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 QT interval prolongation and ventricular tachycardia, 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 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 [seeOverdosage (10.3)].

10.3 Management of Overdose

Treatment should consist of those general measures employed in the management of overdosage with any drug effective in the treatment of Major Depressive Disorder.

Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.

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 [seeDrug Interactions (7. 9)].

Based on experience in animals, which may not be relevant to humans, fluoxetine-induced seizures that fail to remit spontaneously may respond to diazepam.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).

For specific information about overdosage with olanzapine and fluoxetine in combination, refer to the Overdosage section of the Symbyax package insert.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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.

Antagonism of muscarinic, histaminergic, and α 1-adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of classical tricyclic antidepressant (TCA) drugs. Fluoxetine binds to these and other membrane receptors from brain tissue much less potently in vitro than do the tricyclic drugs.

12.3 Pharmacokinetics

Systemic Bioavailability — In man, following a single oral 40 mg dose, peak plasma concentrations of fluoxetine from 15 to 55 ng/mL are observed after 6 to 8 hours.

Food does not appear to affect the systemic bioavailability of fluoxetine, although it may delay its absorption by 1 to 2 hours, which is probably not clinically significant. Thus, fluoxetine may be administered with or without food.

Protein Binding — Over the concentration range from 200 to 1000 ng/mL, approximately 94.5% of fluoxetine is bound in vitro to human serum proteins, including albumin and α1-glycoprotein. The interaction between fluoxetine and other highly protein-bound drugs has not been fully evaluated, but may be important.

Enantiomers — Fluoxetine is a racemic mixture (50/50) of R-fluoxetine and S-fluoxetine enantiomers. In animal models, both enantiomers are specific and potent serotonin uptake inhibitors with essentially equivalent pharmacologic activity. The S-fluoxetine enantiomer is eliminated more slowly and is the predominant enantiomer present in plasma at steady state.

Metabolism — Fluoxetine is extensively metabolized in the liver to norfluoxetine and a number of other unidentified metabolites. The only identified active metabolite, norfluoxetine, is formed by demethylation of fluoxetine. In animal models, S-norfluoxetine is a potent and selective inhibitor of serotonin uptake and has activity essentially equivalent to R- or S-fluoxetine. R-norfluoxetine is significantly less potent than the parent drug in the inhibition of serotonin uptake. The primary route of elimination appears to be hepatic metabolism to inactive metabolites excreted by the kidney.

Variability in Metabolism — A subset (about 7%) of the population has reduced activity of the drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6). Such individuals are referred to as “poor metabolizers” of drugs such as debrisoquin, dextromethorphan, and the TCAs. In a study involving labeled and unlabeled enantiomers administered as a racemate, these individuals metabolized S-fluoxetine at a slower rate and thus achieved higher concentrations of S-fluoxetine. Consequently, concentrations of S-norfluoxetine at steady state were lower. The metabolism of R-fluoxetine in these poor metabolizers appears normal. When compared with normal metabolizers, the total sum at steady state of the plasma concentrations of the 4 active enantiomers was not significantly greater among poor metabolizers. Thus, the net pharmacodynamic activities were essentially the same. Alternative, nonsaturable pathways (non-2D6) also contribute to the metabolism of fluoxetine. This explains how fluoxetine achieves a steady-state concentration rather than increasing without limit.

Because fluoxetine’s metabolism, like that of a number of other compounds including TCAs and other selective serotonin reuptake inhibitors (SSRIs), involves the CYP2D6 system, concomitant therapy with drugs also metabolized by this enzyme system (such as the TCAs) may lead to drug interactions [see Drug Interactions (7.9)].

Accumulation and Slow Elimination — The relatively slow elimination of fluoxetine (elimination half-life of 1 to 3 days after acute administration and 4 to 6 days after chronic administration) and its active metabolite, norfluoxetine (elimination half-life of 4 to 16 days after acute and chronic administration), leads to significant accumulation of these active species in chronic use and delayed attainment of steady state, even when a fixed dose is used [seeWarnings and Precautions (5.12)]. After 30 days of dosing at 40 mg/day, plasma concentrations of fluoxetine in the range of 91 to 302 ng/mL and norfluoxetine in the range of 72 to 258 ng/mL have been observed. Plasma concentrations of fluoxetine were higher than those predicted by single-dose studies, because fluoxetine’s metabolism is not proportional to dose. Norfluoxetine, however, appears to have linear pharmacokinetics. Its mean terminal half-life after a single dose was 8.6 days and after multiple dosing was 9.3 days. Steady-state levels after prolonged dosing are similar to levels seen at 4 to 5 weeks.

The long elimination half-lives of fluoxetine and norfluoxetine assure that, even when dosing is stopped, active drug substance will persist in the body for weeks (primarily depending on individual patient characteristics, previous dosing regimen, and length of previous therapy at discontinuation). This is of potential consequence when drug discontinuation is required or when drugs are prescribed that might interact with fluoxetine and norfluoxetine following the discontinuation of fluoxetine.

17 PATIENT COUNSELING INFORMATION

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking fluoxetine capsules, USP as monotherapy or in combination with olanzapine. When using fluoxetine capsules, USP and olanzapine in combination, also refer to the Patient Counseling Information section of the package insert for Symbyax.

17.1 General Information

Healthcare providers should instruct their patients to read the Medication Guide before starting therapy with fluoxetine capsules, USP and to reread it each time the prescription is renewed.

Healthcare providers should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with fluoxetine capsules, USP and should counsel them in its appropriate use. Healthcare providers should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.

Patients should be advised of the following issues and asked to alert their healthcare provider if these occur while taking fluoxetine capsules, USP.

When using fluoxetine capsules, USPand olanzapine in combination, also refer to the Medication Guide for Symbyax.

17.2 Clinical Worsening and Suicide Risk

Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [seeBox Warning and Warnings and Precautions (5.1)].

17.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like

Reactions

Patients should be cautioned about the risk of serotonin syndrome or NMS-like reactions with the concomitant use of fluoxetine capsules, USP and triptans, tramadol, or other serotonergic agents [seeWarnings and Precautions (5.2) andDrug Interactions (7.3)].

Patients should be advised of the signs and symptoms associated with serotonin syndrome or NMS-like reactions that may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, in which the symptoms may include hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be cautioned to seek medical care immediately if they experience these symptoms.

17.5 Abnormal Bleeding

Patients should be cautioned about the concomitant use of fluoxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents have been associated with an increased risk of bleeding [see Warnings and Precautions (5.7) andDrug Interactions (7.6)]. Patients should be advised to call their doctor if they experience any increased or unusual bruising or bleeding while taking fluoxetine capsules, USP.

17.4 Allergic Reactions and Rash

Patients should be advised to notify their physician if they develop a rash or hives [seeWarnings and Precautions (5.3)]. Patients should also be advised of the signs and symptoms associated with a severe allergic reaction, including swelling of the face, eyes, or mouth, or have trouble breathing. Patients should be cautioned to seek medical care immediately if they experience these symptoms.

17.6 Hyponatremia

Patients should be advised that hyponatremia has been reported as a result of treatment with SNRIs and SSRIs, including fluoxetine capsules, USP. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death [seeWarnings and Precautions (5.8)].

17.7 Potential for Cognitive and Motor Impairment

Fluoxetine capsules, USP may impair judgment, thinking, or motor skills. Patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that their performance is not affected [seeWarnings and Precautions (5.11)].

17.8 Use of Concomitant Medications

Patients should be advised to inform their physician if they are taking, or plan to take, any prescription medication, including Symbyax, Sarafem, or over-the-counter drugs, including herbal supplements or alcohol. Patients should also be advised to inform their physicians if they plan to discontinue any medications they are taking while on fluoxetine capsules, USP.

17.9 Discontinuation of Treatment

Patients should be advised to take fluoxetine capsules, USP exactly as prescribed, and to continue taking fluoxetine capsules, USP as prescribed even after their symptoms improve. Patients should be advised that they should not alter their dosing regimen, or stop taking fluoxetine capsules, USP without consulting their physician [seeWarnings and Precautions (5.13)]. Patients should be advised to consult with their healthcare provider if their symptoms do not improve with fluoxetine capsules, USP.

17.10 Use in Specific Populations

Pregnancy — Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Fluoxetine capsules, USP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [seeUse in Specific Populations (8.1)].

Nursing Mothers — Patients should be advised to notify their physician if they intend to breast-feed an infant during therapy. Because fluoxetine capsules, USP is excreted in human milk, nursing while taking fluoxetine capsules, USP is not recommended [seeUse in Specific Populations (8.3)].

Pediatric Use — Fluoxetine capsules, USP is approved for use in pediatric patients with MDD and OCD [seeBox Warning andWarnings and Precautions (5.1)]. Limited evidence is available concerning the longer-term effects of fluoxetine on the development and maturation of children and adolescent patients. Height and weight should be monitored periodically in pediatric patients receiving fluoxetine. Safety and effectiveness of fluoxetine capsules, USP and olanzapine in combination in patients less than 18 years of age have not been established. [seeWarnings and Precautions (5.6) and Use in Specific Populations (8.4)].

MEDICATION GUIDE

Fluoxetine Capsules, USP

Read the Medication Guide that comes with fluoxetine capsules, USP before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment. Talk with your doctor or pharmacist if there is something you do not understand or you want to learn more about fluoxetine capsules, USP.

What is the most important information I should know about fluoxetine capsules, USP?

Antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions:

Talk to your, or your family member’s, healthcare provider about:

• all risks and benefits of treatment with antidepressant medicines
• all treatment choices for depression or other serious mental illness

1.Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. 2.Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions. 3.How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

• Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
• Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
• Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling very agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• or other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

*Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms. *Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants. *Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member. *Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider. *Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.

What is fluoxetine capsules, USP?

Fluoxetine capsules, USP is a prescription medicine used:

• for short and long-term treatment of depression in adults and children over the age of 8.
• for short and long-term treatment of Obsessive Compulsive Disorder (OCD) in adults and children over the age of 7.
• for short and long-term treatment of Bulimia Nervosa in adults.
• for short-term treatment of Panic Disorder, with or without agoraphobia, in adults.
• with the medicine olanzapine (Zyprexa), for the short-term treatment of episodes of depression that happen with Bipolar I Disorder.

It is not known if fluoxetine capsules, USP and olanzapine (Zyprexa) taken together is safe and works in children under 18 years of age.

The symptoms of depression (Major Depressive Disorder, Bipolar I Disorder include decreased mood, decreased interest, increased guilty feelings, decreased energy, decreased concentration, changes in appetite, and suicidal thoughts or behavior. With treatment, some of your symptoms of depression may improve.

OCD is an anxiety disorder and is characterized by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions). With treatment, some of your symptoms of OCD may improve.

Panic Disorder is an anxiety disorder that includes panic attacks, which are sudden feelings of terror for no reason. You may also have physical symptoms, such as; fast heartbeat, chest pain, breathing difficulty, dizziness. With treatment, some of your symptoms of Panic Disorder may improve.

Bulimia Nervosa, involves periods of overeating followed by purging (e.g. vomiting, excessive laxative use). With treatment, some of your symptoms of Bulimia Nervosa may improve.

If you do not think you are getting better, call your doctor.

Who should not take fluoxetine capsules, USP?

• Do not take fluoxetine capsules, USP if you take a Monoamine Oxidase Inhibitor (MAOI) or if you stopped taking an MAOI in the last2 weeks.
• Do not take an MAOIwithin 5 weeks of stopping fluoxetine capsules, USP. People who take fluoxetine capsules, USP close in time to an MAOI can have serious and life-threatening side effects, with symptoms including:
  • high fever
  • continued muscle spasms that you can not control
  • rigid muscles
  • changes in heart rate and blood pressure that happen fast
  • confusion
  • unconsciousness

Ask your doctor or pharmacist if you are not sure if your medicine is an MAOI.

• Do not take fluoxetine capsules, USP if you take Mellaril® (thioridazine). Do not take Mellarilwithin 5 weeks of stopping fluoxetine capsules, USP. Mellaril can cause serious heart rhythm problems and you could die suddenly.
• Do not take fluoxetine capsules, USP if you take the antipsychotic medicine pimozide (Orap®).

What should I tell my doctor before takingfluoxetine capsules, USP?

Fluoxetine capsules, USP may not be right for you. Before starting fluoxetine capsules, USP, tell your doctor about all your medical conditions, including if you have or had any of the following:

• seizures (convulsions)
• bipolar disorder (mania)
• are pregnant or plan to become pregnant. It is not known if fluoxetine capsules, USP will harm your unborn baby.
• are breast-feeding or plan to breast-feed. Fluoxetine capsules, USP can pass into your breast milk and may harm your baby. You should not breast-feed while taking fluoxetine capsules, USP. Talk to your doctor about the best way to feed your baby if you take fluoxetine capsules, USP.

**Tell your doctor about all the medicines that you take,**including prescription and non-prescription medicines, vitamins, and herbal supplements. Fluoxetine capsules, USP and some medicines may interact with each other and may not work as well, or cause possible serious side effects. Your doctor can tell you if it is safe to take fluoxetine capsules, USP with your other medicines. Do not start or stop any medicine while taking fluoxetine capsules, USP without talking to your doctor first.

If you take fluoxetine capsules, USP, you should not take any other medicines that contain fluoxetine hydrochloride:

• Symbyax
• Sarafem

You could take too much medicine (overdose).

How should I take fluoxetine capsules, USP?

• Take fluoxetine capsules, USP exactly as prescribed. Your doctor may need to change (adjust) the dose of fluoxetine capsules, USP until it is right for you.
• If you miss a dose of fluoxetine capsules, USP, 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, USP at the same time. *To prevent serious side effects, do not stop taking fluoxetine capsules, USP suddenly. If you need to stop taking fluoxetine capsules, USP, your doctor can tell you how to safely stop taking it.
• If you take too much fluoxetine capsules, USP, call your doctor or poison control center right away, or get emergency treatment.
• Fluoxetine capsules, USP can be taken with or without food.
• Fluoxetine capsules, USP is usually taken once a day or once weekly, depending on how your doctor prescribes your medicine.
• If you do not think you are getting better or have any concerns about your condition while taking fluoxetine capsules, USP, call your doctor.

What should I avoid while taking fluoxetine capsules, USP?

• Fluoxetine capsules, USP can cause sleepiness and 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, USP affects you.

What are the possible side effects of fluoxetine capsules, USP?

Fluoxetine capsules, USP****may be associated with the following serious risks:

*Serotonin Syndrome: This is a condition that can be life threatening. Call your doctor right away if you become severely ill and have some or all of these symptoms: * agitation * hallucinations * problems with coordination * racing heart beat * over-active reflexes * fever * nausea, vomiting, and diarrhea

*Severe allergic reactions: Tell your doctor right away if you get red itchy welts (hives) or, a rash alone or with fever and joint pain, while taking fluoxetine capsules, USP. Call your doctor right away if you become severely ill and have some or all of these symptoms: * swelling of your face, eyes, or mouth * trouble breathing *Abnormal bleeding: Tell your doctor if you notice any increased or unusual bruising or bleeding while taking fluoxetine capsules, USP, especially if you take one of these medicines: * the blood thinner warfarin (Coumadin, Jantoven) * a non-steroidal anti-inflammatory drug (NSAID) * aspirin *Mania: You may have a high mood, become extremely irritable, have too much energy, feel pressure to keep talking, or have a decreased need for sleep. *Seizures *Loss of appetite *Low salt (sodium) levels in the blood (hyponatremia): Call your doctor right away if you become severely ill and have some or all of these symptoms: * headache * feel weak * confusion * problems concentrating * memory problems * feel unsteady

**Common possible side effects offluoxetine capsules, USPinclude: **abnormal dreams, orgasm problems, decreased appetite, anxiety, weakness, diarrhea, dry mouth, indigestion, flu, difficulty maintaining an erection for sexual activity, trouble sleeping, decreased sex drive, feeling sick to your stomach, nervousness, sore throat, rash, watery nasal discharge, sleepiness, sweating, tremor (shakes), hot flashes, and yawn.

Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects with fluoxetine capsules, USP. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at1-800-FDA-1088.

How should I store fluoxetine capsules, USP?

• Store fluoxetine capsules, USP at room temperature, between 68 - 77° F (20 - 25° C).
• Keep fluoxetine capsules, USP away from light.
• Keep fluoxetine capsules, USP bottle closed tightly.

Keep fluoxetine capsules, USP****and all medicines out of the reach of children.

General information about fluoxetine capsules, USP

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use fluoxetine capsules, USP for a condition for which it was not prescribed. Do not give fluoxetine capsules, USP 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, USP. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about fluoxetine capsules, USP that was written for healthcare professionals. For more information about fluoxetine capsules, USP call Ranbaxy Pharmaceuticals Inc. at 1-888-Ranbaxy (726-2299).

What are the ingredients in fluoxetine capsules, USP?

**Active ingredients:**fluoxetine hydrochloride, USP

**Inactive ingredients:**colloidal silicon dioxide, FD&C Blue No. 1, FD&C Yellow No. 6, gelatin, magnesium stearate, pregelatinized starch, titanium dioxide, and yellow iron oxide. The imprinting ink also contains D&C Yellow No. 10 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, FD&C Blue No. 1 aluminum lake, propylene glycol, and synthetic black iron oxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Ranbaxy Pharmaceuticals Inc.

Jacksonville, FL 32257 USA

by: Ohm Laboratories Inc.

North Brunswick, NJ 08902 USA

August 2009

Repackaged by:

Rebel Distributors Corp

Thousand Oaks, CA 91320

Sarafem ® and Symbyax® are registered trademarks of Eli Lilly.

Orap ® is a registered trademark of Teva.

Mellaril ® is a registered trademark of Novartis.

Zyprexa is a trademark of Eli Lilly.