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
- INFORMATION FOR PATIENTS
- 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 RiskAll 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.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
Screening 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 Experience
Animal Experience
Management of Overdose
DOSAGE & ADMINISTRATION
Major Depressive Disorder
Initial 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
INFORMATION FOR PATIENTS
FDA-approved Medication GuideGeneral Information
Clinical Worsening and Suicide Risk
Box WarningWarnings and Precautions (5.1)
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions
Warnings and Precautions (5.2Drug Interactions (7.3
Allergic Reactions and Rash
Warnings and Precautions (5.3)
Abnormal Bleeding
Warnings and Precautions (5.7)Drug Interactions (7.6)
Hyponatremia
Warnings and Precautions (5.8)
Potential for Cognitive and Motor Impairment
Warnings and Precautions (5.11)
Use of Concomitant Medications
Discontinuation of Treatment
Warnings and Precautions (5.13)
Use in Specific Populations
Use in Specific Populations (8.1)
Use in Specific Populations (8.3)
Box WarningWarnings and Precautions (5.1)Warnings and Precautions (5.6)Use in Specific Populations (8.4)
SPL MEDGUIDE
What is the most important information I should know about fluoxetine capsules?
Antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions:
Talk to your, or your family member's, healthcare provider about:
-
● all risks and benefits of treatment with antidepressant medicines
-
● all treatment choices for depression or other serious mental illness
2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions
3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
-
● Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
-
● Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
-
● Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
-
● thoughts about suicide or dying
-
● attempts to commit suicide
-
● new or worse depression
-
● new or worse anxiety
-
● feeling very agitated or restless
-
● panic attacks
-
● trouble sleeping (insomnia)
-
● new or worse irritability
-
● acting aggressive, being angry, or violent
-
● acting on dangerous impulses
-
● an extreme increase in activity and talking (mania)
-
● or other unusual changes in behavior or mood
What else do I need to know about antidepressant medicines?
-
● Never stop an antidepressant medicine without first talking to a healthcare provider . Stopping an antidepressant medicine suddenly can cause other symptoms.
-
● Antidepressants are medicines used to treat depression and other illnesses.It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
-
● Antidepressant medicines have other side effects.Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
-
● Antidepressant medicines can interact with other medicines.Know all of the medicines that you or your family member takes.Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
-
● Not all antidepressant medicines prescribed for children are FDA approved for use in children.Talk to your child's healthcare provider for more information.
What are fluoxetine capsules?
-
● for short and long-term treatment of depression in adults and children over the age of 8.
-
● for short and long-term treatment of Obsessive Compulsive Disorder (OCD) in adults and children over the age of 7.
-
● for short and long-term treatment of Bulimia Nervosa in adults.
-
● for short-term treatment of Panic Disorder, with or without agoraphobia, in adults.
-
● with the medicine olanzapine (Zyprexafor the short-term treatment of episodes of depression that happen with Bipolar I Disorder.
Who should not take fluoxetine capsules?
-
● Do not take fluoxetine capsules if you take a Monoamine Oxidase Inhibitor (MAOI) or if you stopped taking an MAOI in the last2weeks.
-
● Do not take an MAOIwithin 5 weeks of stopping fluoxetine capsules. People who take fluoxetine capsules close in time to an MAOI can have serious and life-threatening side effects, with symptoms including:
-
● high fever
-
● continued muscle spasms that you can not control
-
● rigid muscles
-
● changes in heart rate and blood pressure that happen fast
-
● confusion
-
● unconsciousness
-
● Do not take fluoxetine capsules if you take Mellaril(thioridazine). Do not take Mellarilwithin 5 weeks of stopping fluoxetine capsules. Mellaril can cause serious heart rhythm problems and you could die suddenly.
-
● Do not take fluoxetine capsules if you take the antipsychotic medicine pimozide (Orap
-
● seizures (convulsions)
-
● bipolar disorder (mania)
-
● are pregnant or plan to become pregnant. It is not known if fluoxetine capsules will harm your unborn baby.
-
● are breast-feeding or plan to breast-feed. Fluoxetine can pass into your breast milk and may harm your baby. You should not breast-feed while taking fluoxetine capsules. Talk to your doctor about the best way to feed your baby if you take fluoxetine capsules.
Tell your doctor about all the medicines that you take,
If you take fluoxetine capsules, you should not take any other medicines that contain fluoxetine hydrochloride:
-
● Symbyax
-
● Sarafem
How should I take fluoxetine capsules?
-
● Take fluoxetine capsules exactly as prescribed. Your doctor may need to change (adjust) the dose of fluoxetine capsules until it is right for you.
-
● If you miss a dose of fluoxetine capsules, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of fluoxetine capsules at the same time.
-
● To prevent serious side effects, do not stop taking fluoxetine capsules suddenly. If you need to stop taking fluoxetine capsules, your doctor can tell you how to safely stop taking them.
-
● If you take too much fluoxetine capsules, call your doctor or poison control center right away, or get emergency treatment.
-
● Fluoxetine capsules can be taken with or without food.
-
● Fluoxetine capsules are usually taken once a day, depending on how your doctor prescribes your medicine.
-
● If you do not think you are getting better or have any concerns about your condition while taking fluoxetine capsules, call your doctor.
What should I avoid while taking fluoxetine capsules?
-
● Fluoxetine capsules can cause sleepiness and may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how fluoxetine capsules affect you.
What are the possible side effects of fluoxetine capsules?
-
● Serotonin Syndrome: This is a condition that can be life threatening. Call your doctor right away if you become severely ill and have some or all of these symptoms:
-
● agitation
-
● hallucinations
-
● problems with coordination
-
● racing heart beat
-
● over-active reflexes
-
● fever
-
● nausea, vomiting, and diarrhea
-
● Severe allergic reactions:Tell your doctor right away if you get red itchy welts (hives) or, a rash alone or with fever and joint pain, while taking fluoxetine capsules. Call your doctor right away if you become severely ill and have some or all of these symptoms:
-
● swelling of your face, eyes, or mouth
-
● trouble breathing
-
● Abnormal bleeding:Tell your doctor if you notice any increased or unusual bruising or bleeding while taking fluoxetine capsules, especially if you take one of these medicines:
-
● the blood thinner warfarin (CoumadinJantoven
-
● a non-steroidal anti-inflammatory drug (NSAID)
-
● aspirin
-
● Mania:You may have a high mood, become extremely irritable, have too much energy, feel pressure to keep talking, or have a decreased need for sleep.
-
● Seizures
-
● Loss of appetite
-
● Low salt (sodium) levels in the blood (hyponatremia): Call your doctor right away if you become severely ill and have some or all of these symptoms:
-
● headache
-
● feel weak
-
● confusion
-
● problems concentrating
-
● memory problems
-
● feel unsteady
Common possible side effects of fluoxetine capsules include:
How should I store fluoxetine capsules?
-
● Store fluoxetine capsules at 20to 25(68to 77to 30(59to 86[see USP Controlled Room Temperature].
-
● Keep fluoxetine capsules away from light.
-
● Keep fluoxetine capsules bottle closed tightly.
Keep fluoxetine capsules and all medicines out of the reach of children.
General information about fluoxetine capsules
What are the ingredients in fluoxetine capsules?
Active ingredient: fluoxetine hydrochloride
Inactive ingredients:
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
Fluoxetine HydrochlorideFluoxetine Hydrochloride CAPSULE
|
PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!