Anxiety/OCD:
Indications for: CYMBALTA
Generalized anxiety disorder (GAD).
Clinical Trials:
The efficacy of Cymbalta in the treatment of generalized anxiety disorder (GAD) was supported by data from 3 clinical trials. Findings showed that Cymbalta was superior to placebo as measured by greater improvement in the Hamilton Anxiety-Scale (HAM-A) total score and by the Sheehan Disability Scale global functional impairment score.
In Study GAD-4, 429 patients who responded to open-label treatment with Cymbalta were randomly assigned to continue Cymbalta at the same dose (n=216) or to placebo (n=213) and were observed for relapse. Of the patients randomized, 73% had been in a responder status for at least 10 weeks. Cymbalta-treated patients experienced a statistically significantly longer time to relapse of GAD than those who received placebo.
Among patients 65 years of age and older with GAD, Cymbalta demonstrated significantly greater improvement compared with placebo on mean change from baseline to endpoint as measured by the HAMA-A total score.
In patients 7 to 17 years of age with GAD, Cymbalta demonstrated superiority over placebo from baseline to endpoint as measured by greater improvement in the Pediatric Anxiety Rating Scale for GAD severity score.
Adult Dosage:
Swallow whole. Initially 60mg once daily (may start at 30mg once daily for 1 week then increase to 60mg once daily); usual target 60mg/day (doses up to 120mg/day have been given; if needed, may increase by increments of 30mg/day). Maintenance: 60–120mg once daily. Elderly: initially 30mg once daily for 2 weeks then increase to 60mg once daily; if needed, may increase by increments of 30mg/day; max 120mg/day.
Children Dosage:
<7yrs: not established. Swallow whole. 7–17yrs: initially 30mg once daily for 2 weeks then increase to 60mg once daily; usual target 30–60mg/day; if needed, may increase by increments of 30mg/day; max 120mg/day.
CYMBALTA Contraindications:
During or within 14 days of MAOIs. Concomitant MAOIs within 5 days of discontinuing duloxetine. Concomitant linezolid or IV methylene blue.
Boxed Warning:
Suicidal thoughts and behaviors.
CYMBALTA Warnings/Precautions:
Increased risk of suicidal thoughts and behavior in children, adolescents and young adults; monitor for clinical worsening and unusual changes. Screen for bipolar disorder. Monitor for emergence of serotonin syndrome; discontinue if occurs. Risk of bleeding. Consider dose reduction or discontinuation if orthostatic hypotension, falls and/or syncope occur. Monitor BP prior to and during therapy. History of seizure or mania/hypomania. Angle-closure glaucoma. Volume-depleted. Hyponatremia (esp. in elderly). Decreased GI motility. Cardiac disease. Diabetes. Sexual dysfunction. Monitor weight and growth in children. Severe renal impairment (CrCl<30mL/min), end stage renal disease, hepatic insufficiency, chronic liver disease, cirrhosis, or substantial alcohol use: not recommended. Avoid abrupt cessation. Reevaluate periodically. Elderly. Pregnancy; see full labeling for effects on neonates exposed late in the 3rd trimester. Nursing mothers: monitor infants.
CYMBALTA Classification:
SNRI.
CYMBALTA Interactions:
See Contraindications. Concomitant thioridazine (may cause arrhythmias): not recommended. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Potentiated by CYP1A2 inhibitors (eg, cimetidine, fluvoxamine, quinolones): avoid. May potentiate or be potentiated by CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or substrates (eg, tricyclics, phenothiazines, type 1C antiarrhythmics) or other highly protein-bound drugs; caution with CYP2D6 substrates with narrow therapeutic indexes. Caution with potent CYP1A2 inhibitors, antihypertensives, other drugs that induce orthostatic hypotension. Monitor concomitant CNS-acting drugs, and with those that affect gastric pH (eg, proton pump inhibitors). Increased risk of bleeding with NSAIDs, aspirin, or others that affect coagulation.
Adverse Reactions:
Nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis; hepatotoxicity (discontinue if occurs), orthostatic hypotension, falls, syncope, mania/hypomania, increased BP, urinary hesitation/retention; rare: seizure, serious skin reactions (eg, Stevens-Johnson Syndrome). In children: also decreased weight, vomiting, fatigue, diarrhea.
Drug Elimination:
Renal (~70%), fecal (~20%). Half-life: ~12 hours (range: 8–17 hours).
Generic Drug Availability:
YES
How Supplied:
Caps 20mg—60; 30mg—30, 90; 60mg—30, 1000
Fibromyalgia:
Indications for: CYMBALTA
Fibromyalgia.
Clinical Trials:
Two randomized, double-blind, placebo-controlled trials were conducted to establish the efficacy of Cymbalta for the management of fibromyalgia in adults. Study participants met the American College of Rheumatology criteria for fibromyalgia (a history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites). The patients had a baseline pain score of 6.5 on an 11-point scale ranging from 0 (no pain) to 10 (worse possible pain).
Findings showed that treatment with Cymbalta statistically significantly improved the endpoint mean pain scores from baseline and increased the proportion of patients with at least a 50% reduction in pain score from baseline. Some patients experienced a decrease in pain as early as week 1. Improvement was also demonstrated on measures of function (Fibromyalgia Impact Questionnaires) and patient global impression of change. Cymbalta 120mg daily did not demonstrate a benefit over 60mg daily and was associated with more adverse reactions and premature discontinuation.
Results from a separate trial (Study FM-3) evaluating the benefits of up-titration in nonresponders to Cymbalta showed that patients who were nonresponders at 8 weeks were no more likely to meet response criteria at the end of 60 weeks of treatment if blindly treated with Cymbalta 120mg as compared with those who received Cymbalta 60mg.
Among pediatric patients aged 13 to 17 years with juvenile fibromyalgia syndrome (N=184), Cymbalta showed improvement over placebo on the primary endpoint (change from baseline to end-of-treatment on the Brief Pain Inventory [BPI] – Modified Short Form: Adolescent Version 24-hour average pain severity rating).
Adult Dosage:
Swallow whole. Initially 30mg once daily for 1 week, then increase to 60mg once daily.
Children Dosage:
<13yrs: not established. Swallow whole. 13–17yrs: initially 30mg once daily; may increase to 60mg once daily based on response and tolerability.
CYMBALTA Contraindications:
During or within 14 days of MAOIs. Concomitant MAOIs within 5 days of discontinuing duloxetine. Concomitant linezolid or IV methylene blue.
Boxed Warning:
Suicidal thoughts and behaviors.
CYMBALTA Warnings/Precautions:
Increased risk of suicidal thoughts and behavior in children, adolescents and young adults; monitor for clinical worsening and unusual changes. Screen for bipolar disorder. Monitor for emergence of serotonin syndrome; discontinue if occurs. Risk of bleeding. Consider dose reduction or discontinuation if orthostatic hypotension, falls and/or syncope occur. Monitor BP prior to and during therapy. History of seizure or mania/hypomania. Angle-closure glaucoma. Volume-depleted. Hyponatremia (esp. in elderly). Decreased GI motility. Cardiac disease. Diabetes. Sexual dysfunction. Monitor weight and growth in children. Severe renal impairment (CrCl<30mL/min), end stage renal disease, hepatic insufficiency, chronic liver disease, cirrhosis, or substantial alcohol use: not recommended. Avoid abrupt cessation. Reevaluate periodically. Elderly. Pregnancy; see full labeling for effects on neonates exposed late in the 3rd trimester. Nursing mothers: monitor infants.
CYMBALTA Classification:
SNRI.
CYMBALTA Interactions:
See Contraindications. Concomitant thioridazine (may cause arrhythmias): not recommended. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Potentiated by CYP1A2 inhibitors (eg, cimetidine, fluvoxamine, quinolones): avoid. May potentiate or be potentiated by CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or substrates (eg, tricyclics, phenothiazines, type 1C antiarrhythmics) or other highly protein-bound drugs; caution with CYP2D6 substrates with narrow therapeutic indexes. Caution with potent CYP1A2 inhibitors, antihypertensives, other drugs that induce orthostatic hypotension. Monitor concomitant CNS-acting drugs, and with those that affect gastric pH (eg, proton pump inhibitors). Increased risk of bleeding with NSAIDs, aspirin, or others that affect coagulation.
Adverse Reactions:
Nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis; hepatotoxicity (discontinue if occurs), orthostatic hypotension, falls, syncope, mania/hypomania, increased BP, urinary hesitation/retention; rare: seizure, serious skin reactions (eg, Stevens-Johnson Syndrome). In children: also decreased weight, vomiting, fatigue, diarrhea.
Drug Elimination:
Renal (~70%), fecal (~20%). Half-life: ~12 hours (range: 8–17 hours).
Generic Drug Availability:
YES
How Supplied:
Caps 20mg—60; 30mg—30, 90; 60mg—30, 1000
Mood disorders:
Indications for: CYMBALTA
Major depressive disorder.
Clinical Trials:
Efficacy was established in 4 randomized, double-blind, placebo-controlled, fixed-dose trials in adult outpatients (18-83 years) meeting DSM-IV criteria for MDD. In all 4 studies, Cymbalta demonstrated superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score.
In Study MDD-5, patients who responded to open-label treatment with Cymbalta were randomly assigned to continue Cymbalta at the same dose (n=136) or to placebo (n=142). Findings showed Cymbalta-treated patients experienced a statistically significantly longer time to relapse of depression than those who received placebo.
Adult Dosage:
Swallow whole. Initially 40mg/day (given as 20mg twice daily) to 60mg/day (given either once daily or as 30mg twice daily); may start at 30mg once daily for 1 week, if needed; usual target 60mg once daily (doses up to 120mg/day have been given). Maintenance: 60mg once daily.
Children Dosage:
<18yrs: not established.
CYMBALTA Contraindications:
During or within 14 days of MAOIs. Concomitant MAOIs within 5 days of discontinuing duloxetine. Concomitant linezolid or IV methylene blue.
Boxed Warning:
Suicidal thoughts and behaviors.
CYMBALTA Warnings/Precautions:
Increased risk of suicidal thoughts and behavior in children, adolescents and young adults; monitor for clinical worsening and unusual changes. Screen for bipolar disorder. Monitor for emergence of serotonin syndrome; discontinue if occurs. Risk of bleeding. Consider dose reduction or discontinuation if orthostatic hypotension, falls and/or syncope occur. Monitor BP prior to and during therapy. History of seizure or mania/hypomania. Angle-closure glaucoma. Volume-depleted. Hyponatremia (esp. in elderly). Decreased GI motility. Cardiac disease. Diabetes. Sexual dysfunction. Monitor weight and growth in children. Severe renal impairment (CrCl<30mL/min), end stage renal disease, hepatic insufficiency, chronic liver disease, cirrhosis, or substantial alcohol use: not recommended. Avoid abrupt cessation. Reevaluate periodically. Elderly. Pregnancy; see full labeling for effects on neonates exposed late in the 3rd trimester. Nursing mothers: monitor infants.
CYMBALTA Classification:
SNRI.
CYMBALTA Interactions:
See Contraindications. Concomitant thioridazine (may cause arrhythmias): not recommended. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Potentiated by CYP1A2 inhibitors (eg, cimetidine, fluvoxamine, quinolones): avoid. May potentiate or be potentiated by CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or substrates (eg, tricyclics, phenothiazines, type 1C antiarrhythmics) or other highly protein-bound drugs; caution with CYP2D6 substrates with narrow therapeutic indexes. Caution with potent CYP1A2 inhibitors, antihypertensives, other drugs that induce orthostatic hypotension. Monitor concomitant CNS-acting drugs, and with those that affect gastric pH (eg, proton pump inhibitors). Increased risk of bleeding with NSAIDs, aspirin, or others that affect coagulation.
Adverse Reactions:
Nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis; hepatotoxicity (discontinue if occurs), orthostatic hypotension, falls, syncope, mania/hypomania, increased BP, urinary hesitation/retention; rare: seizure, serious skin reactions (eg, Stevens-Johnson Syndrome). In children: also decreased weight, vomiting, fatigue, diarrhea.
Drug Elimination:
Renal (~70%), fecal (~20%). Half-life: ~12 hours (range: 8–17 hours).
Generic Drug Availability:
YES
How Supplied:
Caps 20mg—60; 30mg—30, 90; 60mg—30, 1000
Musculoskeletal pain:
Indications for: CYMBALTA
Chronic musculoskeletal pain (eg, low back pain, osteoarthritis pain).
Clinical Trials:
Cymbalta was evaluated in 3 clinical trials in adults with chronic low back pain. Significantly greater pain reduction was observed with Cymbalta vs placebo in 2 of these trials compared with placebo. Patients in all trials had no signs of radiculopathy or spinal stenosis.
The efficacy of Cymbalta in chronic pain due to osteoarthritis was assessed in 2 double-blind, placebo-controlled trials. Significantly greater pain reduction was observed with Cymbalta vs placebo in 1 of these trials.
Adult Dosage:
Swallow whole. Initially 30mg once daily for 1 week, then increase to 60mg once daily.
Children Dosage:
<18yrs: not established.
CYMBALTA Contraindications:
During or within 14 days of MAOIs. Concomitant MAOIs within 5 days of discontinuing duloxetine. Concomitant linezolid or IV methylene blue.
Boxed Warning:
Suicidal thoughts and behaviors.
CYMBALTA Warnings/Precautions:
Increased risk of suicidal thoughts and behavior in children, adolescents and young adults; monitor for clinical worsening and unusual changes. Screen for bipolar disorder. Monitor for emergence of serotonin syndrome; discontinue if occurs. Risk of bleeding. Consider dose reduction or discontinuation if orthostatic hypotension, falls and/or syncope occur. Monitor BP prior to and during therapy. History of seizure or mania/hypomania. Angle-closure glaucoma. Volume-depleted. Hyponatremia (esp. in elderly). Decreased GI motility. Cardiac disease. Diabetes. Sexual dysfunction. Monitor weight and growth in children. Severe renal impairment (CrCl<30mL/min), end stage renal disease, hepatic insufficiency, chronic liver disease, cirrhosis, or substantial alcohol use: not recommended. Avoid abrupt cessation. Reevaluate periodically. Elderly. Pregnancy; see full labeling for effects on neonates exposed late in the 3rd trimester. Nursing mothers: monitor infants.
CYMBALTA Classification:
SNRI.
CYMBALTA Interactions:
See Contraindications. Concomitant thioridazine (may cause arrhythmias): not recommended. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Potentiated by CYP1A2 inhibitors (eg, cimetidine, fluvoxamine, quinolones): avoid. May potentiate or be potentiated by CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or substrates (eg, tricyclics, phenothiazines, type 1C antiarrhythmics) or other highly protein-bound drugs; caution with CYP2D6 substrates with narrow therapeutic indexes. Caution with potent CYP1A2 inhibitors, antihypertensives, other drugs that induce orthostatic hypotension. Monitor concomitant CNS-acting drugs, and with those that affect gastric pH (eg, proton pump inhibitors). Increased risk of bleeding with NSAIDs, aspirin, or others that affect coagulation.
Adverse Reactions:
Nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis; hepatotoxicity (discontinue if occurs), orthostatic hypotension, falls, syncope, mania/hypomania, increased BP, urinary hesitation/retention; rare: seizure, serious skin reactions (eg, Stevens-Johnson Syndrome). In children: also decreased weight, vomiting, fatigue, diarrhea.
Drug Elimination:
Renal (~70%), fecal (~20%). Half-life: ~12 hours (range: 8–17 hours).
Generic Drug Availability:
YES
How Supplied:
Caps 20mg—60; 30mg—30, 90; 60mg—30, 1000
Nonnarcotic analgesics:
Indications for: CYMBALTA
Diabetic peripheral neuropathic pain.
Clinical Trials:
The efficacy of Cymbalta in the management of neuropathic pain associated with diabetic peripheral neuropathy in adults was established in 2 randomized, 12-week, double-blind, placebo-controlled studies. Study participants had type 1 or 2 diabetes mellitus with a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for at least 6 months. In addition to Cymbalta, participants were allowed up to 4g of acetaminophen per day as needed for pain.
Findings showed that treatment with Cymbalta statistically significantly improved the endpoint mean pain scores from baseline and increased the proportion of patients with at least 50% reduction in pain scores from baseline. Some patients experienced a decrease in pain as early as week 1.
Adult Dosage:
Swallow whole. 60mg once daily (may start at lower dose if 60mg not tolerated). Renal impairment: consider lower starting dose and slow titration.
Children Dosage:
<18yrs: not established.
CYMBALTA Contraindications:
During or within 14 days of MAOIs. Concomitant MAOIs within 5 days of discontinuing duloxetine. Concomitant linezolid or IV methylene blue.
Boxed Warning:
Suicidal thoughts and behaviors.
CYMBALTA Warnings/Precautions:
Increased risk of suicidal thoughts and behavior in children, adolescents and young adults; monitor for clinical worsening and unusual changes. Screen for bipolar disorder. Monitor for emergence of serotonin syndrome; discontinue if occurs. Risk of bleeding. Consider dose reduction or discontinuation if orthostatic hypotension, falls and/or syncope occur. Monitor BP prior to and during therapy. History of seizure or mania/hypomania. Angle-closure glaucoma. Volume-depleted. Hyponatremia (esp. in elderly). Decreased GI motility. Cardiac disease. Diabetes. Sexual dysfunction. Monitor weight and growth in children. Severe renal impairment (CrCl<30mL/min), end stage renal disease, hepatic insufficiency, chronic liver disease, cirrhosis, or substantial alcohol use: not recommended. Avoid abrupt cessation. Reevaluate periodically. Elderly. Pregnancy; see full labeling for effects on neonates exposed late in the 3rd trimester. Nursing mothers: monitor infants.
CYMBALTA Classification:
SNRI.
CYMBALTA Interactions:
See Contraindications. Concomitant thioridazine (may cause arrhythmias): not recommended. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Potentiated by CYP1A2 inhibitors (eg, cimetidine, fluvoxamine, quinolones): avoid. May potentiate or be potentiated by CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or substrates (eg, tricyclics, phenothiazines, type 1C antiarrhythmics) or other highly protein-bound drugs; caution with CYP2D6 substrates with narrow therapeutic indexes. Caution with potent CYP1A2 inhibitors, antihypertensives, other drugs that induce orthostatic hypotension. Monitor concomitant CNS-acting drugs, and with those that affect gastric pH (eg, proton pump inhibitors). Increased risk of bleeding with NSAIDs, aspirin, or others that affect coagulation.
Adverse Reactions:
Nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis; hepatotoxicity (discontinue if occurs), orthostatic hypotension, falls, syncope, mania/hypomania, increased BP, urinary hesitation/retention; rare: seizure, serious skin reactions (eg, Stevens-Johnson Syndrome). In children: also decreased weight, vomiting, fatigue, diarrhea.
Drug Elimination:
Renal (~70%), fecal (~20%). Half-life: ~12 hours (range: 8–17 hours).
Generic Drug Availability:
YES
How Supplied:
Caps 20mg—60; 30mg—30, 90; 60mg—30, 1000
