Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
- Postmarketing Spontaneous Reports: …colitis (microscopic or unspecified),cutaneous vasculitis (sometimes associated with systemic involvement)
- Pediatric Use- Major Depressive Disorder:… The safety and effectiveness in pediatric patients less than 7 years of age have not been established…
WARNINGS AND PRECAUTIONS
Orthostatic Hypotension, Falls and Syncope
- Orthostatic hypotension, falls and syncope have been reported with therapeutic doses of CYMBALTA. Syncope and orthostatic hypotension tend to occur within the first week of therapy but can occur at any time during CYMBALTA treatment, particularly after dose increases. The risk of falling appears to be related to the degree of orthostatic decrease in blood pressure as well as other factors that may increase the underlying risk of falls. In an analysis of patients from all placebo-controlled trials, patients treated with CYMBALTA reported a higher rate of falls compared to patients treated with placebo. Risk appears to be related to the presence of orthostatic decrease in blood pressure. The risk of blood pressure decreases may be greater in patients taking concomitant medications that induce orthostatic hypotension (such as antihypertensives) or are potent CYP1A2 inhibitors [see Warnings and Precautions (5.12) and Drug Interactions (7.1)] and in patients taking CYMBALTA at doses above 60 mg daily.
- Consideration should be given to dose reduction or discontinuation of CYMBALTA in patients who experience symptomatic orthostatic hypotension, falls and/or syncope during CYMBALTA therapy. Risk of falling also appeared to be proportional to a patient’s underlying risk for falls and appeared to increase steadily with age. As elderly patients tend to have a higher underlying risk for falls due to a higher prevalence of risk factors such as use of multiple medications, medical omorbidities and gait disturbances, the impact of increasing age by itself is unclear. Falls with serious consequences including bone fractures and hospitalizations have been reported.
BOXED WARNING: Suicidal Thoughts and Behaviors
The following statement was removed:
- Cymbalta is not approved for use in pediatric patients
Monoamine Oxidase Inhibitors (MAOIs)
- The use of MAOIs intended to treat psychiatric disorders with Cymbalta or within 5 days of stopping treatment with Cymbalta is contraindicated because of an increased risk of serotonin syndrome. The use of Cymbalta within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.
- Starting Cymbalta 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.
WARNINGS AND PRECAUTIONS
- The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Cymbalta, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
- Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.
- The concomitant use of Cymbalta with MAOIs intended to treat psychiatric disorders is contraindicated. Cymbalta should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Cymbalta. Cymbalta should be discontinued before initiating treatment with the MAOI.
- If concomitant use of Cymbalta with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. Treatment with Cymbalta and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.
Discontinuation of Treatment with Cymbalta
- Discontinuation symptoms have been systematically evaluated in patients taking duloxetine. Following abrupt or tapered discontinuation in placebo-controlled clinical trials, the following symptoms occurred at 1% or greater and at a significantly higher rate in duloxetine-treated patients compared to those discontinuing from placebo: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue...
- The effect of duloxetine 160 mg and 200 mg administered twice daily to steady state was evaluated in a randomized, doubleblinded, two-way crossover study in 117 healthy female subjects. No QT interval prolongation was detected. Duloxetine appears to be associated with concentration-dependent but not clinically meaningful QT shortening.
USE IN SPECIFIC POPULATIONS
- Decreased appetite and weight loss have been observed in association with the use of SSRIs and SNRIs. Consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an SNRI such as Cymbalta.
PATIENT COUNSELING INFORMATION
- Patients should be informed that severe liver problems, sometimes fatal, have been reported in patients treated with Cymbalta…
Discontinuation of Treatment
- Patients should be instructed that discontinuation of Cymbalta may be associated with symptoms such as dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue, and should be advised not to alter their dosing regimen, or stop taking Cymbalta without consulting their physician
Activation of Mania or Hypomania
- Patients with depressive symptoms should be adequately screened for risk of bipolar disorder (e.g. family history of suicide, bipolar disorder, and depression) prior to initiating treatment with Cymbalta…
- Patients should be advised to inform their physician if they have a history of seizure disorder.
Effects on Blood Pressure
- Patients should be cautioned that Cymbalta may cause an increase in blood pressure…
- Patients should be advised that hyponatremia has been reported as a result of treatment with SNRIs and SSRIs, including Cymbalta. Patients should be advised of the signs and symptoms of hyponatremia…
- Patients should be advised to inform their physicians about all of their medical conditions…
Urinary Hesitancy and Retention
- Cymbalta is in a class of medicines that may affect urination. Patients should be instructed to consult with their healthcare provider if they develop any problems with urine flow…