Fluoxetine Prescribing Information
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 to 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 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 2.
Age Range | 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.
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 [
It should be noted that fluoxetine is approved in the pediatric population for Major Depressive Disorder and Obsessive Compulsive Disorder; and fluoxetine in combination with olanzapine for the acute treatment of depressive episodes associated with Bipolar I Disorder.
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 to 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 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 2.
Age Range | 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.
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 [
It should be noted that fluoxetine is approved in the pediatric population for Major Depressive Disorder and Obsessive Compulsive Disorder; and fluoxetine in combination with olanzapine for the acute treatment of depressive episodes associated with Bipolar I Disorder.
• Fluoxetine is not approved for use in children less than 7 years of age
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 to 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 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 2.
Age Range | 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.
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 [
It should be noted that fluoxetine is approved in the pediatric population for Major Depressive Disorder and Obsessive Compulsive Disorder; and fluoxetine in combination with olanzapine for the acute treatment of depressive episodes associated with Bipolar I Disorder.
The efficacy of fluoxetine for the treatment of OCD was demonstrated in one 13-week placebo-controlled clinical trial with 103 pediatric outpatients ages 7 to <18
The safety and effectiveness in pediatric patients <8 years of age in Major Depressive Disorder and <7 years of age in OCD have not been established.
Fluoxetine pharmacokinetics were evaluated in 21 pediatric patients (ages 6 to ≤18) with Major Depressive Disorder or OCD
The acute adverse reaction profiles observed in the 3 studies (N=418 randomized; 228 fluoxetine-treated, 190 placebo-treated) were generally similar to that observed in adult studies with fluoxetine. The longer-term adverse reaction profile observed in the 19-week Major Depressive Disorder study (N=219 randomized; 109 fluoxetine-treated, 110 placebo-treated) was also similar to that observed in adult trials with fluoxetine
As with other SSRIs, decreased weight gain has been observed in association with the use of fluoxetine in children and adolescent patients. After 19 weeks of treatment in a clinical trial, pediatric subjects treated with fluoxetine gained an average of 1.1 cm less in height and 1.1 kg less in weight than subjects treated with placebo. In addition, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels. The safety of fluoxetine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than several months in duration. In particular, there are no studies that directly evaluate the longer-term effects of fluoxetine on the growth, development and maturation of children and adolescent patients. Therefore, height and weight should be monitored periodically in pediatric patients receiving fluoxetine
These fluoxetine toxicities in juvenile rats have not been observed in adult animals. Plasma exposures (AUC) to fluoxetine in juvenile rats receiving 3, 10, or 30 mg/kg/day doses in this study are approximately 0.1 to 0.2, 1 to 2, and 5 to 10 times, respectively, the average exposure in pediatric patients receiving the MRHD of 20 mg/day. Rat exposures to the major metabolite, norfluoxetine, are approximately 0.3 to 0.8, 1 to 8, and 3 to 20 times, respectively, the pediatric exposure at the MRHD.
A specific effect on bone development was reported in juvenile mice administered fluoxetine by the intraperitoneal route to 4 week old mice for 4 weeks at doses 0.5 and 2 times the oral MRHD of 20 mg/day on mg/m2 basis. There was a decrease in bone mineralization and density at both doses, but the overall growth (body weight gain or femur length) was not affected.
When using fluoxetine and olanzapine in combination, also refer to Boxed Warning section of the package insert for Symbyax.
Warnings and Precautions (
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, tryptophan, meperidine, methadone, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs
Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
The concomitant use of fluoxetine with MAOIs is contraindicated. In addition, do not initiate fluoxetine in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking fluoxetine, discontinue fluoxetine before initiating treatment with the MAOI
SNRIs and SSRIs, including fluoxetine, may increase the risk of bleeding reactions. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anti-coagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the 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
Patients should be cautioned about the increased risk of bleeding associated with the concomitant use of fluoxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation [
Fluoxetine capsules are indicated for the treatment of:
• Acute and maintenance treatment of Major Depressive Disorder
Adult
Two 6-week controlled studies (N=671, randomized) comparing fluoxetine 20 mg and placebo have shown fluoxetine 20 mg daily to be effective in the treatment of elderly patients (≥60 years of age) with Major Depressive Disorder. In these studies, fluoxetine produced a significantly higher rate of response and remission as defined, respectively, by a 50% decrease in the HAM-D score and a total endpoint HAM-D score of ≤8. Fluoxetine was well tolerated and the rate of treatment discontinuations due to adverse reactions did not differ between fluoxetine (12%) and placebo (9%).
In both studies independently, fluoxetine produced a statistically significantly greater mean change on the Childhood Depression Rating Scale-Revised (CDRS-R) total score from baseline to endpoint than did placebo.
Subgroup analyses on the CDRS-R total score did not suggest any differential responsiveness on the basis of age or gender.
A study was conducted involving depressed outpatients who had responded (modified HAMD-17 score of ≤7 during each of the last 3 weeks of open-label treatment and absence of Major Depressive Disorder by DSM-III-R criteria) by the end of an initial 12-week open-treatment phase on fluoxetine 20 mg/day. These patients (N=298) were randomized to continuation on double-blind fluoxetine 20 mg/day or placebo. At 38 weeks (50 weeks total), a statistically significantly lower relapse rate (defined as symptoms sufficient to meet a diagnosis of Major Depressive Disorder for 2 weeks or a modified HAMD-17 score of ≥14 for 3 weeks) was observed for patients taking fluoxetine compared with those on placebo.
An additional maintenance study was conducted involving adult outpatients meeting DSM-IV criteria for Major Depressive Disorder who had responded (defined as having a modified HAMD-17 score of ≤9, a CGI-Severity rating of ≤2, and no longer meeting criteria for Major Depressive Disorder) for 3 consecutive weeks at the end of 13 weeks of open-label treatment with fluoxetine capsules 20 mg once daily. These patients were randomized to double-blind, once-weekly continuation treatment with fluoxetine delayed-release capsules 90 mg once weekly, fluoxetine capsules 20 mg once daily, or placebo. Fluoxetine capsules 20 mg once daily demonstrated superior efficacy (having a significantly longer time to relapse of depressive symptoms) compared with placebo for a period of 25 weeks.
• Acute and maintenance treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD) [
Outcome Classification (%) on CGI Improvement Scale for Completers in Pool of Two OCD Studies | ||||
Fluoxetine | ||||
| Outcome Classification | Placebo | 20 mg | 40 mg | 60 mg |
| Worse | 8% | 0% | 0% | 0% |
| No change | 64% | 41% | 33% | 29% |
| Minimally improved | 17% | 23% | 28% | 24% |
| Much improved | 8% | 28% | 27% | 28% |
| Very much improved | 3% | 8% | 12% | 19% |
Exploratory analyses for age and gender effects on outcome did not suggest any differential responsiveness on the basis of age or sex.
Subgroup analyses on outcome did not suggest any differential responsiveness on the basis of age or gender.
• Acute and maintenance treatment of binge-eating and vomiting behaviors in patients with moderate to severe Bulimia Nervosa [
The effectiveness of fluoxetine for the treatment of bulimia was demonstrated in two 8-week and one 16-week, multicenter, parallel group studies of adult outpatients meeting DSM-III-R criteria for bulimia. Patients in the 8-week studies received either 20 or 60 mg/day of fluoxetine or placebo in the morning. Patients in the 16-week study received a fixed fluoxetine dose of 60 mg/day (once a day) or placebo. Patients in these 3 studies had moderate to severe bulimia with median binge-eating and vomiting frequencies ranging from 7 to 10 per week and 5 to 9 per week, respectively. In these 3 studies, fluoxetine 60 mg, but not 20 mg, was statistically significantly superior to placebo in reducing the number of binge-eating and vomiting episodes per week. The statistically significantly superior effect of 60 mg versus placebo was present as early as Week 1 and persisted throughout each study. The fluoxetine-related reduction in bulimic episodes appeared to be independent of baseline depression as assessed by the Hamilton Depression Rating Scale. In each of these 3 studies, the treatment effect, as measured by differences between fluoxetine 60 mg and placebo on median reduction from baseline in frequency of bulimic behaviors at endpoint, ranged from 1 to 2 episodes per week for binge-eating and 2 to 4 episodes per week for vomiting. The size of the effect was related to baseline frequency, with greater reductions seen in patients with higher baseline frequencies. Although some patients achieved freedom from binge-eating and purging as a result of treatment, for the majority, the benefit was a partial reduction in the frequency of binge-eating and purging.
In a longer-term trial, 150 patients meeting DSM-IV criteria for Bulimia Nervosa, purging subtype, who had responded during a single-blind, 8-week acute treatment phase with fluoxetine 60 mg/day, were randomized to continuation of fluoxetine 60 mg/day or placebo, for up to 52 weeks of observation for relapse. Response during the single-blind phase was defined by having achieved at least a 50% decrease in vomiting frequency compared with baseline. Relapse during the double-blind phase was defined as a persistent return to baseline vomiting frequency or healthcare provider judgment that the patient had relapsed. Patients receiving continued fluoxetine 60 mg/day experienced a significantly longer time to relapse over the subsequent 52 weeks compared with those receiving placebo.
• Acute treatment of Panic Disorder, with or without agoraphobia [
The effectiveness of fluoxetine in the treatment of Panic Disorder was demonstrated in 2 double-blind, randomized, placebo-controlled, multicenter studies of adult outpatients who had a primary diagnosis of Panic Disorder (DSM-IV), with or without agoraphobia.
Study 1 (N=180 randomized) was a 12-week flexible-dose study. Fluoxetine was initiated at 10 mg/day for the first week, after which patients were dosed in the range of 20 to 60 mg/day on the basis of clinical response and tolerability. A statistically significantly greater percentage of fluoxetine-treated patients were free from panic attacks at endpoint than placebo-treated patients, 42% versus 28%, respectively.
Study 2 (N=214 randomized) was a 12-week flexible-dose study. Fluoxetine was initiated at 10 mg/day for the first week, after which patients were dosed in a range of 20 to 60 mg/day on the basis of clinical response and tolerability. A statistically significantly greater percentage of fluoxetine-treated patients were free from panic attacks at endpoint than placebo-treated patients, 62% versus 44%, respectively.
Fluoxetine capsules and Olanzapine in Combination is indicated for the treatment of:
• Acute treatment of depressive episodes associated with Bipolar I Disorder.
• Treatment Resistant Depression (Major Depressive Disorder in patient, who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode).
Fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder or the treatment of treatment resistant depression.
Indication | Adult | Pediatric | ||||||||||||||||||||
MDD (Initial Treatment Adult - Initiate fluoxetine capsules 20 mg/day orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon). The maximum fluoxetine dose should not exceed 80 mg/day. In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases [ see Clinical Studies (14.1) ].Pediatric (children and adolescents) - [ As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer. see Clinical Studies (14.1)]. All patients - Periodically reassess to determine the need for maintenance treatment. Switching Patients to a Tricyclic Antidepressant (TCA) - Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [ see Warnings and Precautions (5.2) and Drug Interactions (7.7) ]. | 20 mg/day in am (initial dose ) | 10 to 20 mg/day (initial dose ) | ||||||||||||||||||||
OCD (Initial Treatment Adult - Initiate fluoxetine capsules 20 mg/day, orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo [ see Clinical Studies (14.2 )]. In one of these studies, no dose-response relationship for effectiveness was demonstrated.Pediatric (children and adolescents ) — In adolescents and higher weight children, initiate treatment with a dose of 10 mg/day. After 2 weeks, increase the dose to 20 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.In lower weight children, initiate treatment with a dose of 10 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal, and there is no experience with doses greater than 60 mg. In the controlled clinical trial of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [ see Clinical Studies (14.2) ]. Periodically reassess to determine the need for treatment. | 20 mg/day in am (initial dose ) | 10 mg/day (initial dose ) | ||||||||||||||||||||
Bulimia Nervosa (Initial Treatment - Administer fluoxetine capsules 60 mg/day in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Bulimia Nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo [ see Clinical Studies (14.3) ]. Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting.Periodically reassess to determine the need for maintenance treatment. | 60 mg/day in am | | ||||||||||||||||||||
Panic Disorder (Initial Treatment - Initiate treatment with fluoxetine capsules 10 mg/day. After one week, increase the dose to 20 mg/day. Consider a dose increase after several weeks if no clinical improvement is observed. Fluoxetine doses above 60 mg/day have not been systematically evaluated in patients with Panic Disorder. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Panic Disorder, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [ see Clinical Studies (14.4 )]. The most frequently administered dose in the 2 flexible-dose clinical trials was 20 mg/day.Periodically reassess to determine the need for continued treatment. | 10 mg/day (initial dose ) | | ||||||||||||||||||||
Depressive Episode s Associated with Bipolar I Disorder (When using fluoxetine and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax. —Administer fluoxetine in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Make dosage adjustments, if indicated, according to efficacy and tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 12.5 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Periodically re-examine the need for continued pharmacotherapy.Adult Children and adolescents (10 to 17 years of age) — Administer olanzapine and fluoxetine combination once daily in the evening, generally beginning with 2.5 mg of olanzapine and 20 mg of fluoxetine. Make dosage adjustments, if indicated, according to efficacy and tolerability. Safety of co-administration of doses above 12 mg of olanzapine with 50 mg of fluoxetine has not been evaluated in pediatric clinical studies. Periodically re-examine the need for continued pharmacotherapy.Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability. Table 1: Approximate Dose Correspondence between Symbyax1and the Combination of Fluoxetine and Olanzapine
1Symbyax (olanzapine/fluoxetine HCL) is a fixed-dose combination of fluoxetine and olanzapine. | Oral in combination with olanzapine : 5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) | Oral in combination with olanzapine: 2.5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) | ||||||||||||||||||||
Treatment Resistant Depression (When using Fluoxetine and Olanzapine in combination, also refer to the Clinical Studies section of the package insert for symbyax. Administer fluoxetine in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20mg of fluoxetine. Adjust dosage, if indicated, according to efficacy to tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 20 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 18 mg and fluoxetine 25 to 50 mg.Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Symbyaxis dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. Table 1 demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability. Periodically re-examine the need for continued pharmacotherapy Safety of co administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Fluoxetine monotherapy is not indicated for the treatment of treatment resistant depression (Major Depressive Disorder in patient, who do not respond to 2 separate anti depressants of adequate dose and duration in the current episode). | Oral in combination with olanzapine: 5 mg of oral olanzapine and 20 mg of fluoxetine once daily (initial dose) | | ||||||||||||||||||||
• A lower or less frequent dosage should be used in patients with hepatic impairment, the elderly, and for patients with concurrent disease or on multiple concomitant medications (
Hepatic Impairment —
Concomitant Illness —
Adult
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
| For Symbyax (mg/day) | Use in Combination | |
Olanzapine (mg/day) | Fluoxetine(mg/day) | |
| 3 mg olanzapine/25 mg fluoxetine | 2.5 | 20 |
| 6 mg olanzapine/25 mg fluoxetine | 5 | 20 |
| 12 mg olanzapine/25 mg fluoxetine | 10+2.5 | 20 |
| 6 mg olanzapine/50 mg fluoxetine | 5 | 40+10 |
| 12 mg olanzapine/50 mg fluoxetine | 10+2.5 | 40+10 |
1Symbyax (olanzapine/fluoxetine HCL) is a fixed-dose combination of fluoxetine and olanzapine.
Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Symbyaxis dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. Table 1 demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
Periodically re-examine the need for continued pharmacotherapy
Safety of co administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.
Fluoxetine monotherapy is not indicated for the treatment of treatment resistant depression (Major Depressive Disorder in patient, who do not respond to 2 separate
anti depressants of adequate dose and duration in the current episode).
• Fluoxetine monotherapy is not indicated for the treatment of Depressive Episodes associated with Bipolar I Disorder or treatment resistant depression (
Adult
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
| For Symbyax (mg/day) | Use in Combination | |
Olanzapine (mg/day) | Fluoxetine(mg/day) | |
| 3 mg olanzapine/25 mg fluoxetine | 2.5 | 20 |
| 6 mg olanzapine/25 mg fluoxetine | 5 | 20 |
| 12 mg olanzapine/25 mg fluoxetine | 10+2.5 | 20 |
| 6 mg olanzapine/50 mg fluoxetine | 5 | 40+10 |
| 12 mg olanzapine/50 mg fluoxetine | 10+2.5 | 40+10 |
1Symbyax (olanzapine/fluoxetine HCL) is a fixed-dose combination of fluoxetine and olanzapine.
Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Symbyaxis dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. Table 1 demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
Periodically re-examine the need for continued pharmacotherapy
Safety of co administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.
Fluoxetine monotherapy is not indicated for the treatment of treatment resistant depression (Major Depressive Disorder in patient, who do not respond to 2 separate
anti depressants of adequate dose and duration in the current episode).
• Safety of the coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in adults (
Adult
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
| For Symbyax (mg/day) | Use in Combination | |
Olanzapine (mg/day) | Fluoxetine(mg/day) | |
| 3 mg olanzapine/25 mg fluoxetine | 2.5 | 20 |
| 6 mg olanzapine/25 mg fluoxetine | 5 | 20 |
| 12 mg olanzapine/25 mg fluoxetine | 10+2.5 | 20 |
| 6 mg olanzapine/50 mg fluoxetine | 5 | 40+10 |
| 12 mg olanzapine/50 mg fluoxetine | 10+2.5 | 40+10 |
1Symbyax (olanzapine/fluoxetine HCL) is a fixed-dose combination of fluoxetine and olanzapine.
Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Symbyaxis dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. Table 1 demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
Periodically re-examine the need for continued pharmacotherapy
Safety of co administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.
Fluoxetine monotherapy is not indicated for the treatment of treatment resistant depression (Major Depressive Disorder in patient, who do not respond to 2 separate
anti depressants of adequate dose and duration in the current episode).
• Safety of the coadministration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in children and adolescents ages 10 to 17 (
Adult
Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of fluoxetine and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
| For Symbyax (mg/day) | Use in Combination | |
Olanzapine (mg/day) | Fluoxetine(mg/day) | |
| 3 mg olanzapine/25 mg fluoxetine | 2.5 | 20 |
| 6 mg olanzapine/25 mg fluoxetine | 5 | 20 |
| 12 mg olanzapine/25 mg fluoxetine | 10+2.5 | 20 |
| 6 mg olanzapine/50 mg fluoxetine | 5 | 40+10 |
| 12 mg olanzapine/50 mg fluoxetine | 10+2.5 | 40+10 |
1Symbyax (olanzapine/fluoxetine HCL) is a fixed-dose combination of fluoxetine and olanzapine.
Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.
• Fluoxetine Capsules USP, 10 mg are white to off white powder filled in size ''4'' hard gelatin capsules with green opaque cap and green opaque body imprinted ''C28''
• Fluoxetine Capsules USP, 20 mg are white to off white powder filled in size ''2'' hard gelatin capsules with green opaque cap and yellow opaque body imprinted ''C29''
• Fluoxetine Capsules USP, 40 mg white to off white powder filled in size ''0'' hard gelatin capsules with green opaque cap and orange opaque body imprinted ''C30''