Duloxetine Hydrochloride

Commonly reported side effects of duloxetine include: asthenia, constipation, diarrhea, dizziness, drowsiness, fatigue, hypersomnia, insomnia, nausea, sedated state, headache, and xerostomia. Other side effects include: agitation, erectile dysfunction, nervousness, psychomotor agitation, tension, vomiting, abdominal pain, anorexia, decreased appetite, decreased libido, hyperhidrosis, loss of libido, and restlessness. See below for a comprehensive list of adverse effects.

Applies to duloxetine: oral capsule delayed release

Along with its needed effects, duloxetine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking duloxetine:

Incidence not known

• Abdominal or stomach pain
• area rash
• blindness
• blistering, peeling, or loosening of the skin
• blurred vision
• change in consciousness
• chills
• clay-colored stools
• cold sweats
• confusion
• convulsions
• dark urine
• decreased urine output
• decreased vision
• difficulty swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• eye pain
• fainting
• fast or irregular heartbeat
• general tiredness or weakness
• hives or welts, itching, or skin rash
• hives, itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
• increased thirst
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of consciousness
• red skin lesions, often with a purple center
• red, irritated eyes
• redness of the skin
• sores, ulcers, or white spots in the mouth or on the lips
• swelling of the face, ankles, or hands
• tearing
• tightness in the chest
• unpleasant breath odor
• upper right stomach pain
• vomiting of blood
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking duloxetine:

Symptoms of overdose

• Agitation
• diarrhea
• fever
• loss of bladder control
• muscle spasm or jerking of all extremities
• overactive reflexes
• poor coordination
• restlessness
• shivering
• sleepiness or unusual drowsiness
• sudden loss of consciousness
• sweating
• talking or acting with excitement you cannot control
• trembling or shaking
• twitching
• unusual tiredness or weakness
• vomiting

Some side effects of duloxetine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Body aches or pain
• cough
• difficulty having a bowel movement (stool)
• dry mouth
• ear congestion
• frequent urination
• headache
• lack or loss of strength
• loss of appetite
• loss of voice
• muscle aches
• nausea
• sleepiness or unusual drowsiness
• sneezing
• sore throat
• stuffy or runny nose
• sweating increased
• trouble sleeping
• weight loss

Less common

• Abnormal orgasm
• acid or sour stomach
• belching
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in taste
• change or problem with discharge of semen
• decreased interest in sexual intercourse
• difficulty with moving
• feeling of warmth or redness of the face, neck, arms, and occasionally, upper chest
• heartburn
• inability to have or keep an erection
• indigestion
• joint pain
• longer than usual time to ejaculation of semen
• loose stools
• loss in sexual ability, desire, drive, or performance
• loss of taste
• muscle aching or cramping
• muscle pains or stiffness
• shakiness in the legs, arms, hands, or feet
• stomach discomfort or upset
• sudden sweating
• swollen joints
• trembling or shaking of the hands or feet

Applies to duloxetine: oral delayed release capsule

The most commonly reported side effects reported in placebo-controlled clinical trials included nausea, dry mouth, somnolence, constipation, decreased appetite, hyperhidrosis, agitation, fatigue, insomnia, dizziness

The most commonly reported side effects reported in placebo-controlled clinical trials as a reason for treatment discontinuation and considered to be drug-related included nausea, dizziness, somnolence, headache, and fatigue.

Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding.

Very common (10% or more): Constipation, diarrhea, dry mouth, nausea

Common (1% to 10%): Abdominal pain, dyspepsia, flatulence, vomiting

Uncommon (0.1% to 1%): Dysphagia, eructation, gastritis, gastroenteritis, gastrointestinal hemorrhage, halitosis, hematochezia, stomatitis

Rare (less than 0.1%): Gastric ulcer

Postmarketing reports: Gastrointestinal bleeding, pancreatitis, colitis (microscopic or unspecified)

Very common (10% or more): Dizziness, headache, somnolence

Common (1% to 10%): Dysgeusia, lethargy, paraesthesia/hypoesthesia, tremor

Uncommon (0.1% to 1%): Convulsions, disturbance in attention, dyskinesia, extrapyramidal symptoms, myoclonus, psychomotor restlessness, restless legs syndrome, trismus, syncope

Rare (less than 0.1%): Akathisia, dysarthria, gait disturbance

Postmarketing reports: Intracerebral bleeding, seizures upon treatment discontinuation, serotonin syndrome, extrapyramidal disorder

Potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs, including duloxetine as monotherapy, but particularly with concomitant use of other serotonergic drugs and drugs that impair the metabolism of serotonin.

Antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. An increased risk of suicidal thinking and behavior in children, adolescents, and young adults (aged 18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders has been reported with short-term use of antidepressant drugs.

Adult and pediatric patients receiving antidepressants for MDD, as well as for psychiatric and nonpsychiatric indications, have reported symptoms that may be precursors to emerging suicidality, including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Causality has not been established.

Aggression and anger have been reported particularly early in treatment or after treatment discontinuation.

Very common (10% or more): Insomnia

Common (1% to 10%): Abnormal dreams, agitation, anxiety, sleep disorder

Uncommon (0.1% to 1%): Apathy, bruxism, disorientation/confusional state, irritability, mood swings, nervousness, poor quality sleep, suicide attempt

Rare (less than 0.1%): Aggression and anger, completed suicide, hallucinations, mania, suicidal behavior and ideation

Common (1% to 10%): Decreased appetite, weight increase/decrease

Uncommon (0.1% to 1%): Dehydration, hyperlipidemia, hyponatremia, increased blood cholesterol, increased blood creatine phosphokinase

Rare (less than 0.1%): Dyslipidemia, increased blood potassium

Frequency not reported: Abnormal potassium levels, increased bicarbonate

Postmarketing reports: Hyperglycemia

Although infrequent, several cases of duloxetine induced hyponatremia have been reported. In one case report, duloxetine induced hyponatremia was confirmed after inadvertent rechallenge. It has been suggested that there is a dose-related effect in the development of hyponatremia with duloxetine. Numerous cases of hyponatremia have been reported following treatment with an SSRI. Risk factors include advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels.

Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment (e.g., water restriction, dietary sodium). The proposed mechanism for the development of hyponatremia involves the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) via release of antidiuretic hormone.

Falls were reported more commonly in patients 65 years of age or older.

Very common (10% or more): Fatigue

Common (1% to 10%): Asthenia, chills/rigors, pyrexia, vertigo

Uncommon (0.1% to 1%): Ear pain, falls, feeling abnormal, feeling hot and/or cold, malaise, thirst, tinnitus

Orthostatic hypotension and syncope tend to occur within the first week of therapy; however, they may occur at any time during treatment, particularly after dose increases. The risk of blood pressure decreases may be greater when duloxetine is given concomitantly with drugs that may induce orthostatic hypotension, such as antihypertensives, with potent CYP450 1A2 inhibitors, or with duloxetine doses above 60 mg per day.

Common (1% to 10%): Flushing, hot flush, hypertension, increased blood pressure, palpitations

Uncommon (0.1% to 1%): Chest pain, myocardial infarction, orthostatic hypotension, peripheral coldness, tachycardia

Rare (less than 0.1%): Hypertensive crisis, supraventricular arrhythmia (mainly atrial fibrillation)

Postmarketing reports: Hematomas, ventricular arrhythmias

The reporting rate of Stevens-Johnson syndrome associated with duloxetine exceeds the general population background incidence rate (1 to 2 cases per million person years).

Common (1% to 10%): Pruritus, hyperhidrosis

Uncommon (0.1% to 1%): Cold sweat, contact dermatitis, erythema, increased tendency to bruise, night sweats, photosensitivity reaction, urticaria

Rare (less than 0.1%): Angioneurotic edema, ecchymosis, Stevens-Johnson syndrome

Postmarketing reports: Erythema multiforme, petechiae, cutaneous vasculitis (sometimes with systemic involvement)

Uncommon (0.1% to 1%): Hypothyroidism, syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Postmarketing reports: Hyperprolactinemia

The Arizona sexual experience scale, used to identify sexual side effects, was used prospectively in 4 major depressive disorder placebo-controlled trials showed that male patients treated with duloxetine experienced significantly more sexual dysfunction than patients treated with placebo.

Common (1% to 10%): Abnormal orgasm/anorgasmia, decreased libido, delayed ejaculation, ejaculation disorder, erectile dysfunction, urinary frequency

Uncommon (0.1% to 1%): Abnormal urine odor, dysuria, gynecological hemorrhage, menopausal symptoms, micturition urgency, nocturia, pollakiuria, polyuria, sexual dysfunction, testicular pain, urinary hesitation

Rare (less than 0.1%): Decreased urine flow, galactorrhea, menstrual disorder, urinary retention

Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may increase the risk of bleeding events associated with duloxetine.

Postmarketing reports: Life-threatening hemorrhage, blood dyscrasias

Cases of liver failure, including fatalities, have been reported. The majority of cases were reported in patients with past or current risk factors for liver injury, including alcohol abuse, hepatitis, or exposure to drugs with known adverse effects on the liver.

Uncommon (0.1% to 1%): Acute liver injury, elevated liver enzymes (ALT, AST, GGT, alkaline phosphatase), hepatitis, increased blood bilirubin

Rare (less than 0.1%): Hepatic failure, jaundice

Postmarketing reports: Anaphylactic reaction, hypersensitivity

Common (1% to 10%): Influenza

Common (1% to 10%): Back pain, muscle spasms, musculoskeletal pain (including myalgia, neck pain)

Uncommon (0.1% to 1%): Muscle tightness (including musculoskeletal stiffness), muscle twitching

Postmarketing reports: Rhabdomyolysis

Pupillary dilation that occurs following the use of many antidepressant drugs may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Common (1% to 10%): Blurred vision

Uncommon (0.1% to 1%): Diplopia, dry eye, mydriasis, visual impairment

Rare (less than 0.1%): Glaucoma

Postmarketing reports: Renal impairment

Common (1% to 10%): Cough, nasopharyngitis, oropharyngeal pain, pharyngolaryngeal pain, upper respiratory tract infection, yawning

Uncommon (0.1% to 1%): Laryngitis, throat tightness

Rare (less than 0.1%): Epistaxis