Fluoxetine

Unit Dose Services
Unit Dose Services

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use fluoxetine safely and effectively. See full prescribing information for fluoxetine capsules. Fluoxetine Capsules, USP for Oral Use Initial U.S. Approval: 1987 RECENT MAJOR CHANGES(5.10)BOXED WARNING WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS See full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents,and young adults taking antidepressants for Major Depressive Disorder (MDD) and other psychiatric disorders . (5.1) When using fluoxetine and olanzapine in combination, also refer to Boxed Warning section of the package insert for Symbyax. INDICATIONS AND USAGE Acute and maintenance treatment of Major Depressive Disorder (MDD) in adult and pediatric patients aged 8 to 18 years (1.1) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) in adult and pediatric patients aged 7 to 17 years (1.2) Acute and maintenance treatment of Bulimia Nervosa in adult patients (1.3) Acute treatment of Panic Disorder, with or without agoraphobia, in adult patients (1.4) for: Fluoxetine capsules and olanzapine in combination Acute treatment of Depressive Episodes Associated with Bipolar I Disorder in adults   (1.5) DOSAGE AND ADMINISTRATION  Indication Adult Pediatric    MDD (2.1)    20 mg/day in am (initial dose)    10 to 20 mg/day (initial dose)    OCD (2.2)    20 mg/day in am (initial dose)    10 mg/day (initial dose)    Bulimia Nervosa  (2.3)    60 mg/day in am    -    Panic Disorder (2.4)    10 mg/day (initial dose)    -    Depressive Episodes    Associated with Bipolar I Disorder     (2.5)    Oral in combination with olanzapine: 5 mg of oral    olanzapine and 20 mg of fluoxetine once daily (initial dose)    - Consider tapering the dose of fluoxetine for pregnant women during the third trimester (2.7) 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 (2.7)    Fluoxetine capsules and olanzapine in combination: Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability (2.5) Fluoxetine monotherapy is not indicated for the treatment of Depressive Episodes associated with Bipolar I Disorder (2.5) Safety of the coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated   (2.5) DOSAGE FORMS AND STRENGTHS Capsules: 10 mg, 20 mg, and 40 mg (3) CONTRAINDICATIONS Do not use with an MAOI or within 14 days of discontinuing an MAOI due to risk of drug interaction. At least 5 weeks should be allowed after stopping fluoxetine capsules before treatment with an MAOI ( , ) 4 7.1 Do not use with pimozide due to risk of drug interaction or QT prolongation ( , ) c 4 7.9 Do not use with thioridazine due to QT interval prolongation or potential for elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing fluoxetine capsules ( , ) c   4 7.9 When using fluoxetine capsules and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax (4) WARNINGS AND PRECAUTIONS Monitor for clinical worsening and suicidal thinking and behavior Clinical Worsening and Suicide Risk: (5.1) Have been reported with fluoxetine. Discontinue fluoxetine and initiate supportive treatment Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: (5.2) Discontinue upon appearance of rash or allergic phenomena Allergic Reactions and Rash: (5.3) Screen for Bipolar Disorder and monitor for mania/hypomania Activation of Mania/Hypomania: (5.4) Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold Seizures: (5.5) Significant weight loss has occurred Altered Appetite and Weight: (5.6) May increase the risk of bleeding. Use with NSAIDs, aspirin, warfarin, or drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding Abnormal Bleeding: (5.7) Has been reported with fluoxetine in association with syndrome of inappropriate antidiuretic hormone (SIADH) Hyponatremia: (5.8) May occur Anxiety and Insomnia: (5.9) Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery Potential for Cognitive and Motor Impairment: (5.11) Changes in dose will not be fully reflected in plasma for several weeks Long Half-Life: (5.12) When using fluoxetine and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax Fluoxetine and Olanzapine in Combination: (5.14) Side Effects6.1To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS Fluoxetine is contraindicated for use with MAOI’s, or within 14 days of discontinuing an MAOI due to risk of drug interaction. At least 5 weeks should be allowed after stopping fluoxetine before starting treatment with an MAOI ( , ) Monoamine Oxidase Inhibitors (MAOI): 4 7.1 Fluoxetine is contraindicated for use with pimozide due to risk of drug interaction or QT prolongation ( , ) Pimozide: c 4 7.9 Fluoxetine is contraindicated for use with thioridazine due to QT interval prolongation or potential for elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing fluoxetine ( , ) Thioridazine: c 4 7.9 Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( ) Drugs Metabolized by CYP2D6: 7.9 Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued ( ) Tricyclic Antidepressants (TCAs): 7.9 Caution should be used when taken in combination with other centrally acting drugs ( ) CNS Acting Drugs: 7.2 Diazepam - increased t½, alprazolam – further psychomotor performance decrement due to increased levels ( ) Benzodiazepines: 7.9 Potential for elevation of haloperidol and clozapine levels ( ) Antipsycotics: 7.9 Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( ) Anticonvulsants: 7.9 Potential for Serotonin Syndrome ( , ) Serotonergic Drugs: 5.2 7.3 There have been rare postmarketing reports of Serotonin Syndrome with use of an SSRI and a triptan ( , ) Triptans: 5.2 7.4 Concomitant use with tryptophan is not recommended , ) Tryptophan: (5.2 7.5 May potentiate the risk of bleeding ( ) Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin): 7.6 May cause a shift in plasma concentrations ( , ) Drugs Tightly Bound to Plasma Proteins: 7.8 7.9 When used in combination with fluoxetine, also refer to the Drug Interactions section of the package insert for Symbyax Olanzapine: (7.9) USE IN SPECIFIC POPULATIONS Fluoxetine should be used during pregnancy only if the potential benefit justifies the potential risks to the fetus ( ) Pregnancy: 8.1 Breast feeding is not recommended ( ) Nursing Mothers: 8.3 Safety and effectiveness of fluoxetine and olanzapine in combination have not been established in patients less than 18 years of age Pediatric Use: (8.4) Lower or less frequent dosing may be appropriate in patients with cirrhosis ( ) Hepatic Impairment: 8.6

FULL PRESCRIBING INFORMATION: CONTENTS*

• WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
• 1 FLUOXETINE INDICATIONS AND USAGE
  • 1.1 Major Depressive Disorder
  • 1.2 Obsessive Compulsive Disorder
  • 1.3 Bulimia Nervosa
  • 1.4 Panic Disorder
  • 1.5 Fluoxetine Capsules and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder
• 2 FLUOXETINE DOSAGE AND ADMINISTRATION
  • 2.1 Major Depressive Disorder
  • 2.2 Obsessive Compulsive Disorder
  • 2.3 Bulimia Nervosa
  • 2.4 Panic Disorder
  • 2.5 Fluoxetine Capsules and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder
  • 2.7 Dosing in Specific Populations
  • 2.8 Discontinuation of Treatment
• 3 DOSAGE FORMS AND STRENGTHS
• 4 FLUOXETINE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Clinical Worsening and Suicide Risk
  • 5.2 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions
  • 5.3 Allergic Reactions and Rash
  • 5.4 Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania
  • 5.5 Seizures
  • 5.6 Altered Appetite and Weight
  • 5.7 Abnormal Bleeding
  • 5.8 Hyponatremia
  • 5.9 Anxiety and Insomnia
  • 5.10 Use in Patients with Concomitant Illness
  • 5.11 Potential for Cognitive and Motor Impairment
  • 5.12 Long Elimination Half-Life
  • 5.13 Discontinuation of Treatment
  • 5.14 Fluoxetine and Olanzapine in Combination
• 6 FLUOXETINE ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Other Reactions
  • 6.3 Postmarketing Experience
• 7 DRUG INTERACTIONS
  • 7.1 Monoamine Oxidase Inhibitors (MAOI)
  • 7.2 CNS Acting Drugs
  • 7.3 Serotonergic Drugs
  • 7.4 Triptans
  • 7.5 Tryptophan
  • 7.6 Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin)
  • 7.7 Electroconvulsive Therapy (ECT)
  • 7.8 Potential for Other Drugs to affect Fluoxetine
  • 7.9 Potential for Fluoxetine to affect Other Drugs
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.2 Labor and Delivery
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
  • 8.6 Hepatic Impairment
• 9 DRUG ABUSE AND DEPENDENCE
  • 9.3 Dependence
• 10 OVERDOSAGE
  • 10.1 Human Experience
  • 10.2 Animal Experience
  • 10.3 Management of Overdose
• 11 FLUOXETINE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
  • 12.4 Specific Populations
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
  • 13.2 Animal Toxicology and/or Pharmacology
• 14 CLINICAL STUDIES
  • 14.1 Major Depressive Disorder
  • 14.2 Obsessive Compulsive Disorder
  • 14.3 Bulimia Nervosa
  • 14.4 Panic Disorder
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 General Information
  • 17.2 Clinical Worsening and Suicide Risk
  • 17.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions
  • 17.4 Allergic Reactions and Rash
  • 17.5 Abnormal Bleeding
  • 17.6 Hyponatremia
  • 17.7 Potential for Cognitive and Motor Impairment
  • 17.8 Use of Concomitant Medications
  • 17.9 Discontinuation of Treatment
  • 17.10 Use in Specific Populations
• Medication Guide
  • How should I take fluoxetine capsules?
• FLUOXETINE (FLUOXETINE HYDROCHLORIDE) CAPSULE

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Major Depressive Disorder

1.2 Obsessive Compulsive Disorder

1.3 Bulimia Nervosa

1.4 Panic Disorder

1.5 Fluoxetine Capsules and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder

2 DOSAGE AND ADMINISTRATION

2.1 Major Depressive Disorder

2.2 Obsessive Compulsive Disorder

2.3 Bulimia Nervosa

2.4 Panic Disorder

2.5 Fluoxetine Capsules and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder

2.7 Dosing in Specific Populations

2.8 Discontinuation of Treatment

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

When usingfluoxetine capsules and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax.  

• Monoamine Oxidase Inhibitors [see )] Drug Interactions (7.1
• Pimozide [see )] Drug Interactions (7.9
• Thioridazine [see )] Drug Interactions (7.9

5 WARNINGS AND PRECAUTIONS

When usingFluoxetine and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax.

5.1 Clinical Worsening and Suicide Risk

Table 2: Suicidality per 1000 Patients Treated

Age Range	Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated
	Increases Compared to Placebo
<18	14 additional cases
18-24	5 additional cases
	Decreases Compared to Placebo
25-64	1 fewer case
≥65	6 fewer cases

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.







[see ] Warnings and Precautions (5.13) 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.

5.2 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

[see and Contraindications (4) ] Drug Interactions (7.1)

[see ] Drug Interactions (7.4)

[see Drug Interactions (7.3) ]

5.3 Allergic Reactions and Rash

5.4 Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania

[see Warnings and Precautions section of the package insert for Symbyax]

[see ] Use in Specific Populations (8.4)

[see ] Use in Specific Populations (8.4)

5.5 Seizures

5.6 Altered Appetite and Weight

[see ] Use in Specific Populations (8.4)

[see Use in Specific Populations (8.4) ]

5.7 Abnormal Bleeding

[see ] Drug Interactions (7.6)

5.8 Hyponatremia

[see ] Use in Specific Populations (8.5)

5.9 Anxiety and Insomnia

[see Table 5]

5.10 Use in Patients with Concomitant Illness

Cardiovascular

Glycemic Control


Acute Narrow-Angle Glaucoma
has

5.11 Potential for Cognitive and Motor Impairment

5.12 Long Elimination Half-Life

[see ] Clinical Pharmacology (12.3)

5.13 Discontinuation of Treatment

5.14 Fluoxetine and Olanzapine in Combination

6 ADVERSE REACTIONS

When using fluoxetine and olanzapine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax.

6.1 Clinical Trials Experience

Incidence in Major Depressive Disorder, OCD, bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials)

Table 3: Most Common Treatment-Emergent Adverse Reactions: Incidence in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials ^1,2

	Percentage of Patients Reporting Event
	Major Depressive Disorder		OCD		Bulimia		Panic Disorder
Incidence less than 1%. Includes U.S. data for Major Depressive Disorder, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. Denominator used was for males only (N=690 fluoxetine Major Depressive Disorder; N=410 placebo Major Depressive Disorder; N=116 fluoxetine OCD; N=43 placebo OCD; N=14 fluoxetine bulimia; N=1 placebo bulimia; N=162 fluoxetine panic; N=121 placebo panic). 1 2 3
Body System/ Adverse Reaction	(N=1728) Fluoxetine	(N=975) Placebo	(N=266) Fluoxetine	(N=89) Placebo	(N=450) Fluoxetine	(N=267) Placebo	(N=425) Fluoxetine	(N=342) Placebo
Body as a Whole
Asthenia	9	5	15	11	21	9	7	7
Flu syndrome	3	4	10	7	8	3	5	5
Cardiovascular System
Vasodilatation	3	2	5	--	2	1	1	--
Digestive System
Nausea	21	9	26	13	29	11	12	7
Diarrhea	12	8	18	13	8	6	9	4
Anorexia	11	2	17	10	8	4	4	1
Dry mouth	10	7	12	3	9	6	4	4
Dyspepsia	7	5	10	4	10	6	6	2
Nervous System
Insomnia	16	9	28	22	33	13	10	7
Anxiety	12	7	14	7	15	9	6	2
Nervousness	14	9	14	15	11	5	8	6
Somnolence	13	6	17	7	13	5	5	2
Tremor	10	3	9	1	13	1	3	1
Libido decreased	3	--	11	2	5	1	1	2
Abnormal dreams	1	1	5	2	5	3	1	1
Respiratory System
Pharyngitis	3	3	11	9	10	5	3	3
Sinusitis	1	4	5	2	6	4	2	3
Yawn	--	--	7	--	11	--	1	--
Skin and Appendages
Sweating	8	3	7	--	8	3	2	2
Rash	4	3	6	3	4	4	2	2
Urogenital System
Impotence 3	2	--	--	--	7	--	1	--
Abnormal ejaculation 3	--	--	7	--	7	--	2	1

Table 4: Treatment-Emergent Adverse Reactions: Incidence in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials ^{1, 2}

	Percentage of Patients Reporting Event
	Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Combined
Incidence less than 1%. Includes U.S. data for Major Depressive Disorder, OCD, bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. 1 2
Body System/Adverse Reaction	(N=2869) Fluoxetine	(N=1673) Placebo
Body as a Whole
Headache	21	19
Asthenia	11	6
Flu syndrome	5	4
Fever	2	1
Cardiovascular System
Vasodilatation	2	1
Digestive System
Nausea	22	9
Diarrhea	11	7
Anorexia	10	3
Dry mouth	9	6
Dyspepsia	8	4
Constipation	5	4
Flatulence	3	2
Vomiting	3	2
Metabolic and Nutritional Disorders
Weight loss	2	1
Nervous System
Insomnia	19	10
Nervousness	13	8
Anxiety	12	6
Somnolence	12	5
Dizziness	9	6
Tremor	9	2
Libido decreased	4	1
Thinking abnormal	2	1
Respiratory System
Yawn	3	--
Skin and Appendages
Sweating	7	3
Rash	4	3
Pruritus	3	2
Special Senses
Abnormal vision	2	1

Associated with discontinuation in Major Depressive Disorder, OCD, bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials)

Table 5: Most Common Adverse Reactions Associated with Discontinuation in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials ¹

Includes U.S. Major Depressive Disorder, OCD, bulimia, and Panic Disorder clinical trials, plus non-U.S. Panic Disorder clinical trials. 1
(N=1533) Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Combined	(N=392) Major Depressive Disorder	(N=266) OCD	(N=450) Bulimia	(N=425) Panic Disorder
Anxiety (1%)	--	Anxiety (2%)	--	Anxiety (2%)
--	--	--	Insomnia (2%)	--
--	Nervousness (1%)	--	--	Nervousness (1%)
--	--	Rash (1%)	--	--

Other adverse reactions in pediatric patients (children and adolescents)

Male and female sexual dysfunction with SSRIs

6.2 Other Reactions

Body as a Whole

Frequent:Infrequent:Rare:Cardiovascular System

Frequent:Infrequent:¹

Digestive SystemInfrequent:Rare:

Hemic and Lymphatic SystemInfrequent:Rare:

Nervous SystemFrequent:Infrequent:¹¹Rare:

Respiratory SystemRare:

Skin and AppendagesInfrequent:Rare:

Special SensesFrequent:Infrequent:

Urogenital System— Frequent: Infrequent:<sup>2

1
2</sup>

6.3 Postmarketing Experience

<sup>1111111

1</sup>

7 DRUG INTERACTIONS

7.1 Monoamine Oxidase Inhibitors (MAOI)

[see ] Contraindications (4) [see ] Clinical Pharmacology (12.3)

7.2 CNS Acting Drugs

[see ] Clinical Pharmacology (12.3)

7.3 Serotonergic Drugs

[see ] Warnings and Precautions (5.2) [see , ] Drug Interactions (7.4) (7.5)

7.4 Triptans

[see ) and ] Warnings and Precautions (5.2 Drug Interactions (7.3)

7.5 Tryptophan

[see Warnings and Precautions (5.2) and ] Drug Interactions (7.3)

7.6 Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin)

[see ] Warnings and Precautions (5.7)

7.7 Electroconvulsive Therapy (ECT)

7.8 Potential for Other Drugs to affect Fluoxetine

Drugs Tightly Bound to Plasma Proteins —[see ] Clinical Pharmacology (12.3)

7.9 Potential for Fluoxetine to affect Other Drugs

Pimozide —_cc[see ] Contraindications (4) Thioridazine —

[see ] Contraindications (4)

<sub>max

c</sub>Drugs Metabolized by CYP2D6 —

[see ] Contraindications (4) Tricyclic Antidepressants (TCAs)

—[see ] Clinical Pharmacology (12.3) Benzodiazapines

—[see ] Clinical Pharmacology (12.3) Antipsychotics

—[see ] Contraindications (4) Anticonvulsants

—Lithium

—Drugs Tightly Bound to Plasma Proteins

—[see ] Clinical Pharmacology (12.3) Drugs Metabolized by CYP3A4

—in vivo

in vitro
Olanzapine
—

When using fluoxetine and olanzapine and in combination, also refer to the Drug Interactions section of the package insert forSymbyax.

8 USE IN SPECIFIC POPULATIONS

When using fluoxetine and olanzapine in combination, also refer to the Use in Specific Populations section of the package insert for Symbyax.

8.1 Pregnancy

Pregnancy Category C

Treatment of Pregnant Women during the First Trimester

Treatment of Pregnant Women during the Third Trimester



Clinical Considerations

[see ] Dosage and Administration (2.7)

Animal Data²²²²

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

[see ] Clinical Studies (14.1)

[see Clinical Studies (14.2) ]



[see ] Clinical Pharmacology (12.3)

[see ] Adverse Reactions (6.1)



[see ] Warnings and Precautions (5.6)

[see and ) Box Warning Warnings and Precautions (5.1 ]





<sup>2

2</sup>

8.5 Geriatric Use

[see ] Clinical Studies (14.1) [see ] Clinical Pharmacology (12.4) [see )] Warnings and Precautions (5.8

8.6 Hepatic Impairment

[see) and ]. Dosage and Administration (2.7 Clinical Pharmacology (12.4)

9 DRUG ABUSE AND DEPENDENCE

9.3 Dependence

10 OVERDOSAGE

10.1 Human Experience

10.2 Animal Experience

[see ] Overdosage (10.3)

10.3 Management of Overdose

[see )] Drug Interactions (7.9



Physicians’ Desk Reference (PDR)

11 DESCRIPTION

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

₁in vitro

12.3 Pharmacokinetics

Systemic Bioavailability

Protein Binding

in vitro₁Enantiomers

RSSMetabolism

SRSRVariability in Metabolism

SSSR

[see ] Drug Interactions (7.9) Accumulation and Slow Elimination

[see ] Warnings and Precautions (5.12)

12.4 Specific Populations

Liver Disease[see ), ] Dosage and Administration (2.7 Use in Specific Populations (8.6) Renal Disease

Geriatric Pharmacokinetics

Pediatric Pharmacokinetics (children and adolescents)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity²Mutagenicity

in vivo
Impairment of Fertility
²[see ]. Use in Specific Populations (8.4)

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

When usingfluoxetine and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.

14.1 Major Depressive Disorder

Daily Dosing Adult —

.



Pediatric (children and adolescents)

—

14.2 Obsessive Compulsive Disorder

Adult

Table 6: 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%

Pediatric (children and adolescents)

14.3 Bulimia Nervosa

14.4 Panic Disorder

17 PATIENT COUNSELING INFORMATION

See the . FDA-approved Medication Guide

17.1 General Information

When using fluoxetine and olanzapine in combination, also refer to the Medication Guide for Symbyax.

17.2 Clinical Worsening and Suicide Risk

[see and ]. Box Warning Warnings and Precautions (5.1)

17.3 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

[see ) and )]. Warnings and Precautions (5.2 Drug Interactions (7.3

17.4 Allergic Reactions and Rash

[see ]. Warnings and Precautions (5.3)

17.5 Abnormal Bleeding

[see and ]. Warnings and Precautions (5.7) Drug Interactions (7.6)

17.6 Hyponatremia

[see ]. Warnings and Precautions (5.8)

17.7 Potential for Cognitive and Motor Impairment

[see ]. Warnings and Precautions (5.11)

17.8 Use of Concomitant Medications

17.9 Discontinuation of Treatment

[see ] Warnings and Precautions (5.13)

17.10 Use in Specific Populations

Pregnancy[see Use in Specific Populations (8.1) ]Nursing Mothers

[see ] Use in Specific Populations (8.3) Pediatric Use

[see and Box Warning Warnings and Precautions (5.1) ][see and ] Warnings and Precautions (5.6) Use in Specific Populations (8.4)

^®®


Aurobindo Pharma USA, Inc.




Aurobindo Pharma Limited

Medication Guide

Fluoxetine Capsules, USP



What is the most important information I should know about fluoxetine capsules?



1. Suicidal thoughts or actions:

• in some children, teenagers, or young adults within the Fluoxetine capsules and other antidepressant medicines may increase suicidal thoughts or actions first few months of treatment or when the dose is changed.
• Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.
• Watch for these changes and call your healthcare provider right away if you notice:
  • New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.
  • Pay particular attention to such changes when fluoxetine capsules is started or when the dose is changed.

Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you:

• attempts to commit suicide
• acting on dangerous impulses
• acting aggressive or violent
• thoughts about suicide or dying
• new or worse depression
• new or worse anxiety or panic attacks
• feeling agitated, restless, angry or irritable
• trouble sleeping
• an increase in activity or talking more than what is normal for you
• other unusual changes in behavior or mood

Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Fluoxetine capsulesmay be associated with these serious side effects:

2.  Serotonin Syndrome or Neuroleptic Malignant Syndrome-like reactions. This condition can be life-threatening and may include:

• agitation, hallucinations, coma or other changes in mental status
• coordination problems or muscle twitching (overactive reflexes)
• racing heartbeat, high or low blood pressure
• sweating or fever
• nausea, vomiting, or diarrhea
• muscle rigidity

3.Severe allergic reactions: 

• trouble breathing
• swelling of the face, tongue, eyes or mouth
• rash, itchy welts (hives) or blisters, alone or with fever or joint pain

4.Abnormal bleeding:^®®

5.Seizures or convulsions
 
6.Manic episodes:

• greatly increased energy
• severe trouble sleeping
• racing thoughts
• reckless behavior
• unusually grand ideas
• excessive happiness or irritability
• talking more or faster than usual

7. Changes in appetite or weight.

8. Low salt (sodium) levels in the blood.

• headache
• weakness or feeling unsteady
• confusion, problems concentrating or thinking or memory problems

Do not stop fluoxetine capsuleswithout first talking to your healthcare provider.

• anxiety, irritability, high or low mood, feeling restless or changes in sleep habits
• headache, sweating, nausea, dizziness
• electric shock-like sensations, shaking, confusion

What are fluoxetine capsules?

• Major Depressive Disorder (MDD)
• Obsessive Compulsive Disorder (OCD)
• Bulimia Nervosa*
• Panic Disorder*
• Depressive episodes associated with Bipolar I Disorder, taken with olanzapine (Zyprexa)*

Who should not take fluoxetine capsules?  

• are allergic to fluoxetine hydrochloride or any of the ingredients in fluoxetine capsules. See the end of this Medication Guide for a complete list of ingredients in fluoxetine capsules.
• take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI.
• Do not take an MAOI within 5 weeks of stopping fluoxetine capsules.
• Do not start fluoxetine capsules if you stopped taking an MAOI in the last 2 weeks.

People who take fluoxetine capsules close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:

• high fever
• uncontrolled muscle spasms
• stiff muscles
• rapid changes in heart rate or blood pressure
• confusion
• loss of consciousness (pass out) 

 

• take Mellaril (thioridazine). Do not take Mellaril within 5 weeks of stopping fluoxetine capsules because this can cause serious heart rhythm problems or sudden death. ^{® ®}
• take the antipsychotic medicine pimozide (Orap ) because this can cause serious heart problems. ^®

What should I tell my healthcare provider before taking fluoxetine capsules? Ask if you are not sure.

• Are taking certain drugs or treatments such as:
  • Triptans used to treat migraine headache
  • Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, SSRIs, SNRIs, MAOI’s (including linezolid, an antibiotic), or antipsychotics
  • Tramadol
  • Over-the-counter supplements such as tryptophan or St. John’s Wort
  • Electroconvulsive therapy (ECT)
• have liver problems
• have kidney problems
• have heart problems
• have or had seizures or convulsions
• have bipolar disorder or mania
• have low sodium levels in your blood
• have a history of a stroke
• have high blood pressure
• have or had bleeding problems
• are pregnant or plan to become pregnant. It is not known if fluoxetine capsules will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy.
• are breastfeeding or plan to breastfeed. Some fluoxetine may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking fluoxetine capsules.

Tell your healthcare provider about all the medicines that you take,

• Symbyax
• Sarafem

How should I take fluoxetine capsules?

• Take fluoxetine capsules exactly as prescribed. Your healthcare provider may need to change the dose of fluoxetine capsules until it is the right dose for you.
• Fluoxetine capsules may be taken with or without food.
• 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.
• If you take too much fluoxetine call your healthcare provider or poison control center right away, or get emergency treatment.

What should I avoid while taking fluoxetine capsules?



What are the possible side effects of fluoxetine capsules?  

• See “What is the most important information I should know about fluoxetine capsules?”
• People who have diabetes and take fluoxetine capsules may have problems with low blood sugar while taking fluoxetine capsules. High blood sugar can happen when fluoxetine capsules are stopped. Your healthcare provider may need to change the dose of your diabetes medicines when you start or stop taking fluoxetine capsules. Problems with blood sugar control.
• Feeling anxious or trouble sleeping

• unusual dreams
• sexual problems
• loss of appetite, diarrhea, indigestion, nausea or vomiting, weakness, or dry mouth
• flu symptoms
• feeling tired or fatigued
• change in sleep habits
• yawning
• sinus infection or sore throat
• tremor or shaking
• sweating
• feeling anxious or nervous
• hot flashes
• rash

• increased thirst
• abnormal increase in muscle movement or agitation
• nose bleed
• urinating more often
• heavy menstrual periods
• possible slowed growth rate and weight change. Your child’s height and weight should be monitored during treatment with fluoxetine capsules.

CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088. 

How should I store fluoxetine capsules?

• Store fluoxetine capsules at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [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 fluoxetinecapsules? 





Symbyax and Sarafem are registered trademarks of Eli Lilly and Company. ^{® ®
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This Medication Guide has been approved by the U.S. Food and Drug Administration.


Aurobindo Pharma USA, Inc.




Aurobindo Pharma Limited

FLUOXETINE (FLUOXETINE HYDROCHLORIDE) CAPSULE

Fluoxetine Fluoxetine Hydrochloride CAPSULE Product Information Product Type Human prescription drug label Item Code (Source) NDC:50436-0922(NDC:65862-193) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength FLUOXETINE HYDROCHLORIDE FLUOXETINE 20 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN SILICON DIOXIDE FD&C BLUE NO. 1 FERRIC OXIDE YELLOW titanium dioxide SODIUM LAURYL SULFATE GELATIN FERROSOFERRIC OXIDE SHELLAC Product Characteristics Color Size Imprint Code Shape WHITE (Opaque Off white) 16 mm E;91 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50436-0922-1 30 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078619 2008-01-31