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.brexpiprazoleMonitor Closely (1)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. bumetanideMinor (1)bumetanide, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.buprenorphine subdermal implantMonitor Closely (1)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 injectionMonitor Closely (1)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.bupropionMonitor Closely (1)bupropion will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)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.buspironeSerious - Use Alternative (1)duloxetine and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.butabarbitalSerious - Use Alternative (1)butabarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.butalbitalSerious - Use Alternative (1)butalbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.cannabidiolMonitor Closely (1)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.captoprilMonitor Closely (1)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.carbamazepineSerious - Use Alternative (1)carbamazepine will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.carvedilolMinor (1)duloxetine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.celandineMinor (1)celandine decreases effects of duloxetine by pharmacodynamic antagonism. Minor/Significance Unknown. Based on animal studies.celecoxibMonitor Closely (2)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.cenobamateMonitor Closely (1)cenobamate, duloxetine. Either increases effects of the other by sedation. Use Caution/Monitor.chloroquineMinor (1)chloroquine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.chlorpromazineMinor (1)duloxetine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.choline magnesium trisalicylateMonitor Closely (1)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.cigarette smokingSerious - Use Alternative (1)cigarette smoking will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.cimetidineMonitor Closely (1)cimetidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)cimetidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.ciprofloxacinMonitor Closely (1)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.citalopramSerious - Use Alternative (1)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.clobazamMonitor Closely (1)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. clomipramineSerious - Use Alternative (2)duloxetine and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug. duloxetine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.clopidogrelMonitor Closely (1)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 topicalMonitor Closely (1)duloxetine and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeineMonitor Closely (1)duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.cyclobenzaprineSerious - Use Alternative (1)duloxetine and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyproheptadineMonitor Closely (1)cyproheptadine decreases effects of duloxetine by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.dacomitinibSerious - Use Alternative (1)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. daridorexantMonitor Closely (1)duloxetine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. darifenacinMonitor Closely (1)darifenacin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.deferasiroxMonitor Closely (1)deferasirox increases levels of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.desipramineMonitor Closely (1)duloxetine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)duloxetine and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.desvenlafaxineMonitor Closely (1)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 mgSerious - Use Alternative (1)duloxetine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.dexfenfluramineMonitor Closely (1)duloxetine and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)duloxetine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dexmethylphenidateMinor (1)dexmethylphenidate increases effects of duloxetine by decreasing metabolism. Minor/Significance Unknown.dextroamphetamineMonitor Closely (2)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.dextroamphetamine transdermalMonitor Closely (1)duloxetine, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).dextromethorphanSerious - Use Alternative (2)duloxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. duloxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.diazepam intranasalMonitor Closely (1)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.dichlorphenamideMonitor Closely (1)dichlorphenamide and duloxetine both decrease serum potassium. Use Caution/Monitor.diclofenacMonitor Closely (1)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.difelikefalinMonitor Closely (1)difelikefalin and duloxetine both increase sedation. Use Caution/Monitor.diflunisalMonitor Closely (1)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.dihydroergotamineMonitor Closely (1)duloxetine and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.dihydroergotamine intranasalMonitor Closely (1)duloxetine and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.diphenhydramineMonitor Closely (1)diphenhydramine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.dolasetronSerious - Use Alternative (1)dolasetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.donepezilMinor (1)duloxetine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dosulepinSerious - Use Alternative (1)duloxetine and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.doxepinSerious - Use Alternative (1)duloxetine and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)duloxetine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dronedaroneMonitor Closely (1)dronedarone will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.eletriptanMonitor Closely (1)eletriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)duloxetine, eletriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.eliglustatContraindicated (1)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.Monitor Closely (1)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.eluxadolineMonitor Closely (1)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 DFMonitor Closely (1)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.encainideMinor (1)duloxetine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.epcoritamabMonitor Closely (1)epcoritamab, duloxetine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .ergotamineMonitor Closely (1)duloxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.erythromycin baseSerious - Use Alternative (1)erythromycin base will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.erythromycin ethylsuccinateSerious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.erythromycin lactobionateSerious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.erythromycin stearateSerious - Use Alternative (1)erythromycin stearate will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.escitalopramMonitor Closely (1)duloxetine and escitalopram both increase serotonin levels. Use Caution/Monitor.esomeprazoleMonitor Closely (1)esomeprazole will decrease the level or effect of duloxetine by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.ethacrynic acidMinor (1)ethacrynic acid, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.ethanolMonitor Closely (1)ethanol, duloxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hepatotoxicity.ethinylestradiolMinor (1)ethinylestradiol will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.etodolacMonitor Closely (1)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.fedratinibMonitor Closely (1)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.fenbufenMonitor Closely (1)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.fenfluramineMonitor Closely (2)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. duloxetine and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.fenoprofenMonitor Closely (1)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.fesoterodineMonitor Closely (1)duloxetine will increase