INDICATION AND USES:
CYMBALTA® is 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) in adults and pediatric patients 13 years of age and older (1)
- Chronic musculoskeletal pain in adults (1)
DOSAGE AND ADMINISTRATION
Take CYMBALTA once daily, with or without food. Swallow whole; do not crush, chew, or open capsule (2.1)
| Indication | Starting Dose | Target Dose | Maximum Dose |
| MDD (2.2) | 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 (2.3) Adults Geriatric Pediatrics (7 to 17 years of age) |
60m mg/day 30 mg/day 30 mg/day |
60 mg/day (once daily) 60 mg/day (once daily) 30 to 60 mg/day (once daily) |
120 mg/day 120 mg/day 120 mg/day |
| DPNP (2.4) | 60m mg/day | 60 mg/day (once daily) | 60 mg/day |
| FM (2.5) Adults and Pediatrics (13 to 17 years of age) |
30m mg/day | 60 mg/day (once daily) | 60 mg/day |
| Chrnic Musculoskeletal Pain (2.6) | 30m mg/day | 60 mg/day (once daily) | 60 mg/day |
* Discontinuing CYMBALTA: Gradually reduce dosage to avoid discontinuation symptoms (2.8, 5.7)
SIDE EFFECTS:
Most common adverse reactions (≥5% and at least twice the incidence of placebo-treated patients): (6.1)
Adults: nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis
Pediatric Patients: decreased weight, decreased appetite, nausea, vomiting, fatigue, and diarrhea
CONTRAINDICATIONS:
- Concomitant use of an MAOI antidepressant with CYMBALTA is contraindicated
- Use of CYMBALTA within 14 days of stopping an MAOI antidepressant is contraindicated
- In linezolid-or intravenous methylene blue-treated patients, initiation of CYMBALTA is contraindicated (4)
WARNINGS AND PRECAUTIONS:
- Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported. Discontinue CYMBALTA 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 (5.2)
- Orthostatic Hypotension, Falls and Syncope: Consider dosage reduction or discontinuation if these events occur (5.3)
- Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also when taken alone. If it occurs, discontinue CYMBALTA (5.4)
- Increased Risk of Bleeding: May increase the risk of bleeding events. Concomitant use of antiplatelet drugs and anticoagulants may increase this risk (5.5, 7.4, 8.1)
- Severe Skin Reactions: Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS), can occur; Discontinue at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified (5.6)
- Activation of Mania or Hypomania: Prior to initiating, screen patients for personal or family history of bipolar disorder, mania, or hypomania (5.8)
- Angle-Closure Glaucoma: Has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.9)
- Seizures: Prescribe with care in patients with a history of seizure disorder (5.10)
- Blood Pressure Increases: Monitor blood pressure prior to initiating treatment and periodically throughout treatment (5.11)
- Inhibitors of CYP1A2 or Thioridazine: Avoid co-administration with CYMBALTA (5.12)
- Hyponatremia: Can occur in association with SIADH; consider discontinuation (5.13)
- Glucose Control in Diabetes: In DPNP patients, increases in fasting blood glucose, and HbA1c have been observed (5.14)
- Conditions that Slow Gastric Emptying: Use cautiously in these patients (5.14)
DRUG INTERACTIONS:
- Potent inhibitors of CYP1A2 should be avoided (7.1)
- Potent inhibitors of CYP2D6 may increase CYMBALTA concentrations (7.2)
- CYMBALTA is a moderate inhibitor of CYP2D6 (7.9)
OVERDOSE:
In postmarketing experience, fatal outcomes have been reported for acute CYMBALTA overdoses, primarily with mixed overdoses, but also with CYMBALTA only, including 1000 mg of CYMBALTA (approximately 8.3 times the maximum recommended dosage). Signs and symptoms of overdose (CYMBALTA alone or with mixed drugs) included somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting.
Management of Overdose: There is no specific antidote to a CYMBALTA 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 CYMBALTA, 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 Cmax 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 CYMBALTA 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.
- Uses
-
INDICATION AND USES:
CYMBALTA® is 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) in adults and pediatric patients 13 years of age and older (1)
- Chronic musculoskeletal pain in adults (1)
DOSAGE AND ADMINISTRATION
Take CYMBALTA once daily, with or without food. Swallow whole; do not crush, chew, or open capsule (2.1)
Indication Starting Dose Target Dose Maximum Dose MDD (2.2) 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 (2.3)
Adults
Geriatric
Pediatrics (7 to 17 years of age)60m mg/day
30 mg/day
30 mg/day60 mg/day (once daily)
60 mg/day (once daily)
30 to 60 mg/day (once daily)120 mg/day
120 mg/day
120 mg/dayDPNP (2.4) 60m mg/day 60 mg/day (once daily) 60 mg/day FM (2.5)
Adults and Pediatrics (13 to 17 years of age)30m mg/day 60 mg/day (once daily) 60 mg/day Chrnic Musculoskeletal Pain (2.6) 30m mg/day 60 mg/day (once daily) 60 mg/day * Discontinuing CYMBALTA: Gradually reduce dosage to avoid discontinuation symptoms (2.8, 5.7)
- Side Effects
-
SIDE EFFECTS:
Most common adverse reactions (≥5% and at least twice the incidence of placebo-treated patients): (6.1)
Adults: nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis
Pediatric Patients: decreased weight, decreased appetite, nausea, vomiting, fatigue, and diarrhea
- Precautions
-
CONTRAINDICATIONS:
- Concomitant use of an MAOI antidepressant with CYMBALTA is contraindicated
- Use of CYMBALTA within 14 days of stopping an MAOI antidepressant is contraindicated
- In linezolid-or intravenous methylene blue-treated patients, initiation of CYMBALTA is contraindicated (4)
WARNINGS AND PRECAUTIONS:
- Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported. Discontinue CYMBALTA 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 (5.2)
- Orthostatic Hypotension, Falls and Syncope: Consider dosage reduction or discontinuation if these events occur (5.3)
- Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also when taken alone. If it occurs, discontinue CYMBALTA (5.4)
- Increased Risk of Bleeding: May increase the risk of bleeding events. Concomitant use of antiplatelet drugs and anticoagulants may increase this risk (5.5, 7.4, 8.1)
- Severe Skin Reactions: Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS), can occur; Discontinue at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified (5.6)
- Activation of Mania or Hypomania: Prior to initiating, screen patients for personal or family history of bipolar disorder, mania, or hypomania (5.8)
- Angle-Closure Glaucoma: Has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.9)
- Seizures: Prescribe with care in patients with a history of seizure disorder (5.10)
- Blood Pressure Increases: Monitor blood pressure prior to initiating treatment and periodically throughout treatment (5.11)
- Inhibitors of CYP1A2 or Thioridazine: Avoid co-administration with CYMBALTA (5.12)
- Hyponatremia: Can occur in association with SIADH; consider discontinuation (5.13)
- Glucose Control in Diabetes: In DPNP patients, increases in fasting blood glucose, and HbA1c have been observed (5.14)
- Conditions that Slow Gastric Emptying: Use cautiously in these patients (5.14)
- Interactions
-
DRUG INTERACTIONS:
- Potent inhibitors of CYP1A2 should be avoided (7.1)
- Potent inhibitors of CYP2D6 may increase CYMBALTA concentrations (7.2)
- CYMBALTA is a moderate inhibitor of CYP2D6 (7.9)
- Overdose
-
OVERDOSE:
In postmarketing experience, fatal outcomes have been reported for acute CYMBALTA overdoses, primarily with mixed overdoses, but also with CYMBALTA only, including 1000 mg of CYMBALTA (approximately 8.3 times the maximum recommended dosage). Signs and symptoms of overdose (CYMBALTA alone or with mixed drugs) included somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting.
Management of Overdose: There is no specific antidote to a CYMBALTA 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 CYMBALTA, 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 Cmax 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 CYMBALTA 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.