Sprinkleside effects

The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults Hepatotoxicity Orthostatic Hypotension, Falls and Syncope Serotonin Syndrome Increased Risk of Bleeding Severe Skin Reactions Discontinuation Syndrome Activation of Mania/Hypomania Angle-Closure Glaucoma Seizures Increases in Blood Pressure Clinically Important Drug Interactions Hyponatremia Urinary Hesitation and Retention Sexual Dysfunction Most common adverse reactions (≥5% and at least twice the incidence of placebo-treated patients): Adults: nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis Pediatric Patients: nausea, diarrhea, decreased weight To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The stated frequencies of adverse reactions represent the proportion of patients who experienced, at least once, a treatment-emergent adverse reaction of the type listed. Adverse Reactions in Adults The data described below reflect exposure to duloxetine delayed-release capsules in placebo-controlled trials for MDD (N = 3779), GAD (N = 1018), OA (N = 503), CLBP (N = 600), and DPNP (N = 906), and FM (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 FM, respectively. Most patients received doses of a total of 60 to 120 mg per day. The data below do not include results of the trial examining the efficacy of duloxetine delayed-release in patients ≥ 65 years old for the treatment of generalized anxiety disorder; however, the adverse reactions observed in this geriatric sample were generally similar to adverse reactions in the overall adult population. A dverse Reactions Reported as Reasons for Discontinuation of Treatment in Adult Placebo-Controlled Trials Major Depressive Disorder: Approximately 8.4% (319/3779) of the duloxetine delayed-release capsules-treated patients in placebo-controlled adult trials for MDD discontinued treatment due to an adverse reaction, compared with 4.6% (117/2536) of placebo-treated patients. Nausea (duloxetine delayed-release capsules 1.1%, placebo 0.4%) was the only 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 delayed-release capsules-treated patients and at a rate of at least twice that of placebo).

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

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

Fibromyalgia: Approximately 17.5% (227/1294) of the duloxetine delayed-release capsules-treated patients in 3-to 6-month placebo-controlled adult trials for FM discontinued treatment due to an adverse reaction, compared with 10.1% (96/955) for placebo-treated patients. Adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine delayed-release capsules 2.0%, placebo 0.5%), headache (duloxetine delayed-release capsules 1.2%, placebo 0.3%), somnolence (duloxetine delayed-release capsules 1.1%, placebo 0%), and fatigue (duloxetine delayed-release capsules 1.1%, placebo 0.1%). Chronic Pain due to Osteoarthritis: Approximately 15.7% (79/503) of the duloxetine delayed-release capsules-treated patients in 13 week, placebo-controlled adult trials for chronic pain due to OA discontinued treatment due to an adverse reaction, compared with 7.3% (37/508) for placebo-treated patients. Adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine delayed-release capsules 2.2%, placebo 1.0%).

Chronic Low Back Pain: Approximately 16.5% (99/600) of the duloxetine delayed-release capsules-treated patients in 13 week, placebo-controlled adult trials for CLBP discontinued treatment due to an adverse reaction, compared with 6.3% (28/441) for placebo-treated patients. Adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine delayed-release capsules 3.0%, placebo 0.7%), and somnolence (duloxetine delayed-release capsules 1.0%, placebo 0.0%). M ost Common Adverse Reactions (Adults) Diabetic Peripheral Neuropathic Pain: nausea, somnolence, decreased appetite, constipation, hyperhidrosis, and dry mouth.

Fibromyalgia: nausea, dry mouth, constipation, somnolence, decreased appetite, hyperhidrosis, and agitation. Chronic Pain due to Osteoarthritis: nausea, fatigue, constipation, dry mouth, insomnia, somnolence, and dizziness.

Chronic Low Back Pain: nausea, dry mouth, insomnia, somnolence, constipation, dizziness, and fatigue. A dverse Reactions Occurring at an Incidence of 5% or More Among Duloxetine Delayed-Release Capsules Treated Patients in Adult Placebo-Controlled Trials The most commonly observed adverse reactions in duloxetine delayed-release capsule-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. Table 2 displays the incidence of adverse reactions in placebo-controlled trials for approved indications that occurred in 5% or more of patients treated with duloxetine delayed-release capsules and with an incidence greater than placebo-treated patients.

T able 2: Adverse Reactions: Incidence of 5% or More and Greater than Placebo in Placebo-Controlled Trials of Approved Adult Populations a A dverse Reaction P ercentage of Patients Reporting Reaction Duloxetine delayed - release capsules (N = 8100) P lacebo ( N = 5655) Nausea c 23 8 Headache 14 12 Dry mouth 13 5 Somnolence e 10 3 Fatigue b,c 9 5 Insomnia d 9 5 Constipation c 9 4 Dizziness c 9 5 Diarrhea 9 6 Decreased appetite c 7 2 Hyperhidrosis c 6 1 Abdominal pain f 5 4 a Includes adults with MDD, GAD, DPNP, FM, and chronic musculoskeletal pain. The 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 Also includes asthenia. c Events 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. d Also includes initial insomnia, middle insomnia, and early morning awakening. e Also includes hypersomnia and sedation. f Also includes abdominal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness, and gastrointestinal pain. A dverse Reactions in Pooled MDD and GAD Trials in Adults Table 3 displays the incidence of adverse reactions in MDD and GAD placebo-controlled trials for approved indications that occurred in 2% or more of patients treated with duloxetine delayed-release capsules and with an incidence greater than placebo-treated patients.

T able 3: Adverse Reactions: Incidence of 2% or More and Greater than Placebo in MDD and GAD Placebo-Controlled Trials in Adults a,b S y stem Organ Class / Adverse Reaction P ercentage of Patients Reporting Reaction Duloxetine delayed - release capsules (N = 4797) P lacebo ( N = 3303) Cardiac Disorders Palpitations 2 1 E y e Disorders Vision blurred 3 1 G astrointestinal Disorders Nausea c 23 8 Dry mouth 14 6 Constipation c 9 4 Diarrhea 9 6 Abdominal pain d 5 4 Vomiting 4 2 G eneral Disorders and Administration Site Conditions Fatigue e 9 5 M etabolism and Nutrition Disorders Decreased appetite c 6 2 Nervous System Disorders Headache 14 14 Dizziness c 9 5 Somnolence f 9 3 Tremor 3 1 P s ychiatric Disorders Insomnia g 9 5 Agitation h 4 2 Anxiety 3 2 Reproductive System and Breast Disorders Erectile dysfunction 4 1 Ejaculation delayed c 2 1 Libido decreased i 3 1 Orgasm abnormal j 2 <1 Respiratory, Thoracic, and Mediastinal Disorders Yawning 2 <1 S kin and Subcutaneous Tissue Disorders Hyperhidrosis 6 2 a The 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 reactions that were significantly different between treatments in adults ≥65 years that were also not significant in the adults <65 years. c Events 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. d Includes abdominal pain upper, abdominal pain lower, abdominal tenderness, abdominal discomfort, and gastrointestinal pain e Includes asthenia f Includes hypersomnia and sedation g Includes initial insomnia, middle insomnia, and early morning awakening h Includes feeling jittery, nervousness, restlessness, tension and psychomotor hyperactivity i Includes loss of libido j Includes anorgasmia Adverse Reactions in the DPNP, FM, OA, and CLBP Adult Trials: Table 4 displays the incidence of adverse reactions that occurred in 2% or more of duloxetine delayed-release capsules-treated patients (determined prior to rounding) in the premarketing acute phase of DPNP, FM, OA, and CLBP placebo-controlled adult trials and with an incidence greater than placebo-treated patients.

T able 4: Adverse Reactions: Incidence of 2% or More and Greater than Placebo in DPNP, FM, OA, and CLBP Placebo-Controlled Trials in Adults a S y stem Organ Class / Adverse Reaction Percentage of Patients Reporting Reaction Duloxetine delayed-release capsules (N = 3303) Placebo (N = 2352) G astrointestinal Disorders Nausea Dry Mouth b Constipation b Diarrhea Abdominal Pain c Vomiting Dyspepsia 23 11 10 9 5 3 2 7 3 3 5 4 2 1 G eneral Disorders and Administration Site Conditions Fatigue d 11 5 Infections and Infestations Nasopharyngitis Upper Respiratory Tract Infection Influenza 4 3 2 4 3 2 M etabolism and Nutrition Disorders Decreased Appetite b 8 1 M usculoskeletal and Connective Tissue Musculoskeletal Pain e Muscle Spasms 3 2 3 2 Nervous System Disorders Headache Somnolence b,f Dizziness Paraesthesia g Tremor b 13 11 9 2 2 8 3 5 2 <1 P s ychiatric Disorders Insomnia b,h Agitation i 10 3 5 1 Reproductive System and Breast Disorders Erectile Dysfunction b Ejaculation Disorder j 4 2 <1 <1 Respiratory, Thoracic, and Mediastinal Disorders Cough 2 2 S kin and Subcutaneous Tissue Disorders Hyperhidrosis 6 1 V ascular Disorders Flushing k Blood pressure increased l 3 2 1 1 a The 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 Incidence of 120 mg/day is significantly greater than the incidence for 60 mg/day. c Includes abdominal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness and gastrointestinal pain d Includes asthenia e Includes myalgia and neck pain f Includes hypersomnia and sedation g Includes hypoaesthesia, hypoaesthesia facial, genital hypoaesthesia and paraesthesia oral h Includes initial insomnia, middle insomnia, and early morning awakening. i Includes feeling jittery, nervousness, restlessness, tension and psychomotor hyperactivity j Includes ejaculation failure k Includes hot flush l 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 E ff ects on Male and Female Sexual Function in Adults with MDD 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 adult trials. The ASEX scale includes five questions that pertain to the following aspects of sexual function: 1) sex drive, 2) ease of arousal, 3) ability to achieve erection (men) or lubrication (women), 4) ease of reaching orgasm, and 5) orgasm satisfaction. Positive numbers signify a worsening of sexual function from baseline. Negative numbers signify an improvement from baseline level of sexual dysfunction from baseline, which is commonly seen in depressed patients. In these trials, male patients treated with duloxetine delayed-release capsules experienced significantly more sexual dysfunction, as measured by the total score on the ASEX and the ability to reach orgasm, than did placebo-treated male patients (see Table 5). Female patients treated with duloxetine delayed-release capsules did not experience more sexual dysfunction than on placebo-treated female patients as measured by ASEX total score. Healthcare providers should routinely inquire about possible sexual adverse reactions in patients treated with duloxetine delayed-release capsules.

T able 5: Mean Change in ASEX Scores by Gender in MDD Placebo-Controlled Adult Trials Male Patients a Female Patients a Duloxetine delayed - release capsules (n = 175) Placebo (n = 83) Duloxetine delayed - release capsules (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 satisfaction 0.56 b -0.07 0.01 0.03 0.40 c 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 a n = Number of patients with non-missing change score for ASEX total b p = 0.013 versus placebo c p<0.001 versus placebo V ital Sign Changes in Adults In placebo-controlled clinical trials across approved adult populations for change from baseline to endpoint, duloxetine delayed-release capsules-treated patients had mean increases of 0.23 mm Hg in systolic blood pressure (SBP) and 0.73 mm Hg in diastolic blood pressure (DBP) compared to mean decreases of 1.09 mm Hg SBP and 0.55 mm Hg in DBP placebo-treated patients. There was no significant difference in the frequency of sustained (3 consecutive visits) elevated blood pressure. Duloxetine delayed-release capsules treatment, for up to 26 weeks in placebo-controlled trials across approved adult populations, 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 delayed-release capsules-treated patients, decrease of 0.17 beats per minute in placebo-treated patients). Laboratory Changes in Adults Duloxetine delayed-release capsules treatment in placebo-controlled clinical trials across approved adult populations, 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 delayed-release capsules-treated patients when compared with placebo-treated patients. High bicarbonate, cholesterol, and abnormal (high or low) potassium, were observed more frequently in duloxetine delayed-release capsules treated patients compared to placebo-treated patients. Ot her Adverse Reactions Observed During the Premarketing and Postmarketing Clinical Trial Evaluation of Duloxetine Delayed-Release Capsules in Adults Following is a list of adverse reactions reported by patients treated with duloxetine delayed-release capsules in clinical trials. In clinical trials of all approved adult populations, 34,756 patients were treated with duloxetine delayed-release capsules. Of these, 26.9% took duloxetine delayed-release capsules for at least 6 months, and 12% for at least one year. The following listing is not intended to include reactions already listed in previous tables or elsewhere in labeling, for which a drug cause was remote, which were so general as to be uninformative, which were not considered to have significant clinical implications, or 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, tachycardia, and Takotsubo cardiomyopathy. 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 paraesthesia/hypoesthesia;

Infrequent: disturbance in attention, dyskinesia, myoclonus, and poor quality sleep;

R are: 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: pruritus;

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. A dverse Reactions Observed in Placebo-Controlled Clinical Trials in Pediatric Patients The data described below reflect exposure to duloxetine delayed-release capsules in pediatric, 10 week, placebo-controlled trials for MDD (N = 341) and GAD (N = 135). The population studied (N = 476) was 7 to 17 years of age with 42.4% children age 7 to 11 years of age, 50.6% female, and 68.6% white. Patients received 30 to 120 mg per day during placebo-controlled acute treatment studies. Additional data come from the overall total of 822 pediatric patients (age 7 to 17 years of age) with 41.7% children age 7 to 11 years of age and 51.8% female exposed to duloxetine delayed-release capsules in MDD and GAD clinical trials up to 36 weeks in length, in which most patients received 30 to 120 mg per day. The safety and effectiveness of DRIZALMA SPRINKLE have not been established in pediatric patients with major depressive disorder (MDD), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain. Pediatric Clinical Trial Database The adverse drug reaction profile observed in pediatric clinical trials in pediatric patients aged 7 to 17 years old 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. The most common (≥5% and twice placebo) adverse reactions observed in pediatric clinical trials include: nausea, diarrhea, decreased weight, and dizziness. Adverse Reactions in Pediatric Patients Aged 7 to 17 Years Old with MDD and GAD Table 6 provides the incidence of adverse reactions in MDD and GAD pediatric placebo- controlled trials that occurred in greater than 2% of patients treated with duloxetine delayed-release capsules and with an incidence greater than placebo. DRIZALMA SPRINKLE is not approved for the treatment of MDD in pediatric patients T able 6: Adverse Reactions: Incidence of 2% or More and Greater than Placebo in three 10 week Pediatric Placebo-Controlled Trialsin MDD a and GAD b System Organ Class/Adverse Reaction Percentage of Pediatric Patients Reporting Reaction Duloxetine delayed - release capsules (N = 476) Placebo (N = 362) Gastrointestinal Disorders Nausea Abdominal Pain c Vomiting Diarrhea Dry Mouth 18 13 9 6 2 8 10 4 3 1 General Disorders and Administration Site Conditions Fatigue d 7 5 Investigations Decreased Weight e 14 6 Metabolism and Nutrition Disorders Decreased Appetite 10 5 Nervous System Disorders Headache Somnolence f Dizziness 18 11 8 13 6 4 Psychiatric Disorders Insomnia g 7 4 Respiratory, Thoracic, and Mediastinal Disorders Oropharyngeal Pain Cough 4 3 2 1 a DRIZALMA SPRINKLE is not approved for the treatment of pediatric MDD. b The 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. c Also includes abdominal pain upper, abdominal pain lower, abdominal tenderness, abdominal discomfort, and gastrointestinal pain. d Also includes asthenia. e Frequency based on weight measurement meeting potentially clinically significant threshold of ≥3.5% weight loss (N = 467 duloxetine delayed-release capsules; N = 354 Placebo). f Also includes hypersomnia and sedation. g Also includes initial insomnia, insomnia, middle insomnia, and terminal insomnia. Other adverse reactions that occurred at an incidence of less than 2% and were reported by more duloxetine delayed-release capsules treated patients than placebo treated patients in pediatric MDD and GAD clinical trials included abnormal dreams (including nightmare), anxiety, flushing (including hot flush), hyperhidrosis, palpitations, pulse increased, and tremor (DRIZALMA SPRINKLE is not approved for the treatment of pediatric MDD). The most commonly reported symptoms following discontinuation of duloxetine delayed-release capsules in pediatric clinical trials have included headache, dizziness, insomnia, and abdominal pain. Gr owth (Height and Weight) in Pediatric Patients 7 to 17 Years Old with GAD and MDD Decreased appetite and weight loss have been observed in association with the use of SSRIs and SNRIs. Pediatric patients treated with duloxetine delayed-release capsules in clinical trials experienced a 0.1kg mean decrease in weight at 10 weeks, compared with a mean weight gain of approximately 0.9 kg in placebo-treated patients. The proportion of patients who experienced a clinically significant decrease in weight (≥3.5%) was greater in the duloxetine delayed-release capsules group than in the placebo group (16% and 6%, respectively). Subsequently, over the 4- to 6-month uncontrolled extension periods, duloxetine delayed-release capsules-treated patients on average trended toward recovery to their expected baseline weight percentile based on population data from age- and sex-matched peers. In studies up to 9 months, duloxetine delayed-release capsules-treated pediatric patients experienced an increase in height of 1.7 cm on average (2.2 cm increase in patients [7 to 11 years of age] and 1.3 cm increase in patients [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 patients [7 to 11 years of age] and increase of 0.3% in patients [12 to 17 years of age]). Weight and height should be monitored regularly in pediatric patients treated with DRIZALMA SPRINKLE. Additional pediatric use information is approved for Eli Lilly and Company, Inc.’s CYMBALTA (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 Postmarketing

Experience The following adverse reactions have been identified during post approval use of duloxetine delayed-release capsules. 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 delayed-release capsules therapy and not mentioned elsewhere in labeling include: acute pancreatitis, 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.