duloxetine (Rx)

Brand and Other Names:Cymbalta, Irenka, more...Drizalma Sprinkle
  • Print

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule, delayed-release

  • 20mg (Cymbalta, Drizalma Sprinkle, generic)
  • 30mg (Cymbalta, Drizalma Sprinkle, generic)
  • 40mg (Drizalma Sprinkle, Irenka)
  • 60mg (Cymbalta, Drizalma Sprinkle, generic)

Major Depressive Disorder

Indicated for major depressive disorder (MDD)

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

Consider starting at 30 mg qDay for 1 week to allow for therapy adjustment before increasing to 60 mg qDay

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

There is no evidence that doses > 60 mg/day confer additional benefit

Diabetic Peripheral Neuropathic Pain

Indicated for diabetic peripheral neuropathy/neuropathic pain

60 mg PO qDay initially (in single daily dose or divided q12hr); consider lowering initial dose if tolerability is a concern

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

There is no evidence that doses >60 mg/day confer additional benefit

Consider a lower starting dosage and gradually increase dose for patients with renal impairment

Generalized Anxiety Disorder

Indicated for generalized anxiety disorder (GAD)

Age <65 years: 60 mg PO qDay initially

Consider starting at 30 mg qDay for 1 week to allow for therapy adjustment before increasing to 60 mg qDay

Target dosage: 60 mg/day PO qDay

May increase dose in increments of 30 mg qDay; not to exceed 120 mg/day

No additional benefit shown with doses >60 mg/day

Fibromyalgia

Indicated for fibromyalgia

30 mg PO qDay initially for 1 week to allow for therapy adjustment before increasing to 60 mg qDay

Target dosage: 60 mg PO qDay; not to exceed 60 mg/day; no additional benefit shown with doses >60 mg

Chronic Musculoskeletal Pain

Indicated for chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain

30 mg PO qDay initially for 1 week to allow for therapy adjustment before increasing to 60 mg qDay

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

Dosage Modifications

Renal impairment

  • Mild-to-moderate (CrCl 30-80 mL/min): Population PK analyses suggest that no significant effect on duloxetine apparent clearance
  • Severe (CrCl <30 mL/min): Avoid use
  • End-stage renal disease (ESRD): Limited data; peak plasma concentration and AUC were 100% greater for patients with ESRD receiving chronic hemodialysis

Hepatic impairment

  • Avoid use with all degrees of hepatic impairment

Potent CYP1A2 inhibitors

  • Avoid coadministration

Dosing Considerations

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

Monitoring parameters

  • Before initiating treatment, screen for a personal or family history of bipolar disorder, mania, or hypomania
  • GAD and MDD
    • Periodically reassess to determine the continued need for maintenance treatment and appropriate dosage for such treatment

Discontinuation

  • Gradually reduce dosage
  • Abrupt discontinuance may result in symptoms (eg, dizziness, nausea, headache, paresthesia, fatigue, vomiting, irritability, insomnia, diarrhea, anxiety, hyperhidrosis)

Switching to and from a monoamine oxidase inhibitor (MAOI)

  • Wait ≥14 days after discontinuing MAOI to initiate duloxetine therapy
  • Wait ≥5 days after discontinuing duloxetine therapy to initiate MAOI therapy

Other MAO-Is (linezolid or methylene blue)

  • Do not start duloxetine in a patients with linezolid or IV methylene blue due to the potential risk of serotonin syndrome
  • Patients who requires more urgent treatment of a psychiatric condition: Consider other interventions, including hospitalization
  • If linezolid or IV methylene blue must be administered, discontinue duloxetine immediately; monitor for symptoms of serotonin syndrome for 5 days or until 24 hr after the last dose of linezolid or IV methylene blue, whichever comes first
  • Resume duloxetine 24 hr after the last dose of linezolid or IV methylene blue
  • Risk of administering methylene blue by non-IV routes (eg, oral tablets, by local injection) or in IV doses <1 mg/kg with duloxetine is unclear; be aware of potential risk of serotonin syndrome with such use

Dosage Forms & Strengths

capsule, delayed-release

  • 20mg (Cymbalta, Drizalma Sprinkle, generic)
  • 30mg (Cymbalta, Drizalma Sprinkle, generic)
  • 40mg (Drizalma Sprinkle, Irenka)
  • 60mg (Cymbalta, Drizalma Sprinkle, generic)

Generalized Anxiety Disorder

Indicated for generalized anxiety disorder (GAD) in adults and pediatric patients aged ≥7 years

7-17 years

  • 30 mg/day PO qDay initially; after 2 weeks; recommended dose range 30-60 qDay
  • May benefit from doses >60 mg/day; if increased >60 mg/day, use increments of 30 mg/day
  • Maximum dose studied was 120 mg/day

Fibromyalgia

Cymbalta only

Indicated for fibromyalgia in adolescents aged 13-17 yr

<13 years: Safety and efficacy not established

13-17 years

  • 30 mg PO qDay; may increase to 60 mg PO qDay based on response and tolerability

Dosage Modifications

Renal impairment

  • Mild-to-moderate (CrCl 30-80 mL/min): Population PK analyses suggest that no significant effect on duloxetine apparent clearance
  • Severe (CrCl <30 mL/min): Avoid use
  • End-stage renal disease (ESRD): Limited data; peak plasma concentration and AUC were 100% greater for patients with ESRD receiving chronic hemodialysis

Hepatic impairment

  • Avoid use with all degrees of hepatic impairment

Dosing Considerations

Monitoring parameters

  • Before initiating treatment, screen for a personal or family history of bipolar disorder, mania, or hypomania
  • GAD and MDD

    • Periodically reassess to determine the continued need for maintenance treatment and appropriate dosage for such treatment

Discontinuation

  • Gradually reduce dosage
  • Abrupt discontinuance may result in symptoms (eg, dizziness, nausea, headache, paresthesia, fatigue, vomiting, irritability, insomnia, diarrhea, anxiety, hyperhidrosis)

Switching to and from a monoamine oxidase inhibitor (MAOI)

  • Wait ≥14 days after discontinuing MAOI to initiate duloxetine therapy
  • Wait ≥5 days after discontinuing duloxetine therapy to initiate MAOI therapy

Other MAO-Is (linezolid or methylene blue)

  • Do not start duloxetine in patients taking linezolid or IV methylene blue owing to potential risk of serotonin syndrome
  • Patients who requires more urgent treatment of a psychiatric condition: Consider other interventions, including hospitalization
  • If linezolid or IV methylene blue must be administered, discontinue duloxetine immediately; monitor for symptoms of serotonin syndrome for 5 days or until 24 hr after the last dose of linezolid or IV methylene blue, whichever comes first
  • Resume duloxetine 24 hr after the last dose of linezolid or IV methylene blue
  • Risk of administering methylene blue by non-IV routes (eg, oral tablets, by local injection) or in IV doses much <1 mg/kg with duloxetine is unclear; be aware of potential risk of serotonin syndrome with such use

Generalized Anxiety Disorder

Indicated for generalized anxiety disorder (GAD)

≥65 years: 30 mg/day PO qDay initially; after 2 weeks, consider increasing to target dose of 60 mg/day

May benefit from doses >60 mg/day; if increased >60 mg/day, use increments of 30 mg/day

Maximum dose studied was 120 mg/day

Next:

Interactions

Interaction Checker

and duloxetine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (8)

            • eliglustat

              duloxetine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

            • iobenguane I 123

              duloxetine decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

            • isocarboxazid

              isocarboxazid and duloxetine both increase serotonin levels. Contraindicated.

            • phenelzine

              phenelzine and duloxetine both increase serotonin levels. Contraindicated.

            • procarbazine

              procarbazine and duloxetine both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • safinamide

              duloxetine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • selegiline

              selegiline and duloxetine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a serotonergic drug.

            • tranylcypromine

              tranylcypromine and duloxetine both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (86)

            • abametapir

              abametapir will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

            • amitriptyline

              duloxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • amobarbital

              amobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • amoxapine

              duloxetine and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.

            • apixaban

              duloxetine and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

            • armodafinil

              armodafinil will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • bupropion

              duloxetine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • buspirone

              duloxetine and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

            • butabarbital

              butabarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • butalbital

              butalbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • carbamazepine

              carbamazepine will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clomipramine

              duloxetine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • cyclobenzaprine

              duloxetine and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dacomitinib

              dacomitinib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

            • desipramine

              duloxetine and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • desvenlafaxine

              duloxetine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dextromethorphan

              duloxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • dosulepin

              duloxetine and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.

            • doxepin

              duloxetine and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.

            • erythromycin base

              erythromycin base will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and fluoxetine both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

              fluvoxamine and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug.

            • givosiran

              givosiran will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

              givosiran will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

            • granisetron

              granisetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • imipramine

              duloxetine and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • iobenguane I 131

              duloxetine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • levomilnacipran

              duloxetine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • linezolid

              linezolid and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lofepramine

              duloxetine and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              duloxetine and lorcaserin both increase sedation. Avoid or Use Alternate Drug.

            • lumefantrine

              lumefantrine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • maprotiline

              duloxetine and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.

            • meperidine

              duloxetine and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • methylene blue

              methylene blue and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide

              metoclopramide and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Additive effects; increased risk for serotonin syndrome, neuroleptic malignant syndrome, dystonia, or other extrapyramidal reactions

            • metoclopramide intranasal

              duloxetine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • mexiletine

              mexiletine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.

            • milnacipran

              duloxetine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • modafinil

              modafinil will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • nefazodone

              duloxetine and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.

            • netupitant/palonosetron

              netupitant/palonosetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • nortriptyline

              duloxetine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • omeprazole

              omeprazole will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • ondansetron

              ondansetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • ozanimod

              ozanimod increases toxicity of duloxetine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • palonosetron

              palonosetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and paroxetine both increase serotonin levels. Avoid or Use Alternate Drug.

            • pefloxacin

              pefloxacin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • peginterferon alfa 2a

              peginterferon alfa 2a will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • pentobarbital

              pentobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • phenobarbital

              phenobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • phentermine

              duloxetine, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • pipemidic acid

              pipemidic acid will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.

            • pirfenidone

              duloxetine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommended

            • primidone

              primidone will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • protriptyline

              duloxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • pseudoephedrine

              duloxetine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • quinidine

              quinidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • rasagiline

              rasagiline and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Severe CNS toxicity associated with hyperpyrexia has been reported with the combined treatment of an antidepressant and rasagiline. Avoid combination within 14 days of MAOI use.

            • rifampin

              rifampin will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.

            • secobarbital

              secobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • selegiline transdermal

              selegiline transdermal and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug.

            • sertraline

              sertraline will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and sertraline both increase serotonin levels. Avoid or Use Alternate Drug.

            • smoking

              smoking will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • St John's Wort

              duloxetine and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • tedizolid

              tedizolid, duloxetine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

            • thioridazine

              duloxetine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.

              thioridazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.

            • tipranavir

              tipranavir will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • tobacco use

              tobacco use will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • tramadol

              duloxetine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • trazodone

              duloxetine and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.

            • trimipramine

              duloxetine and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • venlafaxine

              duloxetine and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • verapamil

              verapamil will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • vilazodone

              duloxetine, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • vortioxetine

              duloxetine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

            • warfarin

              duloxetine increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • zileuton

              zileuton will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (150)

            • 5-HTP

              duloxetine and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

            • abiraterone

              abiraterone increases levels of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • aceclofenac

              duloxetine, aceclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • acemetacin

              duloxetine, acemetacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • almotriptan

              almotriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • amifostine

              amifostine, duloxetine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • amiodarone

              amiodarone will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • asenapine

              asenapine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • aspirin

              duloxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • aspirin rectal

              duloxetine, aspirin rectal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • aspirin/citric acid/sodium bicarbonate

              duloxetine, aspirin/citric acid/sodium bicarbonate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • atomoxetine

              duloxetine increases levels of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • benazepril

              duloxetine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

            • benzhydrocodone/acetaminophen

              duloxetine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              benzhydrocodone/acetaminophen, duloxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • brexpiprazole

              duloxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

            • buprenorphine subdermal implant

              duloxetine, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • buprenorphine, long-acting injection

              duloxetine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • bupropion

              bupropion will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cannabidiol

              cannabidiol, duloxetine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • captopril

              captopril increases effects of duloxetine by pharmacodynamic synergism. Use Caution/Monitor. Blood pressure lowering drugs may enhance the hypotensive effect of duloxetine. Monitor blood pressure.

            • celecoxib

              celecoxib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              duloxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • cenobamate

              cenobamate, duloxetine. Either increases effects of the other by sedation. Use Caution/Monitor.

            • choline magnesium trisalicylate

              duloxetine, choline magnesium trisalicylate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • cimetidine

              cimetidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ciprofloxacin

              ciprofloxacin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Coadministration of CYP1A2 inhibiting quinolones with duloxetine may lead to significant increases in duloxetine levels, AUC, and half-life. Consider therapy modification if duloxetine is necessary.

            • clobazam

              clobazam will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

            • clopidogrel

              duloxetine increases effects of clopidogrel by pharmacodynamic synergism. Use Caution/Monitor. SNRIs affect platelet activation; coadministration of SNRIs with clopidogrel may increase the risk of bleeding.

            • cocaine

              duloxetine and cocaine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • codeine

              duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • cyproheptadine

              cyproheptadine decreases effects of duloxetine by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.

            • darifenacin

              darifenacin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • deferasirox

              deferasirox increases levels of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • desipramine

              duloxetine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • dexfenfluramine

              duloxetine and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dextroamphetamine

              duloxetine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely.

              duloxetine and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • diazepam intranasal

              diazepam intranasal, duloxetine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • dichlorphenamide

              dichlorphenamide and duloxetine both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              duloxetine, diclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • diflunisal

              duloxetine, diflunisal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • dihydroergotamine

              duloxetine and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dihydroergotamine intranasal

              duloxetine and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • diphenhydramine

              diphenhydramine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • eletriptan

              eletriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • eliglustat

              eliglustat increases levels of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

            • eluxadoline

              duloxetine increases levels of eluxadoline by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP1A2 inhibitors.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • ergotamine

              duloxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • escitalopram

              duloxetine and escitalopram both increase serotonin levels. Use Caution/Monitor.

            • esomeprazole

              esomeprazole will decrease the level or effect of duloxetine by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • ethanol

              ethanol, duloxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hepatotoxicity.

            • etodolac

              duloxetine, etodolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fedratinib

              fedratinib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • fenbufen

              duloxetine, fenbufen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fenfluramine

              duloxetine and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

              fenfluramine, duloxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

            • fenoprofen

              duloxetine, fenoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fesoterodine

              duloxetine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • fexinidazole

              fexinidazole will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of duloxetine by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

            • flurbiprofen

              duloxetine, flurbiprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • frovatriptan

              frovatriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • gabapentin

              gabapentin, duloxetine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, duloxetine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • green tea

              green tea, duloxetine. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.

            • hydrocodone

              duloxetine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, duloxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • hydromorphone

              duloxetine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ibrutinib

              ibrutinib will increase the level or effect of duloxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

            • ibuprofen

              duloxetine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • ibuprofen IV

              duloxetine, ibuprofen IV. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • imatinib

              imatinib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • imipramine

              duloxetine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely.

            • indomethacin

              duloxetine, indomethacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • isoniazid

              isoniazid will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              duloxetine and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

            • ketoprofen

              duloxetine, ketoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • ketorolac

              duloxetine, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • ketorolac intranasal

              duloxetine, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • L-tryptophan

              duloxetine and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lasmiditan

              lasmiditan, duloxetine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

              duloxetine increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • lemborexant

              lemborexant, duloxetine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • lisdexamfetamine

              duloxetine, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).

            • lithium

              duloxetine and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lofepramine

              duloxetine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lorcaserin

              lorcaserin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lornoxicam

              duloxetine, lornoxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • lsd

              duloxetine and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lurasidone

              lurasidone, duloxetine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maraviroc

              maraviroc will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • marijuana

              marijuana will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • meclofenamate

              duloxetine, meclofenamate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • mefenamic acid

              duloxetine, mefenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • meloxicam

              duloxetine, meloxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • methamphetamine

              duloxetine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely.

            • metoprolol

              duloxetine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mexiletine

              duloxetine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, duloxetine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • mirabegron

              mirabegron will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mirtazapine

              duloxetine and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • morphine

              duloxetine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              duloxetine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nabumetone

              duloxetine, nabumetone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • naproxen

              duloxetine, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • naratriptan

              naratriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nebivolol

              duloxetine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • nortriptyline

              duloxetine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • oliceridine

              duloxetine will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

              duloxetine, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • oxaprozin

              duloxetine, oxaprozin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • oxycodone

              duloxetine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • oxymorphone

              duloxetine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • parecoxib

              parecoxib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              duloxetine, parecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • peginterferon alfa 2b

              peginterferon alfa 2b, duloxetine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

              duloxetine and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • pentoxifylline

              duloxetine will increase the level or effect of pentoxifylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • perphenazine

              perphenazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • piroxicam

              duloxetine, piroxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • pregabalin

              pregabalin, duloxetine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • propafenone

              duloxetine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              propafenone will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propranolol

              duloxetine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • quinacrine

              quinacrine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ranolazine

              ranolazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • remifentanil

              remifentanil increases toxicity of duloxetine by serotonin levels. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.

            • remimazolam

              remimazolam, duloxetine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • risperidone

              duloxetine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • rizatriptan

              rizatriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rolapitant

              rolapitant will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

            • rucaparib

              rucaparib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

            • salicylates (non-asa)

              duloxetine, salicylates (non-asa). Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • salsalate

              duloxetine, salsalate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • SAMe

              duloxetine and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              duloxetine, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • stiripentol

              stiripentol, duloxetine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

            • sufentanil SL

              sufentanil SL, duloxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sulfasalazine

              duloxetine, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • sulindac

              duloxetine, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • sumatriptan

              sumatriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tamoxifen

              duloxetine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

            • tamsulosin

              duloxetine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tapentadol

              duloxetine and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • terbinafine

              terbinafine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

              duloxetine will increase the level or effect of terbinafine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • teriflunomide

              teriflunomide decreases levels of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • timolol

              duloxetine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tolfenamic acid

              duloxetine, tolfenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • tolmetin

              duloxetine, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • tramadol

              duloxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • valerian

              valerian and duloxetine both increase sedation. Use Caution/Monitor.

            • venlafaxine

              venlafaxine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • vorapaxar

              duloxetine, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur; SSRIs and SNRIs may cause platelet serotonin depletion .

            • zolmitriptan

              zolmitriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (42)

            • almotriptan

              duloxetine, almotriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • aripiprazole

              duloxetine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • bumetanide

              bumetanide, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • carvedilol

              duloxetine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • celandine

              celandine decreases effects of duloxetine by pharmacodynamic antagonism. Minor/Significance Unknown. Based on animal studies.

            • chloroquine

              chloroquine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • chlorpromazine

              duloxetine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dexfenfluramine

              duloxetine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dexmethylphenidate

              dexmethylphenidate increases effects of duloxetine by decreasing metabolism. Minor/Significance Unknown.

            • donepezil

              duloxetine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • doxepin

              duloxetine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • eletriptan

              duloxetine, eletriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • encainide

              duloxetine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ethacrynic acid

              ethacrynic acid, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • flecainide

              duloxetine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • fluoxetine

              duloxetine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • fluphenazine

              duloxetine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • frovatriptan

              duloxetine, frovatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • furosemide

              furosemide, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • galantamine

              duloxetine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • haloperidol

              duloxetine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              haloperidol will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • iloperidone

              duloxetine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • lithium

              duloxetine, lithium. Mechanism: unknown. Minor/Significance Unknown. Risk of neurotoxicity.

            • loratadine

              duloxetine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • naratriptan

              duloxetine, naratriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • panax ginseng

              panax ginseng increases effects of duloxetine by pharmacodynamic synergism. Minor/Significance Unknown.

            • paroxetine

              duloxetine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perhexiline

              duloxetine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perphenazine

              duloxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • pleurisy root

              pleurisy root decreases effects of duloxetine by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

            • prochlorperazine

              duloxetine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • promazine

              duloxetine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • promethazine

              duloxetine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • rizatriptan

              duloxetine, rizatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • sumatriptan

              duloxetine, sumatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • sumatriptan intranasal

              duloxetine, sumatriptan intranasal. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • tolterodine

              duloxetine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • torsemide

              torsemide, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • trifluoperazine

              duloxetine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tropisetron

              duloxetine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • zolmitriptan

              duloxetine, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            Previous
            Next:

            Adverse Effects

            >10%

            Nausea (23-25%)

            Dry mouth (13-15%)

            Headache (13-14%)

            Somnolence (10-12%)

            Fatigue (9-11%)

            1-10%

            Constipation (9-10%)

            Dizziness (9-10%)

            Insomnia (9-10%)

            Diarrhea (9-10%)

            Anorexia (8%)

            Decreased appetite (7-8%)

            Abdominal pain (4-6%)

            Hyperhidrosis (6%)

            Agitation (5%)

            Nasopharyngitis (5%)

            Vomiting (3-5%)

            Male sexual dysfunction (2-5%)

            Erectile dysfunction (4%)

            Decreased libido (4%)

            Musculoskeletal pain (4%)

            Upper respiratory tract infection (URTI) (4%)

            Decreased libido (3-4%)

            Musculoskeletal pain (3-4%)

            Abnormal orgasm (2-3%)

            Agitation (3%)

            Anxiety (3%)

            Blurred vision (3%)

            Cough (3%)

            Influenza (3%)

            Muscle spasms (2-3%)

            Tremor (3%)

            Abnormal dreams (2%)

            Dyspepsia (2%)

            Hot flushes (2%)

            Oropharyngeal pain (2%)

            Palpitations (2%)

            Paresthesia (2%)

            Weight loss (2%)

            Yawning (2%)

            Blood pressure increase (2%)

            Ejaculation delayed (2%)

            Dysuria (>1%)

            Gastritis (>1%)

            Rash (>1%)

            Postmarketing Reports

            General: Anaphylactic reaction, angioneurotic edema, hypersensitivity, chills/rigors, falls, feeling abnormal, feeling hot and/or cold, malaise, thirst

            Cardiovascular: Hypertensive crisis, supraventricular arrhythmia, myocardial infarction, tachycardia, Takotsubo cardiomyopathy

            Endocrine: Galactorrhea, gynecologic bleeding, hyperglycemia, hyperprolactinemia, hypothyroidism

            Neurologic: Restless legs syndrome, seizures upon treatment discontinuance, extrapyramidal disorders, dysgeusia, lethargy, and paraesthesia/hypoesthesia, disturbance in attention, dyskinesia, myoclonus, poor quality sleep

            Ophthalmic: Glaucoma, blurred vision, diplopia, dry eyes, visual impairment

            Otic: Tinnitus (upon treatment discontinuance), ear pain, vertigo

            Psychiatric: Aggression and anger (particularly early in treatment or after treatment discontinuance), hallucinations; abnormal dreams and sleep disorder; apathy, bruxism, disorientation/confusional state, irritability, mood swings, and suicide attempt; completed suicide (rare)

            Musculoskeletal: Trismus, muscle spasm, muscle tightness, muscle twitching

            Skin: Serious skin reactions (eg, erythema multiforme and Stevens-Johnson syndrome) necessitating drug discontinuance or hospitalization, urticaria, rash, pruritus, dermatitis, cold sweat, erythema, increased tendency to bruise, night sweats, photosensitivity reaction

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

            Infection: Gastroenteritis, laryngitis

            Investigations: Increased/decreased weight, increased blood cholesterol

            Previous
            Next:

            Warnings

            Black Box Warnings

            Suicidal thoughts and behaviors

            • 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

            Use of duloxetine within 14 days of MAOI discontinuation

            Initiating duloxetine in patients who are being treated with linezolid or IV methylene blue

            Cautions

            Prior to initiating treatment with, screen patients for any personal or family history of bipolar disorder, mania, or hypomania

            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 (see Black Box Warnings)

            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-norepinephrine 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

            Increased risk of hepatotoxicity, sometimes fatal; monitor for abdominal pain, hepatomegaly, elevated AST/ALT exceeding 20x ULN, and jaundice; cholestatic jaundice with minimal elevations of hepatic transaminases have also been reported; 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

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

            May lower seizure threshold when administered on currently with other drugs that lower seizure threshold

            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

            Use with caution in patients with conditions that slow gastric emptying

            Sexual dysfunction

            • Changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of psychiatric disorders or diabetes, but may also be a consequence of pharmacologic treatment
            • Use of SNRIs, may cause symptoms of sexual dysfunction; in male patients, SNRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction; in female patients, SNRI use may result in decreased libido and delayed or absent orgasm
            • It is important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment; sexual function may not be spontaneously reported
            • When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder
            • Discuss potential management strategies to support patients in making informed decisions about treatment

            Increased risk of bleeding postpartum

            • Drugs that interfere with serotonin reuptake inhibition, may increase risk of bleeding; case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and occurrence of gastrointestinal bleeding
            • A postmarketing study showed a higher incidence of postpartum hemorrhage in mothers receiving therapy;
            • Other bleeding events related to SSRI and SNRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages; concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk
            • Inform about risk of bleeding associated with concomitant use of drug and NSAIDs, aspirin, or other drugs that affect coagulation

            Drug interaction overview

            • Use caution when administering concomitantly with CNS depressants
            • Duloxetine is CYP1A2 and CYP2D6 substrate; moderate CYP2D6 inhibitor
            • CYP2D6 Inhibitors
              • Concomitant use of duloxetine with potent CYP2D6 inhibitors may result in higher concentrations (on average of 60%) of duloxetine
              • Coadministration of duloxetine with drugs that are extensively metabolized by CYP2D6 with a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs]), phenothiazines and Type 1C antiarrhythmics (eg, propafenone, flecainide), should be used with caution
              • Avoid coadministration with Drizalma Sprinkle and potent CYP2D6
            • Alcohol
              • Cymbalta: Three 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
              • Drizalma Sprinkle: An in vitro study showed significant increases of duloxetine hydrochloride release at 2 hr to ~86% and 56% of the drug release in the presence of 40% and 20% alcohol, respectively
            • Serotonergic drugs
              • 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 is clinically warranted, advise patients 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 initiate supportive symptomatic treatment
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Data from a postmarketing retrospective cohort study indicate that use in the month before delivery may be associated with an increased risk of postpartum hemorrhage; data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes; there are risks associated with untreated depression in pregnancy and with exposure to SNRIs and SSRIs, during pregnancy

            Women who discontinued antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continued antidepressants; consider risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum

            Pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis; not known if adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors

            Animal data

            • Cymbalta
              • In animal studies with duloxetine, fetal weights were decreased but there was no evidence of teratogenicity in pregnant rats and rabbits at oral doses administered during organogenesis up to 4 and 7 times the maximum recommended human dose (MRHD) of 120 mg/day
              • When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD
            • Drizalma Sprinkle
              • In rats and rabbits treated with duloxetine during organogenesis, fetal weights decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the MRHD of 120 mg/day given to adolescents on a mg/m2 basis
              • When oral duloxetine was administered to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD given to adolescents on a mg/m2 basis
            • For both formulations, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed
            • Postweaning growth was not adversely affected
            • Use in pregnancy only if the potential benefit justifies the potential risk to the fetus

            Pregnancy registry

            Clinical considerations

            • Neonates exposed during pregnancy to serotonin - norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding which can arise immediately upon delivery
            • Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying
            • These features are consistent with either a direct toxic effect of the SNRIs or SSRIs, or possibly, a drug discontinuation syndrome
            • In some cases, the clinical picture is consistent with serotonin syndrome

            Lactation

            Cymbalta

            • Drug present in human milk in a published study, lactating women who were weaning their infants were given duloxetine
            • At steady state, duloxetine concentration in breast milk was ~25% that of maternal plasma
            • Estimated daily infant dose was ~0.14% of the maternal dose
            • Exercise caution when administering to a nursing woman

            Drizalma Sprinkle

            • Data from the published literature report the presence of duloxetine in human milk
            • There are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk
            • There are no data on effect of duloxetine on milk production
            • Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition
            • Women given 40 mg of duloxetine PO BID for 3.5 days; peak concentration measured in breast milk occurred at a median of 3 hrs post-dose
            • Amount of duloxetine in breast milk was ~7 mcg/day while on that dose; estimated daily infant dose was ~2 mcg/kg/day, which is <1% of the maternal dose

            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.

            Previous
            Next:

            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

            Duloxetine steady-state plasma concentration was comparable in children (7-12 years), adolescents (13-17 years), and adults

            Peak plasma time

            • Cymbalta: 6 hr (empty stomach); 10 hr (with food)
            • Drizalma Sprinkle: 5 hr; there is a 3 hr delay in absorption and a one-third increase in apparent duloxetine clearance after an evening dose as compared to a morning dose; ~1.7 hr delay when administered with a high-fat meal

            Distribution

            Vd: 1640 L

            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%)

            Previous
            Next:

            Administration

            Oral Administration

            Swallow capsule whole; do not chew or crush

            May be administer without regard to meals

            Cymbalta

            • Do not open capsule and sprinkle its contents on food or mix with liquids
            • All of these might affect the enteric coating

            Drizalma Sprinkle

            • Patients with swallowing difficulty
              • Open capsule and sprinkle contents over applesauce; swallow contents of the capsules along with a small amount (tablespoonful) of applesauce
              • Swallow drug/food mixture immediately and do not store for future use
            • Nasogastric tube administration
              • Open and add contents of capsule to an all plastic catheter tip syringe and add 50 mL of water
              • Gently shake syringe for ~10 seconds
              • Promptly deliver through a 12 French or larger nasogastric tube; ensure no pellets are left in the syringe
              • Rinse with additional water (~15 mL) if needed

            Missed dose

            • If a dose is missed, take missed dose as soon as it is remembered
            • If it is almost time for the next dose, skip missed dose and take the next dose at the regular time; do not take 2 doses at the same time

            Storage

            Cymbalta: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

            Drizalma Sprinkle: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

            Previous
            Next:

            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Cymbalta oral
            -
            30 mg capsule
            Cymbalta oral
            -
            60 mg capsule
            Cymbalta oral
            -
            20 mg capsule
            Cymbalta oral
            -
            60 mg capsule
            duloxetine oral
            -
            40 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            20 mg capsule
            duloxetine oral
            -
            40 mg capsule
            duloxetine oral
            -
            40 mg capsule
            duloxetine oral
            -
            30 mg capsule
            duloxetine oral
            -
            60 mg capsule
            duloxetine oral
            -
            30 mg capsule

            Copyright © 2010 First DataBank, Inc.

            Previous
            Next:

            Patient Handout

            Patient Education
            duloxetine oral

            DULOXETINE - ORAL

            (doo-LOX-e-teen)

            COMMON BRAND NAME(S): Cymbalta

            WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

            USES: Duloxetine is used to treat depression and anxiety. In addition, duloxetine is used to help relieve nerve pain (peripheral neuropathy) in people with diabetes or ongoing pain due to medical conditions such as arthritis, chronic back pain, or fibromyalgia (a condition that causes widespread pain).Duloxetine may improve your mood, sleep, appetite, and energy level, and decrease nervousness. It can also decrease pain due to certain medical conditions. Duloxetine is known as a serotonin-norepinephrine reuptake inhibitor (SNRI). This medication works by helping to restore the balance of certain natural substances (serotonin and norepinephrine) in the brain.

            HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using duloxetine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually 1 or 2 times a day with or without food. If you have nausea, it may help to take this drug with food. Swallow the capsule whole. Do not crush or chew the capsule or mix the contents with food or liquid. Doing so can release all of the drug at once, increasing the risk of side effects.The dosage is based on your age, medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as dizziness, confusion, mood swings, headache, tiredness, diarrhea, sleep changes, and brief feelings similar to electric shock. Your dose may need to be gradually decreased to reduce side effects. Report any new or worsening symptoms right away.Tell your doctor if your condition persists or worsens.

            SIDE EFFECTS: See also Warning section.Nausea, dry mouth, constipation, loss of appetite, tiredness, drowsiness, or increased sweating may occur. If any of these effects persist or worsen, tell your doctor promptly.Dizziness or lightheadedness may occur, especially when you first start or increase your dose of this drug. To reduce the risk of dizziness, lightheadedness, or falling, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.Tell your doctor right away if any of these serious side effects occur: confusion, easy bruising/bleeding, decreased interest in sex, changes in sexual ability, muscle cramps/weakness, shaking (tremor), difficulty urinating, signs of liver problems (such as stomach/abdominal pain, persistent nausea, vomiting, yellowing eyes/skin, dark urine).Get medical help right away if you have any very serious side effects, including: black/bloody stools, vomit that looks like coffee grounds, seizure, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night, blurred vision).This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing, skin blisters, mouth sores.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking duloxetine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal or family history of psychiatric disorders (such as bipolar/manic-depressive disorder), personal or family history of suicide attempts, bleeding problems, personal or family history of glaucoma (angle-closure type), high blood pressure, kidney disease, liver disease, seizure disorder, stomach problems (such as slow emptying of the stomach), use/abuse of alcohol.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).If you have diabetes, duloxetine may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially bleeding, dizziness, lightheadedness, or loss of coordination. Older adults may also be more likely to develop a type of salt imbalance (hyponatremia), especially if they are taking "water pills" (diuretics). Dizziness, lightheadedness, or loss of coordination can increase the risk of falling.Children may be more sensitive to the side effects of this drug, especially loss of appetite and weight loss. Monitor weight and height in children who are taking this drug. See also Warning.During pregnancy, this medication should be used only when clearly needed. When this medication is taken during the last 30 days of pregnancy, the mother may be at an increased risk of bleeding at birth. This medication may also harm an unborn baby. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.Since untreated mental/mood problems (such as depression, anxiety) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss the benefits and risks of using this medication during pregnancy with your doctor.This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen, "blood thinners" such as warfarin).Other medications can affect the removal of duloxetine from your body, which may affect how duloxetine works. Examples include cimetidine, viloxazine, certain quinolone antibiotics (such as ciprofloxacin, enoxacin), among others.This medication can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include antiarrhythmic drugs (such as propafenone, flecainide, quinidine), antipsychotics (such as thioridazine), tricyclic antidepressants (such as desipramine, imipramine), among others.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and at least 5 days after treatment with this medication. Ask your doctor when to start or stop taking this medication.The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, other SNRIs such as desvenlafaxine/venlafaxine), tryptophan, among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and opioid pain relievers (such as codeine). Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness, fainting.

            NOTES: Do not share this medication with others.Keep all regular medical and psychiatric appointments. Laboratory and/or medical tests (such as blood pressure, liver function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            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.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.