duloxetine (Rx)

Brand and Other Names:Cymbalta
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule, delayed-release

  • 20mg
  • 30mg
  • 40mg
  • 60mg
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Major Depressive Disorder

40-60 mg/day PO initially (in single daily dose or divided q12hr for 1 week if patient needs to adjust to therapy)

Titrate dose in increments of 30 mg/day over 1 week as tolerated

Target dosage: 60 mg/day PO (in single daily dose or divided q12hr); not to exceed 120 mg/day (safety of dosages >120 mg/day has not been evaluated)

Diabetic Peripheral Neuropathic Pain

60 mg/day PO initially (in single daily dose or divided q12hr); consider lowering dosage if tolerability is concern

Target dosage: 60 mg/day PO; not to exceed 60 mg/day

Generalized Anxiety Disorder

60 mg/day PO initially (in single daily dose or divided q12hr); may be increased in increments of 30 mg/day if tolerability is concern

Target dosage: 60 mg/day PO; not to exceed 120 mg/day

Fibromyalgia

30 mg/day PO initially for 1 week to allow for therapy adjustment

Target dosage: 60 mg/day PO; not to exceed 60 mg/day; no additional benefit shown by doses > 60 mig in clinical trials

Chronic Musculoskeletal Pain

Treatment of chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain

30 mg/day PO initially for 1 week to allow for therapy adjustment

Target dosage: 60 mg/day PO; not to exceed 60 mg/day

Dosing Modifications

Severe renal impairment (CrCl <30 mL/min) or end-stage renal disease (ESRD): Use not recommended

Hepatic impairment: Use not recommended, because of risk of hepatic injury

Dosing Considerations

Dosages ≥60 mg/day have not been shown to offer additional benefits

Major depressive disorder and generalized anxiety disorder: Acute episodes often necessitate several months of sustained therapy

Diabetic peripheral neuropathic pain: Efficacy for >12 weeks has not been studied; if diabetes is complicated by renal disease, consider lower starting dosage with gradual increase to effective dosage

Fibromyalgia: Efficacy for ≥12 weeks has not been studied; continue treatment on basis of individual patient response

Chronic musculoskeletal pain: Efficacy for ≥13 weeks has not been studied

Uncontrolled narrow-angle glaucoma: Use not recommended due to increased risk of mydriasis

Discontinuance

  • Gradually reduce dosage
  • Abrupt discontinuance may result in symptoms (eg, dizziness, nausea, headache, paresthesia, fatigue, vomiting, irritability, insomnia, diarrhea, anxiety, hyperhidrosis)
  • Wait ≥14 days after discontinuance of monoamine oxidase inhibitor (MAOI) therapy to initiate duloxetine therapy; wait ≥5 days after discontinuance of duloxetine therapy to initiate MAOI therapy

Renal Impairment

Avoid use in patients with severe renal impairment (GFR <30 mL/min)

Hepatic Impairment

Avoid use in patients with chronic liver disease or cirrhosis

Administration

Because of enteric coating, must be swallowed whole; do not chew, crush, or open capsule and sprinkle contents in food or liquid

Can be taken without regard to meals

Dosage Forms & Strengths

capsule, delayed-release

  • 20mg
  • 30mg
  • 40mg
  • 60mg
more...

Generalized Anxiety Disorder

<7 years: Safety and efficacy not established

7-17 years: 30 mg PO qDay initially; after 2 weeks, may consider increasing dose to 60 mg/day

Recommended dosage range: 30-60 mg/day

Some patients may benefit from doses >60 mg/day; if increased beyond 60 mg/day, use increments of 30 mg/day

Maximum dose studied was 120 mg/day; safety of doses >120 mg/day has not been evaluated

Major Depressive Disorder

May initiate at 20 mg PO qDay or divided BID; increase to 40-60 mg qDay or divided doses; alternatively, initiate at 30 mg/day for 1 week, then increase to 60 mg/day as tolerated

Generalized Anxiety Disorder

30 mg/day PO qDay initially; after 2 weeks, consider increasing to target dose of 60 mg/day

Some patients may benefit from doses >60 mg/day; if increased beyond 60 mg/day, use increments of 30 mg/day

Maximum dose studied was 120 mg/day; safety of doses >120 mg/day has not been evaluated

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Interactions

Interaction Checker

and duloxetine

No Results

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Nausea (23-25%)

            Dry mouth (13-15%)

            Headache (13-14%)

            Somnolence (10-12%)

            Fatigue (10-11%)

            1-10%

            Constipation (10%)

            Dizziness (10%)

            Insomnia (10%)

            Diarrhea (9-10%)

            Anorexia (8%)

            Decreased appetite (7-8%)

            Abdominal pain (6%)

            Hyperhidrosis (6%)

            Increased sweating (6%)

            Agitation (5%)

            Nasopharyngitis (5%)

            Vomiting (3-5%)

            Male sexual dysfunction (2-5%)

            Abdominal pain (4%)

            Decreased libido (4%)

            Musculoskeletal pain (4%)

            Upper respiratory tract infection (URTI) (4%)

            Abnormal orgasm (3%)

            Agitation (3%)

            Anxiety (3%)

            Blurred vision (3%)

            Cough (3%)

            Influenza (3%)

            Muscle spasms (3%)

            Tremor (3%)

            Abnormal dreams (2%)

            Dyspepsia (2%)

            Hot flushes (2%)

            Nausea (2%)

            Oropharyngeal pain (2%)

            Palpitations (2%)

            Paresthesia (2%)

            Weight loss (2%)

            Yawning (2%)

            Dysuria (>1%)

            Gastritis (>1%)

            Rash (>1%)

            Postmarketing Reports

            General: Anaphylactic reaction, angioneurotic edema, hypersensitivity

            Cardiovascular: Hypertensive crisis, supraventricular arrhythmia

            Endocrine: Galactorrhea, gynecologic bleeding, hyperglycemia, hyperprolactinemia

            Neurologic: Restless legs syndrome, seizures upon treatment discontinuance, extrapyramidal disorders

            Ophthalmic: Glaucoma

            Otic: Tinnitus (upon treatment discontinuance)

            Psychiatric: Aggression and anger (particularly early in treatment or after treatment discontinuance), hallucinations

            Musculoskeletal: Trismus, muscle spasm

            Skin: Serious skin reactions (eg, erythema multiforme and Stevens-Johnson syndrome) necessitating drug discontinuance or hospitalization, urticaria, rash

            Gastrointestinal: Colitis (microscopic or unspecified),cutaneous vasculitis (sometimes associated with systemic involvement), acute pancreatitis

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            Warnings

            Black Box Warnings

            Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies

            These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients >24 yr

            There was a reduction in risk with antidepressant use in patients ≥65 yr

            In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors

            Advise families and caregivers of the need for close observation and communication with the prescriber

            Contraindications

            Concomitant use of duloxetine with MAOIs intended to treat psychiatric disorders

            Coadministration with serotonergic drugs

            • Wait ≥14 days between discontinuance of MAOI and initiation of duloxetine; wait ≥5 days between discontinuance of duloxetine and initiation of MAOI
            • Starting duloxetine in patient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome
            • If linezolid or IV methylene blue must be administered, discontinue duloxetine immediately and monitor for central nervous system (CNS) toxicity; duloxetine may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

            Cautions

            CYP1A2 inhibitors or thioridazine should not be coadministered

            Use caution in severe renal impairment, ESRD

            Heavy alcohol use

            Suicidality; monitor for clinical worsening and suicide risk, especially in children, adolescents and young adults (18-24 years) during early phases of treatment and alterations in dosage

            Serotonin syndrome or neuroleptic malignant syndrome-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics and serotonin precursors

            Neonates exposed to serotonin-noreponephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

            Screen patients for bipolar disorder; risk of mixed/manic episodes is increased in patients treated with antidepressants

            May cause activation of mania or hypomania

            Increased risk of hepatotoxicity, sometimes fatal; monitor for abdominal pain, hepatomegaly, elevations in hepatic transaminases exceeding 20 times upper limit of normal; jaundice; cholestatic jaundice with minimal elevations of hepatic transaminases have also been reported; use not recommended in patients with substantial alcohol use or chronic liver disease

            SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk

            Severe skin reactions (eg, erythema multiforme and Stevens-Johnson syndrome); discontinue at first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified

            Orthostatic hypotension and syncope, especially during week 1 of therapy; monitor patients taking drugs that increase risk of orthostatic hypotension; consider dose reduction or discontinue therapy in patients who experience symptomatic orthostatic hypotension, falls and/or syncope

            Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium <110 mmol/L have been reported to be reversible upon discontinuance

            Diabetes due to worsening of glycemic control in some patients; monitor increases in fasting blood glucose and hemoglobin A1c

            Monitor weight and growth in adolescents and children; decrease in appetite and weight loss reported

            Urinary hesitation and retention

            Cognitive or motor function impairment; use with caution when operating heavy machinery

            Bone fractures reported with antidepressant treatment; consider possibility of bone fracture if patient complains of unexplained bone pain or joint tenderness or experiences bruising or swelling

            May cause or exacerbate sexual dysfunction

            Use caution in gastroparesis, hypertension, controlled narrow angle glaucoma, renal impairment, or seizure disorders

            May lower seizure threshold when administered oncurrently with other drugs that lower seizure threshold

            Use caution when administering concomitantly with CNS depressants

            Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

            Headache, dizziness, nausea, diarrhea, paresthesia, vomiting, irritability, insomnia, hyperhidrosis, anxiety, and fatigue reported in patients following abrupt discontinuation of duloxetine

            Therapy may increase blood pressure; measure blood prior to initiating treatment and periodically throughout treatment

            Abnormal bleeding reported when used in combination with aspirin, NSAIDs, or other drugs that affect coagulation

            Angle closure glaucoma reported in patients with untreated anatomically narrow angles that do not have a patent iridectomy and are being treated with antidepressants

            Use with caution in patients with conditions that slow gastric emptying

            Drug interaction overview

            • The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including duloxetine, when administered concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue)
            • If concomitant use with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamines, and St. John’s Wort is clinically warranted, patients should be made aware of potential risk for serotonin syndrome, particularly during treatment initiation and dose increases; treatment with concomitant serotonergic agents, should be discontinued immediately if above events occur and supportive symptomatic treatment should be initiated
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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: Drug enters breast milk; use not recommended unless benefits greatly outweigh risks

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Exact mechanism of action unknown; inhibits reuptake of serotonin and norepinephrine; weakly inhibits reuptake of dopamine; has no MAOI activity; has no significant activity for histaminergic H1 receptor or alpha2-adrenergic receptor

            Absorption

            Well absorbed

            Peak plasma time: 6 hr (Empty stomach); 10 hr (with food)

            Distribution

            Vd: 3.4 L/kg

            Protein bound: >90%

            Metabolism

            Metabolized in liver by CYP2D6 and CYP1A2

            Metabolites: 4-Hydroxy duloxetine glucuronide; 5-hydroxy, 6-methoxy duloxetine sulfate

            Enzymes inhibited: CYP2D6

            Elimination

            Half-life: 12 hr

            Excretion: Urine (70% as metabolites; <1% unchanged), feces (20%)

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
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            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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