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.sulfasalazinemilnacipran, 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.sulindacmilnacipran, 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.sumatriptansumatriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.sumatriptan intranasalsumatriptan intranasal and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.tapentadolmilnacipran and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.thiothixenemilnacipran, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).tolfenamic acidmilnacipran, 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.tolmetinmilnacipran, 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.tramadolmilnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.trifluoperazinemilnacipran, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).valerianvalerian and milnacipran both increase sedation. Use Caution/Monitor.vorapaxarmilnacipran, 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 .warfarinmilnacipran, warfarin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serotonin release by platelets plays an important role in hemostasis. SSRIs and SNRIs may increase anticoagulation effect of warfarin. .ziprasidonemilnacipran, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).zolmitriptanzolmitriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (18)almotriptanmilnacipran, almotriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.bumetanidebumetanide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.celandinecelandine decreases effects of milnacipran by pharmacodynamic antagonism. Minor/Significance Unknown. Based on animal studies.dexmethylphenidatedexmethylphenidate increases effects of milnacipran by decreasing metabolism. Minor/Significance Unknown.eletriptanmilnacipran, eletriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.ethacrynic acidethacrynic acid, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.frovatriptanmilnacipran, frovatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.furosemidefurosemide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.lithiummilnacipran, lithium. Mechanism: unknown. Minor/Significance Unknown. Risk of neurotoxicity.naratriptanmilnacipran, naratriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.panax ginsengpanax ginseng increases effects of milnacipran by pharmacodynamic synergism. Minor/Significance Unknown.pleurisy rootpleurisy root decreases effects of milnacipran by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.rizatriptanmilnacipran, rizatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.serdexmethylphenidate/dexmethylphenidateserdexmethylphenidate/dexmethylphenidate increases effects of milnacipran by decreasing metabolism. Minor/Significance Unknown.sumatriptanmilnacipran, sumatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.sumatriptan intranasalmilnacipran, sumatriptan intranasal. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.torsemidetorsemide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.zolmitriptanmilnacipran, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.5-HTPMonitor Closely (1)milnacipran and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.aceclofenacMonitor Closely (1)milnacipran, 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.acemetacinMonitor Closely (1)milnacipran, 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.almotriptanMonitor Closely (1)almotriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)milnacipran, almotriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.amitriptylineSerious - Use Alternative (1)milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.amoxapineSerious - Use Alternative (1)milnacipran and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.apixabanSerious - Use Alternative (1)milnacipran and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.aripiprazoleMonitor Closely (1)milnacipran, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).asenapineMonitor Closely (1)milnacipran, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).aspirinMonitor Closely (1)milnacipran, 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 rectalMonitor Closely (1)milnacipran, 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 bicarbonateMonitor Closely (1)milnacipran, 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.benzhydrocodone/acetaminophenMonitor Closely (1)benzhydrocodone/acetaminophen, milnacipran. 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.bumetanideMinor (1)bumetanide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.buprenorphine subdermal implantMonitor Closely (1)milnacipran, 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)milnacipran, 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.bupropionSerious - Use Alternative (1)milnacipran 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)milnacipran and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.cariprazineMonitor Closely (1)milnacipran, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).celandineMinor (1)celandine decreases effects of milnacipran by pharmacodynamic antagonism. Minor/Significance Unknown. Based on animal studies.celecoxibMonitor Closely (1)milnacipran, 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.choline magnesium trisalicylateMonitor Closely (1)milnacipran, 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.citalopramSerious - Use Alternative (1)citalopram and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.clomipramineMonitor Closely (1)milnacipran, clomipramine. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Risk of euphoria, postural hypot'n when switching from clomipramine to milnacipran.Serious - Use Alternative (1)milnacipran and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.clonidineMonitor Closely (1)milnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.clopidogrelMonitor Closely (1)milnacipran 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.clozapineMonitor Closely (1)milnacipran, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).cocaine topicalMonitor Closely (1)milnacipran and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.cyclobenzaprineSerious - Use Alternative (1)milnacipran and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyproheptadineMonitor Closely (1)cyproheptadine decreases effects of milnacipran by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.desipramineSerious - Use Alternative (1)milnacipran and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.desvenlafaxineSerious - Use Alternative (1)milnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.dexfenfluramineMonitor Closely (1)milnacipran and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.dexmethylphenidateMinor (1)dexmethylphenidate increases effects of milnacipran by decreasing metabolism. Minor/Significance Unknown.dextroamphetamineMonitor Closely (1)milnacipran and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.dextroamphetamine transdermalMonitor Closely (1)milnacipran, 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 (1)milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.diazepam intranasalMonitor Closely (1)diazepam intranasal, milnacipran. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.diclofenacMonitor Closely (1)milnacipran, 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.diflunisalMonitor Closely (1)milnacipran, 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)milnacipran and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.dihydroergotamine intranasalMonitor Closely (1)milnacipran and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.dolasetronSerious - Use Alternative (1)dolasetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.dosulepinSerious - Use Alternative (1)milnacipran and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.doxepinSerious - Use Alternative (1)milnacipran and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.duloxetineSerious - Use Alternative (1)duloxetine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.eletriptanMonitor Closely (1)eletriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)milnacipran, eletriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.epinephrineSerious - Use Alternative (1)milnacipran increases levels of epinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.epinephrine racemicSerious - Use Alternative (1)milnacipran increases levels of epinephrine racemic by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.ergotamineMonitor Closely (1)milnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.escitalopramSerious - Use Alternative (1)escitalopram and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.ethacrynic acidMinor (1)ethacrynic acid, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.etodolacMonitor Closely (1)milnacipran, 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.fenbufenMonitor Closely (1)milnacipran, 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, milnacipran. 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. milnacipran and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.fenoprofenMonitor Closely (1)milnacipran, 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.fish oil triglyceridesMonitor Closely (1)fish oil triglycerides will increase the level or effect of milnacipran 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.fluoxetineSerious - Use Alternative