2 DOSAGE AND ADMINISTRATION • Take duloxetine delayed-release capsules once daily, with or without food. Swallow duloxetine delayed-release capsules 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 duloxetine delayed-release capsules at the same time. ( 2 ). Indication Starting Dose Target Dose Maximum Dose MDD ( 2.1 ) 40 mg/day to 60 mg/day Acute Treatment: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or as 30 mg twice daily); Maintenance Treatment: 60 mg/day 120 mg/day GAD ( 2.2 ) Adults 60 mg/day 60 mg/day (once daily) 120 mg/day DPNP ( 2.3 ) 60 mg/day 60 mg/day (once daily) 60 mg/day Chronic Musculoskeletal Pain (2.5) 30 mg/day 60 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 duloxetine delayed-release capsules: Gradually reduce dosage to avoid discontinuation symptoms (2.7, 5.7 ) 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/min ( 5.14 ) Swallow duloxetine delayed-release capsules whole. Do not chew or crush. Do not open the capsule and sprinkle its contents on food or mix with liquids. All of these might affect the enteric coating. Duloxetine delayed-release capsules can be given without regard to meals. 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. 2.1 Dosage for Treatment of Major Depressive Disorder Administer duloxetine delayed-release capsules at a total dose of 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits. The safety of doses above 120 mg/day has not been adequately evaluated. Periodically reassess to determine the need for maintenance treatment and the appropriate dose for such treatment [see CLINICAL STUDIES ( 14.1 )] . 2.2 Dosage for Treatment of Generalized Anxiety Disorder Adults For most patients, initiate duloxetine delayed-release capsules 60 mg once daily. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg once daily dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit. Nevertheless, if a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated. Periodically reassess to determine the continued need for maintenance treatment and the appropriate dose for such treatment [see CLINICAL STUDIES ( 14.2 )] . Pediatric use information for patient's ages 7 to 17 years 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. 2.3 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain Administer duloxetine delayed-release capsules 60 mg once daily. There is no evidence that doses higher than 60 mg confer additional significant benefit and the higher dose is clearly less well tolerated [see CLINICAL STUDIES ( 14.3 )] . For patients for whom tolerability is a concern, a lower starting dose may be considered. Since diabetes is frequently complicated by renal disease, consider a lower starting dose and gradual increase in dose for patients with renal impairment [see DOSAGE AND ADMINISTRATION ( 2.6 ), USE IN SPECIFIC POPULATIONS ( 8.10 ), and CLINICAL PHARMACOLOGY ( 12.3 )] . 2.5 Dosage for Treatment of Chronic Musculoskeletal Pain Administer duloxetine delayed-release capsules 60 mg once daily. Begin treatment at 30 mg for one week, to allow patients to adjust to the medication before increasing to 60 mg once daily. There is no evidence that higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see CLINICAL STUDIES ( 14.5 )]. 2.6 Dosing in Special Populations Hepatic Impairment Avoid use in patients with chronic liver disease or cirrhosis [see WARNINGS AND PRECAUTIONS ( 5.14 ) and USE IN SPECIFIC POPULATIONS ( 8.9 )] . Severe Renal Impairment Avoid use in patients with severe renal impairment, GFR <30 mL/min [see WARNINGS AND PRECAUTIONS ( 5.14 ) and USE IN SPECIFIC POPULATIONS ( 8.10 )] . 2.7 Discontinuing Duloxetine Delayed-release Capsules Adverse reactions after discontinuation of duloxetine delayed-release capsules, after abrupt or tapered discontinuation, include: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see WARNINGS AND PRECAUTIONS ( 5.7 )] . 2.8 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with duloxetine delayed-release capsules. Conversely, at least 5 days should be allowed after stopping duloxetine delayed-release capsules before starting an MAOI intended to treat psychiatric disorders [see CONTRAINDICATIONS ( 4 )]. 2.9 Use of Duloxetine Delayed-release Capsules with Other MAOIs such as Linezolid or Methylene Blue Do not start duloxetine delayed-release capsules in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see CONTRAINDICATIONS ( 4 )]. In some cases, a patient already receiving duloxetine delayed-release capsules therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, duloxetine delayed-release capsules should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with duloxetine delayed-release capsules may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see WARNINGS AND PRECAUTIONS ( 5.4 )]. The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with duloxetine delayed-release capsules is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see WARNINGS AND PRECAUTIONS ( 5.4 )] .