Fluoxetine Hydrochloride
FULL PRESCRIBING INFORMATION: CONTENTS*
- BOXED WARNING
- FLUOXETINE HYDROCHLORIDE DESCRIPTION
- CLINICAL PHARMACOLOGY
- INDICATIONS & USAGE
- FLUOXETINE HYDROCHLORIDE CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- INFORMATION FOR PATIENTS
- LABORATORY TESTS
- DRUG INTERACTIONS
- CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
- PREGNANCY
- LABOR & DELIVERY
- NURSING MOTHERS
- PEDIATRIC USE
- GERIATRIC USE
- FLUOXETINE HYDROCHLORIDE ADVERSE REACTIONS
- DRUG ABUSE AND DEPENDENCE
- OVERDOSAGE
- DOSAGE & ADMINISTRATION
- HOW SUPPLIED
- STORAGE AND HANDLING
- ANIMAL PHARMACOLOGY & OR TOXICOLOGY
- SPL MEDGUIDE
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
FULL PRESCRIBING INFORMATION
BOXED WARNING
Suicidality and Antidepressant DrugsAntidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of fluoxetine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Fluoxetine is approved for use in pediatric patients with MDD and obsessive compulsive disorder (OCD). (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use)
FLUOXETINE HYDROCHLORIDE DESCRIPTION
CLINICAL PHARMACOLOGY
PharmacodynamicsAbsorption, Distribution, Metabolism, and Excretion
Systemic bioavailability
Protein binding
Enantiomers
Metabolism
Clinical issues related to metabolism/elimination
Variability in metabolism
Accumulation and slow elimination
Liver disease
Renal disease
Age
Geriatric pharmacokinetics
Pediatric pharmacokinetics (children and adolescents)
CLINICAL TRIALS
Major Depressive Disorder
Daily Dosing
Adult
Pediatric (children and adolescents)
has been studied in two 8- to 9-week placebo-controlled clinical trials.
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.
Obsessive Compulsive Disorder
Adult
The effectiveness of fluoxetine for the treatment of obsessive compulsive disorder (OCD) was demonstrated in two 13-week, multicenter, parallel group studies (Studies 1 and 2) of adult outpatients who received fixed fluoxetine doses of 20, 40, or 60 mg/day (on a once-a-day schedule, in the morning) or placebo. Patients in both studies had moderate to severe OCD (DSM-III-R), with mean baseline ratings on the Yale-Brown Obsessive Compulsive Scale (YBOCS, total score) ranging from 22 to 26. In Study 1, patients receiving fluoxetine experienced mean reductions of approximately 4 to 6 units on the YBOCS total score, compared with a 1-unit reduction for placebo patients. In Study 2, patients receiving fluoxetine experienced mean reductions of approximately 4 to 9 units on the YBOCS total score, compared with a 1-unit reduction for placebo patients. While there was no indication of a dose-response relationship for effectiveness in Study 1, a dose-response relationship was observed in Study 2, with numerically better responses in the two higher dose groups. The following table provides the outcome classification by treatment group on the Clinical Global Impression (CGI) improvement scale for Studies 1 and 2 combined:
Outcome Classification (%) on CGI Improvement Scale for Completers in Pool of Two OCD Studies
FluoxetineOutcome ClassificationPlacebo20 mg40 mg60 mgWorse8%0%0%0%No change64%41%33%29%Minimally improved17%23%28%24%Much improved8%28%27%28%Very much improved3%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.
Pediatric (children and adolescents)
's Yale-Brown Obsessive Compulsive Scale (CY-BOCS).
Subgroup analyses on outcome did not suggest any differential responsiveness on the basis of age or gender.
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 three 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 three 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 three 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 one to two episodes per week for binge-eating and two to four 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 physician 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.
Panic Disorder
The effectiveness of fluoxetine in the treatment of panic disorder was demonstrated in two 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.
INDICATIONS & USAGE
Major Depressive DisorderAdult
Pediatric (children and adolescents)
Obsessive Compulsive Disorder
Adult
Pediatric (children and adolescents)
Bulimia Nervosa
Panic Disorder
FLUOXETINE HYDROCHLORIDE CONTRAINDICATIONS
Monoamine oxidase inhibitors
Pimozide
Thioridazine
WARNINGS
Clinical Worsening and Suicide RiskScreening Patients for Bipolar Disorder
Rash and Possibly Allergic Events
Serotonin Syndrome
Potential Interaction with Thioridazine
PRECAUTIONS
GeneralAbnormal Bleeding
Anxiety and Insomnia
Altered Appetite and Weight
Activation of Mania/Hypomania
Hyponatremia
Seizures
The Long Elimination Half-Lives of Fluoxetine and its Metabolites
Use in Patients With Concomitant Illness
Interference With Cognitive and Motor Performance
Discontinuation of Treatment with Fluoxetine
INFORMATION FOR PATIENTS
Clinical Worsening and Suicide Risk
Serotonin Syndrome
LABORATORY TESTS
DRUG INTERACTIONS
Drugs metabolized by CYP2D6
Drugs metabolized by CYP3A4
CNS active drugs
Anticonvulsants
Antipsychotics
Benzodiazepines
Lithium
Tryptophan
Monoamine oxidase inhibitors
Other drugs effective in the treatment of major depressive disorder
Serotonergic drugs
Triptans
Potential effects of coadministration of drugs tightly bound to plasma proteins
Drugs that interfere with hemostasis (NSAIDs, aspirin, warfarin, etc.)
Warfarin
Electroconvulsive therapy (ECT)
CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
Carcinogenicity
Mutagenicity
Impairment of fertility
PREGNANCY
Pregnancy Category CNonteratogenic effects
LABOR & DELIVERY
NURSING MOTHERS
PEDIATRIC USE
GERIATRIC USE
FLUOXETINE HYDROCHLORIDE ADVERSE REACTIONS
Incidence in major depressive disorder, OCD, bulimia, and panic disorder placebo-controlled clinical trials (excluding data from extensions of trials).
Associated with discontinuation in major depressive disorder, OCD, bulimia, and panic disorder placebo-controlled clinical trials (excluding data from extensions of trials)
Other adverse events in pediatric patients (children and adolescents)
Male and female sexual dysfunction with SSRIs
Other Events Observed in Clinical Trials
Body as a Whole
Cardiovascular System
Digestive System
Endocrine System
Hemic and Lymphatic System
Metabolic and Nutritional
Musculoskeletal System
Nervous System
Respiratory System
Skin and Appendages
Special Senses
Urogenital System
Postintroduction Reports
DRUG ABUSE AND DEPENDENCE
Controlled substance classPhysical and psychological dependence
OVERDOSAGE
Human ExperienceAnimal Experience
Management of Overdose
DOSAGE & ADMINISTRATION
Major Depressive DisorderInitial Treatment
Adult
Pediatric (children and adolescents)
All patients
Maintenance/Continuation/Extended Treatment
Daily Dosing
Switching Patients to a Tricyclic Antidepressant (TCA)
Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI)
Obsessive Compulsive Disorder
Initial Treatment
Adult
Pediatric (children and adolescents)
All Patients
Maintenance/Continuation Treatment
Bulimia Nervosa
Initial Treatment
Maintenance/Continuation Treatment
Panic Disorder
Initial Treatment
Maintenance/Continuation Treatment
Special Populations
Treatment of Pregnant Women During the Third Trimester
Discontinuation of Treatment with Fluoxetine
HOW SUPPLIED
STORAGE AND HANDLING
ANIMAL PHARMACOLOGY & OR TOXICOLOGY
SPL MEDGUIDE
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● Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is first started or when the dose is changed.
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● Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
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● Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
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● Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
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● Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
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● Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
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● Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
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● Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
Fluoxetine HydrochlorideFluoxetine Hydrochloride CAPSULE
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PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
