duloxetine (duloxetine 20 mg delayed release oral capsule) Dailymed

6 Adverse Reactions

• Most common adverse reactions (≥5% and at least twice the incidence of placebo patients): nausea, dry mouth,somnolence, constipation, decreased appetite, and hyperhidrosis (6.3).

To report SUSPECTED ADVERSE REACTIONS, contact SETON PHARMACEUTICALS at 1-800-510-3401 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

The following serious adverse reactions are described below and elsewhere in the labeling:

• Suicidal Thoughts and Behaviors in Children, Adolescents and Young Adults [see Boxed Warning and Warnings and Precautions (5.1)]
• Hepatotoxicity [see Warnings and Precautions (5.2)]
• Orthostatic Hypotension, Falls and Syncope [see Warnings and Precautions (5.3)]
• Serotonin Syndrome [see Warnings and Precautions (5.4)]
• Abnormal Bleeding [see Warnings and Precautions (5.5)]
• Severe Skin Reactions [see Warnings and Precautions (5.6)]
• Discontinuation of Treatment with duloxetine [see Warnings and Precautions (5.7)]
• Activation of Mania/Hypomania [see Warnings and Precautions (5.8)]
• Angle-Closure Glaucoma [see Warnings and Precautions (5.9)]
• Seizures [see Warnings and Precautions (5.10)]
• Effect on Blood Pressure [see Warnings and Precautions (5.11)]
• Clinically Important Drug Interactions [see Warnings and Precautions (5.12)]
• Hyponatremia [see Warnings and Precautions (5.13)]
• Urinary Hesitation and Retention [see Warnings and Precautions (5.15)]

6.1 Clinical Trial Data Sources

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 the rates observed in practice.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type uled. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Reactions reported during the studies were not necessarily caused by the therapy, and the frequencies do not reflect investigator impression (assessment) of causality.

Adults - The data described below reflect exposure to duloxetine in placebo-controlled trials for MDD (N=3779), GAD (N=1018), OA (N=503), CLBP (N=600), DPNP (N=906), and another indication (N=1294). The population studied was 17 to 89 years of age; 65.7%, 60.8%, 60.6%, 42.9%, and 94.4% female; and 81.8%, 72.6%, 85.3 %, 74.0%, and 85.7% Caucasian for MDD, GAD, OA and CLBP, DPNP, and another indication  respectively. Most patients received doses of a total of 60 to 120 mg per day [see Clinical Studies (14)].

Information describing two additional clinical studies in which efficacy was not demonstrated in patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.'s Duloxetine Delayed-release Capsules. Other pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.'s Duloxetine Delayed-release Capsules. However, due to Eli Lilly and Company, Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

6.2 Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Adult Placebo-Controlled Trials

Major Depressive Disorder — Approximately 8.4% (319/3779) of the patients who received duloxetine in placebo-controlled trials for MDD discontinued treatment due to an adverse reaction, compared with 4.6% (117/2536) of the patients receiving placebo. Nausea (duloxetine 1.1%, placebo 0.4%) was the only common adverse reaction reported as a reason for discontinuation and considered to be drug-related (i.e., discontinuation occurring in at least 1% of the duloxetine -treated patients and at a rate of at least twice that of placebo).

Generalized Anxiety Disorder — Approximately 13.7% (139/1018) of the patients who received duloxetine in placebo-controlled trials for GAD discontinued treatment due to an adverse reaction, compared with 5.0% (38/767) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 3.3%, placebo 0.4%), and dizziness (duloxetine 1.3%, placebo 0.4%).

Diabetic Peripheral Neuropathic Pain — Approximately 12.9% (117/906) of the patients who received duloxetine in placebo-controlled trials for DPNP discontinued treatment due to an adverse reaction, compared with 5.1% (23/448) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 3.5%, placebo 0.7%), dizziness (duloxetine 1.2%, placebo 0.4%), and somnolence (duloxetine 1.1%, placebo 0.0%). 

Chronic Pain due to Osteoarthritis — Approximately 15.7% (79/503) of the patients who received duloxetine in 13-week, placebo-controlled trials for chronic pain due to OA discontinued treatment due to an adverse reaction, compared with 7.3% (37/508) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 2.2%, placebo 1.0%).

Chronic Low Back Pain — Approximately 16.5% (99/600) of the patients who received duloxetine in 13-week, placebo-controlled trials for CLBP discontinued treatment due to an adverse reaction, compared with 6.3% (28/441) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 3.0%, placebo 0.7%), and somnolence (duloxetine 1.0%, placebo 0.0%).

6.3 Most Common AdultAdverse Reactions

Pooled Trials for all Approved Indications — The most commonly observed adverse reactions in duloxetine-treated patients (incidence of at least 5% and at least twice the incidence in placebo patients) were nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis.

Diabetic Peripheral Neuropathic Pain — The most commonly observed adverse reactions in duloxetine-treated patients (as defined above) were nausea, somnolence, decreased appetite, constipation, hyperhidrosis, and dry mouth.

Chronic Pain due to Osteoarthritis — The most commonly observed adverse reactions in duloxetine-treated patients (as defined above) were nausea, fatigue, constipation, dry mouth, insomnia, somnolence and dizziness.

Chronic Low Back Pain — The most commonly observed adverse reactions in duloxetine-treated patients (as defined above) were nausea, dry mouth, insomnia, somnolence, constipation, dizziness, and fatigue.

6.4 Adverse Reactions Occurring at an Incidence of 5% or More AmongDuloxetine -Treated Patients in Adult Placebo-Controlled Trials

Table 2 gives the incidence of treatment-emergent adverse reactions in placebo-controlled trials for approved indications that occurred in 5% or more of patients treated with duloxetine and with an incidence greater than placebo.

Table 2: Treatment-Emergent Adverse Reactions: Incidence of 5% or More and Greater than Placebo in Placebo-Controlled Trials of Approved Indications^a

a T h e i n c l u s i o n o f a n e v e n t i n t h e t a b l e i s d e t e r m i n e d b a s e d o n t h e p e r c e n t a g e s b e f o r e r o u n d i n g ; h o w e v e r , t h e p e r c e n t a g e s d i s p l a y e d i n t h e
t a b l e a r e r o u n d e d t o t h e n e a r e s t i n t e g e r .
b A l s o i n c l u d e s a s t h e n i a
c E v e n t s f o r w h i c h t h e r e w a s a s i g n i f i c a n t d o s e - d e p e n d e n t r e l a t i o n s h i p i n f i x e d - d o s e s t u d i e s , e x c l u d i n g t h r e e M D D
s t u d i e s w h i c h d i d n o t h a v e a p l a c e b o l e a d - i n p e r i o d o r d o s e t i t r a t i o n .
d A l s o i n c l u d e s i n i t i a l i n s o m n i a , m i d d l e i n s o m n i a a n d e a r l y m o r n i n g a w a k e n i n g .
e A l s o i n c l u d e s h y p e r s o m n i a a n d s e d a t i o n .
f A l s o i n c l u d e s a b d o m i n a l d i s c o m f o r t , a b d o m i n a l p a i n l o w e r , a b d o m i n a l p a i n u p p e r , a b d o m i n a l t e n d e r n e s s , a n d
g a s t r o i n t e s t i n a l p a i n .
Adverse  Reaction		Percentage  of  Patients  Reporting  Reaction
		Duloxetine  ( N = 8100 )Â	Placebo   ( N = 5655 )Â
Nauseac		23	8Â
HeadacheÂ		14Â	12
Dry mouthÂ		13Â	5
Somnolencee		10	3
Fatigueb , c		9	5Â
Insomniad		9	5Â
Constipationc		9	4Â
Dizzinessc		9	5Â
DiarrheaÂ		9Â	6
Decreased appetitec		7Â	2Â
Hyperhidrosisc		6	1Â
Abdominal painf		5	4

6.5 Adverse Reactions Occurring at an Incidence of 2% or More AmongDuloxetine -Treated Patients in Adult Placebo-Controlled Trials

Pooled MDD and GAD Trials — Table 3 gives the incidence of treatment-emergent adverse reactions in MDD and GAD placebo-controlled trials for approved indications that occurred in 2% or more of patients treated with duloxetine and with an incidence greater than placebo.

Table 3: Treatment-Emergent Adverse Reactions: Incidence of 2% or More and Greater than Placebo in MDD and GAD Placebo-Controlled Trialsa,b

aThe inclusion of an event in the table is determined based on the percentages before rounding; however, the percentages displayed in the table are rounded to the nearest integer.
b For GAD, there were no adverse events that were significantly different between treatments in adults ≥65 years that were also not significant in the adults <65 years.
cEvents for which there was a significant dose-dependent relationship in fixed-dose studies, excluding three MDD studies which did not have a placebo lead-in period or dose titration.
dAlso includes abdominal pain upper, abdominal pain lower, abdominal tenderness, abdominal discomfort, and gastrointestinal pain
eAlso includes asthenia
fAlso includes hypersomnia and sedation
gAlso includes initial insomnia, middle insomnia, and early morning awakening
hAlso includes feeling jittery, nervousness, restlessness, tension, and psychomotor hyperactivity
iAlso includes loss of libido
j Also includes anorgasmia
System  Organ  Class  /  Adverse  Reaction		Percentage  of  Patients  Reporting  Reaction
		Duloxetine  ( N = 4797 )	Placebo   ( N = 3303 )
Cardiac  Disorders  Palpitations		2	1
Eye  Disorders  Vision blurred		3	1
Gastrointestinal  Disorders  Nauseac Dry mouth ConstipationcDiarrhea Abdominal paind Vomiting		23149954	864642
General  Disorders  and  Administration  Site  Conditions  Fatiguee		9	5
Metabolism  and  Nutrition  Disorders  Decreased appetitec		6	2
Nervous  System  Disorders  HeadacheDizzinessc Somnolencef Tremor		14993	14531
Psychiatric  Disorders  Insomniag Agitationh Anxiety		943	522
Reproductive  System  and  Breast  Disorders Erectile dysfunctionEjaculation delayedcLibido decreasedi Orgasm abnormalj		4232	 111 <1
Respiratory ,  Thoracic ,  and  Mediastinal  Disorders  Yawning		2	<1
Skin  and  Subcutaneous  Tissue  Disorders Hyperhidrosis		6	2

DPNP, another indication, OA, and CLBP— Table 4 gives the incidence of treatment-emergent adverse events that occurred in 2% or more of patients treated with duloxetine (determined prior to rounding) in the premarketing acute phase of DPNP, another indication, OA and CLBP placebo-controlled trials and with an incidence greater than placebo.

Table 4: Treatment-Emergent Adverse Reactions: Incidence of 2% or More and Greater than Placebo in DPNP, another indication, OA and CLBPPlacebo-Controlled Trials^a

aThe inclusion of an event in the table is determined based on the percentages before rounding; however, the percentages displayed in the table are rounded to the nearest integer.
bIncidence of 120 mg/day is significantly greater than the incidence for 60 mg/day.
cAlso includes abdominal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness and gastrointestinal pain
dAlso includes asthenia
eAlso includes myalgia and neck pain
fAlso includes hypersomnia and sedation
gAlso includes hypoaesthesia, hypoaesthesia facial, genial hypoaesthesia and paraesthesia oral
hAlso includes initial insomnia , and middle insomnia, early morning awakening .
iAlso includes feeling jittery, nervousness, restlessness, tension and psychomotor hyperactivity
jAlso includes ejaculation failure
kAlso includes hot flush
lAlso includes blood pressure diastolic increased, blood pressure systolic increased, diastolic hypertension, essential hypertension, hypertension, hypertensive crisis, labile hypertension, orthostatic hypertension, secondary hypertension, and systolic hypertension.
System  Organ  Class  /	Adverse  Reaction	Percentage  of  Patients  Reporting	  Reaction
		Duloxetine  ( N = 3303 )	Placebo ( N = 2352 )
Gastrointestinal  Disorders NauseaDry mouthb Constipationb DiarrheaAbdominal Painc VomitingDyspepsia		2311109532	7335421
General  Disorders  and  Administration  Site  Conditions Fatigued		11	5
Infections  and  Infestations  NasopharyngitisUpper Respiratory Tract InfectionInfluenza		432	432
Metabolism  and  Nutrition  Disorders  Decreased Appetiteb		8	1
Musculoskeletal  and  Connective  Tissue  Musculoskeletal Paine Muscle Spasms		32	32
Nervous  System  Disorders  HeadacheSomnolenceb , fDizzinessParaesthesiag Tremorb		1311922	8352<1
Psychiatric  Disorders  Insomniab , hAgitationl		103	51
Reproductive  System  and  Breast  Disorders  Erectile Dysfunctionb Ejaculation Disorderj		42	<1<1
Respiratory ,  Thoracic ,  and  Mediastinal  Disorders  Cough		2	2Â
Skin  and  Subcutaneous  Tissue  Disorders  HyperhidrosisÂ		6Â	1
Vascular  Disorders Flushingk  Blood pressure increased l		32	11

6.6 Effects on Male and Female Sexual Function in Adults

Changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of psychiatric disorders or diabetes, but they may also be a consequence of pharmacologic treatment. Because adverse sexual reactions are presumed to be voluntarily underreported, the Arizona Sexual Experience Scale (ASEX), a validated measure designed to identify sexual side effects, was used prospectively in 4 MDD placebo-controlled trials. In these trials, as shown in Table 5 below, patients treated with duloxetine experienced significantly more sexual dysfunction, as measured by the total score on the ASEX, than did patients treated with placebo. Gender analysis showed that this difference occurred only in males. Males treated with duloxetine experienced more difficulty with ability to reach orgasm (ASEX Item 4) than males treated with placebo. Females did not experience more sexual dysfunction on duloxetine than on placebo as measured by ASEX total score. Negative numbers signify an improvement from a baseline level of dysfunction, which is commonly seen in depressed patients. Physicians should routinely inquire about possible sexual side effects.

Table 5: Mean Change in ASEX Scores by Gender in MDD Placebo-Controlled Trials

an=Number of patients with non-missing change score for ASEX total
bp=0.013 versus placebo
cp<0.001 versus placebo
	Male  Patientsa		Female  Patientsa
	Duloxetine  ( n = 175 )	Placebo  ( n = 83 )	Duloxetine  ( n = 241 )	Placebo  ( n = 126 )
 ASEX Total (Items 1-5) Item 1 — Sex drive Item 2 — Arousal Item 3 — Ability to achieve erection (men); Lubrication (women) Item 4 — Ease of reaching orgasm Item 5 — Orgasm satisfactionÂ	0.56b -0.070.010.03 0.40c 0.09	-1.07-0.12-0.26-0.25 -0.24-0.13	-1.15-0.32-0.21 -0.17 -0.09-0.11	-1.07-0.24-0.18-0.18 -0.13-0.17

6.7 Vital Sign Changes in Adults

In placebo-controlled clinical trials across approved indications for change from baseline to endpoint, duloxetine treatment was

associated with mean increases of 0.23 mm Hg in systolic blood pressure and 0.73 mm Hg in diastolic blood pressure compared to mean

decreases of 1.09 mm Hg systolic and 0.55 mm Hg diastolic in placebo-treated patients. There was no significant difference in the frequency of

sustained (3 consecutive visits) elevated blood pressure [see Warnings and Precautions (5.3, 5.11)].

Duloxetine treatment, for up to 26 weeks in placebo-controlled trials across approved indications, typically caused a small increase in

heart rate for change from baseline to endpoint compared to placebo of up to 1.37 beats per minute (increase of 1.20 beats per minute in

duloxetine - treated patients, decreased of 0.17 beats per minute in placebo-treated patients).

6.8 Laboratory Changes in Adults

Duloxetine treatment in placebo-controlled clinical trials across approved indications was associated with small mean increases from baseline to endpoint in ALT, AST, CPK, and alkaline phosphatase; infrequent, modest, transient, abnormal values were observed for these analytes in duloxetine -treated patients when compared with placebo-treated patients [see Warnings and Precautions (5.2)]. High bicarbonate, cholesterol, and abnormal (high or low) potassium, were observed more frequently in duloxetine-treated patients compared to placebo.

6.9 Electrocardiogram Changes in Adults

The effect of duloxetine 160 mg and 200 mg administered twice daily to steady state was evaluated in a randomized, double-blinded, two-way crossover study in 117 healthy female subjects. No QT interval prolongation was detected. Duloxetine appears to be associated with concentration-dependent but not clinically meaningful QT shortening.

6.10 Other Adverse Reactions Observed During the Premarketing and Postmarketing

Clinical Trial Evaluation of Duloxetine in Adults

Following is a ul of treatment-emergent adverse reactions reported by patients treated with duloxetine in clinical trials. In clinical trials of all indications, 34,756 patients were treated with duloxetine. Of these, 26.9% (9337) took duloxetine for at least 6 months, and 12.4% (4317) for at least one year. The following uling is not intended to include reactions (1) already uled 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 categorized by body system according to 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 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients.

Cardiac Disorders — Frequent: palpitations; Infrequent: myocardial infarction and tachycardia.

Ear and Labyrinth Disorders — Frequent: vertigo; Infrequent: ear pain and tinnitus.

Endocrine Disorders — Infrequent: hypothyroidism.

Eye Disorders — Frequent: vision blurred; Infrequent: diplopia, dry eye, and visual impairment.

Gastrointestinal Disorders — Frequent: flatulence; Infrequent: dysphagia, eructation, gastritis, gastrointestinal hemorrhage, halitosis, and stomatitis; Rare: gastric ulcer.

General Disorders and Administration Site Conditions — Frequent: chills/rigors; Infrequent: falls,feeling abnormal, feeling hot and/or cold, malaise, and thirst; Rare: gait disturbance.

Infections and Infestations — Infrequent: gastroenteritis and laryngitis.

Investigations — Frequent: weight increased, weight decreased; Infrequent: blood cholesterol increased.

Metabolism and Nutrition Disorders — Infrequent: dehydration and hyperlipidemia; Rare: dyslipidemia.

Musculoskeletal and Connective Tissue Disorders — Frequent: musculoskeletal pain; Infrequent: muscle tightness and muscle twitching.

Nervous System Disorders — Frequent: dysgeusia, lethargy, and parasthesia/hypoesthesia; Infrequent: disturbance in attention, dyskinesia, myoclonus, and poor quality sleep; Rare: dysarthria.

Psychiatric Disorders — Frequent: abnormal dreams and sleep disorder; Infrequent: apathy, bruxism, disorientation/confusional state, irritability, mood swings, and suicide attempt; Rare: completed suicide.

Renal and Urinary Disorders — Frequent: urinary frequency; Infrequent: dysuria, micturition urgency, nocturia, polyuria, and urine odor abnormal.

Reproductive System and Breast Disorders — Frequent: anorgasmia/orgasm abnormal; Infrequent: menopausal symptoms, sexual dysfunction, and testicular pain; Rare: menstrual disorder.

Respiratory, Thoracic and Mediastinal Disorders — Frequent: yawning, oropharyngeal pain; Infrequent: throat tightness.

Skin and Subcutaneous Tissue Disorders — Frequent: pruritis; Infrequent: cold sweat, dermatitis contact, erythema, increased tendency to bruise, night sweats, and photosensitivity reaction; Rare: ecchymosis.

Vascular Disorders — Frequent: hot flush; Infrequent: flushing, orthostatic hypotension, and peripheral coldness.

6.11 Adverse Reactions Observed in Children and Adolescent Placebo-Controlled Clinical Trials

The adverse drug reaction profile observed in pediatric clinical trials (children and adolescents) was consistent with the adverse drug reaction profile observed in adult clinical trials. The specific adverse drug reactions observed in adult patients can be expected to be observed in pediatric patients (children and adolescents) [see Adverse Reactions (6.5)]. The most common (≥5% and twice placebo) adverse reactions observed in pediatric clinical trials include: nausea, diarrhea, decreased weight, and dizziness.

Table 6 provides the incidence of treatment-emergent adverse reactions in pediatric placebo- controlled trials that occurred in greater than 2% of patients treated with duloxetine and with an incidence greater than placebo.

Table 6: Treatment-Emergent Adverse Reactions: Incidence of 2% or More and Greater than Placebo in three 10 week Pediatric Placebo-Controlled Trials^a

aThe inclusion of an event in the table is determined based on the percentages before rounding; however, the
percentages displayed in the table are rounded to the nearest integer.
bAlso includes abdominal pain upper, abdominal pain lower, abdominal tenderness, abdominal discomfort,
and gastrointestinal pain.
cAlso includes asthenia.
dFrequency based on weight measurement meeting potentially clinically significant threshold of ≥3.5%
weight loss(N=467 duloxetine; N=354 Placebo).
eAlso includes hypersomnia and sedation.
fAlso includes initial insomnia, insomnia, middle insomnia, and terminal insomnia.
$EndTableFooter
$FootNote
$EndFootNote
System Organ Class / Adverse Reaction		Percentage of Pediatric Patients Reporting Reaction
		Duloxetine ( N = 476 )	Placebo ( N = 362 )
Gastrointestinal Disorders Nausea Abdominal Painb VomitingDiarrheaDry Mouth		18 13 9 6 2	8 10 4 3 1
General Disorders and Administration Site Conditions Fatiguec		7	5
Investigations Decreased Weightd		14	6
Metabolism and Nutrition Disorders Decreased Appetite		10	5
Nervous System Disorders HeadacheSomnolencee Dizziness		18 11 8	1364
Psychiatric Disorders Insomniaf		7	4
Respiratory , Thoracic , and Mediastinal Disorders Oropharyngeal Pain Cough		43	21

Other adverse reactions that occurred at an incidence of less than 2% but were reported by more duloxetine treated patients than placebo treated patients and are associated duloxetine treatment: abnormal dreams (including nightmare), anxiety, flushing (including hot flush), hyperhidrosis, palpitations, pulse increased, and tremor.

Discontinuation-emergent symptoms have been reported when stopping duloxetine. The most commonly reported symptoms following discontinuation of duloxetine in pediatric clinical trials have included headache, dizziness, insomnia, and abdominal pain [see Warnings and Precautions (5.7) and Adverse Reactions (6.2)].

Growth (Height and Weight) — Decreased appetite and weight loss have been observed in association with the use of SSRIs and SNRIs. In studies up to 9 months, duloxetine -treated pediatric patients experienced an increase in height of 1.7 cm on average (2.2 cm increase in children [7 to 11 years of age] and 1.3 cm increase in adolescents [12 to 17 years of age]). While height increase was observed during these studies, a mean decrease of 1% in height percentile was observed (decrease of 2% in children [7 to 11 years of age] and increase of 0.3% in adolescents [12 to 17 years of age]). Weight and height should be monitored regularly in children and adolescents treated with duloxetine.

Information describing two additional clinical studies in which efficacy was not demonstrated in patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.'s Duloxetine Delayed-release Capsules. Other pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.'s Duloxetine Delayed-release Capsules. However, due to Eli Lilly and Company, Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

6.12 Postmarketing Spontaneous Reports

The following adverse reactions have been identified during post approval use of duloxetine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported since market introduction that were temporally related to duloxetine therapy and not mentioned elsewhere in labeling include: anaphylactic reaction, aggression and anger (particularly early in treatment or after treatment discontinuation), angioneurotic edema, angle-closure glaucoma,colitis (microscopic or unspecified), cutaneous vasculitis (sometimes associated with systemic involvement), extrapyramidal disorder, galactorrhea, gynecological bleeding, hallucinations, hyperglycemia, hyperprolactinemia, hypersensitivity, hypertensive crisis, muscle spasm, rash, restless legs syndrome, seizures upon treatment discontinuation, supraventricular arrhythmia, tinnitus (upon treatment discontinuation), trismus, and urticaria.