Fluoxetine tablets are indicated for the treatment of: Major Depressive Disorder (MDD). The efficacy of fluoxetine in MDD was established in one 5 week trial, three 6 week trials, and one maintenance study in adults. The efficacy of fluoxetine was also established in two 8 to 9 week trials in pediatric patients 8 to 18 years of age [see Clinical Studies (14.1) ]. Obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD).
The efficacy of fluoxetine in OCD was demonstrated in two 13 week trials in adults and one 13 week trial in pediatric patients 7 to 17 years of age [see Clinical Studies (14.2) ]. Binge-eating and vomiting behaviors in patients with moderate to severe Bulimia Nervosa. The efficacy of fluoxetine in Bulimia Nervosa was demonstrated in two 8 week trials and one 16 week trial in adults [see Clinical Studies (14.3) ]. Panic Disorder, with or without agoraphobia.
The efficacy of fluoxetine in Panic Disorder was demonstrated in two 12 week trials in adults [see Clinical Studies ( 14.4 )]. Fluoxetine tablets are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of: Major Depressive Disorder (MDD) ( 1 )
Adults: Efficacy was established in one 5 week trial, three 6-week trials, and one maintenance study (14.1)
Pediatrics: Efficacy was established in two 8 to 9 week trials of patients 8 to 18 years of age (14.1 ) Obsessive Compulsive Disorder (OCD) (1)
Adults: Efficacy was established in two 13 week trials (14.2)
Pediatrics: Efficacy was established in one 13 week trial in patients 7 to 17 years of age (14.2) Bulimia Nervosa ( 1)
Adults: Efficacy was established in two 8 week trials and one 16 week trial (14.3) Panic Disorder, with or without agoraphobia (1)
Adults: Efficacy was established in two 12 week trials (14.4)
Contraindications
Monoamine Oxidase Inhibitors (MAOIs) : Do not use MAOIs intended to treat psychiatric disorders with fluoxetine or within 5 weeks of stopping treatment with fluoxetine. Do not use fluoxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start fluoxetine in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 , 7.1 ) Pimozide ( 4.2 , 5.11 , 7.6 , 7.7 ) Thioridazine: Do not use concomitantly with or within 5 weeks of discontinuing fluoxetine ( 4.2 , 5.11 , 7.6 , 7.7 ) Known hypersensitivity to fluoxetine products ( 4.2 , 5.3 )
The use of MAOIs intended to treat psychiatric disorders with fluoxetine or within 5 weeks of stopping treatment with fluoxetine is contraindicated because of an increased risk of serotonin syndrome. The use of fluoxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration ( 2.6 ) and Warnings and Precautions (5.2) ]. Starting fluoxetine in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration ( 2.7 ) and Warnings and Precautions ( 5.2 )].
4.2Other Contraindications
The use of fluoxetine is contraindicated with the following:
Pimozide [see Warnings and Precautions ( 5.11) and Drug Interactions ( 7.6 , 7.7) ]
Thioridazine [see Warnings and Precautions ( 5.11 ) and Drug Interactions ( 7.6 , 7.7 )] Pimozide and thioridazine prolong the QT interval. Fluoxetine can increase the levels of pimozide and thioridazine through inhibition of CYP2D6. Fluoxetine can also prolong the QT interval.
Known hypersensitivity to fluoxetine: Do not use this product in patients with known hypersensitivity to fluoxetine due to risk of anaphylactoid reactions, including bronchospasm, angioedema, laryngospasm, and urticaria [see Warnings and Precautions ( 5.3 )].
Warnings and precautions
Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults: Monitor for clinical worsening and suicidal thinking and behavior ( 5.1 ) Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), including fluoxetine, both when taken alone, but especially when co-administered with other serotonergic agents. If such symptoms occur, discontinue fluoxetine and serotonergic agents and initiate supportive treatment.
If concomitant use of fluoxetine with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 5.2 ) Activation of Mania/Hypomania: Screen for Bipolar Disorder and monitor for mania/hypomania ( 5.4 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold ( 5.5 ) Altered Appetite and Weight: Significant weight loss has occurred ( 5.6 ) Increased Risk of Bleeding: May increase the risk of bleeding.
Use with NSAIDs, aspirin, warfarin, or drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding ( 5.7 , 7.4 ) Angle-closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.8) Hyponatremia: Has been reported with fluoxetine in association with syndrome of inappropriate antidiuretic hormone (SIADH). Consider discontinuing if symptomatic hyponatremia occurs ( 5.9 ) QT Prolongation: QT prolongation and ventricular arrhythmia including Torsades de Pointes have been reported with fluoxetine use.
Use with caution in conditions that predispose to arrhythmias or increase fluoxetine exposure. Use cautiously in patients with risk factors for QT prolongation ( 4.2 , 5.11 , 7.6 , 7.7 , 10) Long Half-life: Changes in dose will not be fully reflected in plasma for several weeks ( 5.14 ) Sexual Dysfunction: Fluoxetine may cause symptoms of sexual dysfunction (5.16)
5.1 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients with 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 to 24) with 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, OCD, or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 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 versus 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 1,000 patients treated) are provided in Table 1. Table 1. Risk Differences in the Number of Suicidality Cases by Age Group in the Pooled Placebo-controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated Increases Compared to Placebo < 18 14 additional cases 18 to 24 5 additional cases Decreases Compared to Placebo 25 to 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 MDD 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 Warnings and Precautions ( 5.15 )].
Families and caregivers of patients being treated with antidepressants for MDD 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 health care providers. Such monitoring should include daily observation by families and caregivers.
Prescriptions for fluoxetine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. It should be noted that fluoxetine is approved in the pediatric population only for MDD and OCD.
5.2Serotonin Syndrome
Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair
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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. Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( 7.6 ) Tricyclic Antidepressants (TCAs): Monitor TCA levels during co-administration with fluoxetine or when fluoxetine has been recently discontinued ( 5.2 , 7.6 ) Benzodiazepines: Diazepam—increased t1/2, alprazolam—further psychomotor performance decrement due to increased levels ( 7.6 ) Antipsychotics: Potential for elevation of haloperidol and clozapine levels (7.6 ) Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity (7.6) Serotonergic Drugs: ( 2.6 , 2.7 , 4.1 , 5.2 ) Drugs that Prolong the QT Interval: Do not use fluoxetine with thioridazine or pimozide.
Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.6 , 7.7 )
7.1Monoamine Oxidase Inhibitors
(MAOIs) [See Dosage and Administration ( 2.6, 2.7 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.2 )].
7.2CNS Acting Drugs
Caution is advised if the concomitant administration of fluoxetine and such drugs is required. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status [see Clinical Pharmacology ( 12.3 )].
7.3Other Serotonergic Drugs
The concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) with ýuoxetine increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of ýuoxetine and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )].
7.4 Drugs that Interfere with Hemostasis (e.g., NSAIDS, Aspirin, Warfarin) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding.
Altered anticoagulant effects, including increased bleeding, have been reported when SNRIs or SSRIs are co-administered with warfarin. Patients receiving warfarin therapy should be carefully monitored when fluoxetine is initiated or discontinued [see Warnings and Precautions ( 5.7 )].
7.5Potential for Other Drugs to Affect Fluoxetine
Drugs tightly bound to plasma proteins —Because fluoxetine is tightly bound to plasma proteins, adverse effects may result from displacement of protein-bound fluoxetine by other tightly bound drugs [see Clinical Pharmacology ( 12.3 )].
7.6Potential for Fluoxetine to Affect Other Drugs
Pimozide —Concomitant use in patients taking pimozide is contraindicated. Pimozide can prolong the QT interval. Fluoxetine can increase the level of pimozide through inhibition of CYP2D6. Fluoxetine can also prolong the QT interval. Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QT prolongation. While a specific study with pimozide and fluoxetine has not been conducted, the potential for drug interactions or QT prolongation warrants restricting the concurrent use of pimozide and fluoxetine [see Contraindications ( 4.2 ), Warnings and Precautions ( 5.11 ), and Drug Interactions ( 7.7 )].
Thioridazine —Thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued, because of the risk of QT prolongation [see Contraindications ( 4.2) , Warnings and Precautions ( 5.11 ), and Drug Interactions ( 7.7 )]. 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 C max and a 4.5-fold higher area under the curve (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. Thioridazine administration produces a dose-related prolongation of the QT 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. Drugs metabolized by CYP2D6 —Fluoxetine inhibits the activity of CYP2D6, and may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Co-administration 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, his/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 ( 4.2 )]. Tricyclic antidepressants (TCAs) —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.
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Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.7) and Clinical Considerations].
Available data from published epidemiologic studies and postmarketing reports over several decades have not established an increased risk of major birth defects or miscarriage. Some studies have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship [see Data]. There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and poor neonatal adaptationwith exposure to selective serotonin reuptake inhibitors (SSRIs), including ýuoxetine tablets, during pregnancy (see Clinical Considerations).
In rats and rabbits treated with ýuoxetine during the period of organogenesis, there was no evidence of developmental eúects at doses up to 1.6 and 3.9 times, respectively, the maximum recommended human dose (MRHD) of 60 mg on a mg/m 2 given to adolescents on a mg/m 2 basis.However, in other reproductive studies in rats, an increase in stillborn pups, a decrease in pupweight, and an increase in pup deaths early after birth occurred at doses that are 1.5 times (during gestation) and 0.97 times (during gestation and lactation) the MRHD given to adolescents on a mg/m 2 basis.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants.
This ünding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of ýuoxetine tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [seeWarnings and Precautions (5.7)].
Fetal/Neonatal Adverse Reactions Neonates exposed to ýuoxetine tablets and other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical ündings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding diûculty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreýexia, tremors, jitteriness, irritability, and constant crying.
These ündings are consistent with either a direct toxic eúect of SSRIs and SNRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.2 )]. Data Human Data It has been shown that SSRIs (including ýuoxetine) can cross the placenta. Published epidemiological studies of pregnant women exposed to ýuoxetine have not established an increased risk of major birth defects, miscarriage, and other adverse developmental outcomes.
Several publications reported an increased incidence of cardiovascular malformations in children with in utero exposure to ýuoxetine. However, these studies results do not establish a causal relationship. Methodologic limitations of these observational studies include possible exposure and outcome misclassiücation, lack of adequate controls, adjustment for confounders and conürmatory studies. However, these studies cannot deünitely establish or exclude any drug-associated risk during pregnancy.
Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1 to 2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal data In embryofetal development studies in rats and rabbits, there was no evidence of malformations or developmental variations following administration of fluoxetine at doses up to 12.5 and 15 mg/kg/day, respectively (1.6 and 3.9 times, respectively, the MRHD of 60 mg given to adolescents on a mg/m 2 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 ürst 7 days postpartum occurred following maternal exposure to 12 mg/kg/day (1.5 times the MRHD given to adolescents on a mg/m 2 basis) during gestation or 7.5 mg/kg/day (0.97 times the MRHD given to adolescents on a mg/m 2 basis) during gestation and lactation. There was no evidence of developmental neurotoxicity in the surviving oúspring of rats treated with 12 mg/kg/day during gestation.
The no-eúect dose for rat pup mortality was 5 mg/kg/day (0.65 times the MRHD given to adolescents on a mg/m2 basis).
Adverse reactions
The following adverse reactions are discussed in more detail in other sections of the labeling:
Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see Boxed Warning and Warnings and Precautions ( 5.1 )]
Serotonin Syndrome [see Warnings and Precautions ( 5.2 )]
Allergic Reactions and Rash [see Warnings and Precautions ( 5.3 )]
Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania [see Warnings and Precautions ( 5.4 )]
Seizures [see Warnings and Precautions ( 5.5 )]
Altered Appetite and Weight [see Warnings and Precautions ( 5.6 )]
Increased Risk of Bleeding [see Warnings and Precautions ( 5.7 )]
Angle-closure Glaucoma [see Warnings and Precautions ( 5.8 )]
Hyponatremia [see Warnings and Precautions ( 5.9 )]
Anxiety and Insomnia [see Warnings and Precautions ( 5.10 )]
QT Prolongation [see Warnings and Precautions ( 5.11 )]
Potential for Cognitive and Motor Impairment [see Warnings and Precautions ( 5.13 )]
Discontinuation Adverse Reactions [see Warnings and Precautions (5.15 )] Most common adverse reactions (≥ 5% and at least twice that for placebo): abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido decreased, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawn (6.1) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar RxLLC at 1-800-206-7821. or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice. Multiple doses of fluoxetine have been administered to 10,782 patients with various diagnoses in U.S. clinical trials. In addition, there have been 425 patients administered fluoxetine in panic clinical trials.
The stated frequencies represent the proportion of individuals who experienced, at least once, an adverse reaction of the type listed. An adverse reaction was included if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Incidence in MDD, OCD, Bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials)—Table 2 enumerates the most common adverse reactions associated with the use of fluoxetine (incidence of at least 5% for fluoxetine and at least twice that for placebo within at least 1 of the indications) for the treatment of MDD, OCD, and bulimia in U.S. controlled clinical trials and Panic Disorder in U.S. plus non-U.S. controlled trials.
Table 3 provides combined data for the pool of studies that are provided separately by indication in Table 2. Table 2. Most Common Adverse Reactions: Incidence in Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder Placebo-controlled Clinical Trials Percentage of Patients Reporting Event MDD OCD Bulimia Panic Disorder Body System/Adverse Reaction Fluoxetine (N = 1728) Placebo (N = 975) Fluoxetine (N = 266) Placebo (N = 89) Fluoxetine (N = 450) Placebo (N = 267) Fluoxetine (N = 425) Placebo (N = 342) Body as a Whole Asthenia 9 5 15 11 21 9 7 7 Flu syndrome 3 4 10 7 8 3 5 5 Cardiovascular System Vasodilatation 3 2 5 — 2 1 1 — Digestive System Nausea 21 9 26 13 29 11 12 7 Diarrhea 12 8 18 13 8 6 9 4 Anorexia 11 2 17 10 8 4 4 1 Dry mouth 10 7 12 3 9 6 4 4 Dyspepsia 7 5 10 4 10 6 6 2 Nervous System Insomnia 16 9 28 22 33 13 10 7 Anxiety 12 7 14 7 15 9 6 2 Nervousness 14 9 14 15 11 5 8 6 Somnolence 13 6 17 7 13 5 5 2 Tremor 10 3 9 1 13 1 3 1 Libido decreased 3 — 11 2 5 1 1 2 Abnormal dreams 1 1 5 2 5 3 1 1 Respiratory System Pharyngitis 3 3 11 9 10 5 3 3 Sinusitis 1 4 5 2 6 4 2 3 Yawn — — 7 — 11 — 1 — Skin and Appendages Sweating 8 3 7 — 8 3 2 2 Rash 4 3 6 3 4 4 2 2 Urogenital System Impotence a 2 — — — 7 — 1 — Abnormal ejaculation a — — 7 — 7 — 2 1 Note: Includes U.S. data for MDD, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. a = Denominator used was for males only (N = 690 fluoxetine MDD; N = 410 placebo MDD; N = 116 fluoxetine OCD; N = 43 placebo OCD; N = 14 fluoxetine Bulimia; N = 1 placebo Bulimia; N = 162 fluoxetine Panic Disorder; N = 121 placebo Panic Disorder). — = Incidence less than 1%.
Table 3. Adverse Reactions: Incidence in Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder Placebo-controlled Clinical Trials Percentage of Patients Reporting Event MDD, OCD, Bulimia, and Panic Disorder Combined Body System/Adverse Reaction Fluoxetine (N = 2869) Placebo (N = 1673) Body as a Whole Headache 21 19 Asthenia 11 6 Flu syndrome 5 4 Fever 2 1 Cardiovascular System Vasodilatation 2 1 Digestive System Nausea 22 9 Diarrhea 11 7 Anorexia 10 3 Dry mouth 9 6 Dyspepsia 8 4 Constipation 5 4 Flatulence 3 2 Vomiting 3 2 Metabolic and Nutritional Disorders Weight loss 2 1 Nervous System Insomnia 19 10 Nervousness 13 8 Anxiety 12 6 Somnolence 12 5 Dizziness 9 6 Tremor 9 2 Libido decreased 4 1 Thinking abnormal 2 1 Respiratory System Yawn 3 — Skin and Appendages Sweating 7 3 Rash 4 3 Pruritus 3 2 Special Senses Abnormal vision 2 1 Note: Includes U.S. data for MDD, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. — = Incidence less than 1%.
Associated with discontinuation in MDD, OCD, Bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials)—Table 4 lists the adverse reactions associated with discontinuation of fluoxetine treatment (incidence at least twice that for placebo and at least 1% for fluoxetine in clinical trials collecting only a primary reaction associated with discontinuation) in MDD, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S.
Panic Disorder clinical trials. Table 4. Most Common Adverse Reactions Associated with Discontinuation in Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder Placebo-controlled Clinical Trials MDD, OCD, Bulimia, and Panic Disorder Combined (N = 1533) MDD (N = 392) OCD (N = 266) Bulimia (N = 450) Panic Disorder (N = 425) Anxiety (1%) — Anxiety (2%) — Anxiety (2%) — — — Insomnia (2%) — — Nervousness (1%) — — Nervousness (1%) — — Rash (1%) — — Note: Includes U.S. data for MDD, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. — = Incidence less than 1%.
Other adverse reactions in pediatric patients (children and adolescents)—Adverse reactions were collected in 322 pediatric patients (180 fluoxetine-treated, 142 placebo-treated). The overall profile of adverse reactions was generally similar to that seen in adult studies, as shown in Table 2 and Table 3. However, the following adverse reactions (excluding those which appear in the body or footnotes of Table 2 and Table 3 and those for which the COSTART terms were uninformative or misleading) were reported at an incidence of at least 2% for fluoxetine and greater than placebo: thirst, hyperkinesia, agitation, personality disorder, epistaxis, urinary frequency, and menorrhagia.
The most common adverse reaction (incidence at least 1% for fluoxetine and greater than placebo) associated with discontinuation in 3 pediatric placebo-controlled trials (N = 418 randomized; 228 fluoxetine-treated; 190 placebo-treated) was mania/hypomania (1.8% for fluoxetine-treated, 0% for placebo-treated). In these clinical trials, only a primary reaction associated with discontinuation was collected. Male and female sexual dysfunction with SSRIs—Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of p
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Composition
Active ingredients
FLUOXETINE HYDROCHLORIDE EQ 60MG BASE
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is co-administered or has been recently discontinued [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )]. Benzodiazepines —The half-life of concurrently administered diazepam may be prolonged in some patients [see Clinical Pharmacology ( 12.3 )].
Co-administration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels. Antipsychotics —Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine.
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. 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.
