Cymbalta欣百達

Cymbalta Adverse Reactions

duloxetine

Manufacturer:

Eli Lilly

Distributor:

Zuellig
/
Agencia Lei Va Hong
Full Prescribing Info
Adverse Reactions
The following serious adverse reactions are described as follows and in Precautions: Suicidal Thoughts and Behaviors in Children, Adolescents and Young Adults [see also Warnings]; Hepatotoxicity; Orthostatic Hypotension, Falls and Syncope; Serotonin Syndrome; Abnormal Bleeding; Severe Skin Reactions; Discontinuation of Treatment with CYMBALTA; Activation of Mania/Hypomania; Angle-Closure Glaucoma; Seizures; Effect on Blood Pressure; Clinically Important Drug Interactions; Hyponatremia; Urinary Hesitation and Retention.
Clinical Studies Experience: 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.
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.
Adults: The data described as follows reflect exposure to CYMBALTA in placebo-controlled trials for MDD (N=3779), GAD (N=1018), OA (N=503), CLBP (N=600), DPNP (N=906), and FM (N=1294). The population studied was 17 to 89 years of age; 65.7%, 60.8%, 60.6%, 42.9%, and 94.4% female; and 81.8%, 72.6%, 85.3%, 74.0%, and 85.7% Caucasian for MDD, GAD, OA and CLBP, DPNP, and FM, respectively. Most patients received doses of a total of 60 to 120 mg per day [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. The data as follows do not include results of the trial examining the efficacy of CYMBALTA in patients ≥ 65 years old for the treatment of generalized anxiety disorder; however, the adverse reactions observed in this geriatric sample were generally similar to adverse reactions in the overall adult population.
Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Adult Placebo-Controlled Trials: Major Depressive Disorder: Approximately 8.4% (319/3779) of the patients who received CYMBALTA in placebo-controlled trials for MDD discontinued treatment due to an adverse reaction, compared with 4.6% (117/2536) of the patients receiving placebo. Nausea (CYMBALTA 1.1%, placebo 0.4%) 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 CYMBALTA-treated patients and at a rate of at least twice that of placebo).
Generalized Anxiety Disorder: Approximately 13.7% (139/1018) of the patients who received CYMBALTA in placebo-controlled trials for GAD discontinued treatment due to an adverse reaction, compared with 5.0% (38/767) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined previously) included nausea (CYMBALTA 3.3%, placebo 0.4%), and dizziness (CYMBALTA 1.3%, placebo 0.4%).
Diabetic Peripheral Neuropathic Pain: Approximately 12.9% (117/906) of the patients who received CYMBALTA in placebo-controlled trials for DPNP discontinued treatment due to an adverse reaction, compared with 5.1% (23/448) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined previously) included nausea (CYMBALTA 3.5%, placebo 0.7%), dizziness (CYMBALTA 1.2%, placebo 0.4%), and somnolence (CYMBALTA 1.1%, placebo 0.0%).
Fibromyalgia: Approximately 17.5% (227/1294) of the patients who received CYMBALTA in 3 to 6 month placebo-controlled trials for FM discontinued treatment due to an adverse reaction, compared with 10.1% (96/955) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined previously) included nausea (CYMBALTA 2.0%, placebo 0.5%), headache (CYMBALTA 1.2%, placebo 0.3%), somnolence (CYMBALTA 1.1%, placebo 0.0%), and fatigue (CYMBALTA 1.1%, placebo 0.1%).
Chronic Pain due to Osteoarthritis: Approximately 15.7% (79/503) of the patients who received CYMBALTA in 13-week, placebo-controlled trials for chronic pain due to OA discontinued treatment due to an adverse reaction, compared with 7.3% (37/508) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined previously) included nausea (CYMBALTA 2.2%, placebo 1.0%).
Chronic Low Back Pain: Approximately 16.5% (99/600) of the patients who received CYMBALTA in 13-week, placebo-controlled trials for CLBP discontinued treatment due to an adverse reaction, compared with 6.3% (28/441) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined previously) included nausea (CYMBALTA 3.0%, placebo 0.7%), and somnolence (CYMBALTA 1.0%, placebo 0.0%).
Most Common Adult Adverse Reactions: 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, somnolence, constipation, decreased appetite, and hyperhidrosis.
Diabetic Peripheral Neuropathic Pain: The most commonly observed adverse reactions in CYMBALTA-treated patients (as defined previously) were nausea, somnolence, decreased appetite, constipation, hyperhidrosis, and dry mouth.
Fibromyalgia: The most commonly observed adverse reactions in CYMBALTA-treated patients (as defined previously) were nausea, dry mouth, constipation, somnolence, decreased appetite, hyperhidrosis, and agitation.
Chronic Pain due to Osteoarthritis: The most commonly observed adverse reactions in CYMBALTA-treated patients (as defined previously) were nausea, fatigue, constipation, dry mouth, insomnia, somnolence, and dizziness.
Chronic Low Back Pain: The most commonly observed adverse reactions in CYMBALTA-treated patients (as defined previously) were nausea, dry mouth, insomnia, somnolence, constipation, dizziness, and fatigue.
Adverse Reactions Occurring at an Incidence of 5% or More Among CYMBALTA-Treated Patients in Adult Placebo-Controlled Trials: Table 4 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 CYMBALTA and with an incidence greater than placebo. (See Table 4.)

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Adverse Reactions Occurring at an Incidence of 2% or More Among CYMBALTA-Treated Patients in Adult Placebo-Controlled Trials: Pooled MDD and GAD Trials: Table 5 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 CYMBALTA and with an incidence greater than placebo. (See Table 5.)

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DPNP, FM, OA, and CLBP: Table 6 gives the incidence of treatment-emergent adverse events that occurred in 2% or more of patients treated with CYMBALTA (determined prior to rounding) in the premarketing acute phase of DPNP, FM, OA, and CLBP placebo-controlled trials and with an incidence greater than placebo. (See Table 6.)

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Effects on Male and Female Sexual Function in Adults: 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 7 as follows, 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. (See Table 7.)

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Vital Sign Changes in Adults: In placebo-controlled clinical trials across approved indications for change from baseline to endpoint, CYMBALTA treatment was associated with mean increases of 0.23 mm Hg in systolic blood pressure and 0.73 mm Hg in diastolic blood pressure compared to mean decreases of 1.09 mm Hg systolic and 0.55 mm Hg diastolic in placebo-treated patients. There was no significant difference in the frequency of sustained (3 consecutive visits) elevated blood pressure [see Orthostatic Hypotension, Falls and Syncope and Effect on Blood Pressure under Precautions].
CYMBALTA treatment, for up to 26 weeks in placebo-controlled trials across approved indications, 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).
Laboratory Changes in Adults: CYMBALTA treatment in placebo-controlled clinical trials across approved indications, 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 Hepatotoxicity under Precautions]. High bicarbonate, cholesterol, and abnormal (high or low) potassium, were observed more frequently in CYMBALTA treated patients compared to placebo.
Electrocardiogram Changes in Adults: The effect of CYMBALTA 160 mg and 200 mg administered twice daily to steady state was evaluated in a randomized, double-blinded, two-way crossover study in 117 healthy female subjects. No QT interval prolongation was detected. CYMBALTA appears to be associated with concentration-dependent but not clinically meaningful QT shortening.
Other Adverse Reactions Observed During the Premarketing and Postmarketing Clinical Trial Evaluation of CYMBALTA in Adults: Following is a list of treatment-emergent adverse reactions reported by patients treated with CYMBALTA in clinical trials. In clinical trials of all indications, 34,756 patients were treated with CYMBALTA. Of these, 26.9% (9337) took CYMBALTA for at least 6 months, and 12.4% (4317) for at least one year. The following listing is not intended to include reactions (1) already listed in previous tables or sections, (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, tachycardia, and Takotsubo cardiomyopathy.
Ear and Labyrinth Disorders: Frequent: vertigo.
Infrequent: ear pain and tinnitus.
Endocrine Disorders: Infrequent: hypothyroidism.
Eye Disorders: Frequent: vision blurred.
Infrequent: diplopia, dry eye, and visual impairment.
Gastrointestinal Disorders: Frequent: flatulence.
Infrequent: dysphagia, eructation, gastritis, gastrointestinal hemorrhage, halitosis, and stomatitis.
Rare: gastric ulcer.
General Disorders and Administration Site Conditions: Frequent: chills/rigors.
Infrequent: falls, feeling abnormal, feeling hot and/or cold, malaise, and thirst.
Rare: gait disturbance.
Infections and Infestations: Infrequent: gastroenteritis and laryngitis.
Investigations: Frequent: weight increased, weight decreased.
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 paraesthesia/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: Frequent: urinary frequency.
Infrequent: dysuria, micturition urgency, nocturia, polyuria, and urine odor abnormal.
Reproductive System and Breast Disorders: Frequent: anorgasmia/orgasm abnormal.
Infrequent: menopausal symptoms, sexual dysfunction, and testicular pain.
Rare: menstrual disorder.
Respiratory, Thoracic and Mediastinal Disorders: Frequent: yawning, oropharyngeal pain.
Infrequent: throat tightness.
Skin and Subcutaneous Tissue Disorders: Frequent: pruritus.
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.
Postmarketing Experience: The following adverse reactions have been identified during post approval 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 CYMBALTA therapy and not mentioned in other sections include: acute pancreatitis, anaphylactic reaction, aggression and anger (particularly early in treatment or after treatment discontinuation), angioneurotic edema, angle-closure glaucoma, colitis (microscopic or unspecified), cutaneous vasculitis (sometimes associated with systemic involvement), extrapyramidal disorder, galactorrhea, gynecological bleeding, hallucinations, hyperglycemia, hyperprolactinemia, hypersensitivity, hypertensive crisis, muscle spasm, rash, restless legs syndrome, seizures upon treatment discontinuation, supraventricular arrhythmia, tinnitus (upon treatment discontinuation), trismus, and urticaria.
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