon). A dose range of 20 mg/day to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose shoul …

3 DOSAGE FORMS AND STRENGTHS Fluoxetine Tablets, USP are available containing fluoxetine hydrochloride, USP equivalent to 10 mg or 20 mg of fluoxetine. Fluoxetine Tablets, USP 10 mg are "White to Off white, film coated Oval, scored tablets debossed with "F" on the left of the score and "10" on the right of score on one side of the tablet and plain on other side. Fluoxetine Tablets, USP 20 mg are "White to Off white, film coated Oval, scored tablets debossed with "F" on the left of the score and "20" on the right of score on one side of the tablet and plain on other side. Tablets: 10 mg, 20 mg (3)

4 CONTRAINDICATIONS When using fluoxetine 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 or within 5 weeks of stopping treatment with fluoxetine. Do not use fluoxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start fluoxetine 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 fluoxetine (4.2, 5.11, 7.7, 7.8) When using fluoxetine and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax ® (4) 4.1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with fluoxetine or within 5 weeks of stopping treatment with fluoxetine is contraindicated because of an increased risk of serotonin syndrome. The use of fluoxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.9) and Warnings and Precautions (5.2)]. Starting fluoxetine in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.10) and Warnings and Precautions (5.2)]. 4.2 Other Contraindications The use of fluoxetine is contraindicated with the following: Pimozide [see Warnings and Precautions (5.11) and Drug Interactions (7.7, 7.8)] Thioridazine [see Warnings and Precautions (5.11) and Drug Interactions (7.7, 7.8)] Pimozide and thioridazine prolong the QT interval. Fluoxetine can increase the levels of pimozide and thioridazine through inhibition of CYP2D6. Fluoxetine can also prolong the QT interval.

6 ADVERSE REACTIONS 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 and 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) ] Most common adverse reactions (≥ 5% and at least twice that for placebo): 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 ) To report SUSPECTED ADVERSE REACTIONS, contact ScieGen Pharmaceuticals Inc at 1-855-724-3436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience 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. Multiple doses of fluoxetine have been administered to 10,782 patients with various diagnoses in US clinical trials. In addition, there have been 425 patients administered fluoxetine in panic clinical trials. The stated frequencies represent the proportion of individuals who experienced, at least once, an adverse reaction of the type listed. An adverse reaction was included if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Incidence in MDD, OCD, Bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials)-Table 2 enumerates the most common adverse reactions associated with the use of fluoxetine (incidence of at least 5% for fluoxetine and at least twice that for placebo within at least 1 of the indications) for the treatment of MDD, OCD, and bulimia in US controlled clinical trials and Panic Disorder in US plus non-US controlled trials. Table 3 provides combined data for the pool of studies that are provided separately by indication in Table 2. Table 2: Most Common Adverse Reactions: Incidence in Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder Placebo-controlled Clinical Trials Percentage of Patients Reporting Event MDD OCD Bulimia Panic Disorder Body System/Adverse Reaction Fluoxetine (N = 1,728) Placebo (N = 975) Fluoxetine (N = 266) Placebo (N = 89) Fluoxetine (N = 450) Placebo (N = 267) Fluoxetine (N = 425) Placebo (N = 342) 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 …

7 DRUG INTERACTIONS Monoamine Oxidase Inhibitors (MAOI): Fluoxetine is contraindicated for use with MAOI's, or within 14 days of discontinuing an MAOI due to risk of drug interaction. At least 5 weeks should be allowed after stopping fluoxetine before starting treatment with an MAOI ( 4 , 7.1 ) Pimozide: Fluoxetine is contraindicated for use with pimozide due to risk of drug interaction or QTc prolongation ( 4 , 7.9 ) Thioridazine: Fluoxetine is contraindicated for use with thioridazine due to QTc interval prolongation or potential for elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing fluoxetine tablet. ( 4 , 7.9 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( 7.9 ) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine hydrochloride or when fluoxetine hydrochloride has been recently discontinued ( 7.9 ) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs ( 7.2 ) Benzodiazepines: Diazepam – increased t 1⁄2 , alprazolam - further psychomotor performance decrement due to increased levels ( 7.9 ) Antipsychotics: Potential for elevation of haloperidol and clozapine levels ( 7.9 ) Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( 7.9 ) Serotonergic Drugs: Potential for Serotonin Syndrome ( 5.2 , 7.3 ) Triptans: There have been rare post marketing reports of Serotonin Syndrome with use of an SSRI and a triptan ( 5.2 , 7.4 ) Tryptophan: Concomitant use with tryptophan is not recommended ( 5.2 , 7.5 ) Drugs that Interfere with Hemostasis (for example, NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding ( 7.6 ) Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations ( 7.8 , 7.9 ) The potential for interaction by a variety of mechanisms (for example, pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility. 7.1 Monoamine Oxidase Inhibitors (MAOI) Concomitant use of fluoxetine tablets in patients taking MAOIs is contraindicated. There have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) in patients receiving fluoxetine in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, fluoxetine, including fluoxetine tablet , should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI [see Contraindications ( 4 )]. Since fluoxetine and its major metabolite have very long elimination half-lives, at least 5 weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should be allowed after stopping fluoxetine before starting an MAOI [see Dosage and Administration ( 2.4 and 2.5 ), Contraindications ( 4.1 ), Warnings and Precautions ( 5.2 ), and Clinical Pharmacology ( 12.3 )]. 7.2 CNS Acting Drugs Caution is advised if the concomitant administration of fluoxetine, including fluoxetine tablet, and other CNS acting 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 )] . 7.3 Serotonergic Drugs Based on the mechanism of action of SNRIs and SSRIs, including fluoxetine hydrochloride, and the potential for serotonin syndrome, caution is advised when fluoxetine hydrochloride is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, s …

8 USE IN SPECIFIC POPULATIONS Pregnancy : SSRI use, particularly later in pregnancy, may increase risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate ( 8.1 ) Pediatric Use: Safety and effectiveness of fluoxetine in patients < 8 years of age with MDD and < 7 years of age with OCD have not been established ( 8.4 ). 8.1 Pregnancy 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 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.7) and Clinical Considerations] . Available data from published epidemiologic studies and postmarketing reports over several decades have not established an increased risk of major birth defects or miscarriage. Some studies have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship [ see Data ]. There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including Fluoxetine Tablets, during pregnancy (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 1.6 times and 3.9 times, respectively, the maximum recommended human dose (MRHD) of 60 mg on a mg/m 2 given to adolescents on a mg/m 2 basis. However, in other reproductive studies in rats, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths early after birth occurred at doses that are 1.5 times (during gestation) and 0.97 times (during gestation and lactation) the MRHD given to adolescents on a mg/m 2 basis. 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 Disease-Associated Maternal and/or Embryo/Fetal Risk 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. Maternal Adverse Reactions Use of Fluoxetine Tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.7) ] . Fetal/Neonatal Adverse Reactions Neonates exposed to Fluoxetine Tablets and other SSRIs 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, hypoton …

12.1 Mechanisam of Action Although the exact mechanism of fluoxetine hydrochloride is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.

11 DESCRIPTION Fluoxetine is a selective serotonin reuptake inhibitor for oral administration. It is also marketed for the treatment of premenstrual dysphoric disorder (Sarafem ® , fluoxetine hydrochloride). It is designated (±)- N -methyl-3-phenyl-3-[(α,α,α-trifluoro- p -tolyl)oxy]propylamine hydrochloride and has the molecular formula of C 17 H 18 F 3 NO.HCl. Its molecular weight is 345.79. The structural formula is: Fluoxetine hydrochloride, USP is a white to off-white crystalline solid with a solubility of 14 mg/mL in water. Each tablet contains fluoxetine hydrochloride equivalent to 10 mg (32.3 μmol) or 20 mg (64.7 μmol) of fluoxetine. In addition, each tablet also contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, Pre-gelatinized Starch and titanium dioxide. Fluoxetine Structural Formula

10 OVERDOSAGE 10.1 Human Experience 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. 10.2 Animal Experience Studies in animals do not provide precise or necessarily valid information about the treatment of human overdose. However, animal experiments can provide useful insights into possible treatment strategies. The oral median lethal dose in rats and mice was found to be 452 mg/kg and 248 mg/kg, respectively. Acute high oral doses produced hyperirritability and convulsions in several animal species. Among 6 dogs purposely overdosed with oral fluoxetine, 5 experienced grand mal seizures. Seizures stopped immediately upon the bolus intravenous administration of a standard veterinary dose of diazepam. In this short-term study, the lowest plasma concentration at which a seizure occurred was only twice the maximum plasma concentration seen in humans taking 80 mg/day, chronically. In a separate single-dose study, the ECG of dogs given high doses did not reveal prolongation of the PR, QRS, or QT intervals. Tachycardia and an increase in blood pressure were observed. Consequently, the value of the ECG in predicting cardiac toxicity is unknown. Nonetheless, the ECG should ordinarily be monitored in cases of human overdose [see Overdosage (10.3)]. 10.3 Management of Overdose For current information on the management of fluoxetine 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. Activate …

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Fluoxetine Tablets, USP are available containing fluoxetine hydrochloride, USP equivalent to 10 mg or 20 mg of fluoxetine. Fluoxetine Tablets, USP 10 mg are White to Off white, film coated Oval, scored tablets debossed with "F" on the left of the score and "10" on the right of score on one side of the tablet and plain on other side. They are available as follows: NDC 64380-902-04 bottles of 30 tablets NDC 64380-902-06 bottles of 100 tablets NDC 64380-902-08 bottles of 1000 tablets Fluoxetine Tablets, USP 20 mg are White to Off white, film coated Oval, scored tablets debossed with "F" on the left of the score and "20" on the right of score on one side of the tablet and plain on other side. They are available as follows: NDC 64380-903-04 bottles of 30 tablets NDC 64380-903-06 bottles of 100 tablets 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Medication Guide with each prescription.

16.1 How Supplied Fluoxetine Tablets, USP are available containing fluoxetine hydrochloride, USP equivalent to 10 mg or 20 mg of fluoxetine. Fluoxetine Tablets, USP 10 mg are White to Off white, film coated Oval, scored tablets debossed with "F" on the left of the score and "10" on the right of score on one side of the tablet and plain on other side. They are available as follows: NDC 64380-902-04 bottles of 30 tablets NDC 64380-902-06 bottles of 100 tablets NDC 64380-902-08 bottles of 1000 tablets Fluoxetine Tablets, USP 20 mg are White to Off white, film coated Oval, scored tablets debossed with "F" on the left of the score and "20" on the right of score on one side of the tablet and plain on other side. They are available as follows: NDC 64380-903-04 bottles of 30 tablets NDC 64380-903-06 bottles of 100 tablets