For various degrees of improvement in pain from baseline to study endpoint, Figure 7 shows the fraction of patients achieving that degree of improvement in Study FM-4. b For GAD, there were no adverse reactions that were significantly different between treatments in adults ≥65 years that were also not significant in the adults <65 years. Negative numbers signify an improvement from a baseline level of dysfunction, which is commonly seen in depressed patients. Advise the patient to read the FDA-approved patient labeling (Medication Guide). Cases with serum sodium lower than 110 mmol/L have been reported with Cymbalta use and appeared to be reversible when Cymbalta was discontinued. Cymbalta (N=91) was initiated at a dosage of 30 mg once daily for one week and titrated to 60 mg once daily for 12 weeks, as tolerated. Alcohol — Use of Cymbalta concomitantly with heavy alcohol intake may be associated with severe liver injury. Nevertheless, if a decision is made to increase the dosage beyond 60 mg once daily, increase dosage in increments of 30 mg once daily. Patients considering Cymbalta should first understand these pros and cons before starting the medication 1. Results of in vitro studies demonstrate that duloxetine does not inhibit activity. The most common (≥5% and twice placebo) adverse reactions observed in these pediatric clinical trials included: nausea, diarrhea, decreased weight, and dizziness. Patients who did not complete the trial were assigned 0% improvement. Patients had a mean baseline pain rating of 6 on a numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). Dosage adjustment based on the age of the adult patient is not necessary. 2. Advise pregnant women that there is a risk of relapse with discontinuation of antidepressants. 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. **Patients with depression and general anxiety disorder have a variety of medication options. Figure 1: Cumulative Proportiona of Adult Patients with MDD Relapse (Study MDD-5), GAD Trials in Adults (Including Geriatric Patients). The concomitant use of Cymbalta with MAOI antidepressants is contraindicated. There are no data on the effect of duloxetine on milk production. Patients assigned to Cymbalta started treatment in both trials at a dose of 30 mg once daily for one week. Following abrupt or tapered discontinuation in adult placebo-controlled clinical trials, the following symptoms occurred at 1% or greater and at a significantly higher rate in CYMBALTA-treated patients compared to those discontinuing from placebo: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis [excess sweating], and fatigue. Both trials compared Cymbalta 60 mg once daily or 60 mg twice daily with placebo. The data described below reflect exposure to Cymbalta (N=567) in pediatric patients aged 7 to 18 years of age from two 10-week, placebo-controlled trials in patients with MDD (N=341) (Studies MDD-6 and MDD-7), one 10-week placebo-controlled trial in GAD (N=135) (Study GAD-6), and a 13-week trial in fibromyalgia (N=91). Cymbalta may: 3. Cymbalta is a registered trademark of Eli Lilly and Company. Because duloxetine is highly bound to plasma protein, administration of Cymbalta to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse reactions. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. In placebo-controlled clinical trials across approved adult populations for change from baseline to endpoint, Cymbalta-treated patients had mean increases of 0.23 mm Hg in systolic blood pressure (SBP) and 0.73 mm Hg in diastolic blood pressure (DBP) compared to mean decreases of 1.09 mm Hg in SBP and 0.55 mm Hg in DBP in placebo-treated patients. PACKAGE LABEL- Cymbalta 20 mg, bottle of 60. Conversely, at least 5 days should be allowed after stopping Cymbalta before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4)]. Your healthcare provider may need to change the dose of Cymbalta until it is the right dose for you. Cymbalta should be discontinued at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified. In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity. Some patients may respond to the starting dosage. Call your healthcare provider right away if you have any of the following symptoms or feelings, especially if they are new, worse, or worry you. Anti-depressants like Prozac, Paxil, Zoloft, Lexapro and Effexor are available with a doctor’s prescription. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Cymbalta must be consumed daily to avoid withdrawal symptoms 1. If a decision is made to increase the dose beyond 60 mg once daily, increase dosage in increments of 30 mg once daily. Depression and other serious mental illnesses are the most important causes of suicidal thoughts or actions. This may need to be treated in a hospital and may be life-threatening. Table 7 provides the incidence of adverse reactions in a fibromyalgia pediatric placebo-controlled trial (Study FM-4) that occurred in greater than 5% of patients treated with Cymbalta and with an incidence greater than patients treated with placebo [see Clinical Studies (14.5)]. After Cymbalta, you may require ongoing treatment. Please check with the appropriate physician regarding health questions and concerns. Figure 8: Percentage of Adult Patients with CLBP Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity (Study CLBP-1), Figure 9: Percentage of Adult Patients with CLBP Achieving Various Levels of Pain Relief as Measured by 24-Hour Average Pain Severity (Study CLBP-3), Trials in Chronic Pain Due to Osteoarthritis in Adults. Our team periodically reviews articles in order to ensure content quality. Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Cymbalta. Both CYP1A2 and CYP2D6 are responsible for Cymbalta metabolism. The no-effect dose was 50 mg/kg/day (1 time the MRHD given to children). Study FM-1 was three months in duration and enrolled female patients only. Avoid use in patients with severe renal impairment, GFR <30 mL/minute. This requires close work with doctors to determine the best course of action outside of Cymbalta 1. a Difference (drug minus placebo) in least-squares mean change from baseline. Furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. Duloxetine does not inhibit monoamine oxidase (MAO). No suicides occurred in any of the pediatric Cymbalta trials. No more extreme lows with suicidal thoughts, sleeping all day long, just wanting life to end. If a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. Copyright © 2004, 2020, Eli Lilly and Company. Because of the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, Cymbalta and thioridazine should not be co-administered [see Drug Interactions (7.9)]. Steady-state plasma concentrations are typically achieved after 3 days of dosing. Chronic Pain due to Osteoarthritis: nausea, fatigue, constipation, dry mouth, insomnia, somnolence, and dizziness. Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. A specific caution involves patients who overdose with Cymbalta and tricyclic antidepressants. Most Common Adverse Reactions in Pediatric Trials. However, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (approximately equal to the MRHD in rats and 2 times the MRHD in rabbits). While height increase was observed during these studies, a mean decrease of 1% in height percentile was observed (decrease of 2% in patients 7 to 11 years of age and increase of 0.3% in patients 12 to 17 years of age). Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. There is no evidence that doses greater than 60 mg/day confer additional benefits. Especially tell your healthcare provider if you take: Ask your healthcare provider for a list of these medicines if you are not sure. Cymbalta should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. There’s no way to tell when a brain zap will occur so it can happen at a bad time and possibly cause a more dangerous situation if a patient is doing things like driving, exercising or holding a child. These enteric-coated pellets are designed to prevent degradation of the drug in the acidic environment of the stomach. Of the Cymbalta-treated patients in these studies, 36% were 7 to 11 years of age (64% were between 12 to 18 years old), 55% were female, and 69% were Caucasian. Advise women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with Cymbalta. Some people may have a particularly high risk of having suicidal thoughts or actions. Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment [see Adverse Reactions (6.1)]. If you become pregnant while taking Cymbalta, talk to your healthcare provider about registering with the Cymbalta Pregnancy Registry. In the 12-week acute treatment phase of these studies, Cymbalta was associated with a small increase in mean fasting blood glucose as compared to placebo. In Study GAD-6, the starting dosage was 30 mg once daily for 2 weeks. Duloxetine undergoes extensive metabolism, but the major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine. Fifteen percent of patients were down titrated. Cymbalta should be prescribed with care in patients with a history of a seizure disorder. The efficacy of Cymbalta for the management of neuropathic pain associated with diabetic peripheral neuropathy in adults was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose trials in adult patients having diabetic peripheral neuropathic pain (DPNP) for at least 6 months (Study DPNP-1 and Study DPNP-2). Cymbalta belongs to a class of medicines known as SNRIs (or serotonin-norepinephrine reuptake inhibitors). In animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. Treatment with Cymbalta and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. Cymbalta treatment, for up to 26 weeks in placebo-controlled trials across approved adult populations, typically caused a small increase in heart rate for change from baseline to endpoint compared to placebo of up to 1.37 beats per minute (increase of 1.20 beats per minute in Cymbalta-treated patients, decrease of 0.17 beats per minute in placebo-treated patients). Since diabetes is frequently complicated by renal disease, consider a lower starting dosage and gradual increase in dosage for patients with renal impairment [see Dosage and Administration (2.7) and Use in Specific Populations (8.10)]. Tell your healthcare provider about all the medicines that you take. g Includes initial insomnia, middle insomnia, and early morning awakening. However, co-administration of Cymbalta with aluminum- and magnesium-containing antacids (51 mEq) or Cymbalta with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose. Of the patients randomized, 73% had been in a responder status for at least 10 weeks. Last updated on Nov 1, 2020. Stopping abruptly or missing several doses can cause withdrawal-like symptoms such as nausea, dizziness, lethargy, and anxiety. Increased plasma concentration of Cymbalta, and especially of its metabolites, occurred in patients with end-stage renal disease (requiring dialysis) [see Dosage and Administration (2.7) and Use in Specific Populations (8.10)]. It may take four to eight weeks to get the maximum benefit once the right dose is determined. You may ask your healthcare provider or pharmacist for information about Cymbalta that is written for healthcare professionals. There is a 3 hour delay in absorption and a one-third increase in apparent clearance of duloxetine after an evening dose as compared to a morning dose. For various degrees of improvement in pain from baseline to study endpoint, Figures 8 and 9 show the fraction of patients in Studies CLBP-1 and CLBP-3 achieving that degree of improvement, respectively. Following is a list of adverse reactions reported by patients treated with Cymbalta in clinical adult trials. Recommended Dosage in Pediatric Patients 13 to 17 Years of Age. General information about the safe and effective use of Cymbalta. Avoid heavy alcohol use while taking Cymbalta. Under steady-state conditions for Cymbalta (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration. Antidepressants increased the risk of suicidal thoughts and behavior in pediatric patients. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. The AUCs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. Avoid use in patients with severe renal impairment, GFR <30 mL/minute [see Warnings and Precautions (5.14) and Use in Specific Populations (8.10)]. Use of Cymbalta concomitantly with heavy alcohol intake may be associated with severe liver injury. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The purpose of this registry is to monitor the pregnancy outcomes in women who have been treated with Cymbalta at any time during pregnancy. Study CLBP-3: Four hundred and one patients were randomized to receive fixed doses of Cymbalta 60 mg daily or placebo (N=198 on Cymbalta, N=203 on placebo), and 303 (76%) completed the trial. Drugs Metabolized by CYP2D6 — Co-administration of Cymbalta with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution. Periodically reassess to determine the continued need for maintenance treatment and the appropriate dosage for such treatment. Other common reports include dry mouth, drowsiness, constipation, excessive sweating and decreased appetite. If a dose of Cymbalta is missed, take the missed dose as soon as it is remembered. Concomitant administration of warfarin (2-9 mg once daily) under steady state conditions with Cymbalta 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0.07). Duloxetine comprises about 3% of the total radiolabeled material in the plasma, indicating that it undergoes extensive metabolism to numerous metabolites. This has been established in trials in adult patients with chronic low back pain and chronic pain due to osteoarthritis. Adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (Cymbalta 2.0%, placebo 0.5%), headache (Cymbalta 1.2%, placebo 0.3%), somnolence (Cymbalta 1.1%, placebo 0%), and fatigue (Cymbalta 1.1%, placebo 0.1%). The efficacy of Cymbalta in the treatment of patients ≥65 years of age with GAD was established in one 10-week flexible-dose, randomized, double-blind, placebo-controlled trial in adults ≥65 years of age meeting the DSM-IV criteria for GAD (Study GAD-5). Figure 7: Percentage of Pediatric Patients Aged 13 to 17 Years Old with Juvenile Fibromyalgia Syndrome Achieving Various Levels of Pain Relief at Week 12 (Study FM-4)a. a Pain relief Measured by Brief Pain Inventory – Modified Short Form: Adolescent Version Average Pain Score. The data described below reflect exposure to Cymbalta in placebo-controlled adult trials for MDD (N=3779), GAD (N=1018), OA (N=503), CLBP (N=600), DPNP (N=906), and FM (N=1294). Patients with depression and general anxiety disorder have a variety of medication options. Data from published literature report the presence of duloxetine in human milk (see Data). Glycemic Control in Patients with Diabetes. Cymbalta literally has saved my life and my marriage PRAISE GOD!!!!! Further, most people who experienced withdrawal symptoms stated they were mild or moderate.. Risk of falling also appeared to be proportional to a patient's underlying risk for falls and appeared to increase steadily with age. Additionally, the benefit of up-titration in non-responders to Cymbalta at 60 mg/day was evaluated in a separate trial (Study FM-3). Call your healthcare provider right away or get emergency help if you have skin blisters, peeling rash, sores in the mouth, hives or any other allergic reactions. Dosage adjustment based on gender is not necessary. Although Cmax was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see Dosage and Administration (2.7) and Warnings and Precautions (5.14)]. Talk to your healthcare provider about the best way to feed your baby while taking Cymbalta. Cymbalta increased the risk of elevation of serum transaminase levels in development program clinical trials. Subsequently, over the 4- to 6-month uncontrolled extension periods, Cymbalta-treated patients on average trended toward recovery to their expected baseline weight percentile based on population data from age- and sex-matched peers. Post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. Data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see Data). Cymbalta is not approved in the treatment of MDD in pediatric patients [see Use in Specific Populations (8.4)]. f Also includes initial insomnia, insomnia, middle insomnia, and terminal insomnia. Approximately 12.9% (117/906) of the Cymbalta-treated patients in placebo-controlled adult trials for DPNP discontinued treatment due to an adverse reaction, compared with 5.1% (23/448) for placebo-treated patients. This Medication Guide summarizes the most important information about Cymbalta. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Find everything you need to know about Cymbalta (duloxetine), including what it is used for, warnings, reviews, side effects, and interactions. Talk to your healthcare provider about the risk to your unborn baby if you take Cymbalta during pregnancy. 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. Each capsule contains 33.7 mg of duloxetine hydrochloride equivalent to 30 mg duloxetine. You can register by calling 1-866-814-6975 or by visiting www.Cymbaltapregnancyregistry.com. Study GAD-1 evaluated Cymbalta dosages of 60 mg once daily (N=168) and 120 mg once daily (N=170) compared to placebo (N=175) over a 9-week treatment period. What is the most important information I should know about antidepressant medicines, depression, other serious mental illnesses, and suicidal thoughts or actions? Provided by (August 2019) Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. For various degrees of improvement in pain from baseline to study endpoint, Figures 5 and 6 show the fraction of patients achieving that degree of improvement in Studies FM-1 and FM-2, respectively. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. Adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (Cymbalta 3%, placebo 0.7%), and somnolence (Cymbalta 1%, placebo 0%). Duloxetine was administered in the diet to mice and rats for 2 years. In Study MDD-5, 533 adult patients meeting DSM-IV criteria for MDD received Cymbalta 60 mg once daily during an initial 12-week open-label treatment phase. In adult placebo-controlled trials in patients with MDD, activation of mania or hypomania was reported in 0.1% (4/3779) of Cymbalta-treated patients and 0.04% (1/2536) of placebo-treated patients. a Includes adults with MDD, GAD, DPNP, FM, and chronic musculoskeletal pain. Approximately 8.4% (319/3779) of Cymbalta-treated patients in placebo-controlled adult trials for MDD discontinued treatment due to an adverse reaction, compared with 4.6% (117/2536) of placebo-treated patients. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness). Because adverse sexual reactions are presumed to be voluntarily underreported, the Arizona Sexual Experience Scale (ASEX), a validated measure designed to identify sexual adverse reactions, was used prospectively in 4 MDD placebo-controlled adult trials (Studies MDD-1, MDD-2, MDD-3, and MDD-4) [see Clinical Studies (14.2)]. Many additional metabolites have been identified in urine, some representing only minor pathways of elimination. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% CI: 1.08-2.18). There was no significant difference in the frequency of sustained (3 consecutive visits) elevated blood pressure. Potential for Cymbalta to Affect Other Drugs. The following adverse reactions have been identified during post approval use of Cymbalta. After 13 weeks of treatment, patients taking Cymbalta had significantly greater pain reduction than patients taking placebo. After 7 weeks of treatment with Cymbalta 60 mg once daily, in Study OA-1 patients with sub-optimal response to treatment (<30% pain reduction) and tolerated Cymbalta 60 mg once daily had their dose increased to 120 mg.