Drug. Avoid leniolisib with CYP1A2 substrates that have a narrow therapeutic indexlevomilnacipranduloxetine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.linezolidlinezolid 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.lofepramineduloxetine and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.lorcaserinduloxetine and lorcaserin both increase sedation. Avoid or Use Alternate Drug.lumefantrinelumefantrine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.maprotilineduloxetine and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.meperidineduloxetine and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.methylene bluemethylene 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.metoclopramidemetoclopramide 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 reactionsmetoclopramide intranasalduloxetine, 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.mexiletinemexiletine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.milnacipranduloxetine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.modafinilmodafinil will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.nefazodoneduloxetine and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.netupitant/palonosetronnetupitant/palonosetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.nortriptylineduloxetine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.olopatadine intranasalduloxetine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. omeprazoleomeprazole will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.ondansetronondansetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.ozanimodozanimod 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.palonosetronpalonosetron, duloxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.paroxetineparoxetine 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.pefloxacinpefloxacin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.peginterferon alfa 2apeginterferon alfa 2a will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.pentobarbitalpentobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.phenobarbitalphenobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.phentermineduloxetine, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.pipemidic acidpipemidic acid will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.primidoneprimidone will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.protriptylineduloxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.pseudoephedrineduloxetine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.quinidinequinidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.rasagilinerasagiline 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.rifampinrifampin will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.ropeginterferon alfa 2bropeginterferon alfa 2b and duloxetine both increase Other (see comment). Avoid or Use Alternate Drug. Narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity.secobarbitalsecobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.selegiline transdermalselegiline transdermal and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug.sertralinesertraline 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.smokingsmoking will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.St John's Wortduloxetine and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.tedizolidtedizolid, 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.thioridazineduloxetine 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.tipranavirtipranavir will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.tobacco usetobacco use will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.tramadolduloxetine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.trazodoneduloxetine and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.trimipramineduloxetine and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.venlafaxineduloxetine and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.verapamilverapamil will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.vilazodoneduloxetine, 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. .vortioxetineduloxetine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.zileutonzileuton will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.Monitor Closely (162)5-HTPduloxetine and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.abirateroneabiraterone 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.aceclofenacduloxetine, 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.acemetacinduloxetine, 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.almotriptanalmotriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.amifostineamifostine, duloxetine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.amiodaroneamiodarone will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.asenapineasenapine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.aspirinduloxetine, 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 rectalduloxetine, 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 bicarbonateduloxetine, 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.atomoxetineduloxetine increases levels of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.benazeprilduloxetine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.benzhydrocodone/acetaminophenduloxetine 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.brexpiprazoleduloxetine 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 implantduloxetine, 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 injectionduloxetine, 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.bupropionbupropion will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.cannabidiolcannabidiol, 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.captoprilcaptopril increases effects of duloxetine by pharmacodynamic synergism. Use Caution/Monitor. Blood pressure lowering drugs may enhance the hypotensive effect of duloxetine. Monitor blood pressure.celecoxibcelecoxib 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.cenobamatecenobamate, duloxetine. Either increases effects of the other by sedation. Use Caution/Monitor.choline magnesium trisalicylateduloxetine, 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.cimetidinecimetidine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.ciprofloxacinciprofloxacin 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.clobazamclobazam 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. clopidogrelduloxetine 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 topicalduloxetine and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeineduloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.cyproheptadinecyproheptadine decreases effects of duloxetine by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.daridorexantduloxetine 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. darifenacindarifenacin will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.deferasiroxdeferasirox increases levels of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.desipramineduloxetine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.desvenlafaxinedesvenlafaxine 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 mgdexfenfluramineduloxetine and dexfenfluramine both increase