HIGHLIGHTS OF PRESCRIBING INFORMATION • Use of …

1 1 HIGHLIGHTS OF PRESCRIBING INFORMATIONT hese HIGHLIGHTS do not include all the INFORMATION needed to use CYMBALTA safely and effectively. See full PRESCRIBING INFORMATION for (Duloxetine Delayed-Release Capsules) for Oral Approval: 2004 WARNING: SUICIDALTHOUGHTSAND BEHAVIORSSee full PRESCRIBING INFORMATION for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants ( ) Monitor for worsening and emergence of suicidal thoughts and behaviors ( )---------------------------RECENT MAJOR AND USAGE---------------------------CYMBALTA is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for.

2 Major Depressive Disorder (MDD) (1) Generalized Anxiety Disorder (GAD) (1) Diabetic Peripheral Neuropathic Pain (DPNP) (1) Fibromyalgia (FM) (1) Chronic Musculoskeletal Pain (1)------------------------DOSAGE AND ADMINISTRATION----------------------- Take CYMBALTA once daily, with or without food. Swallow CYMBALTA whole; do not crush or chew, do not open capsule. Take a missed dose as soon as it is remembered. Do not take two doses of CYMBALTA at the same time.(2)IndicationStarting DoseTarget DoseMaximum DoseMDD ( )40 mg/day to 60 mg/dayAcute Treatment: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or as 30 mg twice daily); Maintenance Treatment: 60 mg/day120 mg/dayGAD ( )Adults60 mg/day 60 mg/day (once daily)120 mg/dayElderly30 mg/day60 mg/day (once daily)120 mg/dayChildren and Adolescents (7 to 17 years of age)30 mg/day30 to 60 mg/day (once daily)120 mg/dayDPNP ( )60 mg/day60 mg/day (once daily)60 mg/dayFM ( )30 mg/day60 mg/day (once daily)60 mg/dayChronic Musculoskeletal Pain ( )30 mg/day60 mg/day (once daily)60 mg/day Some patients may benefit from starting at 30 mg once daily(2) There is no evidence that doses greater than 60 mg/day confers additional benefit, while some adverse reactions were observed to be dose-dependent(2) Discontinuing CYMBALTA.

3 Gradually reduce dosageto avoid discontinuation symptoms ( , ) Hepatic Impairment: Avoid use in patients with chronic liver disease or cirrhosis( ) Renal Impairment: Avoid use in patients with severe renal impairment, GFR <30 mL/min( )----------------------DOSAGE FORMS AND STRENGTHS---------------------20 mg, 30 mg, and 60 mg delayed-releasecapsules (3)-------------------------------CONTRA INDICATIONS----------------------------- - Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorderswith CYMBALTAor within 5 days of stopping treatment with CYMBALTA. Do not use CYMBALTA within 14 days of stopping an MAOI intended to treatpsychiatric disorders.

4 In addition, do not start CYMBALTAin a patient who is being treated with linezolid or intravenous methyleneblue (4)------------------------WARNINGS AND PRECAUTIONS----------------------- Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported in patients treated with CYMBALTA. CYMBALTA should be discontinued in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established. CYMBALTA should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease ( ) Orthostatic Hypotension, Fallsand Syncope: Cases have been reported with CYMBALTA therapy ( ) Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including with CYMBALTA, both when taken alone, but especially when co-administered with other serotonergic agents(including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines,and St.)

5 John s Wort). If such symptoms occur, discontinueCYMBALTAand initiate supportive treatment. If concomitant use of CYMBALTA with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases( ) Abnormal Bleeding: CYMBALTAmay increase the risk of bleeding events. Patients should be cautioned about the risk of bleeding associated with the concomitant use of CYMBALTAand NSAIDs, aspirin, or other drugs that affect coagulation ( , ) Severe Skin Reactions: Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS), can occur with CYMBALTA.

6 CYMBALTA should be discontinued at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified.( ) Discontinuation: May result in symptoms, including dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue ( ) Activation of mania or hypomania has occurred ( ) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. ( ) Seizures: Prescribe with care in patients with a history of seizure disorder ( ) Blood Pressure: Monitor blood pressure prior to initiating treatment and periodically throughout treatment ( ) Inhibitors of CYP1A2 or Thioridazine: Should not administer with CYMBALTA( ) Hyponatremia: Cases of hyponatremia have been reported ( ) Glucose Control in Diabetes: In diabetic peripheral neuropathic pain patients, small increases in fasting blood glucose,and HbA1chave been observed ( ) Conditions that Slow Gastric Emptying.

7 Usecautiously in these patients ( ) Urinary Hesitation and Retention ( )-------------------------------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 ( ).To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx(1-800-545-5979) or FDA at 1-800-FDA-1088 or INTERACTIONS---------------------------- -- Potent inhibitors of CYP1A2 should be avoided ( ). Potent inhibitors of CYP2D6 may increase CYMBALTA concentrations ( ). CYMBALTAis a moderate inhibitor of CYP2D6 ( ).

8 ------------------------USE IN SPECIFIC POPULATIONS----------------------- Pregnancy: Based on animal data may cause fetal harm( )2 Nursing Mothers: Exercise caution when administeredto a nursing woman ( )See 17 for PATIENT COUNSELING INFORMATION and FDA-approved Medication : 12/2017 FULL PRESCRIBING INFORMATION : CONTENTS*WARNING: SUICIDAL THOUGHTS AND BEHAVIORS1 INDICATIONS AND USAGE2 DOSAGE AND forTreatmentof Major Depressive forTreatmentof Generalized Anxiety for Treatment of Diabetic Peripheral Neuropathic for Treatment of for Treatment of Chronic Musculoskeletal in Special a Patientto or from a Monoamine Oxidase Inhibitor(MAOI)

9 Intended to Treat Psychiatric of CYMBALTA with Other MAOIs such as Linezolid or Methylene Blue3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND Thoughts and Behaviors in Children, Adolescents, and Young Hypotension, Fallsand Skin of Treatment with of on Blood Important Drug in Patients with Concomitant Hesitation and Tests6 ADVERSE Trial Data Reactions Reported as Reasons for Discontinuation of Treatment in AdultPlacebo-Controlled Common AdultAdverse Reactions Occurring at an Incidence of 5% or More Among CYMBALTA-Treated Patients in AdultPlacebo-Controlled Reactions Occurring at an Incidence of 2% or More Among CYMBALTA-Treated Patients in AdultPlacebo-Controlled on Male and Female Sexual Functionin Sign Changesin Changes in Changesin Adverse Reactions Observed During the Premarketing and Postmarketing Clinical Trial

10 Evaluation of CYMBALTA in Reactions Observed in Children and Adolescent Placebo-Controlled Clinical Spontaneous Reports7 DRUG of of Inhibition of CYP1A2 and that Interfere with Hemostasis ( , NSAIDs, Aspirin, and Warfarin) that Affect Gastric Metabolized by Metabolized by Metabolized by Metabolized by Metabolized by Oxidase Inhibitors (MAOIs) CNS Drugs Highly Bound to Plasma Protein8 USE IN SPECIFIC Renal Impairment9 DRUG ABUSE AND and of Overdose11 DESCRIPTION12 CLINICAL of NONCLINICAL , Mutagenesis, Impairment of Fertility14 CLINICAL Depressive Anxiety Peripheral Neuropathic Musculoskeletal Pain16 HOW SUPPLIED/STORAGE AND Handling17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full PRESCRIBING INFORMATION are not PRESCRIBING INFORMATIONWARNING.