Duloxetine

Boxed Warning: Suicidal Thoughts and Behaviors 10/2014 Indications and Usage ( 1 ) 10/2014 Dosage and Administration: Dosage for Treatment of Generalized Anxiety Disorder ( 2.2 ) 10/2014 Contraindications: Uncontrolled Narrow-Angle Glaucoma ( 4.2 ) Removed 07/2014 Warnings and Precautions: Orthostatic Hypotension, Falls and Syncope ( 5.3 ) 11/2014 Angle-Closure Glaucoma ( 5.9 ) 07/2014

1 INDICATIONS AND USAGE Duloxetine delayed-release capsules are indicated for the treatment of: • Major depressive disorder in adults • Generalized anxiety disorder in adults and pediatric patients 7 years of age and older • Diabetic peripheral neuropathic pain in adults • Fibromyalgia in adults • Chronic musculoskeletal pain in adults 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. Duloxetine delayed-release capsules are a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of the following conditions: • Major depressive disorder (MDD) in adults ( 1 ) • Generalized anxiety disorder (GAD) in adults and pediatric patients 7 years of age and older ( 1 ) • Diabetic peripheral neuropathic pain (DPNP) in adults ( 1 ) • Fibromyalgia (FM) ( 1 ) • Chronic musculoskeletal pain in adults ( 1 )

2 DOSAGE AND ADMINISTRATION Do not initiate treatment with Duloxetine Delayed-Release Capsules. Use another duloxetine delayed-release capsule product for initial dosage, titration, and doses below 80 mg per day. ( 2.1 ) Administer Duloxetine Delayed-Release Capsules once daily on an empty stomach at least one hour before or two hours after a meal. Swallow whole, do not open, chew or crush. Do not sprinkle the capsule contents on food or mix with liquids. ( 2.1 ) MDD: Administer Duloxetine Delayed-Release Capsules in doses of 80 mg, 90 mg, or 120 mg. Periodically reassess for appropriate dosing. ( 2.2 ) GAD: Administer Duloxetine Delayed-Release Capsules in doses of 90 mg or 120 mg. Periodically reassess for appropriate dosing. ( 2.3 ) The maximum dosage is 120 mg once daily ( 2.2 , 2.3 ) When discontinuing treatment, reduce dose gradually whenever possible to avoid discontinuation symptoms. Gradual dosage reduction will require use of another duloxetine delayed-release capsule product. ( 2.6 ) 2.1 Important Administration Instructions Do not initiate treatment with Duloxetine Delayed-Release Capsules 80 mg, 90 mg, and 120 mg. Use another duloxetine delayed-release capsule product for initial dosage, titration, and doses below 80 mg per day. Refer to the Prescribing Information of other duloxetine delayed-release capsule products for the recommended dosage of those products. Administer Duloxetine Delayed-Release Capsules orally once daily on an empty stomach at least one hour before or two hours after a meal [see Pharmacokinetics ( 12.3 )] . Swallow whole and do not chew or crush. Do not open the delayed-release capsule and sprinkle its contents on food or mix with liquids because these actions might affect the enteric coating. If a dose of Duloxetine Delayed-Release Capsules is missed, take the missed dose as soon as it is remembered. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular time. Do not take two doses of Duloxetine Delayed-Release Capsules at the same time. 2.2 Dosage for Treatment of Major Depressive Disorder Administer Duloxetine Delayed-Release Capsules in adults with MDD receiving at least 60 mg per day of another duloxetine delayed-release capsule product for one week [see Dosage and Administration ( 2.1 ), Clinical Studies ( 14.1 )] . While duloxetine at a 120 mg per day dose was shown to be effective, there is no evidence that doses greater than 60 mg per day confer any additional benefits. Administer Duloxetine Delayed-Release Capsules once daily in doses of 80 mg, 90 mg, or 120 mg, titrating dose as tolerated when appropriate. Periodically reassess patients to determine the need for maintenance treatment and the appropriate dosage for such treatment. The maximum studied dosage is 120 mg once daily. 2.3 Dosage for Treatment of Generalized Anxiety Disorder Adults Less than 65 Years of Age with GAD Administer Duloxetine Delayed-Release Capsules in adults less than 65 years of age with GAD receiving at least 60 mg once daily of another duloxetine delayed-release capsule product for one week [see Dosage and Administration ( 2.1 ), Clinical Studies ( 14.2 )] . While duloxetine at a 120 mg once daily dosage was shown to be effective, there is no evidence that doses greater than 60 mg per day confer additional benefit. Nevertheless, if a decision is made to increase the dosage beyond 60 mg once daily, increase dosage in increments of 30 mg once daily. Administer Duloxetine Delayed-Release Capsules once daily in doses of 90 mg or 120 mg. Periodically reassess patients to determine the need for maintenance treatment and the appropriate dosage for such treatment. The maximum studied dosage is 120 mg once daily. Geriatric Patients with GAD Administer Duloxetine Delayed-Release Capsules in geriatric patients with GAD receiving at least 60 mg once daily of another duloxetine delayed-release capsule product for two weeks [see Dosage and Administration ( 2.1 ), Clinical Stud …

3 DOSAGE FORMS & STRENGTHS Duloxetine delayed-release capsule USP is available as: 20 mg – Off white to light brown spherical to oval pellets filled in hard gelatin capsule shells of size “4” with “ ” imprinted in grey colour ink on opaque green colored cap and “007” imprinted in black ink on clear transparent body. 30 mg – Off white to light brown spherical to oval pellets filled in hard gelatin capsule shells of size “3” with “ ” imprinted in grey colour ink on opaque white colored cap and “008” imprinted in black ink on clear transparent body. 60 mg – Off white to light brown spherical to oval pellets filled in hard gelatin capsule shells of size “1” with “ ” imprinted in grey colour ink on opaque blue colored cap and “009” imprinted in black ink on clear transparent body. Delayed-release capules: 20 mg, 30 mg, and 60 mg (3) imprint imprint imprint

4 CONTRAINDICATIONS Monoamine Oxidase Inhibitors (MAOIs) — The use of MAOIs intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. The use of duloxetine delayed-release capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.8) and Warnings and Precautions (5.4) ] . Starting duloxetine delayed-release capsules in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.9) and Warnings and Precautions (5.4) ] . • Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules. Do not use duloxetine delayed-release capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start duloxetine delayed-release capsules in a patient who is being treated with linezolid or intravenous methylene blue ( 4 ).

6 ADVERSE REACTIONS 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 Delayed-Release Capsules [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 )] • 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 Ajanta Pharma USA Inc. at 1-855-664-7744 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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 listed. 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 delayed-release capsules 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 )]. The data below do not include results of the trial examining the efficacy of duloxetine delayed-release capsules 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. Children and Adolescents — 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 30-120 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 30-120 mg per day. 6.2 Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Adult Placebo-Controlled Trials Major Depressive Disorder — Approximately 8.4% (31 …

7 DRUG INTERACTIONS Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism. Potent inhibitors of CYP1A2 should be avoided (7.1) Potent inhibitors of CYP2D6 may increase duloxetine delayed-release capsules concentrations (7.2) Duloxetine delayed-release capsules are a moderate inhibitor of CYP2D6 (7.9) 7.1 Inhibitors of CYP1A2 When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the C max was increased about 2.5-fold, and duloxetine t 1/2 was increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin [see Warnings and Precautions (5.12) ] . 7.2 Inhibitors of CYP2D6 Concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) increased the concentration of duloxetine AUC by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see Warnings and Precautions (5.12) ] . 7.3 Dual Inhibition of CYP1A2 and CYP2D6 Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and C max . 7.4 Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are co-administered with warfarin. Concomitant administration of warfarin (2-9 mg once daily) under steady state conditions with duloxetine delayed-release capsules 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0.07).The total warfarin (protein bound plus free drug) pharmacokinetics (AUC τ,ss , C max, ss or t max,ss ) for both R- and S-warfarin were not altered by duloxetine. Because of the potential effect of duloxetine on platelets, patients receiving warfarin therapy should be carefully monitored when duloxetine delayed-release capsules are initiated or discontinued [see Warnings and Precautions (5.5) ] . 7.5 Lorazepam Under steady-state conditions for duloxetine delayed-release capsules (60 mg Q 12 hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration. 7.6 Temazepam Under steady-state conditions for duloxetine delayed-release capsules (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration. 7.7 Drugs that Affect Gastric Acidity Duloxetine delayed-release capsules have an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, duloxetine delayed-release capsules, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using duloxetine delayed-release capsules in patients with conditions that may slow gastric emptying (e.g., some diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. However, co- administration of duloxetine delayed-release capsules with aluminum- and magnesium-containing antacids (51 mEq) or duloxetine delayed-release capsules with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral do …

8 USE IN SPECIFIC POPULATIONS Pregnancy : Third trimester use may increase risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate ( 8.1 ) Hepatic Impairment : Avoid use in patients with chronic liver disease or cirrhosis ( 5.14 ) Renal Impairment : Avoid use in patients with severe renal impairment, GFR <30 mL/minute ( 5.14 ) 8.1 Pregnancy Risk Summary Data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. Data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see Data). There are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to SNRIs and SSRIs, including duloxetine, during pregnancy (see Clinical Considerations) . In rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (MRHD) of 120 mg/day given to adolescents on a mg/m 2 basis. When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD given to adolescents on a mg/m 2 basis. At this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. Post-weaning growth was not adversely affected. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis. It is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. Maternal Adverse Reactions Use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 )]. Fetal/Neonatal Adverse Reaction Neonates exposed to duloxetine and other SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of the SNRIs or SSRIs, or possibly, a drug discontinuation syndrome. It should be n …

12.1 Mechanism of Action Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS.

11 DESCRIPTION Duloxetine hydrochloride USP is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) for oral administration. Its chemical designation is (+)-( S )- N -methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride. The molecular formula is C 18 H 19 NOS•HCl, which corresponds to a molecular weight of 333.88. The structural formula is: Duloxetine hydrochloride USP is a white to brownish-white solid, which is slightly soluble in water. Each capsule contains enteric-coated pellets of 20 mg, 30 mg, 40 mg or 60 mg of duloxetine hydrochloride USP (equivalent to 22.4 mg, 33.7 mg, 44.9 mg or 67.3 mg of duloxetine, respectively). These enteric-coated pellets are designed to prevent degradation of the drug in the acidic environment of the stomach. Inactive ingredients include sugar spheres, hypromellose, sucrose, talc, methacrylic acid copolymer dispersion, and triethyl citrate. The capsule shell contains gelatin, FD&C Red No. 3 (40 mg), FD&C Blue No. 1 (40 mg), FD&C Blue No. 2 (20 mg, 30 mg, 60 mg), titanium dioxide, and sodium lauryl sulfate. For 20 mg, 30 mg, 40 mg (body & cap) and 60 mg (body only) strengths, imprinting black ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, potassium hydroxide and purified water. For 60 mg (cap only) strength, imprinting white ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, purified water, potassium hydroxide, and titanium dioxide. USP Assay & Organic Impurities test pending. structure

10 OVERDOSAGE 10.1 Signs and Symptoms In postmarketing experience, fatal outcomes have been reported for acute duloxetine overdoses, primarily with mixed overdoses, but also with duloxetine only, including 1000 mg of duloxetine (approximately 8.3 times the maximum recommended dosage). Signs and symptoms of overdose (duloxetine alone or with mixed drugs) included somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting. 10.2 Management of Overdose There is no specific antidote to a duloxetine delayed-release capsules overdosage, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In case of acute overdose with duloxetine delayed-release capsules, treatment should consist of those general measures employed in the management of overdose with any drug, such as assuring an adequate airway, oxygenation, and ventilation and monitoring cardiac rhythm and vital signs. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Induction of emesis is not recommended. Activated charcoal may be useful in limiting absorption of duloxetine from the gastrointestinal tract. Administration of activated charcoal has been shown to decrease duloxetine AUC and C max by an average of one-third, although some patients had a limited effect of activated charcoal. Due to the large volume of distribution of duloxetine, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. In managing overdose, the possibility of multiple drug involvement should be considered. A specific caution involves patients who overdose with duloxetine delayed-release capsules and tricyclic antidepressants. In such a case, decreased clearance of the parent tricyclic and/or its active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation [see Warnings and Precautions (5.4) and Drug Interactions (7) ] . Consider contacting a poison control center (1-800-222-1222 or www.poison.org) for additional information on the treatment of overdosage.

10.1 Signs and Symptoms In postmarketing experience, fatal outcomes have been reported for acute duloxetine overdoses, primarily with mixed overdoses, but also with duloxetine only, including 1000 mg of duloxetine (approximately 8.3 times the maximum recommended dosage). Signs and symptoms of overdose (duloxetine alone or with mixed drugs) included somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting.

10.2 Management of Overdose There is no specific antidote to a duloxetine delayed-release capsules overdosage, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In case of acute overdose with duloxetine delayed-release capsules, treatment should consist of those general measures employed in the management of overdose with any drug, such as assuring an adequate airway, oxygenation, and ventilation and monitoring cardiac rhythm and vital signs. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Induction of emesis is not recommended. Activated charcoal may be useful in limiting absorption of duloxetine from the gastrointestinal tract. Administration of activated charcoal has been shown to decrease duloxetine AUC and C max by an average of one-third, although some patients had a limited effect of activated charcoal. Due to the large volume of distribution of duloxetine, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. In managing overdose, the possibility of multiple drug involvement should …

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Duloxetine Delayed-Release Capsules USP, 20 mg: Opaque green/opaque green size '4' hard gelatin capsule filled with white to off-white-spherical enteric coated pellets and imprinted 'RDY608' on opaque green cap and '20 mg' on opaque green body with black ink. Bottles of 60 NDC 25000-608-06 Duloxetine Delayed-Release Capsules USP, 30 mg: Opaque blue/opaque white size '3' hard gelatin capsule filled with white to off-white-spherical enteric coated pellets and imprinted 'RDY609' on opaque blue cap and '30 mg' on opaque white body with golden yellow ink. Bottles of 30 NDC 25000-609-03 Bottles of 90 NDC 25000-609-07 Duloxetine Delayed-Release Capsules USP, 60 mg: Opaque blue/opaque green size '1' hard gelatin capsule filled with white to off-white spherical enteric coated pellets and imprinted 'RDY610' on opaque blue cap and '60 mg' on opaque green body with white ink. Bottles of 30 NDC 25000-610-03 Bottles of 90 NDC 25000-610-07 16.2 Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

16.1 How Supplied Duloxetine Delayed-Release Capsules USP, 20 mg: Opaque green/opaque green size '4' hard gelatin capsule filled with white to off-white-spherical enteric coated pellets and imprinted 'RDY608' on opaque green cap and '20 mg' on opaque green body with black ink. Bottles of 60 NDC 25000-608-06 Duloxetine Delayed-Release Capsules USP, 30 mg: Opaque blue/opaque white size '3' hard gelatin capsule filled with white to off-white-spherical enteric coated pellets and imprinted 'RDY609' on opaque blue cap and '30 mg' on opaque white body with golden yellow ink. Bottles of 30 NDC 25000-609-03 Bottles of 90 NDC 25000-609-07 Duloxetine Delayed-Release Capsules USP, 60 mg: Opaque blue/opaque green size '1' hard gelatin capsule filled with white to off-white spherical enteric coated pellets and imprinted 'RDY610' on opaque blue cap and '60 mg' on opaque green body with white ink. Bottles of 30 NDC 25000-610-03 Bottles of 90 NDC 25000-610-07