Sarafem (Fluoxetine Hydrochloride)
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Sarafem (Fluoxetine Hydrochloride)

SARAFEM®
(fluoxetine hydrochloride) Tablets

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of SARAFEM (fluoxetine hydrochloride) or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. SARAFEM (fluoxetine hydrochloride) is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PATIENT INFORMATION, and PRECAUTIONS: Pediatric Use)

DRUG DESCRIPTION

SARAFEM® (fluoxetine hydrochloride tablets) is a selective serotonin reuptake inhibitor (SSRI) for oral administration. It is designated (±)-N-methyl-3-phenyl-3-[α,α,α-trifluoro-p-tolyl)oxy]propylamine hydrochloride and has the empirical formula of C17H18F3NO·HCl. Its molecular weight is 345.79. The structural formula is:

SARAFEM®
  (fluoxetine hydrochloride) Structural Formula Illustration

Fluoxetine hydrochloride is a white to off-white crystalline solid with a solubility of 14 mg/mL in water.

Each SARAFEM tablet contains fluoxetine hydrochloride equivalent to 10 mg (32.3 µmol), 15 mg (48.5 µmol) or 20 mg (64.7 µmol) of fluoxetine. Each tablet also contains microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, FD&C Yellow No. 6 aluminum lake (10 mg and 20 mg tablets) and D&C Yellow No. 10 aluminum lake (10 mg and 20 mg tablets).

What are the possible side effects of fluoxetine (Prozac, Prozac Weekly, Rapiflux, Sarafem, Selfemra)?

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these...

Read All Potential Side Effects and See Pictures of Sarafem »

What are the precautions when taking fluoxetine hydrochloride (Sarafem)?

Before taking fluoxetine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal or family history of bipolar/manic-depressive disorder, personal or family history of suicide attempts, liver problems, diabetes, low sodium in the blood (such as may occur while taking "water pills" - diuretics), severe loss of body water (dehydration), seizures, stomach/intestinal ulcers, glaucoma.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness...

Read All Potential Precautions of Sarafem »

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

SARAFEM (fluoxetine hydrochloride) is indicated for the treatment of premenstrual dysphoric disorder (PMDD).

The efficacy of fluoxetine in the treatment of PMDD was established in 3 placebo-controlled trials (see Clinical Trials).

The essential features of PMDD, according to the DSM-IV, include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating, and weight gain. These symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school or with usual social activities and relationships with others. In making the diagnosis, care should be taken to rule out other cyclical mood disorders that may be exacerbated by treatment with an antidepressant.

The effectiveness of SARAFEM (fluoxetine hydrochloride) in long-term use, that is, for more than 6 months, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use SARAFEM (fluoxetine hydrochloride) for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

DOSAGE AND ADMINISTRATION

Premenstrual Dysphoric Disorder

Initial Treatment

The recommended dose of SARAFEM (fluoxetine hydrochloride) for the treatment of PMDD is 20 mg/day given continuously (every day of the menstrual cycle) or intermittently (defined as starting a daily dose 14 days prior to the anticipated onset of menstruation through the first full day of menses and repeating with each new cycle). The dosing regimen should be determined by the physician based on individual patient characteristics. In a study comparing continuous dosing of fluoxetine 20 and 60 mg/day to placebo, both doses were proven to be effective, but there was no statistically significant added benefit for the 60 mg/day compared with the 20 mg/day dose. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with PMDD. The maximum fluoxetine dose should not exceed 80 mg/day.

As with many other medications, a lower or less frequent dosage should be considered in patients with hepatic impairment. A lower or less frequent dosage should also be considered for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary (see Liver disease and Renal disease under CLINICAL PHARMACOLOGY, Special Populations, and Use in Patients with Concomitant Illness under PRECAUTIONS, General).

Maintenance/Continuation Treatment

Systematic evaluation of SARAFEM (fluoxetine hydrochloride) has shown that its efficacy in PMDD is maintained for periods of up to 6 months at a dose of 20 mg/day given continuously and up to 3 months at a dose of 20 mg/day given intermittently, (see Clinical Trials). Patients should be periodically reassessed to determine the need for continued treatment.

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to fluoxetine and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see Nonteratogenic Effects under PRECAUTIONS, Pregnancy). When treating pregnant women with fluoxetine during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering fluoxetine in the third trimester.

Discontinuation of Treatment with SARAFEM (fluoxetine hydrochloride)

Symptoms associated with discontinuation of SARAFEM (fluoxetine hydrochloride) and other SSRIs and SNRIs, have been reported (see PRECAUTIONS, General). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. Plasma fluoxetine and norfluoxetine concentration decrease gradually at the conclusion of therapy which may minimize the risk of discontinuation symptoms with this drug.

HOW SUPPLIED

SARAFEM® (fluoxetine hydrochloride tablets) is available in 10 mg1, 15 mg1 and 20 mg1 strengths.

The 10 mg tablet is a cream, round tablet embossed with S10 on one side:

N 0430-0210-14 - Four blister cards of 7 tablets each

The 15 mg tablet is a white, round tablet embossed with S15 on one side:

N 0430-0215-14 - Four blister cards of 7 tablets each

The 20 mg tablet is a yellow, round tablet embossed with S20 on one side:

N 0430-0220-14 - Four blister cards of 7 tablets each

Store at 25° C (77° F); excursions permitted to 15° - 30° C (59° - 86° F) [see USP Controlled Room Temperature]

REFERENCES

1 Equivalent to fluoxetine base.

Manufactured by: Pharmaceutics International, Inc.Hunt Valley, MD 21031Manufactured for: Warner Chilcott Company, Inc.Fajardo, PR 00738. Marketed by: Warner Chilcott (US) LLC., Rockaway.

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

In 1 of 3 placebo-controlled, continuous-dosing trials and 1 placebo-controlled, intermittent-do sing trial of fluoxetine in PMDD, treatment-emergent adverse events reporting rates were assessed. The information from Table 3 included under ADVERSE REACTIONS is based on data from the continuous-dosing trial at the recommended dose of SARAFEM (fluoxetine hydrochloride) (SARAFEM (fluoxetine hydrochloride) 20 mg, N = 104; placebo, N = 108) and data from the intermittent-dosing trial of fluoxetine in PMDD (SARAFEM (fluoxetine hydrochloride) 20 mg, N = 86; placebo, N = 88). In addition, a broader set of information on treatment-emergent adverse events in the population of female patients, 18 to 45 years of age from the US placebo-controlled depression, OCD, and bulimia clinical trials, is presented for comparison (see Table 3).

Adverse events were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a limited (i.e., reduced) number of standardized event categories.

In the tables and tabulations that follow, COSTART Dictionary terminology has been used to classify reported adverse events. The stated frequencies represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.

Incidence in placebo-controlled PMDD clinical trials — Table 3 enumerates the most common treatment-emergent adverse events associated with the use of SARAFEM (fluoxetine hydrochloride) 20 mg (incidence of at least 5% for SARAFEM (fluoxetine hydrochloride) 20 mg and greater than placebo) for the treatment of PMDD.

Table 3: Most Common Treatment-Emergent Adverse Events: Incidence in PMDD Placebo-Controlled Clinical Trials

Body System/Adverse Eventa Percentage of Patients Reporting Event
SARAFEM (fluoxetine hydrochloride)
20 mg/day Continuously
(N = 104)
SARAFEM (fluoxetine hydrochloride)
20 mg/day Intermittently
(N = 86)
Placebo (Pooled)
(N=196)
Body as a Whole
  Headache 13 15 11
  Asthenia 12 8 4
  Pain 9 3 7
  Accidental injury 8 1 5
  Infection 7 0 3
  Flu syndrome 12 3 7
Digestive System
  Nausea 13 9 6
  Diarrhea 6 2 6
Nervous System
  Insomnia 9 10 7
  Dizziness 7 2 3
  Nervousness 7 3 3
  Thinking abnormalb 6 5 0
  Libido decreased 3 9 1
Respiratory System
  Rhinitis 23 16 15
  Pharyngitis 10 6 5
a) Included in the table are events reported by at least 5% of patients taking SARAFEM (fluoxetine hydrochloride) 20 mg either continuously or intermittently. For additional adverse event terms referenced in PRECAUTIONS, reporting rates for SARAFEM (fluoxetine hydrochloride) 20 mg continuous and intermittent were, respectively: anxiety 4.8%, 1.2% and anorexia 3.8%, 3.5%.
b) Thinking abnormal is the COSTART term that captures concentration difficulties.

Incidence in US depression, OCD, and bulimia placebo-controlled clinical trials (excluding data from extensions of trials) — Table 4 enumerates the most common treatment-emergent adverse events associated with the use of fluoxetine up to 80 mg (incidence of at least 2% for fluoxetine and greater than placebo) in female patients ages 18 to 45 years from US placebo-controlled clinical trials in the treatment of depression, OCD, and bulimia.

Table 4: Treatment-Emergent Adverse Events: Incidence in Female Patients Ages 18 to 45 Years in US Depression, OCD, and Bulimia Placebo-Controlled Clinical Trials

Body System/Adverse Eventa Percentage of Patients Reporting Event
Fluoxetine
(N = 1145)
Placebo
(N = 553)
Body as a Whole
  Headache 24 21
  Asthenia 14 6
  Flu syndrome 7 3
  Abdominal pain 6 5
  Accidental injury 4 3
  Fever 3 2
Cardiovascular System
  Palpitation 3 2
  Vasodilatation 3 1
Digestive System
  Nausea 27 11
  Anorexia 11 4
  Dry mouth 11 8
  Diarrhea 10 7
  Dyspepsia 7 5
  Constipation 5 3
  Vomiting 3 2
Metabolic and Nutritional Disorders
  Weight loss 3 1
Nervous System
  Insomnia 24 11
  Nervousness 14 10
  Anxiety 13 9
  Somnolence 13 6
  Tremor 12 1
  Dizziness 11 5
  Libido decreased 4 1
  Abnormal dreams 3 2
  Thinking abnormalb 3 2
Respiratory System
  Pharyngitis 6 5
  Yawn 5 < 0.5
Skin and Appendages
  Sweating 8 3
  Rash 5 3
Special Senses
  Abnormal vision 3 1
Urogenital System
  Urinary frequency 2 1
a) Included are events reported by at least 2% of patients taking fluoxetine, except the following events, which had an incidence on placebo > fluoxetine (depression, OCD, and bulimia combined): back pain, cough increased, depression (includes suicidal thoughts), dysmenorrhea, flatulence, infection, myalgia, pain, pruritus, rhinitis, sinusitis.
b) Thinking abnormal is the COSTART term that captures concentration difficulties.

Associated with discontinuation in two placebo-controlled PMDD clinical trials — In a continuous-dosing PMDD placebo-controlled trial, the most common adverse event (incidence at least 2% for SARAFEM (fluoxetine hydrochloride) 20 mg and greater than placebo) associated with discontinuation was nausea (3% for SARAFEM (fluoxetine hydrochloride) 20 mg, N = 104 and 1% for placebo, N = 108). In an intermittent-do sing placebo-controlled trial, no events associated with discontinuation reached an incidence of 2% for SARAFEM (fluoxetine hydrochloride) 20 mg. In these clinical trials, more than one event may have been recorded as the cause of discontinuation.

Associated with discontinuation in US depression, OCD, and bulimia placebo-controlled clinical trials (excluding data from extensions of trials)— In female patients age 18 to 45 years in US depression, OCD, and bulimia placebo-controlled clinical trials combined, which collected a single primary event associated with discontinuation (incidence at least 1% for fluoxetine and at least twice that for placebo), insomnia (1%, N = 561) was the only event reported.

Female sexual dysfunction with SSRIs — Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a mood-related disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance, cited in product labeling, are likely to underestimate their actual incidence. For example, in women (age 18 to 45) receiving fluoxetine for indications other than PMDD, decreased libido was seen at an incidence of 4% for fluoxetine compared with 1% for placebo. There have been spontaneous reports in women (age 18 to 45) taking fluoxetine for indications other than PMDD of orgasmic dysfunction, including anorgasmia.

There are no adequate and well-controlled studies examining sexual dysfunction with fluoxetine treatment.

While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.

Other Events Observed in US Clinical Trials

Following is a list of all treatment-emergent adverse events reported at anytime by females and males taking fluoxetine in all US clinical trials for conditions other than PMDD as of May 8, 1995 (10,782 patients) except (1) those listed in the body or footnotes of Tables 2 or 3 above or elsewhere in labeling; (2) those for which the COSTART terms were uninformative or misleading; (3) those events for which a causal relationship to fluoxetine use was considered remote; (4) events occurring in only 1 patient treated with fluoxetine and which did not have a substantial probability of being acutely life-threatening; and (5) events that could only occur in males.

Events are classified within body system categories using the following definitions: frequent adverse events are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in less than 1/1000 patients.

Body as a Whole Frequent: chest pain and chills; Infrequent: chills and fever, face edema, intentional overdose, malaise, pelvic pain, suicide attempt; Rare: acute abdominal syndrome, hypothermia, intentional injury, neuroleptic malignant syndrome, photosensitivity reaction.

Cardiovascular SystemFrequent: hemorrhage, hypertension; Infrequent: angina pectoris, arrhythmia, congestive heart failure, hypotension, migraine, myocardial infarct, postural hypotension, syncope, tachycardia, vascular headache; Rare: atrial fibrillation, bradycardia, cerebral embolism, cerebral ischemia, cerebrovascular accident, extrasystoles, heart arrest, heart block, pallor, peripheral vascular disorder, phlebitis, shock, thrombophlebitis, thrombosis, vasospasm, ventricular arrhythmia, ventricular extrasystoles, ventricular fibrillation.

Digestive System Frequent: increased appetite, nausea and vomiting; Infrequent: aphthous stomatitis, cholelithiasis, colitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, glossitis, gum hemorrhage, hyperchlorhydria, increased salivation, liver function tests abnormal, melena, mouth ulceration, nausea/vomiting/diarrhea, stomach ulcer, stomatitis, thirst; Rare: biliary pain, bloody diarrhea, cholecystitis, duodenal ulcer, enteritis, esophageal ulcer, fecal incontinence, gastrointestinal hemorrhage, hematemesis, hemorrhage of colon, hepatitis, intestinal obstruction, liver fatty deposit, pancreatitis, peptic ulcer, rectal hemorrhage, salivary gland enlargement, stomach ulcer hemorrhage, tongue edema.

Endocrine SystemInfrequent: hypothyroidism; Rare: diabetic acidosis, diabetes mellitus.

Hemic and Lymphatic SystemInfrequent: anemia, ecchymosis; Rare: blood dyscrasia, hypochromic anemia, leukopenia, lymphedema, lymphocytosis, petechia, purpura, thrombocythemia, thrombocytopenia.

Metabolic and Nutritional Frequent: weight gain; Infrequent: dehydration, generalized edema, gout, hypercholesteremia, hyperhpemia, hypokalemia, peripheral edema; Rare: alcohol intolerance, alkaline phosphatase increased, BUN increased, creatine phosphokinase increased, hyperkalemia, hyperuricemia, hypocalcemia, iron deficiency anemia, SGPT increased.

Musculoskeletal SystemInfrequent: arthritis, bone pain, bursitis, leg cramps, tenosynovitis; Rare: arthrosis, chondrodystrophy, myasthenia, myopathy, myositis, osteomyelitis, osteoporosis, rheumatoid arthritis.

Nervous SystemFrequent: agitation, amnesia, confusion, emotional lability, paresthesia, and sleep disorder; Infrequent: abnormal gait, acute brain syndrome, akathisia, apathy, ataxia, buccoglossal syndrome, CNS depression, CNS stimulation, depersonalization, euphoria, hallucinations, hostility, hyperkinesia, hypertonia, hypesthesia, incoordination, libido increased, myoclonus, neuralgia, neuropathy, neurosis, paranoid reaction, personality disorder1, psychosis, vertigo; Rare: abnormal electroencephalogram, antisocial reaction, circumoral paresthesia, coma, delusions, dysarthria, dystonia, extrapyramidal syndrome, foot drop, hyperesthesia, neuritis, paralysis, reflexes decreased, reflexes increased, stupor.

Respiratory SystemInfrequent: asthma, epistaxis, hiccup, hyperventilation; Rare: apnea, atelectasis, cough decreased, emphysema, hemoptysis, hypoventilation, hypoxia, larynx edema, lung edema, pneumothorax, stridor.

Skin and AppendagesInfrequent: acne, alopecia, contact dermatitis, eczema, maculopapular rash, skin discoloration, skin ulcer, vesiculobullous rash; Rare: furunculosis, herpes zoster, hirsutism, petechial rash, psoriasis, purpuric rash, pustular rash, seborrhea.

Special Senses Frequent: ear pain, taste perversion, tinnitus; Infrequent: conjunctivitis, dry eyes, mydriasis, photophobia; Rare: blepharitis, deafness, diplopia, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, iritis, parosmia, scleritis, strabismus, taste loss, visual field defect.

Urogenital SystemInfrequent: abortion2, albuminuria, amenorrhea2, anorgasmia, breast enlargement, breast pain, cystitis, dysuria, female lactation2, fibrocystic breast , hematuria, leukorrhea2, menorrhagia2, metrorrhagia2, nocturia, polyuria, urinary incontinence, urinary retention, urinary urgency, vaginal hemorrhage2; Rare: breast engorgement, glycosuria, hypomenorrhea , kidney pain, oliguria, uterine hemorrhage2, uterine fibroids enlarged2.

1. Personality disorder is the COSTART term for designating non-aggressive objectionable behavior.
2. Adjusted for gender.

Postintroduction Reports

Voluntary reports of adverse events temporally associated with fluoxetine that have been received since market introduction of fluoxetine and that may have no causal relationship with the drug include the following: aplastic anemia, atrial fibrillation, cataract, cerebral vascular accident, cholestatic jaundice, confusion, dyskinesia (including, for example, a case of buccal-lingual-masticatory syndrome with involuntary tongue protrusion reported to develop in a 77 year-old female after 5 weeks of fluoxetine therapy and which completely resolved over the next few months following drug discontinuation), eosinophilic pneumonia, epidermal necrolysis, erythema multiforme, erythema nodosum, exfoliative dermatitis, gynecomastia, heart arrest, hepatic failure/necrosis, hyperprolactinemia, hypoglycemia, immune-related hemolytic anemia, kidney failure, misuse/abuse, movement disorders developing in patients with risk factors including drugs associated with such events and worsening of preexisting movement disorders, optic neuritis, pancreatitis, pancytopenia, priapism, pulmonary embolism, pulmonary hypertension, QT prolongation, Stevens-Johnson syndrome, sudden unexpected death, suicidal ideation, thrombocytopenia, thrombocytopenic purpura, vaginal bleeding after drug withdrawal, ventricular tachycardia (including torsades de pointes-type arrhythmias), and violent behaviors.

Drug Abuse And Dependence

Controlled substance class — Fluoxetine is not a controlled substance.

Physical and psychological dependence — Fluoxetine has not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. While the premarketing clinical experience with fluoxetine did not reveal any tendency for a withdrawal syndrome or any drug seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of fluoxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

Read the Sarafem (fluoxetine hydrochloride) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility (see Accumulation and slow elimination under CLINICAL PHARMACOLOGY).

Drugs metabolized by CYP2D6 — Approximately 7% of the normal population has a genetic defect that leads to reduced levels of activity of the cytochrome P450 isoenzyme 2D6. Such individuals have been referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, and TCAs. Many drugs, including fluoxetine and other selective uptake inhibitors of serotonin, are metabolized by this isoenzyme; thus, both the pharmacokinetic properties and relative proportion of metabolites are altered in poor metabolizers. However, for fluoxetine and its metabolite, the sum of the plasma concentrations of the 4 active enantiomers is comparable between poor and extensive metabolizers (see Variability in metabolism under CLINICAL PHARMACOLOGY).

Fluoxetine, inhibits the activity of CYP2D6 and thus may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index (see list below) should be initiated at the low end of the dose range if a patient is receiving fluoxetine concurrently or has taken it in the previous 5 weeks. Thus, her dosing requirements resemble those of poor metabolizers. If fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued (see CONTRAINDICATIONS and WARNINGS).

Drugs metabolized by CYP3A4 — In an in vivo interaction study involving coadministration of fluoxetine with single doses of terfenadine (a CYP3A4 substrate), no increase in plasma terfenadine concentrations occurred with concomitant fluoxetine. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam. These data indicate that fluoxetine's extent of inhibition of CYP3A4 activity is not likely to be of clinical significance.

CNS active drugs — The risk of using fluoxetine in combination with other CNS active drugs has not been systematically evaluated. Nonetheless, 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 Accumulation and slow elimination under CLINICAL PHARMACOLOGY).

Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment.

Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between serotonin specific reuptake inhibitors (SSRIs) and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QTC prolongation. While a specific study with pimozide and fluoxetine has not been conducted, the potential for drug interactions or QTC prolongation warrants restricting the concurrent use of pimozide and fluoxetine. Concomitant use of fluoxetine and pimozide is contraindicated (see CONTRAINDICATIONS). For thioridazine, see CONTRAINDICATIONS and WARNINGS.

Benzodiazepines — The half-life of concurrently administered diazepam may be prolonged in some patients (see Accumulation and slow elimination under CLINICAL PHARMACOLOGY). Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels.

Lithium— There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine. Cases of lithium toxicity and increased serotonergic effects have been reported. Lithium levels should be monitored when these drugs are administered concomitantly.

Tryptophan — Five patients receiving fluoxetine in combination with tryptophan experienced adverse reactions, including agitation, restlessness, and gastrointestinal distress.

Monoamine oxidase inhibitors — See CONTRAINDICATIONS.

Antidepressants — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of 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 Accumulation and slow elimination under CLINICAL PHARMACOLOGY, and Drugs metabolized by CYP2D6 under DRUG INTERACTIONS).

Serotonergic Drugs — Based on the mechanism of action of SNRIs and SSRIs, including SARAFEM (fluoxetine hydrochloride) , and the potential for serotonin syndrome, caution is advised when SARAFEM (fluoxetine hydrochloride) is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible nonselective MAOI), lithium, tramadol, or St. John's Wort, (see Serotonin Syndrome under WARNINGS.) The concomitant use of SARAFEM (fluoxetine hydrochloride) with other SSRIs, SNRIs or tryptophan is not recommended, (see DRUG INTERACTIONS under PRECAUTIONS.)

Triptans - There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of SARAFEM (fluoxetine hydrochloride) with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases, (see Serotonin Syndrome under WARNINGS.)

Potential effects of coadministration of drugs tightly bound to plasma proteins — Because fluoxetine is tightly bound to plasma protein, the administration of fluoxetine to a patient taking another drug that is tightly bound to protein (e.g., warfarin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect. Conversely, adverse effects may result from displacement of protein-bound fluoxetine by other tightly bound drugs (see Accumulation and slow elimination under CLINICAL PHARMACOLOGY).

Drugs that interfere with hemostasis (NSAIDs, aspirin, warfarin, etc.) — 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 potentiated the risk of bleeding. Thus, patients should be cautioned about the use of such drugs concurrently with fluoxetine.

Warfarin — Altered anticoagulant effects, including increased bleeding, have been reported when fluoxetine is coadministered with warfarin. Patients receiving warfarin therapy should receive careful coagulation monitoring when fluoxetine is initiated or stopped.

Electroconvulsive therapy (ECT) — 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.

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 2.

Table 2

Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated
  Drug-Related Increases
< 18 14 additional cases
18-24 5 additional cases
  Drug-Related Decreases
25-64 1 fewer case
≥ 65 6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION - Discontinuation of Treatment with SARAFEM (fluoxetine hydrochloride) , for a description of the risks of discontinuation of SARAFEM (fluoxetine hydrochloride) ).

Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for SARAFEM (fluoxetine hydrochloride) should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that SARAFEM (fluoxetine hydrochloride) is not approved for use in treating bipolar depression.

Rash and Possibly Allergic Events — In 4 clinical trials for PMDD, 4% of 415 patients treated with SARAFEM (fluoxetine hydrochloride) reported rash and/or urticaria. None of these cases were classified as serious and 2 of 415 patients (both receiving 60 mg) were withdrawn from treatment because of rash and/or urticaria.

In US fluoxetine clinical trials for conditions other than PMDD, 7% of 10,782 patients developed various types of rashes and/or urticaria. Among the cases of rash and/or urticaria reported in premarketing clinical trials, almost a third were withdrawn from treatment because of the rash and/or systemic signs or symptoms associated with the rash. Clinical findings reported in association with rash include fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase elevation. Most patients improved promptly with discontinuation of fluoxetine and/or adjunctive treatment with antihistamines or steroids, and all patients experiencing these events were reported to recover completely.

In premarketing clinical trials of fluoxetine for conditions other than PMDD, 2 patients are known to have developed a serious cutaneous systemic illness. In neither patient was there an unequivocal diagnosis, but one was considered to have a leukocytoclastic vasculitis, and the other, a severe desquamating syndrome that was considered variously to be a vasculitis or erythema multiforme. Other patients have had systemic syndromes suggestive of serum sickness.

Since the introduction of fluoxetine for other indications, systemic events, possibly related to vasculitis and including lupus-like syndrome, have developed in patients with rash. Although these events are rare, they may be serious, involving the lung, kidney, or liver. Death has been reported to occur in association with these systemic events.

Anaphylactoid events, including bronchospasm, angioedema, laryngospasm, and urticaria alone and in combination, have been reported.

Pulmonary events, including inflammatory processes of varying histopathology and/or fibrosis, have been reported rarely. These events have occurred with dyspnea as the only preceding symptom.

Whether these systemic events and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known. Furthermore, a specific underlying immunologic basis for these events has not been identified. Upon the appearance of rash or of other possibly allergic phenomena for which an alternative etiology cannot be identified, SARAFEM (fluoxetine hydrochloride) should be discontinued.

Potential Interaction with Thioridazine — In a study of 19 healthy male subjects, which included 6 slow and 13 rapid hydroxylators of debrisoquin, a single 25 mg oral dose of thioridazine produced a 2.4-fold higher Cmax and a 4.5-fold higher AUC for thioridazine in the slow hydroxylators compared with the rapid hydroxylators. The rate of debrisoquin hydroxylation is felt to depend on the level of CYP2D6 isozyme activity. Thus, this study suggests that drugs which inhibit CYP2D6, such as certain SSRIs, including fluoxetine, will produce elevated plasma levels of thioridazine (see PRECAUTIONS: DRUG INTERACTIONS).

Thioridazine administration produces a dose-related prolongation of the QTC interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias, and sudden death. This risk is expected to increase with fluoxetine-induced inhibition of thioridazine metabolism (see CONTRAINDICATIONS). Thioridazine should not be administered with SARAFEM (fluoxetine hydrochloride) or within a minimum of 5 weeks after SARAFEM (fluoxetine hydrochloride) has been discontinued.

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions — The development of a potentially life-threatening serotonin syndrome, or Neuroleptic Malignant Syndrome (NMS)-like reactions, has been reported with SNRIs and SSRIs alone, including SARAFEM (fluoxetine hydrochloride) treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms 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, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.

The concomitant use of SARAFEM (fluoxetine hydrochloride) with MAOIs intended to treat depression is contraindicated. (see CONTRAINDICATIONS and WARNINGS.)

If concomitant treatment of SARAFEM (fluoxetine hydrochloride) with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases, (see DRUG INTERACTIONS under PRECAUTIONS.)

The concomitant use of SARAFEM (fluoxetine hydrochloride) with serotonin precursors (such as tryptophan) is not recommended, (see DRUG INTERACTIONS under PRECAUTIONS.)

PRECAUTIONS

General

Abnormal Bleeding — Published case reports have documented the occurrence of bleeding episodes in patients treated with psychotropic drugs that interfere with serotonin reuptake. Subsequent epidemiological studies, both of the case-control and cohort design, have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of a nonsteroidal anti-inflammatory drug (NSAID) or aspirin potentiated the risk of bleeding (see PRECAUTIONS: DRUG INTERACTIONS). Although these studies focused on upper gastrointestinal bleeding, there is reason to believe that bleeding at other sites may be similarly potentiated. Patients should be cautioned regarding the risk of bleeding associated with the concomitant use of SARAFEM (fluoxetine hydrochloride) with NSAIDs, aspirin, or other drugs that affect coagulation.

Anxiety and Insomnia — In 2 placebo-controlled trials of fluoxetine in PMDD, treatment-emergent adverse events were assessed. Rates were as follows for SARAFEM (fluoxetine hydrochloride) 20 mg (the recommended dose) continuous and intermittent pooled, SARAFEM (fluoxetine hydrochloride) 60 mg continuous, and pooled placebo, respectively: anxiety (3%, 9%, and 4%); nervousness (5%, 9%, and 3%); and insomnia (9%, 26%, and 7%). For individual rates for SARAFEM (fluoxetine hydrochloride) 20 mg given as continuous and intermittent dosing, see Table 2 and accompanying footnote under ADVERSE REACTIONS. Events associated with discontinuation for SARAFEM (fluoxetine hydrochloride) 20 mg continuous and intermittent pooled, SARAFEM (fluoxetine hydrochloride) 60 mg continuous, and pooled placebo, respectively, were: anxiety (0%, 6%, and 1%); nervousness (1%, 0%, and 0.5%); and insomnia (1%, 4%, and 0.5%). In US placebo-controlled clinical trials of fluoxetine for other approved indications, anxiety, nervousness, and insomnia have been among the most commonly reported adverse events (see Table 3 under ADVERSE REACTIONS).

Altered Appetite and Weight — In 2 placebo-controlled trials of fluoxetine in PMDD, rates for anorexia were as follows for SARAFEM (fluoxetine hydrochloride) 20 mg (the recommended dose) continuous and intermittent pooled, SARAFEM (fluoxetine hydrochloride) 60 mg continuous, and pooled placebo, respectively: 4%, 13%, and 2%. For individual rates for SARAFEM (fluoxetine hydrochloride) 20 mg continuous and intermittent, see footnote accompanying Table 2 under ADVERSE REACTIONS. In 2 placebo-controlled trials (only one of which included a dose of 60 mg/day), potentially clinically significant weight gain ( ≥ 7%) occurred in 8% of patients on SARAFEM (fluoxetine hydrochloride) 20 mg, 6% of patients on SARAFEM (fluoxetine hydrochloride) 60 mg, and 1% of patients on placebo. Potentially clinically significant weight loss ( ≥ 7%) occurred in 7% of patients on SARAFEM (fluoxetine hydrochloride) 20 mg, 12% of patients on SARAFEM (fluoxetine hydrochloride) 60 mg, and 3% of patients on placebo. In US placebo-controlled clinical trials of fluoxetine for other approved indications, changes in appetite and weight have also been reported (see Table 3 and Other Events Observed in US Clinical Trials under ADVERSE REACTIONS).

Activation of Mania/Hypomania — No patients treated with SARAFEM (fluoxetine hydrochloride) in 4 PMDD clinical trials (N = 415) reported mania/hypomania. In all US fluoxetine clinical trials for conditions other than PMDD, 0.7% of 10,782 patients reported mania/hypomania. Activation of mania/hypomania may occur with medications used to treat depression, especially in patients predisposed to Bipolar Affective Disorder.

Hyponatremia — Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including SARAFEM (fluoxetine hydrochloride) . In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk. Discontinuation of SARAFEM (fluoxetine hydrochloride) should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.

Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.

Seizures — No patients treated with SARAFEM (fluoxetine hydrochloride) in 4 PMDD clinical trials (N = 415) reported seizures. In all US fluoxetine clinical trials for conditions other than PMDD, 0.2% of 10,782 patients reported seizures. Antidepressant medication should be introduced with care in patients with a history of seizures.

The Long Elimination Half-Lives of Fluoxetine and its Metabolites — Because of the long elimination half-lives of the parent drug and its major active metabolite, changes in dose will not be fully reflected in plasma for several weeks, affecting both strategies for titration to final dose and withdrawal from treatment (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Use in Patients with Concomitant Illness — Clinical experience with fluoxetine in patients with concomitant systemic illness is limited. Caution is advisable in using fluoxetine in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Fluoxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from clinical studies during the product's premarket testing. However, the electrocardiograms of 312 patients who received fluoxetine in double-blind trials for a condition other than PMDD were retrospectively evaluated; no conduction abnormalities that resulted in heart block were observed. The mean heart rate was reduced by approximately 3 beats/min.

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 (see Liver disease under CLINICAL PHARMACOLOGY, Special Populations). A lower or less frequent dose should be used in patients with cirrhosis (see DOSAGE AND ADMINISTRATION).

Studies in depressed patients on dialysis did not reveal excessive accumulation of fluoxetine or norfluoxetine in plasma (see Renal disease under CLINICAL PHARMACOLOGY, Special Populations). Use of a lower or less frequent dose for renally impaired patients is not routinely necessary (see DOSAGE AND ADMINISTRATION).

In patients with diabetes, fluoxetine may alter glycemic control. Hypoglycemia has occurred during therapy with fluoxetine, and hyperglycemia has developed following discontinuation of the drug. As is true with many other types of medication when taken concurrently by patients with diabetes, insulin and/or oral hypoglycemic dosage may need to be adjusted when therapy with fluoxetine is instituted or discontinued.

Discontinuation of Treatment with SARAFEM (fluoxetine hydrochloride) — During marketing of SARAFEM (fluoxetine hydrochloride) and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms. Patients should be monitored for these symptoms when discontinuing treatment with SARAFEM (fluoxetine hydrochloride) . A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. Plasma fluoxetine and norfluoxetine concentration decrease gradually at the conclusion of therapy, which may minimize the risk of discontinuation symptoms with this drug (see DOSAGE AND ADMINISTRATION).

Interference with Cognitive and Motor Performance— Any psychoactive drug may impair judgment, thinking, or motor skills, and patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely.

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with SARAFEM (fluoxetine hydrochloride) and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions" is available for SARAFEM (fluoxetine hydrochloride) . The prescriber or health professional 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. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking SARAFEM (fluoxetine hydrochloride) .

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.

Laboratory Tests

There are no specific laboratory tests recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There is no evidence of carcinogenicity or mutagenicity from in vitro or animal studies.

Carcinogenicity — The dietary administration of fluoxetine to rats and mice for 2 years at doses of up to 10 and 12 mg/kg/day, respectively [approximately 1.2 and 0.7 times, respectively, the maximum recommended human dose (MRHD) of 80 mg on a mg/m2 basis], produced no evidence of carcinogenicity.

Mutagenicity — Fluoxetine and norfluoxetine have been shown to have no genotoxic effects based on the following assays: bacterial mutation assay, DNA repair assay in cultured rat hepatocytes, mouse lymphoma assay, and in vivo sister chromatid exchange assay in Chinese hamster bone marrow cells.

Impairment of fertility — Two fertility studies conducted in adult rats at doses of up to 7.5 and 12.5 mg/kg/day (approximately 0.9 and 1.5 times the MRHD on a mg/m2 basis) indicated that fluoxetine had no adverse effects on fertility (see Pediatric Use).

Pregnancy

Pregnancy Category C — In embryo-fetal development studies in rats and rabbits, there was no evidence of teratogenicity following administration of up to 12.5 and 15 mg/kg/day, respectively (1.5 and 3.6 times, respectively, the MRHD of 80 mg on a mg/m2 basis), throughout organogenesis. However, in rat reproduction studies, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths during the first 7 days postpartum occurred following maternal exposure to 12 mg/kg/day (1.5 times the MRHD on a mg/m2 basis) during gestation or 7.5 mg/kg/day (0.9 times the MRHD on a mg/m2 basis) during gestation and lactation. There was no evidence of developmental neurotoxicity in the surviving offspring of rats treated with 12 mg/kg/day during gestation. The no-effect dose for rat pup mortality was 5 mg/kg/day (0.6 times the MRHD on a mg/m2 basis). Fluoxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects — Neonates exposed to fluoxetine and other SSRIs or serotonin and norepinephrine reuptake inhibitors (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, tremor, jitteriness, irritability, and constant crying. These features 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 Monoamine oxidase inhibitors under CONTRAINDICATIONS).

Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately sixfold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. There is currently no corroborative evidence regarding the risk for PPHN following exposure to SSRIs in pregnancy; this is the first study that has investigated the potential risk. The study did not include enough cases with exposure to individual SSRIs to determine if all SSRIs posed similar levels of PPHN risk.

When treating a pregnant woman with fluoxetine during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment (see DOSAGE AND ADMINISTRATION). Physicians should note that in a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.

Labor and Delivery

The effect of fluoxetine on labor and delivery in humans is unknown. However, because fluoxetine crosses the placenta and because of the possibility that fluoxetine may have adverse effects on the newborn, fluoxetine should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Because fluoxetine is excreted in human milk, nursing while on fluoxetine is not recommended. In one breast-milk sample, the concentration of fluoxetine plus norfluoxetine was 70.4 ng/mL. The concentration in the mother's plasma was 295.0 ng/mL. No adverse effects on the infant were reported. In another case, an infant nursed by a mother on fluoxetine developed crying, sleep disturbance, vomiting, and watery stools. The infant's plasma drug levels were 340 ng/mL of fluoxetine and 208 ng/mL of norfluoxetine on the second day of feeding.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS, Clinical Worsening and Suicide Risk). Anyone considering the use of SARAFEM (fluoxetine hydrochloride) in a child or adolescent must balance the potential risks with the clinical need.

Significant toxicity, including myotoxicity, long term neurobehavioral and reproductive toxicity, and impaired bone development, has been observed following exposure of juvenile animals to fluoxetine. Some of these effects occurred at clinically relevant exposures.

In a study in which fluoxetine (3, 10, or 30 mg/kg) was orally administered to young rats from weaning (Postnatal Day 21) through adulthood (Day 90), male and female sexual development was delayed at all doses, and growth (body weight gain, femur length) was decreased during the dosing period in animals receiving the highest dose. At the end of the treatment period, serum levels of creatine kinase (marker of muscle damage) were increased at the intermediate and high doses, and abnormal muscle and reproductive organ histopathology (skeletal muscle degeneration and necrosis, testicular degeneration and necrosis, epididymal vacuolation and hypospermia) was observed at the high dose. When animals were evaluated after a recovery period (up to 11 weeks after cessation of dosing), neurobehavioral abnormalities (decreased reactivity at all doses and learning deficit at the high dose) and reproductive functional impairment (decreased mating at all doses and impaired fertility at the high dose) were seen; in addition, testicular and epididymal microscopic lesions and decreased sperm concentrations were found in the high dose group, indicating that the reproductive organ effects seen at the end of treatment were irreversible. The reversibility of fluoxetine induced muscle damage was not assessed. Adverse effects similar to those observed in rats treated with fluoxetine during the juvenile period have not been reported after administration of fluoxetine to adult animals. Plasma exposures (AUC) to fluoxetine in juvenile rats receiving the low, intermediate, and high dose in this study were approximately 0.1-0.2, 1-2, and 5-10 times, respectively, the average exposure in pediatric patients receiving the maximum recommended dose (MRD) of 20 mg/day. Rat exposures to the major metabolite, norfluoxetine, were approximately 0.3-0.8, 1-8, and 3-20 times, respectively, pediatric exposure at the MRD.

A specific effect of fluoxetine on bone development has been reported in mice treated with fluoxetine during the juvenile period. When mice were treated with fluoxetine (5 or 20 mg/kg, intraperitoneal) for 4 weeks starting at 4 weeks of age, bone formation was reduced resulting in decreased bone mineral content and density. These doses did not affect overall growth (body weight gain or femoral length). The doses administered to juvenile mice in this study are approximately 0.5 and 2 times the MRD for pediatric patients on a body surface area (mg/m2) basis.

In another mouse study, administration of fluoxetine (10 mg/kg intraperitoneal) during early postnatal development (Postnatal Days 4 to 21) produced abnormal emotional behaviors (decreased exploratory behavior in elevated plus maze, increased shock avoidance latency) in adulthood (12 weeks of age). The dose used in this study is approximately equal to the pediatric MRD on a mg/m2 basis. Because of the early dosing period in this study, the significance of these findings to the approved pediatric use in humans is uncertain.

Geriatric Use

The diagnosis of PMDD is not applicable to postmenopausal women.

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

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 non-lethal.

Other important adverse events 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 events, pyrexia, stupor, and syncope.

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 (see Management of Overdose).

Management of Overdose

Treatment should consist of those general measures employed in the management of overdosage with any SSRI.

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 (see Antidepressants under PRECAUTIONS: DRUG INTERACTIONS).

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).

CONTRAINDICATIONS

SARAFEM (fluoxetine hydrochloride) is contraindicated in patients known to be hypersensitive to it.

Monoamine oxidase inhibitors — 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 should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI. 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 (see Accumulation and slow elimination under CLINICAL PHARMACOLOGY] should be allowed after stopping fluoxetine before starting an MAOI.

Pimozide — Concomitant use in patients taking pimozide is contraindicated (see Antipsychotics under PRECAUTIONS: DRUG INTERACTIONS).

Thioridazine — Thioridazine should not be administered with SARAFEM (fluoxetine hydrochloride) or within a minimum of 5 weeks after SARAFEM has been discontinued (see WARNINGS).

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Pharmacodynamics

The mechanism of action of fluoxetine in premenstrual dysphoric disorder (PMDD) is unknown, but is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Studies at clinically relevant doses in humans 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 (α1-adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of certain psychoactive drugs. Fluoxetine has little affinity for these receptors.

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.

Pharmacokinetics

Absorption—Mean plasma fluoxetine concentrations following single-dose administration of SARAFEM (fluoxetine hydrochloride) 20 mg tablets are shown in Figure 1; fluoxetine and norfluoxetine pharmacokinetic parameters are shown in Table 1.

Figure 1. Mean (+ SD) Plasma Fluoxetine Concentrations Following Single-Dose Administration of SARAFEM (fluoxetine hydrochloride) 20 mg Tablets to Healthy Female Volunteers (n=23)

Mean (+ SD) Plasma Fluoxetine Concentrations - Illustration

Table 1. Summary of Mean Pharmacokinetic Parameters Following Single-Dose Administration of SARAFEM (fluoxetine hydrochloride) 20 mg Tablets to Healthy Female Volunteers (n = 23) (Cmax andAUC(0-t): shown as Mean (% Coefficient of Variation); Tmax and 77/2: shown as median (range))

Dose Analyte Cmax
(ng/mL)
Tmax
(hour)
AUC(0-t)
(ng-h/mL)
Tl/2a
(hour)
SARAFEM 20 mg Fluoxetine 13.2
(22)
8.0
(2.0-10.0)
722.4
(138)
26.5
(15.7-310.0)
Norfluoxetine 9.7
(37)
48.0
(11.0-144.0)
2114.3
(41)
110.4
(66.8-308.0)
a) 3 subjects had longer fluoxetine elimination half-life values ranging from 100-300 hours; see Clinical issues relating to metabolism/elimination for more information on "poor metabolizers"

Food does not appear to affect the systemic bioavailability of fluoxetine, although it may delay its absorption inconsequentially. Thus, fluoxetine may be administered with or without food.

Distribution — 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 (see PRECAUTIONS).

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.

Clinical issues related to metabolism/elimination— The complexity of the metabolism of fluoxetine has several consequences that may potentially affect fluoxetine's clinical use.

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 tricyclic antidepressants (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 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 under PRECAUTIONS).

Excretion— The primary route of elimination of fluoxetine appears to be hepatic metabolism to inactive metabolites that are then excreted by the kidney.

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. 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 SARAFEM (fluoxetine hydrochloride) .

Special Populations

Liver disease — As might be predicted from its primary site of metabolism, liver impairment can affect the elimination of fluoxetine. The elimination half-life of fluoxetine was prolonged in a study of cirrhotic patients, with a mean of 7.6 days compared with the range of 2 to 3 days seen in subjects without liver disease; norfluoxetine elimination was also delayed, with a mean duration of 12 days for cirrhotic patients compared with the range of 7 to 9 days in normal subjects. This suggests that the use of fluoxetine in patients with liver disease must be approached with caution. If fluoxetine is administered to patients with liver disease, a lower or less frequent dose should be used (see Use in Patients with Concomitant Illness under PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

Renal disease — In depressed patients on dialysis (N = 12), fluoxetine administered as 20 mg once daily for 2 months produced steady-state fluoxetine and norfluoxetine plasma concentrations comparable with those seen in patients with normal renal function. While the possibility exists that renally excreted metabolites of fluoxetine may accumulate to higher levels in patients with severe renal dysfunction, use of a lower or less frequent dose is not routinely necessary in renally impaired patients (see Use in Patients with Concomitant Illness under PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

Pediatric: Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS, Clinical Worsening and Suicide Risk, Pediatric use).

Geriatric: The diagnosis of PMDD is not applicable to postmenopausal women.

Clinical Trials

Premenstrual Dysphoric Disorder (PMDD)

The effectiveness of SARAFEM (fluoxetine hydrochloride) for the treatment of PMDD was established in 3 placebo-controlled trials (1 intermittent and 2 continuous dosing). In an intermittent dosing trial described below, patients met Diagnostic and Statistical Manual-4th edition (DSM-IV) criteria for PMDD. In the continuous dosing trials described below, patients met Diagnostic and Statistical Manual-3rd edition revised (DSM-IIIR) criteria for Late Luteal Phase Dysphoric Disorder (LLPDD), the clinical entity now referred to as PMDD in the DSM-IV. Patients on oral contraceptives were excluded from these trials; therefore, the efficacy of fluoxetine in combination with oral contraceptives for the treatment of PMDD is unknown.

In an intermittent dosing double-blind, parallel group study of 3 months duration, patients (N = 260 randomized) were treated with fluoxetine 10 mg/day, fluoxetine 20 mg/day, or placebo. Fluoxetine or placebo was started 14 days prior to the anticipated onset of menstruation and was continued through the first full day of menses. Efficacy was assessed with the Daily Record of Severity of Problems (DRSP), a patient-rated instrument that mirrors the diagnostic criteria for PMDD as identified in the DSM-IV, and includes assessments for mood, physical symptoms, and other symptoms. Fluoxetine 20 mg/day was shown to be significantly more effective than placebo as measured by the DRSP total score. Fluoxetine 10 mg/day was not shown to be significantly more effective than placebo on this outcome. The average DRSP total score decreased 38% on fluoxetine 20 mg/day, 35% on fluoxetine 10 mg/day, and 30% on placebo.

In the first continuous dosing double-blind, parallel group study of 6 months duration involving N = 320 patients, fixed doses of fluoxetine 20 and 60 mg/day given daily throughout the menstrual cycle were shown to be significantly more effective than placebo as measured by a Visual Analogue Scale (VAS) total score (including mood and physical symptoms). The average total VAS score decreased 7% on placebo treatment, 36% on 20 mg, and 39% on 60 mg fluoxetine. The difference between the 20 and 60 mg doses was not statistically significant. The following table shows the percentage of patients meeting criteria for either moderate or marked improvement on the VAS total score:

Percentage of Patients Moderately and Markedly Improved ( > 50% and 75% reduction, respectively, from baseline Luteal Phase VAS total score)

Improvement N Placebo N Fluoxetine 20 mg N Fluoxetine 60 mg
Moderate 94 11% 95 37% 85 38%
Marked 94 4% 95 6% 85 18%

In a second continuous dosing double-blind, cross-over study, patients (N = 19) were treated with fluoxetine 20 to 60 mg/day (mean dose = 27 mg/day) and placebo daily throughout the menstrual cycle for a period of 3 months each. Fluoxetine was significantly more effective than placebo as measured by within cycle follicular to luteal phase changes in the VAS total score (mood, physical, and social impairment symptoms). The average VAS total score (follicular to luteal phase increase) was 3.8 times higher during placebo treatment than what was observed during fluoxetine treatment.

In another continuous dosing double-blind, parallel group study, patients with LLPDD (N = 42) were treated daily with fluoxetine 20 mg/day, bupropion 300 mg/day, or placebo for 2 months. Neither fluoxetine nor bupropion was shown to be superior to placebo on the primary endpoint, i.e., response rate [defined as a rating of 1 (very much improved) or 2 (much improved) on the CGI], possibly due to sample size.

Animal Toxicology

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.

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions

Read the Medication Guide that comes with you or your family member's antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. 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

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

  1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults when the medicine is first started.
  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 first 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)
  • 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 foruse in children. Talk to your child's healthcare provider for more information.

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

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions

Read the Medication Guide that comes with you or your family member's antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. 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

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

  1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults when the medicine is first started.
  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 first 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)
  • 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 foruse in children. Talk to your child's healthcare provider for more information.

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

Last reviewed on RxList: 5/20/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Sarafem Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

FLUOXETINE - ORAL

(floo-OX-e-teen)

COMMON BRAND NAME(S): Prozac, Sarafem

WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. Therefore, it is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.

Tell the doctor immediately if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

USES: Fluoxetine is used to treat depression, panic attacks, obsessive compulsive disorder, a certain eating disorder (bulimia), and a severe form of premenstrual syndrome (premenstrual dysphoric disorder).

This medication may improve your mood, sleep, appetite, and energy level and may help restore your interest in daily living. It may decrease fear, anxiety, unwanted thoughts, and the number of panic attacks. It may also reduce the urge to perform repeated tasks (compulsions such as hand-washing, counting, and checking) that interfere with daily living. Fluoxetine may lessen premenstrual symptoms such as irritability, increased appetite, and depression. It may decrease bingeing and purging behaviors in bulimia.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug is also used to treat a certain other eating disorder (anorexia nervosa), post traumatic stress disorder (PTSD), and certain nervous system/sleep disorders (catalepsy, narcolepsy).

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using fluoxetine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily in the morning. If you are taking this medication twice a day, your doctor may direct you to take it in the morning and at noon.

If you are taking fluoxetine for premenstrual problems, your doctor may direct you to take it every day of the month or just for the 2 weeks before your period through the first full day of your period. To help you remember, mark your calendar.

If you are using the liquid form of this medication, measure the dose carefully using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

It is important to continue taking this medication as prescribed even if you feel well. Do not stop taking this medication without first consulting your doctor. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased.

You should see some improvement in 1 to 2 weeks. It may take 4 to 5 weeks before you feel the full benefit.

Tell your doctor if your condition does not improve or if it worsens.

Disclaimer

Sarafem Consumer (continued)

SIDE EFFECTS: See also Warning section.

Nausea, drowsiness, dizziness, anxiety, trouble sleeping, loss of appetite, tiredness, sweating, or yawning may occur. If any of these effects persist or worsen, tell your doctor promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious side effects occur: unusual or severe mental/mood changes (such as agitation, unusual high energy/excitement, thoughts of suicide), easy bruising/bleeding, muscle weakness/spasm, shakiness (tremor), decreased interest in sex, changes in sexual ability, unusual weight loss, large pupils.

Get medical help right away if any of these rare but serious side effects occur: bloody/black/tarry stools, vomit that looks like coffee grounds, seizures, change in amount of urine.

If you have diabetes, fluoxetine may affect your blood sugar levels. Monitor your blood sugar regularly and share the results with your doctor. Your doctor may need to adjust your medication, diet, and exercise when you start or stop fluoxetine.

This medication may rarely cause a very serious condition called serotonin syndrome. The risk increases when this medication is used with certain other drugs (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: hallucinations, unusual restlessness, loss of coordination, fast heartbeat, severe dizziness, unexplained fever, severe nausea/vomiting/diarrhea, twitchy muscles.

Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Sarafem (fluoxetine hydrochloride) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking fluoxetine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal or family history of bipolar/manic-depressive disorder, personal or family history of suicide attempts, liver problems, diabetes, low sodium in the blood (such as may occur while taking "water pills" - diuretics), severe loss of body water (dehydration), seizures, stomach/intestinal ulcers, glaucoma.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.

The liquid form of this medication contains alcohol. Caution is advised if you have diabetes, alcohol dependence, or liver disease. Some medications (such as metronidazole, disulfiram) can cause a serious reaction when combined with alcohol. Ask your doctor or pharmacist about using this product safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be at greater risk for bleeding while taking this drug. Older adults may also be more likely to develop low sodium in the blood, especially if they are taking "water pills" (diuretics).

During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Also, babies born to mothers who have used this drug during the last 3 months of pregnancy may infrequently develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.

Since untreated depression can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss the benefits and risks of using this medication during pregnancy with your doctor.

This drug may pass into breast milk and could have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Disclaimer

Sarafem Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Fluoxetine can stay in your body for many weeks after your last dose and may interact with many other medications. Before using any medication, tell your doctor or pharmacist if you have taken fluoxetine in the previous 5 weeks.

Some products that may interact with this drug include: pimozide, thioridazine, drugs removed from your body by certain liver enzymes including carbamazepine, vinblastine, antiarrhythmics such as propafenone/flecainide, tricyclic antidepressants such as desipramine/imipramine, other drugs that can cause bleeding/bruising including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen, "blood thinners" such as warfarin.

Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) with fluoxetine for 2 weeks before, during treatment, and at least 5 weeks after your last dose of fluoxetine. In some cases a serious (possibly fatal) drug interaction may occur.

Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day), you should continue taking it unless your doctor instructs you otherwise.

Before taking fluoxetine, report the use of other drugs that increase serotonin, such as dextromethorphan, lithium, St. John's wort, sibutramine, street drugs such as MDMA/"ecstasy," tramadol, tryptophan, certain antidepressants including SSRIs (such as citalopram, paroxetine) and SNRIs (such as duloxetine, venlafaxine), "triptans" used to treat migraine headaches (such as eletriptan, sumatriptan), among others. The risk of serotonin syndrome may be more likely when you start or increase the dose of these medications.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine). Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

NOTES: Do not share this medication with others.

Keep all regular medical and psychiatric appointments.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised October 2011. Copyright(c) 2011 First Databank, Inc.

Sarafem Patient Information Including Side Effects

Brand Names: Prozac, Prozac Weekly, Rapiflux, Sarafem, Selfemra

Generic Name: fluoxetine (Pronunciation: floo OX e teen)

What is fluoxetine (Sarafem)?

Fluoxetine is a selective serotonin reuptake inhibitors (SSRI) antidepressant. Fluoxetine affects chemicals in the brain that may become unbalanced and cause depression, panic, anxiety, or obsessive-compulsive symptoms.

Fluoxetine is used to treat major depressive disorder, bulimia nervosa (an eating disorder) obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder (PMDD).

Fluoxetine is sometimes used together with another medication called olanzapine (Zyprexa) to treat depression caused by bipolar disorder (manic depression). This combination is also used to treat depression after at least 2 other medications have been tried without successful treatment of symptoms.

Fluoxetine may also be used for purposes not listed in this medication guide.

Fluoxetine 10 mg Cap-BAR

blue/yellow, imprinted with barr 10 mg, 876

Fluoxetine 10 mg Tab-BAR

oval, beige, imprinted with b, 201 10

Fluoxetine 10 mg Tab-TEV

oval, blue, imprinted with 9 3, 7188

Fluoxetine 10 mg-GEN

white, imprinted with GG 575

Fluoxetine 10 mg-IVA

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Fluoxetine 10 mg-MAL

green, imprinted with M 0661

Fluoxetine 10 mg-MYL

pink/white, imprinted with MYLAN 4210

Fluoxetine 10 mg-PAR

oval, white, imprinted with G, FL 10

Fluoxetine 10 mg-TEV

blue, imprinted with 93 42

Fluoxetine 20 mg Cap-BAR

blue/gray, imprinted with barr 20 mg, 877

Fluoxetine 20 mg4356-TEV

turquoise, imprinted with 4356, 20 mg

Fluoxetine 20 mg-EON

green/white, imprinted with E85

Fluoxetine 20 mg-GEN

white, imprinted with GG 550

Fluoxetine 20 mg-IVA

turquoise, imprinted with Logo 4356, 20 mg

Fluoxetine 20 mg-MAL

green/white, imprinted with M inside a box 0663

Fluoxetine 20 mg-MYL

blue/pink, imprinted with MYLAN 4220

Fluoxetine 20 mg-PAR

oval, white, imprinted with G, FL 20

Fluoxetine 20 mg-TEV

blue/white, imprinted with 93 43

Fluoxetine 40 mg-IVA

blue, imprinted with Logo 4346, 40 mg

Fluoxetine 40 mg-MYL

blue/white, imprinted with MYLAN 4350

Fluoxetine 40 mg-PAR

white, imprinted with GG 540

Fluoxetine 40 mg-TEV

blue/orange, imprinted with 93 7198

Fluoxetine DR 90 mg-BAR

turquoise/white, imprinted with barr 90 mg, 871

Prozac 10 mg Tab

elliptical, green, imprinted with PROZAC 10

Prozac 10 mg

green, imprinted with DISTA 3104, PROZAC 10 mg

Prozac 20 mg

green/yellow, imprinted with DISTA 3105, PROZAC 20 mg

Prozac 40 mg

green/orange, imprinted with DISTA 3107, PROZAC 40mg

Selfemra 10 mg

blue, imprinted with 93 7225

Selfemra 20 mg

blue/pink, imprinted with 93 7226

What are the possible side effects of fluoxetine (Sarafem)?

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

  • severe blistering, peeling, and red skin rash;
  • very stiff (rigid) muscles, high fever, sweating, fast or uneven heartbeats, tremors, overactive reflexes;
  • nausea, vomiting, diarrhea, loss of appetite, feeling unsteady, loss of coordination; or
  • headache, trouble concentrating, memory problems, weakness, confusion, hallucinations, fainting, seizure, shallow breathing or breathing that stops.

Less serious side effects may include:

  • cold symptoms such as stuffy nose, sneezing, sore throat;
  • drowsiness, dizziness, feeling nervous;
  • mild nausea, upset stomach, constipation;
  • increased appetite, weight changes;
  • sleep problems (insomnia);
  • decreased sex drive, impotence, or difficulty having an orgasm; or
  • dry mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Sarafem (fluoxetine hydrochloride) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about fluoxetine (Sarafem)?

Do not take fluoxetine together with pimozide (Orap), thioridazine (Mellaril), or an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). A dangerous drug interaction could occur, leading to serious side effects.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

This medication may cause serious lung problems in a newborn if you take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you become pregnant while taking fluoxetine, do not stop taking the medication without first talking to your doctor.

Side Effects Centers

Sarafem Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking fluoxetine (Sarafem)?

Do not use fluoxetine if you are using any of the following drugs:

  • pimozide (Orap);
  • thioridazine (Mellaril); or
  • an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate).

Serious and sometimes fatal reactions can occur when these medicines are taken with fluoxetine. You must wait at least 14 days after stopping an MAO inhibitor before you can take fluoxetine. You must wait 5 weeks after stopping fluoxetine before you can take thioridazine (Mellaril) or an MAOI.

To make sure you can safely take fluoxetine, tell your doctor if you have any of these other conditions:

  • cirrhosis of the liver;
  • kidney disease;
  • diabetes;
  • glaucoma;
  • seizures or epilepsy;
  • bipolar disorder (manic depression); or
  • a history of drug abuse or suicidal thoughts.

You may have thoughts about suicide while taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. This medication may cause serious lung problems in a newborn if you take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you become pregnant while taking fluoxetine, do not stop taking the medication without first talking to your doctor.

Fluoxetine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give fluoxetine to anyone younger than 18 years old without a doctor's advice.

How should I take fluoxetine (Sarafem)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Do not crush, chew, break, or open an extended-release capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

Measure liquid medicine with a special dose measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose measuring device, ask your pharmacist for one.

It may take 4 weeks or longer before you start feeling better. Do not stop using fluoxetine without first talking to your doctor. You may have unpleasant side effects if you stop taking this medication suddenly.

To treat premenstrual dysphoric disorder, the usual dose of fluoxetine is once daily while you are having your period, or 14 days before you expect your period to start. Follow your doctor's instructions.

Store at room temperature away from moisture and heat.

Side Effects Centers

Sarafem Patient Information including If I Miss a Dose

What happens if I miss a dose (Sarafem)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

If you miss a dose of Prozac Weekly, take the missed dose as soon as you remember and take the next dose 7 days later. However, if it is almost time for the next regularly scheduled weekly dose, skip the missed dose and take the next one as directed.Do not take extra medicine to make up the missed dose.

What happens if I overdose (Sarafem)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose may cause nausea, vomiting, fever, sleepiness, rapid or uneven heartbeat, confusion, fainting, seizures, or coma.

What should I avoid while taking fluoxetine (Sarafem)?

Drinking alcohol can increase certain side effects of fluoxetine.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

What other drugs will affect fluoxetine (Sarafem)?

Ask your doctor before taking a nonsteroidal anti-inflammatory drug (NSAID) for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others. Using an NSAID with fluoxetine may cause you to bruise or bleed easily.

Tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures or anxiety). They can add to sleepiness caused by fluoxetine.

Tell your doctor about all other medications you are using, especially:

  • alprazolam (Xanax);
  • clopidogrel (Plavix);
  • clozapine (Clozaril, Fazaclo);
  • flecainide (Tambocor);
  • haloperidol (Haldol);
  • seizure medication such as phenytoin (Dilantin) or carbamazepine (Tegretol);
  • tryptophan (also called L-tryptophan);
  • vinblastine (Velban);
  • a blood thinner such as warfarin (Coumadin, Jantoven);
  • almotriptan (Axert), frovatriptan (Frova), sumatriptan (Imitrex, Treximet), naratriptan (Amerge), rizatriptan (Maxalt), or zolmitriptan (Zomig); or
  • any other antidepressants such as amitriptyline (Elavil, Vanatrip, Limbitrol), escitalopram (Lexapro), imipramine (Tofranil), sertraline (Zoloft), and others.

This list is not complete and other drugs may interact with fluoxetine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about fluoxetine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 21.01. Revision date: 8/15/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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Side Effects Centers

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