Duloxetine

DRIZALMA SPRINKLE is 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 Neuropathy 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. DRIZALMA SPRINKLE is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of following conditions: • Major Depressive Disorder (MDD) in adults. • Generalized Anxiety Disorder (GAD) in adults and pediatric patients ages 7 years of age and older. • Diabetic Peripheral Neuropathic Pain (DPNP) in adults.

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.

• Take DRIZALMA SPRINKLE with or without food. • DRIZALMA SPRINKLE may be: swallowed whole (do not crush or chew capsule), opened and sprinkled over applesauce, or administered via nasogastric tube. • Take a missed dose as soon as it is remembered. Do not take two doses of DRIZALMA SPRINKLE at the same time. Indication Starting Dose Target Dose Maximum Dose MDD. Adults 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. Adults 60 mg/day 60 mg/day (once daily) 120 mg/day Geriatric 30 mg/day 60 mg/day (once daily) 120 mg/day Pediatrics (7 to 17 years of age) 30 mg/day 30 to 60 mg/day (once daily) 120 mg/day DPNP 60 mg/day 60 mg/day (once daily) 60 mg/day FM. Adults 30 mg/day 60 mg/day (once daily) 60 mg/day Chronic Musculoskeletal Pain.

The use of MAOIs intended to treat psychiatric disorders with DRIZALMA SPRINKLE, or within 5 days of stopping treatment with DRIZALMA SPRINKLE, are contraindicated because of an increased risk of serotonin syndrome. The use of DRIZALMA SPRINKLE within 14 days of stopping an MAOI intended to treat psychiatric disorders is contraindicated. Starting DRIZALMA SPRINKLE in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is contraindicated because of an increased risk of serotonin syndrome.

Boxed warning (suicidal thoughts and behaviors): Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported. Discontinue DRIZALMA SPRINKLE in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established. Avoid use in patients with substantial alcohol use or evidence of chronic liver disease. Orthostatic Hypotension, Falls and Syncope: Consider dosage reduction or discontinuation if these events occur. S ero t on in Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.

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

• Potent CYP1A2 Inhibitors: Avoid concomitant use. • CYP2D6 Substrates: Consider dose reduction with concomitant use Drugs Having Clinically Important Interactions with DRIZALMA SPRINKLE Table 7: Clinically Important Drug Interactions Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of SSRIs and SNRIs including duloxetine with MAOIs increases the risk of serotonin syndrome. Intervention • The use of MAOIs intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated. • The use of duloxetine delayed-release capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. • Starting duloxetine in a patient who is being treated with MAOIs is also contraindicated.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).