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Adverse Reactions

Drug Interactions

Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism.

Clinical Trial Data Sources

The data described below reflect exposure to duloxetine in placebo-controlled trials for MDD (N=2,327), GAD (N=668), DPNP (N=568), and FM (N=876). The population studied was 17 to 89 years of age; 64.8%, 64.7%, 38.7%, and 94.6% female; and 85.5%, 84.6%, 77.6%, and 88% Caucasian for MDD, GAD, DPNP, and FM, respectively. Most patients received doses of a total of 60 to 120 mg per day. For more information about trial data sources, see Clinical Studies.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Reactions reported during the studies were not necessarily caused by the therapy, and the frequencies do not reflect investigator impression (assessment) of causality.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

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Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials
  • Major Depressive Disorder—Approximately 9% (209/2,327) of the patients who received duloxetine in placebo-controlled trials for MDD discontinued treatment due to an adverse reaction, compared with 4.7% (68/1,460) of the patients receiving placebo. Nausea (duloxetine 1.3%, placebo 0.5%) was the only common adverse reaction reported as a reason for discontinuation and considered to be drug-related (i.e., discontinuation occurring in at least 1% of the duloxetine-treated patients and at a rate of at least twice that of placebo).
  • Generalized Anxiety Disorder—Approximately 15.3% (102/668) of the patients who received duloxetine in placebo-controlled trials for GAD discontinued treatment due to an adverse reaction, compared with 4.0% (20/495) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 3.7%, placebo 0.2%), vomiting (duloxetine 1.3%, placebo 0.0%), and dizziness (duloxetine 1.0%, placebo 0.2%).
  • Diabetic Peripheral Neuropathic Pain—Approximately 14.3% (81/568) of the patients who received duloxetine in placebo-controlled trials for DPNP discontinued treatment due to an adverse reaction, compared with 7.2% (16/223) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) were nausea (duloxetine 3.5%, placebo 0.4%), dizziness (duloxetine 1.6%, placebo 0.4%), somnolence (duloxetine 1.6%, placebo 0.0%) and fatigue (duloxetine 1.1%, placebo 0.0%).
  • Fibromyalgia—Approximately 19.5% (171/876) of the patients who received duloxetine in 3 to 6 month placebo-controlled trials for FM discontinued treatment due to an adverse reaction, compared with 11.8% (63/535) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 1.9%, placebo 0.7%), somnolence (duloxetine 1.5%, placebo 0.0%), and fatigue (duloxetine 1.3%, placebo 0.2%).
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Adverse Reactions Occurring at an Incidence of 5% or More and at least Twice Placebo Among Duloxetine-Treated Patients in Placebo-Controlled Trials

Pooled Trials for all Approved Indications — The most commonly observed adverse reactions in Cymbalta-treated patients (incidence of at least 5% and at least twice the incidence in placebo patients) were nausea, dry mouth, constipation, somnolence, hyperhidrosis, and decreased appetite.

In addition to the adverse reactions listed above, DPNP trials also included dizziness and asthenia.

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Adverse Reactions Occurring at an Incidence of 5% or More Among Duloxetine-Treated Patients in Placebo-Controlled Trials

Table 2 gives the incidence of treatment-emergent adverse reactions in placebo-controlled trials for approved indications that occurred in 5% or more of patients treated with duloxetine and with an incidence greater than placebo.

Table 2: Treatment-Emergent Adverse Reactions: Incidence of 5% or More in Placebo-Controlled Trials of Approved Indications

  Percentage of Patients Reporting Reaction
Adverse Reaction Cymbalta
(N=4843)		 Placebo
(N=3048)
Nausea 25 9
Headache 16 15
Dry mouth 14 6
Fatigueb 11 6
Insomniaa,c 11 7
Dizziness 11 6
Somnolencea,d 11 3
Constipationa 11 4
Diarrhea 10 7
Decreased appetitea,e 8 2
Hyperhidrosis 7 2

a Events for which there was a significant dose-dependent relationship in fixed-dose studies, excluding three MDD studies which did not have a placebo lead-in period or dose titration.
b Also includes asthenia
c Also includes middle insomnia, early morning awakening, and initial insomnia
d Also includes hypersomnia and sedation
e Also includes anorexia

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Adverse Reactions Occurring at an Incidence of 2% or More Among Duloxetine-Treated Patients in Placebo-Controlled Trials

Pooled MDD and GAD Trials—Table 3 gives the incidence of treatment-emergent adverse reactions in MDD and GAD placebo-controlled trials for approved indications that occurred in 2% or more of patients treated with duloxetine and with an incidence greater than placebo.

Table 3: Treatment-Emergent Adverse Reactions: Incidence of 2% or More in MDD and GAD Placebo-Controlled Trials

System Organ Class/Adverse Reaction Percentage of Patients Reporting Reaction
  Cymbalta
(N=2995)		 Placebo
(N=1955)
Cardiac Disorders 2  
Palpitations 2  
Eye Disorders    
Vision blurred 3 2
Gastrointestinal Disorders    
Nausea 25 9
Dry mouth 15 6
Diarrhea 10 7
Constipationa 10 4
Abdominal painb 4 4
Vomiting 5 2
General Disorders and Administration Site Conditions    
Fatiguec 10 6
Investigations    
Weight decreaseda 2 <1
Metabolism and Nutrition Disorders    
Decreased appetitec 7 2
Nervous System Disorders    
Dizziness 10 6
Somnolencee 10 4
Tremor 3 <1
Psychiatric Disorders    
Insomniaf 10 6
Agitationg 5 3
Anxiety 3 2
Libido decreasedh 4 1
Orgasm abnormali 3 <1
Abnormal dreamsj 2 1
Reproductive Systems and Breast Disorders    
Erectile dysfunctionk 5 1
Ejaculation delayeda,k 3 <1
Ejaculation disorderk,l 2 <1
Respiratory, Thoracic, and Mediastinal Disorders    
Yawning 2 <1
Skin and Subcutaneous Tissue Disorders    
Hyperhidrosis 6 2
Vascular Disorders    
Hot flush 2 <1

a Events for which there was a significant dose-dependent relationship in fixed-dose studies, excluding three MDD studies which did not have a placebo lead-in period or dose titration.
b Also includes abdominal pain upper, abdominal pain lower, abdominal tenderness, abdominal discomfort, and gastrointestinal pain
c Also includes asthenia
d Also includes anorexia
e Also includes hypersomnia and sedation
f Also includes middle insomnia, early morning awakening, and initial insomnia
g Also includes feeling jittery, nervousness, restlessness, tension, and psychomotor agitation
h Also includes loss of libido
i Also includes anorgasmia
j Also includes nightmare
k Male patients only
l Also includes ejaculation failure and ejaculation dysfunction

Diabetic Peripheral Neuropathic Pain—Table 4 gives the incidence of treatment-emergent adverse events that occurred in 2% or more of patients treated with Cymbalta in the premarketing acute phase of DPNP placebo-controlled trials (doses of 20 to 120 mg/day) and with an incidence greater than placebo.

Table 4: Treatment-Emergent Adverse Reactions Incidence of 2% or More in DPNP Placebo-Controlled Trials

System Organ Class/Adverse Reaction Percentage of Patients Reporting Reaction
  Cymbalta
20 mg once daily
(N=115)		 Cymbalta
60 mg once daily
(N=228)		 Cymbalta
60 mg twice daily
(N=225)		 Placebo

(N=223)
Gastrointestinal Disorders        
Nausea 14 22 30 9
Constipation 5 11 15 3
Diarrhea 13 11 7 6
Dry mouth 5 7 12 4
Vomiting 6 5 5 4
Dyspepsia 4 4 4 3
Loose stools 2 3 2 1
General Disorders and Administration Site Conditions        
Fatigue 2 10 12 5
Asthenia 2 4 8 1
Pyrexia 2 1 3 1
Infections and Infestations        
Nasopharyngitis 9 7 9 5
Metabolism and Nutrition Disorders        
Decreased appetite 3 4 11 <1
Anorexia 3 3 5 <1
Musculoskeletal and Connective Tissue Disorders        
Muscle cramp 5 4 4 3
Myalgia 3 1 4 <1
Nervous System Disorders        
Somnolence 7 15 21 5
Headache 13 13 15 10
Dizziness 6 14 17 6
Tremor 0 1 5 0
Psychiatric Disorders        
Insomnia 9 8 13 7
Renal and Urinary Disorders        
Pollakiuria 3 1 5 2
Reproductive System and Breast Disorders        
Erectile dysfunctiona 0 1 4 0
Respiratory, Thoracic and Mediastinal Disorders        
Cough 6 3 5 4
Pharyngolaryngeal pain 3 1 6 1
Skin and Subcutaneous Tissue Disorders        
Hyperhidrosis 6 6 8 2

a Male patients only

Fibromyalgia—Table 5 gives the incidence of treatment-emergent adverse events that occurred in 2% or more of patients treated with Cymbalta in the premarketing acute phase of FM placebo-controlled trials and with an incidence greater than placebo.

Table 5: Treatment-Emergent Adverse Reactions: Incidence of 2% or More in Fibromyalgia Placebo-Controlled Trials

System Organ Class/Adverse Reaction Percentage of Patients Reporting Reaction
  Cymbalta
(N=876)		 Placebo
(N=535)
Cardiac Disorders    
Palpitations 2 2
Eye Disorders    
Vision blurred 2 1
Gastrointestinal Disorders    
Nausea 29 11
Dry mouth 18 5
Constipation 15 4
Diarrhea 12 8
Dyspepsia 5 3
General Disorders and Administration Site Conditions    
Fatigueb 15 8
Immune System Disorders    
Seasonal allergy 3 2
Infections and Infestations    
Upper respiratory tract infection 7 6
Urinary tract infection 3 3
Influenza 2 2
Gastroenteritis viral 2 2
Investigations    
Weight increased 2 1
Metabolism and Nutrition Disorders    
Decreased appetitec 11 2
Muscoskeletal and Connective Tissue Disorders    
Musculoskeletal pain 5 4
Muscle spasms 4 3
Nervous System Disorders    
Headache 20 12
Dizziness 11 7
Somnolenced 11 3
Tremor 4 1
Paraesthesia 4 4
Migraine 3 3
Dysgeusia 3 1
Psychiatric Disorders    
Insomniae 16 10
Agitationf 6 2
Sleep disorder 3 2
Abnormal dreamsg 3 1
Orgasm abnormalh 3 <1
Libido decreasedi 2 <1
Reproductive System and Breast Disorders    
Ejaculation disordera,j 4 0
Penis disordera 2 0
Respiratory, Thoracic, and Mediastinal Disorders    
Cough 4 3
Pharyngolaryngeal pain 3 3
Skin and Subcutaneous Tissue Disorders    
Hyperhidrosis 7 1
Rash 4 2
Pruritis 3 2
Vascular Disorders    
Hot flush 3 2

a Male patients only (N = 46 duloxetine-treated patients versus 26 placebo patients)
b Also includes asthenia
c Also includes anorexia
d Also includes hypersomnia and sedation
e Also includes middle insomnia, early morning awakening, and initial insomnia
f Also includes feeling jittery, nervousness, restlessness, tension, and psychomotor agitation
g Also includes nightmare
h Also includes anorgasmia
i Also includes loss of libido
j Also includes ejaculation failure and ejaculation dysfunction

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Effects on Male and Female Sexual Function

Changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of psychiatric disorders or diabetes, but they may also be a consequence of pharmacologic treatment. Because adverse sexual reactions are presumed to be voluntarily underreported, the Arizona Sexual Experience Scale (ASEX), a validated measure designed to identify sexual side effects, was used prospectively in 4 MDD placebo-controlled trials. In these trials, as shown in Table 6 below, patients treated with Cymbalta experienced significantly more sexual dysfunction, as measured by the total score on the ASEX, than did patients treated with placebo. Gender analysis showed that this difference occurred only in males. Males treated with Cymbalta experienced more difficulty with ability to reach orgasm (ASEX Item 4) than males treated with placebo. Females did not experience more sexual dysfunction on Cymbalta than on placebo as measured by ASEX total score. Negative numbers signify an improvement from a baseline level of dysfunction, which is commonly seen in depressed patients. Physicians should routinely inquire about possible sexual side effects.

Table 6: Mean Change in ASEX Scores by Gender in MDD Placebo-Controlled Trials

  Male Patientsa Female Patientsa
  Cymbalta
(n=175)		 Placebo
(n=83)		 Cymbalta
(n=241)		 Placebo
(n=126)
ASEX Total (Items 1-5) 0.56b -1.07 -1.15 -1.07
Item 1—Sex drive -0.07 -0.12 -0.32 -0.24
Item 2—Arousal -0.01 -0.26 -0.21 -0.18
Item 3—Ability to achieve erection (men); Lubrication (women) -0.03 -0.25 -0.17 -0.18
Item 4—Ease of reaching orgasm 0.40c -0.24 -0.09 -0.13
Item 5—Orgasm satisfaction 0.09 -0.13 -0.11 -0.17

a n=Number of patients with non-missing change score for ASEX total
b p=0.013 versus placebo
c p<0.001 versus placebo

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Vital Sign Changes

In clinical trials across indications, relative to placebo, duloxetine treatment was associated with mean increases of up to 2.1 mm Hg in systolic blood pressure and up to 2.3 mm Hg in diastolic blood pressure. There was no significant difference in the frequency of sustained (3 consecutive visits) elevated blood pressure.

Duloxetine treatment, for up to 26 weeks in placebo-controlled trials typically caused a small increase in heart rate compared to placebo of up to 3-4 beats per minute.

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Weight Changes

In placebo-controlled clinical trials, MDD and GAD patients treated with Cymbalta for up to 10 weeks experienced a mean weight loss of approximately 0.5 kg, compared with a mean weight gain of approximately 0.2 kg in placebo-treated patients. In DPN placebo-controlled clinical trials, patients treated with Cymbalta for up to 13-weeks experienced a mean weight loss of approximately 1.1 kg, compared with a mean weight gain of approximately 0.2 kg in placebo-treated patients. In fibromyalgia studies, patients treated with Cymbalta for up to 26 weeks experienced a mean weight loss of approximately 0.4 kg compared with a mean weight gain of approximately 0.3 kg in placebo-treated patients. In one long-term fibromyalgia 60-week uncontrolled study, duloxetine patients had a mean weight increase of 0.7 kg.

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Laboratory Changes

Cymbalta treatment in placebo-controlled clinical trials, was associated with small mean increases from baseline to endpoint in ALT, AST, CPK, and alkaline phosphatase; infrequent, modest, transient, abnormal values were observed for these analytes in Cymbalta-treated patients when compared with placebo-treated patients. See Warnings and Precautions.

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Electrocardiogram Changes

Electrocardiograms were obtained from duloxetine-treated patients and placebo-treated patients in clinical trials lasting up to 13 weeks. No clinically significant differences were observed for QTc, QT, PR, and QRS intervals between duloxetine-treated and placebo-treated patients. There were no differences in clinically meaningful QTcF elevations between duloxetine and placebo. In a positive-controlled study in healthy volunteers using duloxetine up to 200 mg twice daily, no prolongation of the corrected QT interval was observed.

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Other Adverse Reactions Observed During the Premarketing and Postmarketing Clinical Trial Evaluation of Duloxetine

Following is a list of treatment-emergent adverse reactions reported by patients treated with duloxetine in clinical trials. In clinical trials of all indications, 27,229 patients were treated with duloxetine. Of these, 29% (7,886) took duloxetine for at least 6 months, and 13.3% (3,614) for at least one year. The following listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo.

Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients.

  • Cardiac Disorders—Frequent: palpitations; Infrequent: myocardial infarction and tachycardia.
  • Ear and Labyrinth Disorders—Frequent: vertigo; Infrequent: ear pain and tinnitus.
  • Endocrine Disorders—Infrequent: hypothyroidism.
  • Eye Disorders—Frequent: vision blurred; Infrequent: diplopia and visual disturbance.
  • Gastrointestinal Disorders—Frequent: flatulence; Infrequent: eructation, gastritis, halitosis, and stomatitis; Rare: gastric ulcer, hematochezia, and melena.
  • General Disorders and Administration Site Conditions—Frequent: chills/rigors; Infrequent: feeling abnormal, feeling hot and/or cold, malaise, and thirst; Rare: gait disturbance.
  • Infections and Infestations—Infrequent: gastroenteritis and laryngitis.
  • Investigations—Frequent: weight increased; Infrequent: blood cholesterol increased.
  • Metabolism and Nutrition Disorders—Infrequent: dehydration and hyperlipidemia; Rare: dyslipidemia.
  • Musculoskeletal and Connective Tissue Disorders—Frequent: musculoskeletal pain; Infrequent: muscle tightness and muscle twitching.
  • Nervous System Disorders—Frequent: dysgeusia, lethargy, and parasthesia/hypoesthesia; Infrequent: disturbance in attention, dyskinesia, myoclonus, and poor quality sleep; Rare: dysarthria.
  • Psychiatric Disorders—Frequent: abnormal dreams and sleep disorder; Infrequent: apathy, bruxism, disorientation/confusional state, irritability, mood swings, and suicide attempt; Rare: completed suicide.
  • Renal and Urinary Disorders—Infrequent: dysuria, micturition urgency, nocturia, polyuria, and urine odor abnormal.
  • Reproductive System and Breast Disorders—Frequent: anorgasmia/orgasm abnormal; Infrequent: menopausal symptoms, and sexual dysfunction.
  • Respiratory, Thoracic and Mediastinal Disorders—Frequent: yawning; Infrequent: throat tightness.
  • Skin and Subcutaneous Tissue Disorders—Infrequent: cold sweat, dermatitis contact, erythema, increased tendency to bruise, night sweats, and photosensitivity reaction; Rare: ecchymosis.
  • Vascular Disorders—Frequent: hot flush; Infrequent: flushing, orthostatic hypotension, and peripheral coldness.
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Postmarketing Spontaneous Reports

The following adverse reactions have been identified during postapproval use of Cymbalta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported since market introduction that were temporally related to duloxetine therapy and not mentioned elsewhere in labeling include: anaphylactic reaction, aggression and anger (particularly early in treatment or after treatment discontinuation), angioneurotic edema, erythema multiforme, extrapyramidal disorder, glaucoma, gynecological bleeding, hallucinations, hyperglycemia, hypersensitivity, hypertensive crisis, muscle spasm, rash, restless legs syndrome, seizures upon treatment discontinuation, supraventricular arrhythmia, tinnitus (upon treatment discontinuation), trismus, and urticaria.

Serious skin reactions including Stevens-Johnson Syndrome that have required drug discontinuation and/or hospitalization have been reported with duloxetine.

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Drug Interactions

Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism.

Inhibitors of CYP1A2

When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the Cmax was increased about 2.5-fold, and duloxetine t1/2 was increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin.

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Inhibitors of CYP2D6

Concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) increased the concentration of duloxetine AUC by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine).

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Dual Inhibition of CYP1A2 and CYP2D6

Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and Cmax.

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Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin)

Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued.

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Lorazepam

Under steady-state conditions for duloxetine (60 mg Q 12 hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration.

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Temazepam

Under steady-state conditions for duloxetine (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration.

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Drugs that Affect Gastric Acidity

Cymbalta has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, Cymbalta, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using Cymbalta in patients with conditions that may slow gastric emptying (e.g., some diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. 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. It is unknown whether the concomitant administration of proton pump inhibitors affects duloxetine absorption.

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Drugs Metabolized by CYP1A2

In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity. Therefore, an increase in the metabolism of CYP1A2 substrates (e.g., theophylline, caffeine) resulting from induction is not anticipated, although clinical studies of induction have not been performed. Duloxetine is an inhibitor of the CYP1A2 isoform in in vitro studies, and in two clinical studies the average (90% confidence interval) increase in theophylline AUC was 7% (1%-15%) and 20% (13%-27%) when co-administered with duloxetine (60 mg twice daily).

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Drugs Metabolized by CYP2D6

Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered (at a dose of 60 mg twice daily) in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold.

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Drugs Metabolized by CYP2C9

Duloxetine does not inhibit the in vitro enzyme activity of CYP2C9. Inhibition of the metabolism of CYP2C9 substrates is therefore not anticipated, although clinical studies have not been performed.

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Drugs Metabolized by CYP3A

Results of in vitro studies demonstrate that duloxetine does not inhibit or induce CYP3A activity. Therefore, an increase or decrease in the metabolism of CYP3A substrates (e.g., oral contraceptives and other steroidal agents) resulting from induction or inhibition is not anticipated, although clinical studies have not been performed.

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Drugs Metabolized by CYP2C19

Results of in vitro studies demonstrate that duloxetine does not inhibit CYP2C19 activity at therapeutic concentrations. Inhibition of the metabolism of CYP2C19 substrates is therefore not anticipated, although clinical studies have not been performed.

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Monoamine Oxidase Inhibitors

For information regarding Cymbalta and MAOIs, please see Dosage and Administration, Contraindications, and Warnings and Precautions.

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Serotonergic Drugs

Based on the mechanism of action of SNRIs and SSRIs, including Cymbalta, and the potential for serotonin syndrome, caution is advised when Cymbalta is co-administered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John's Wort. The concomitant use of Cymbalta with other SSRIs, SNRIs or tryptophan is not recommended.

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Triptans

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Cymbalta with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. For more information about Cymbalta and triptans, please see Warnings and Precautions.

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Alcohol

When Cymbalta and ethanol were administered several hours apart so that peak concentrations of each would coincide, Cymbalta did not increase the impairment of mental and motor skills caused by alcohol.

In the Cymbalta clinical trials database, three Cymbalta-treated patients had liver injury as manifested by ALT and total bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, and this may have contributed to the abnormalities seen.

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CNS Drugs

For information regarding Cymbalta and CNS drugs, see Warnings and Precautions.

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Drugs Highly Bound to Plasma Protein

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.

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Mechanism of Action

Cymbalta is believed to modulate both serotonin and norepinephrine in the brain and spinal cord. Learn more about the MOA of Cymbalta.

Formulary Access Finder

Cymbalta has been added to the Anthem Blue Cross Blue Shield National Preferred Formulary.

Get more information about the formulary access for Cymbalta. Download PDF files of insurance providers covering Cymbalta in your state.