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Fluoxetine Hydrochloride is a brand name for Fluoxetine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE 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…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION This product is only available in a 60 mg dosage form. A 30 mg dose may be achieved with one-half of the scored tablet. Use of this product requires initial titration with another fluoxetine product according to the dosing guidelines indicated below.
1) 20 mg/day in morning (initial dose) 20 mg/day (target dose) 80 mg/day (maximum dose studied) 10 to 20 mg/day (initial dose)* *This product has not been studied in doses greater than 20 mg/day in pediatric MDD. 1 Major Depressive Disorder Initial Treatment Adult —Initiate fluoxetine 20 mg/day orally in the morning.
Consider a dose increase after several weeks if insufficient clinical improvement is observed. , 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.
1) ]. Pediatric (children and adolescents) —Treatment should be initiated with a dose of 10 or 20 mg/day. After 1 week at 10 mg/day, the dose should be increased to 20 mg/day. However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day.
A dose increase to 20 mg/day may be considered after several weeks if insufficient clinical improvement is observed. 1 )]. Doses greater than 20 mg/day have not been studied in pediatric patients with MDD. This product is only available in a 60 mg dosage form.
Administration of doses with demonstrated efficacy of fluoxetine 10 to 20 mg/day in pediatric MDD requires the use of another formulation. All patients —As with other drugs effective in the treatment of MDD, the full effect may be delayed until 4 weeks of treatment or longer.
Periodically reassess to determine the need for maintenance treatment. 6) ]. 2 Obsessive Compulsive Disorder Initial Treatment Adults —Initiate fluoxetine 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. , 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.
1) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar RxLLC at 1-800-206-7821. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.
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. S. S. S. controlled trials. Table 3 provides combined data for the pool of studies that are provided separately by indication in Table 2.
Table 2. S. 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. S. S. data for Panic Disorder clinical trials. — = Incidence less than 1%. S. Panic Disorder clinical trials. Table 4. S. 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.
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. 6 ) Increased Risk of Bleeding: May increase the risk of bleeding. 8) Hyponatremia: Has been reported with fluoxetine in association with syndrome of inappropriate antidiuretic hormone (SIADH).
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. 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.
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.
1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with fluoxetine or within 5 weeks of stopping treatment with fluoxetine is contraindicated because of an increased risk of serotonin syndrome.
2) ]. 2 )]. 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. 3 )].
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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2 )]. In one of these studies, no dose-response relationship for effectiveness was demonstrated. Pediatric (children and adolescents) —In adolescents and higher weight children, treatment should be initiated with a dose of 10 mg/day.
After 2 weeks, the dose should be increased to 20 mg/day. Additional dose increases may be considered 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, treatment should be initiated with a dose of 10 mg/day.
Additional dose increases may be considered 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.
2 )]. Periodically reassess to determine the need for treatment. 3 Bulimia Nervosa Initial Treatment —Administer fluoxetine 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 Nervosa. 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. 4 Panic Disorder Initial Treatment —Treatment should be initiated with a dose of 10 mg/day. After 1 week, the dose should be increased to 20 mg/day. A dose increase may be considered 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. 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.
5 )]. 6 )]. 6 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with fluoxetine.
1) ]. 7 Use of Fluoxetine with Other MAOIs Such as Linezolid or Methylene Blue Do not start fluoxetine in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome.
1) ]. In some cases, a patient already receiving fluoxetine therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, fluoxetine should be stopped promptly, and linezolid or intravenous methylene blue can be administered.
The patient should be monitored for symptoms of serotonin syndrome for 5 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. 2) ]. The risk of administering methylene blue by nonintravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with fluoxetine is unclear.
2) ].
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 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. S. MDD, OCD, and bulimia placebo-controlled clinical trials, decreased libido was the only sexual adverse reaction reported by at least 2% of patients taking fluoxetine (4% fluoxetine, <1% placebo).
There have been spontaneous reports in women taking fluoxetine of orgasmic dysfunction, including anorgasmia. There are no adequate and well-controlled studies examining sexual dysfunction with fluoxetine treatment. Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment.
Priapism has been reported with all SSRIs. 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 adverse reactions. Other adverse reactions observed during the premarketing evaluation of fluoxetine —Following is a list of adverse reactions reported by patients treated with fluoxetine in clinical trials.
This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo.
Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare reactions are those occurring in fewer than 1/1,000 patients.
Body as a Whole —Frequent: chills; Infrequent: suicide attempt; Rare: acute abdominal syndrome, photosensitivity reaction. Cardiovascular System —Frequent: palpitation; Infrequent: arrhythmia, hypotension 1 . Digestive System —Infrequent: dysphagia, gastritis, gastroenteritis, melena, stomach ulcer; Rare: bloody diarrhea, duodenal ulcer, esophageal ulcer, gastrointestinal hemorrhage, hematemesis, hepatitis, peptic ulcer, stomach ulcer hemorrhage.
Hemic and Lymphatic System —Infrequent: ecchymosis; Rare: petechia, purpura. Nervous System —Frequent: emotional lability; Infrequent: akathisia, ataxia, balance disorder 1 , bruxism 1 , buccoglossal syndrome, depersonalization, euphoria, hypertonia, libido increased, myoclonus, paranoid reaction; Rare: delusions.
Respiratory System —Rare: larynx edema. Skin and Appendages —Infrequent: alopecia; Rare: purpuric rash. Special Senses —Frequent: taste perversion; Infrequent: mydriasis. Urogenital System —Frequent: micturition disorder; Infrequent: dysuria, gynecological bleeding 2 .
1 MedDRA dictionary term from integrated database of placebo-controlled trials of 15,870 patients, of which 9,673 received fluoxetine. 2 Group term that includes individual MedDRA terms: cervix hemorrhage uterine, dysfunctional uterine bleeding, genital hemorrhage, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal hemorrhage, uterine hemorrhage, vaginal hemorrhage.
Adjusted for gender. 2 Postmarketing Experience The following adverse reactions have been identiüed during postapproval use of ýuoxetine. Because these reactions are reported voluntarily from a population of uncertain size, it is diûcult to reliably estimate their frequency or evaluate a causal relationship to drug exposure.
Voluntary reports of adverse reactions temporally associated with ýuoxetine that have been received since market introduction and that may have no causal relationship with the drug include the following: anosmia, aplastic anemia, atrial übrillation 1 , cataract, cerebrovascular accident1, cholestatic jaundice, drug reaction with eosinophilia and systemic symptoms (DRESS), 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 ýuoxetine therapy and which completely resolved over the next few months following drug discontinuation), eosinophilic pneumonia 1 , epidermal necrolysis, erythema multiforme, erythema nodosum, exfoliative dermatitis, galactorrhea, gynecomastia, heart arrest 1 , hepatic failure/necrosis, hyperprolactinemia, hypoglycemia, hyposmia, immune-related hemolytic anemia, kidney failure, memory impairment, movement disorders developing in patients with risk factors including drugs associated with such reactions and worsening of preexisting movement disorders, optic neuritis, pancreatitis 1 , pancytopenia, pulmonary embolism, pulmonary hypertension, QT prolongation, Stevens-Johnson syndrome, thrombocytopenia 1 , thrombocytopenic purpura, ventricular tachycardia (including Torsades de Pointes-type arrhythmias), vaginal bleeding, and violent behaviors 1 .
1 These terms represent serious adverse events, but do not meet the deünition for adverse drug reactions. They are included here because of their seriousness.
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. , 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.
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. 2 Serotonin 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. 3)]. Serotonin syndrome can also occur when these drugs are used alone.
, 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).
1)]. Monitor all patients taking fluoxetine for the emergence of serotonin syndrome. Discontinue treatment with fluoxetine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment.
If concomitant use of fluoxetine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. S. fluoxetine clinical trials, 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 reactions were reported to recover completely. In premarketing clinical trials, 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, systemic reactions, possibly related to vasculitis and including lupus-like syndrome, have developed in patients with rash.
Although these reactions are rare, they may be serious, involving the lung, kidney, or liver. Death has been reported to occur in association with these systemic reactions. Anaphylactoid reactions, including bronchospasm, angioedema, laryngospasm, and urticaria alone and in combination, have been reported.
Pulmonary reactions, including inflammatory processes of varying histopathology and/or fibrosis, have been reported rarely. These reactions have occurred with dyspnea as the only preceding symptom. Whether these systemic reactions 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 reactions has not been identified. Upon the appearance of rash or of other possibly allergic phenomena for which an alternative etiology cannot be identified, fluoxetine should be discontinued.
4 Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania 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 for clinical worsening and suicide risk 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.
Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder. S. 1% of patients treated with placebo. 4 )]. S. 8% of patients treated with fluoxetine and no patients treated with placebo.
S. placebo-controlled clinical trials for bulimia. S. 4 )]. S. 2% of patients treated with placebo. S. placebo-controlled clinical trials for either OCD or bulimia. S. 2% of 10,782 patients reported convulsions. The percentage appears to be similar to that associated with other marketed drugs effective in the treatment of MDD.
Fluoxetine should be introduced with care in patients with a history of seizures. There have been rare reports of prolonged seizures in patients taking fluoxetine who are also receiving electroconvulsive therapy (ECT) treatment. 6 Altered Appetite and Weight Significant weight loss, especially in underweight depressed or bulimic patients, may be an undesirable result of treatment with fluoxetine.
S. placebo-controlled clinical trials for MDD, 11% of patients treated with fluoxetine and 2% of patients treated with placebo reported anorexia (decreased appetite). 5% of patients treated with placebo. 4) ]. S. placebo-controlled clinical trials for OCD, 17% of patients treated with fluoxetine and 10% of patients treated with placebo reported anorexia (decreased appetite).
4 )]. S. placebo-controlled clinical trials for Bulimia Nervosa, 8% of patients treated with fluoxetine 60 mg and 4% of patients treated with placebo reported anorexia (decreased appetite). 16 kg by patients treated with placebo in the 16 week double-blind trial.
Weight change should be monitored during therapy. 7 Increased Risk of Bleeding 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. 1 )]. Bleeding reactions related to SNRIs and SSRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
4 )]. 8 Angle-closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including fluoxetine may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
9 Hyponatremia Hyponatremia has been reported during treatment with SNRIs and SSRIs, including fluoxetine. 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 and appeared to be reversible when fluoxetine was discontinued. Elderly patients may be at greater risk of developing hyponatremia with SNRIs and SSRIs. 5 )]. Discontinuation of fluoxetine 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. More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death.
S. placebo-controlled clinical trials for MDD, 12% to 16% of patients treated with fluoxetine and 7% to 9% of patients treated with placebo reported anxiety, nervousness, or insomnia. S. placebo-controlled clinical trials for OCD, insomnia was reported in 28% of patients treated with fluoxetine and in 22% of patients treated with placebo.
Anxiety was reported in 14% of patients treated with fluoxetine and in 7% of patients treated with placebo. S. placebo-controlled clinical trials for Bulimia Nervosa, insomnia was reported in 33% of patients treated with fluoxetine 60 mg, and 13% of patients treated with placebo.
Anxiety and nervousness were reported, respectively, in 15% and 11% of patients treated with fluoxetine 60 mg and in 9% and 5% of patients treated with placebo. S. placebo-controlled fluoxetine clinical trials were anxiety (2% in OCD), insomnia (1% in combined indications and 2% in bulimia), and nervousness (1% in MDD) [Table 4].
11 QT Prolongation Postmarketing cases of QT interval prolongation and ventricular arrhythmia including Torsades de Pointes have been reported in patients treated with fluoxetine. Fluoxetine should be used with caution in patients with congenital long QT syndrome; a previous history of QT prolongation; a family history of long QT syndrome or sudden cardiac death; and other conditions that predispose to QT prolongation and ventricular arrhythmia.
Such conditions include concomitant use of drugs that prolong the QT interval; hypokalemia or hypomagnesemia; recent myocardial infarction, uncompensated heart failure, bradyarrhythmias, and other significant arrhythmias; and conditions that predispose to increased fluoxetine exposure (overdose, hepatic impairment, use of CYP2D6 inhibitors, CYP2D6 poor metabolizer status, or use of other highly protein-bound drugs).
3 )]. Pimozide and thioridazine are contraindicated for use with fluoxetine. Avoid the concomitant use of drugs known to prolong the QT interval. 3 )]. Consider ECG assessment and periodic ECG monitoring if initiating treatment with fluoxetine in patients with risk factors for QT prolongation and ventricular arrhythmia.
Consider discontinuing fluoxetine and obtaining a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia. 12 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. Cardiovascular—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 ECGs of 312 patients who received fluoxetine in double-blind trials were retrospectively evaluated; no conduction abnormalities that resulted in heart block were observed.
The mean heart rate was reduced by approximately 3 beats/min. Glycemic Control—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. 13 Potential for Cognitive and Motor Impairment As with any CNS-active drug, fluoxetine has the potential to impair judgment, thinking, or motor skills.
Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely. 14 Long Elimination Half-Life 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.
3 )]. , paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these reactions are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored for these symptoms when discontinuing treatment with fluoxetine. 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.
1 )]. In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of fluoxetine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported.
When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.