Brand name: Cymbalta
Drug class: Selective Serotonin- and Norepinephrine-reuptake Inhibitors

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Antidepressant and anxiolytic; a selective serotonin- and norepinephrine-reuptake inhibitor (SNRI).^{1 2 29 30 31}

Uses for DULoxetine Hydrochloride

Major Depressive Disorder

Treatment of major depressive disorder in adults.^{1 34 44 45}

Guidelines from the American Psychiatric Association (APA) and the Department of Veterans Affairs/Department of Defense state that there is no evidence to suggest superiority of one first-line antidepressant over another.^{500 501} Recommended first-line agents for initial treatment of major depressive disorder include bupropion, mirtazapine, selective serotonin-reuptake inhibitors (SSRIs), SNRIs, trazodone, vilazodone, and vortioxetine.^{500 501} Select appropriate drug based on patient preference, response to prior therapies, and other patient- and drug-related factors.^{498 499 500 501}

Generalized Anxiety Disorder

Acute management of generalized anxiety disorder in adults and pediatric patients ≥7 years of age.^{1 29 30 31 502 503 504}

First-line treatments for adults with generalized anxiety disorder include cognitive behavioral therapy, pharmacotherapy (SSRIs or SNRIs), or a combination of both.⁵⁰⁵ SSRIs approved for use in generalized anxiety disorder include paroxetine, sertraline, and escitalopram; approved SNRIs include venlafaxine and duloxetine.⁵⁰⁶

Guidelines from the American Academy of Child and Adolescent Psychiatry (AACAP) recommend cognitive behavioral therapy or an SSRI for treatment of patients 6–18 years of age with generalized anxiety.⁵⁰⁷ SNRIs can also be considered.⁵⁰⁷

Neuropathic Pain

Management of neuropathic pain associated with diabetic peripheral neuropathy in adults.^{1 48 49}

The American Diabetes Association (ADA) stresses importance of optimal glucose, serum lipid, and blood pressure control along with lifestyle changes to help prevent or delay the development of diabetic neuropathies.⁵⁰⁸ Pharmacologic recommendations for neuropathic pain include gabapentinoids, SNRIs, sodium channel blockers, and tricyclic antidepressants.⁵⁰⁸

Fibromyalgia

Management of fibromyalgia in adults and pediatric patients ≥13 years of age.^{1 46 47 65 510}

CDC guidelines recommend use of nonpharmacologic therapies (e.g., exercise, cognitive behavioral therapy, massage) for initial management of chronic pain.⁵¹⁶ Nonopioid analgesics can be used if nonpharmacologic approaches are not sufficient for pain relief.⁵¹⁶ In patients with fibromyalgia, CDC guidelines state that tricyclic and SNRI antidepressants (including duloxetine), NSAIAs, and the gabapentinoids may be used.⁵¹⁶

Chronic Musculoskeletal Pain

Management of chronic musculoskeletal pain in adults.^{1 511 513 514}

CDC guidelines recommend use of nonpharmacologic therapies (e.g., exercise, cognitive behavioral therapy, massage) for initial management of chronic pain.⁵¹⁶ Nonopioid analgesics can be used if nonpharmacologic approaches are not sufficient for pain relief.⁵¹⁶ In patients with osteoarthritis or chronic low back pain who have an insufficient response to nonpharmacologic interventions, CDC guidelines state that topical NSAIAs, systemic NSAIAs, or duloxetine may be considered.⁵¹⁶

Stress Urinary Incontinence

Has been used for management of moderate to severe stress urinary incontinence (SUI)^{† [off-label]} in women.^{20 21 22 23 24 25 26 33 35 36 37 38 39 40 41 42 43}

Chemotherapy-induced Peripheral Neuropathy

Has been used for management of chemotherapy induced peripheral neuropathy.^{† [off-label]518}

American Society of Clinical Oncology (ASCO) guidelines state that duloxetine may be offered to patients with painful peripheral chemotherapy-induced neuropathy who have completed neurotoxic chemotherapy.⁵¹⁸

DULoxetine Hydrochloride Dosage and Administration

General

Pretreatment Screening

• Screen patients with depressive symptoms for a personal or family history of suicide, bipolar disorder, and depression.¹

• Assess BP prior to initiating therapy.¹

Patient Monitoring

• Monitor BP periodically during duloxetine therapy.¹

• Monitor patients for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.¹

• Monitor patients for serotonin syndrome.¹

• Regular monitoring of weight and growth is recommended in pediatric patients receiving duloxetine.¹

Other General Considerations

• If patient is being transitioned to duloxetine therapy from a monoamine oxidase (MAO) inhibitor intended to treat psychiatric disorders, allow 14 days to elapse between discontinuation of the MAO inhibitor and initiation of duloxetine.¹ Conversely, if switching from duloxetine to an MAO inhibitor, allow 5 days to elapse between discontinuation of duloxetine and initiation of the MAO inhibitor.¹

• Do not initiate duloxetine in patients receiving linezolid or IV methylene blue; if urgent treatment with linezolid or IV methylene blue is required, stop duloxetine and monitor for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or IV methylene blue (whichever comes first).¹ Resume duloxetine 24 hours after the last dose of linezolid or IV methylene blue.¹

• When duloxetine therapy is discontinued, dosage should be tapered gradually and the patient carefully monitored to reduce the risk of withdrawal symptoms.¹

Administration

Oral Administration

Administer orally without regard to meals.¹

Swallow delayed-release capsules whole; do not chew or crush.¹

Do not sprinkle contents of delayed-release capsules on food or mix with liquids.¹

If a dose is missed, take missed dose as soon as it is remembered; if it is almost time for the next scheduled dose, skip the missed dose and take next dose at the regularly scheduled time.¹ Do not take 2 doses at the same time.¹

Dosage

Available as duloxetine hydrochloride; dosage expressed in terms of duloxetine.¹

Pediatric Patients

Generalized Anxiety Disorder

Oral

Pediatric patients ≥7 years of age: Initially, 30 mg daily.¹ After 2 weeks, may increase to 60 mg once daily.¹ Recommended dosage is 30–60 mg once daily; however, dosage may be titrated in increments of 30 mg once daily to a maximum of 120 mg daily.¹

Fibromyalgia

Oral

Pediatric patients ≥13 years of age: Initially, 30 mg daily.¹ Based on response and tolerability, may increase to 60 mg once daily.¹

Adults

Major Depressive Disorder

Oral

Initially, 40 mg daily (given as 20 mg twice daily) to 60 mg daily (as a single dose or as 30 mg twice daily).¹ In some patients, it may be desirable to initiate therapy with a dosage of 30 mg once daily given for 1 week to allow patients to adjust to duloxetine before increasing to 60 mg once daily.¹

Maintenance treatment: 60 mg once daily.^{1 34} Dosages of up to 120 mg daily have been effective; however, no additional benefit demonstrated from dosages >60 mg daily.¹

Periodically reassess need for continued therapy and appropriateness of dosage.¹

Generalized Anxiety Disorder

Oral

Adults <65 years of age: Initially, 60 mg once daily.¹ In some patients, it may be desirable to initiate therapy with a dosage of 30 mg once daily given for 1 week to allow patients to adjust to duloxetine before increasing to 60 mg once daily.¹ Dosage may be increased in increments of 30 mg once daily (up to a maximum dosage of 120 mg once daily).¹ However, no additional benefit demonstrated from dosages >60 mg once daily.¹

Adults ≥65 years of age: Initially, 30 mg once daily.¹ After 2 weeks, may increase to target dosage of 60 mg once daily.¹ Dosage may be increased in increments of 30 mg once daily (up to a maximum dosage of 120 mg once daily).¹

Periodically reassess need for continued therapy.¹

Neuropathic Pain

Diabetic Peripheral Neuropathy

Oral

60 mg once daily; consider lower initial dosage if tolerability issues in patient.¹ Dosages >60 mg daily do not provide additional therapeutic benefit and are associated with a higher incidence of adverse effects.¹

Because renal disease is often present in patients with diabetes, consider initiating duloxetine at a reduced starting dose and gradually increasing.¹

Fibromyalgia

Oral

60 mg once daily; initiate therapy with 30 mg once daily for 1 week to allow patients to adjust to drug before increasing to 60 mg once daily.¹ Some patients may respond to the initial dosage of 30 mg once daily.¹ Dosages >60 mg daily do not provide additional therapeutic benefit and are associated with a higher incidence of adverse effects.¹

Chronic Musculoskeletal Pain

Oral

60 mg once daily; initiate therapy with 30 mg once daily for 1 week to allow patients to adjust to drug before increasing to 60 mg once daily.¹ Dosages >60 mg daily do not provide additional therapeutic benefit and are associated with a higher incidence of adverse effects.¹

Stress Urinary Incontinence† [off-label]

Oral

Optimum dosage not established; 80 mg daily (given in 2 divided doses) usually has been given.^{20 21 22 23 24 25 26 36} Dosages have ranged from 20–120 mg daily in clinical studies.^{20 21 22 23 24 25 26 36 38 41 43}

Special Populations

Hepatic Impairment

No specific dosage recommendations for patients with hepatic impairment.¹ Avoid use in patients with chronic liver disease or cirrhosis.¹

Renal Impairment

No specific dosage recommendations for patients with mild or moderate renal impairment.¹ Avoid use in patients with Cl_cr <30 mL/minute.¹

Geriatric Patients

When treating generalized anxiety disorder in patients ≥65 years of age, initiate at 30 mg once daily for 2 weeks before considering dosage increase.¹

Consider dosage reduction or discontinuation if symptomatic orthostatic hypotension, falls, or syncope occur.¹ Increased risk of falls in geriatric patients.¹

Cautions for DULoxetine Hydrochloride

Contraindications

• Concurrent or recent (i.e., within 14 days) therapy with an MAO inhibitor intended to treat psychiatric disorders.¹ Use of an MAO inhibitor within 5 days of duloxetine discontinuance.¹

• Initiation in patients receiving linezolid or IV methylene blue.¹

Warnings/Precautions

Warnings

Suicidal Thoughts and Behaviors

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (18–24 years of age).¹ (See Boxed Warning.) Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.¹

Appropriately monitor and closely observe patients receiving duloxetine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.¹

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.¹ Consider changing or discontinuing therapy in patients whose depression is persistently worse and in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality.¹

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.¹

Bipolar disorder can initially present as a major depressive episode; screen all patients with depressive symptoms for risk of bipolar disorder.¹ Treatment of bipolar disorder with an antidepressant alone can trigger a mixed/manic episode.¹ Duloxetine is not indicated for bipolar disorder.¹

Other Warnings and Precautions

Hepatotoxicity

Hepatic failure, sometimes fatal, reported; cases presented as hepatitis accompanied by abdominal pain, hepatomegaly, and markedly elevated serum transaminase concentrations (>20 times ULN) with or without jaundice.¹ Cases of cholestatic jaundice with minimal elevation of serum transaminase concentrations also reported.¹ Postmarketing reports indicate that elevated serum transaminase, bilirubin, and alkaline phosphatase concentrations have occurred in duloxetine-treated patients with chronic hepatic disease or cirrhosis.¹

Discontinue duloxetine in any patient who develops jaundice or other evidence of clinically important hepatic dysfunction; do not resume therapy unless another cause for the hepatic dysfunction can be established.¹

Do not prescribe to patients with substantial alcohol consumption or evidence of chronic hepatic disease.¹

Orthostatic Hypotension, Falls, and Syncope

Orthostatic hypotension and syncope reported with therapeutic dosages; these effects tend to occur within first week of therapy, but may occur any time, particularly following dosage increases.¹ Falls resulting in serious injury also have been reported.¹ Degree of orthostatic decrease in BP appears related to risk of falls.^{1 1}

Patients receiving concomitant therapy with other drugs that produce orthostatic hypotension (e.g., antihypertensive agents) or potent CYP1A2 inhibitors, or receiving duloxetine dosages >60 mg daily may be at increased risk.¹

Consider dosage reduction or discontinuing duloxetine in patients experiencing symptomatic orthostatic hypotension, falls, and/or syncope.¹

Fall risk appears to increase with age.¹

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported with SNRIs, especially during concurrent therapy with other serotonergic drugs (e.g., 5-HT₁ receptor agonists [“triptans”]), tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort [Hypericum perforatum]), or drugs that impair serotonin metabolism (e.g., MAO inhibitors).¹ Signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).¹

Bleeding

Drugs that inhibit serotonin reuptake, including duloxetine, may increase risk of bleeding.¹ Bleeding events have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.¹ Concomitant use of aspirin, NSAIAs, warfarin, or other anticoagulants may potentiate risk.¹

Advise patients of risk of bleeding associated with concomitant use of duloxetine and aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation.¹

Severe Skin Reactions

Erythema multiforme and Stevens-Johnson Syndrome (SJS) reported.¹ Discontinue duloxetine at the first appearance of blisters, peeling rash, mucosal erosions, or other signs of hypersensitivity if not attributed to another condition.¹

Discontinuation Syndrome

Possibly severe withdrawal reactions (e.g., dysphoric mood, irritability, agitation, nausea/vomiting, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, seizures); avoid abrupt discontinuance of therapy.¹ Taper dosage gradually and monitor patients for possible withdrawal symptoms when discontinuing therapy.¹

Activation of Mania/Hypomania

Activation of mania and hypomania has occurred in patients with major depressive disorder receiving duloxetine; use with caution in patients with history of mania.¹

Angle-closure Glaucoma

Can cause pupillary dilation, which can trigger an angle closure attack in patients without a patent iridectomy with anatomically narrow angles.¹

Seizures

Use of duloxetine not systematically evaluated in patients with seizures, but seizures have been reported in patients receiving the drug.¹ Use with caution in patients with a history of seizures.¹

Elevated BP

Possible increased BP; monitor BP prior to and periodically during therapy.¹

Clinically Important Drug Interactions

Because CYP1A2 and CYP2D6 are responsible for duloxetine metabolism, potential exists for clinically important drug interactions when duloxetine is used concomitantly with CYP1A2 inhibitors, CYP2D6 inhibitors, and CYP2D6 substrates.¹

Concurrent therapy with MAO inhibitors used for treatment of depression is contraindicated.¹

Possible hepatotoxicity when duloxetine and alcohol are used together; avoid use of duloxetine in patients with substantial alcohol use.¹

Caution advised when duloxetine is given with or substituted for other centrally acting drugs, including those with a similar mechanism of action.¹

Hyponatremia

Possible hyponatremia during treatment with SSRIs and SNRIs, including duloxetine; in many cases, hyponatremia appears to be due to syndrome of inappropriate antidiuretic hormone (SIADH).¹ Geriatric patients and patients receiving diuretics or who are otherwise volume depleted may be at greater risk.¹

Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.¹

Use in Patients with Concomitant Illnesses

Limited experience in patients with concomitant diseases.¹

Because of enteric coating on pellets in duloxetine capsules, use with caution in patients with conditions that may slow gastric emptying (e.g., in some patients with diabetes mellitus).¹

Not systematically evaluated in patients with a recent history of MI or unstable CAD.¹

Possible worsening of glycemic control in patients with diabetes mellitus.¹

Urinary Hesitation and Retention

May affect urethral resistance.¹ Urinary retention reported; hospitalization and/or catheterization were necessary in some cases.¹ If symptoms of urinary hesitation develop, consider possibility that symptoms may be drug-related.¹

Sexual Dysfunction

Sexual dysfunction can occur.¹

Inquire about sexual function prior to initiation of and during treatment with duloxetine, since sexual function may not be spontaneously reported.¹

Specific Populations

Pregnancy

National Pregnancy Registry for Antidepressants available at 1-866-961-2388.¹

Drug-associated risk of major birth defects or adverse developmental outcomes not identified.¹ Consider risks associated with untreated condition (e.g., depression, fibromyalgia) and also the exposure to SNRIs or SSRIs during pregnancy.¹

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, and tube feeding in neonates exposed to SSRIs late in the third trimester; may arise immediately upon delivery.¹

Lactation

Distributed into milk in humans.¹ Because exposure to duloxetine through breast milk has resulted in cases of sedation, poor feeding, and poor weight gain in breast-fed infants, monitor breast-fed infants for these symptoms.¹

Not known if duloxetine affects milk production.¹

Pediatric Use

Safety and efficacy established in children 7 to <17 years of age for generalized anxiety disorder; not established in children <7 years of age for this indication.¹

Safety and efficacy established in children 13-17 years of age for fibromyalgia; not established in children <13 years of age for this indication.¹

Safety and efficacy not established in pediatric patients with major depressive disorder, diabetic peripheral neuropathic pain, or chronic musculoskeletal pain.¹

Greater risk of suicidal thinking or behavior (suicidality) during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).¹ No suicides occurred in these pediatric trials.^{1 32}

Monitor for clinical worsening and the development of suicidal thinking or behavior, especially during the first few months of treatment and during dosage changes.¹ Decreased appetite and loss of weight have been observed with use of SSRIs and SNRIs.¹ Regular monitoring of weight and growth also recommended in pediatric patients receiving duloxetine.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Clinically important hyponatremia reported in geriatric patients.¹

Hepatic Impairment

Possible risk of severe hepatic toxicity; use not recommended in patients with chronic liver disease or excessive alcohol use.¹

Renal Impairment

Increased AUC and peak plasma concentrations of duloxetine and its metabolites observed in patients with end-stage renal disease requiring dialysis.¹ Use not recommended in severe renal impairment (Cl_cr<30 mL/minute).¹

Mild to moderate renal impairment does not appear to have a clinically important effect on duloxetine apparent clearance.¹

Pharmacogenomic Considerations

Genetic variations in CYP2D6, CYP2C19, CYP2B6, SLC6A4(gene encoding serotonin transporter), and HTR2A (gene encoding postsynaptic serotonin-2A receptor) can influence metabolism, efficacy, and adverse effect profile of serotonin reuptake inhibitor antidepressants.⁴⁰⁰

The Clinical Pharmacogenetics Implementation Consortium (CPIC) has developed guidelines for dosing or selection of these antidepressants based on genotype testing.⁴⁰⁰

Although duloxetine is a substrate of CYP2D6, CPIC states the currently available data do not support a clinically meaningful impact of CYP2D6 on duloxetine.⁴⁰⁰

There is insufficient evidence to support any clinical recommendations based on SLC6A4and HTR2A.⁴⁰⁰

Common Adverse Effects

Adverse effects (≥5%) in adults: nausea, dry mouth, somnolence, constipation, decreased appetite, increased sweating.¹

Adverse effects (≥5%) in pediatric patients: decreased weight, decreased appetite, nausea, vomiting, fatigue, diarrhea.¹

Drug Interactions

Metabolized by CYP isoenzymes, principally CYP2D6 and CYP1A2.¹

Moderately inhibits CYP2D6.¹

Does not induce CYP1A2, but inhibits CYP1A2 in vitro.¹

Does not inhibit CYP2C9 or CYP2C19 in vitro, or induce or inhibit CYP3A in vitro.¹

Drugs Affecting Hepatic Microsomal Enzymes

Potent inhibitors of CYP1A2: potential pharmacokinetic interaction (increased plasma duloxetine concentrations); avoid concomitant use.¹

Potent inhibitors of CYP2D6: potential pharmacokinetic interaction (increased plasma duloxetine concentrations).¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: potential pharmacokinetic interaction (increased plasma substrate concentrations).¹ Use concomitantly with caution.¹

Substrates of CYP1A2, CYP3A, CYP2C9, or CYP2C19: pharmacokinetic interaction unlikely.¹

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect coagulation; use with caution.¹

Drugs Associated with Serotonin Syndrome

Potential pharmacologic interaction (serotonin syndrome) with serotonergic agents.¹ Avoid such use or use with caution.¹

Drugs Affecting Gastric Acidity

Theoretical risk of early duloxetine release from enteric-coated pellets if administered with drugs that increase gastric pH.¹

Protein-bound Drugs

Not fully evaluated.¹ Potential for duloxetine to displace other highly protein-bound drugs; may result in increased plasma concentrations and adverse effects of other drug.¹

Specific Drugs

DULoxetine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration usually attained in 6 hours.¹

Steady state concentrations attained after 3 days of once daily dosing.¹ Duloxetine pharmacokinetics are dose-proportional over the therapeutic dose range (30-120 mg daily).¹

Food

Food decreases rate and marginally decreases extent (about 10%) of absorption.¹

Special Populations

In patients with end-stage renal disease (requiring dialysis), AUCs and peak plasma concentration of duloxetine and its metabolites are increased.¹

Bioavailability decreased by approximately 33% in smokers.¹

Mean steady state concentrations 30% lower in pediatric patients 7-17 years of age relative to adult patients; considered comparable between age groups.¹

Distribution

Extent

Distributed into milk in humans.¹

Plasma Protein Binding

>90%.¹

Elimination

Metabolism

Extensively metabolized to numerous metabolites.¹

Metabolized by CYP isoenzymes, principally CYP2D6 and CYP1A2.¹

Elimination Route

Excreted principally in urine as metabolites (about 70%) and unchanged drug (<1%), and in feces (20%).¹

Half-life

Approximately 12 hours.¹

Special Populations

In patients with hepatic impairment, metabolism and clearance are decreased.¹

In patients with end-stage renal disease (requiring dialysis), plasma half-life may be unchanged; in patients with mild to moderate renal impairment (Cl_cr 30–80 mL/min), there is no clinically important effect on clearance.¹

Pharmacokinetics of duloxetine are not affected by sex; half-life is similar in men and women.¹

Impact of race on duloxetine pharmacokinetics not evaluated.¹

Stability

Storage

Oral

Delayed-release Capsules

25°C (excursions permitted to 15-30°C).¹

Actions

• Mechanism of antidepressant effects, anxiolytic effects, or CNS pain inhibition not established but presumed to be linked to potentiation of serotonergic and noradrenergic activity in the CNS resulting from inhibition of CNS neuronal reuptake of serotonin (5-HT) and norepinephrine.^{1 49}

• Precise mechanism of action in stress urinary incontinence unknown, but thought to be related to potentiation of serotonin and norepinephrine activity in sacral spinal cord, which increases urethral closure forces and thereby reduces involuntary urine loss.^{36 37 39 40 41 43}

• Potent inhibitor of serotonin and norepinephrine reuptake; less potent inhibitor of dopamine reuptake.¹

• Does not inhibit MAO and has not demonstrated significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opiate, glutamate, or GABA receptors in vitro.¹

Advice to Patients

• Risk of suicidality; stress importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.¹ Advise patients to read the FDA-approved patient information (medication guide).¹

• Advise patients to promptly report any manifestations of liver dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness) to their clinician.¹ Instruct patients that they should talk to their healthcare provider about alcohol consumption.¹

• Inform patients of risk of severe liver injury associated with concomitant use of duloxetine and heavy alcohol intake.¹

• Risk of psychomotor impairment; stress importance of exercising caution while operating hazardous machinery, including automobile driving, until patient gains experience with the drug’s effects.¹

• Advise patients of risk of orthostatic hypotension and syncope, particularly during initial therapy and subsequent dosage escalation and during concomitant therapy with drugs that may potentiate these effects.¹

• Inform patients of the risk of serotonin syndrome with concurrent use of duloxetine and other serotonergic agents including SNRIs, SSRIs, triptans, TCAs, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John’s wort (Hypericum perforatum).¹ Stress importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.¹

• Inform patients of the risk of serious skin reactions that can be severe and life-threatening.¹ Stress importance of seeking immediate medical attention if skin blisters, peeling rash, mouth sores, hives, or other allergic reactions occur.¹

• Inform patients that discontinuation of duloxetine can be associated with symptoms of dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue.¹ Advise patients of the importance of not discontinuing treatment or altering the dosage regimen until speaking with their healthcare provider.¹

• Advise patients of the importance of taking medication exactly as prescribed by the clinician.¹ Stress importance of swallowing the capsule whole, without chewing, crushing, sprinkling on food, or mixing with liquids.¹

• Advise patients of the importance of adequately screening for risk of bipolar disorder (e.g., family history of suicide, bipolar disorder, and depression) prior to initiating of duloxetine therapy.¹ Inform patients that they should report any symptoms of a manic reaction (e.g., great increases in energy, significant issues sleeping, racing thoughts, reckless behavior, excessive talking or talking faster than usual, unusual grand ideas, excessive happiness or irritability).¹

• Inform patients of the risk of mild pupillary dilation, which can cause angle-closure glaucoma in susceptible individuals.¹

• Advise patients to inform their clinicians of a history of seizure disorder.¹

• Inform patients that duloxetine may increase blood pressure.¹

• Inform patients that hyponatremia has been reported with duloxetine.¹

• Instruct patients to report any changes in urine flow.¹

• Inform patients that duloxetine can cause sexual dysfunction, and to discuss any changes and potential management strategies with their healthcare provider.¹

• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Inform patients that duloxetine use can increase the risk of neonatal complications that necessitate prolonged hospitalization, respiratory support, and tube feeding.¹ Inform pregnant women of the risk of major depression relapse with discontinuation of duloxetine.¹ Inform patients of the pregnancy exposure registry that monitors outcomes in women exposed to duloxetine.¹ Advise breastfeeding women to monitor infants for sedation, poor feeding, and poor weight gain and to seek medical attention if these symptoms occur.¹

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., bipolar disorder, liver disease) or family history of suicidality or bipolar disorder.¹ Advise patients of the risk of bleeding associated with concomitant use of duloxetine with aspirin or other nonsteroidal anti-inflammatory agents, warfarin, or other drugs that affect coagulation.¹

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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