(1)fluoxetine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.fluphenazineMonitor Closely (1)milnacipran, fluphenazine. 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).flurbiprofenMonitor Closely (1)milnacipran, 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.fluvoxamineSerious - Use Alternative (1)fluvoxamine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.frovatriptanMonitor Closely (1)frovatriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)milnacipran, frovatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.furosemideMinor (1)furosemide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.gabapentinMonitor Closely (1)gabapentin, milnacipran. 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 enacarbilMonitor Closely (1)gabapentin enacarbil, milnacipran. 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.ganaxoloneMonitor Closely (1)milnacipran and ganaxolone both increase sedation. Use Caution/Monitor.granisetronSerious - Use Alternative (1)granisetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.green teaMonitor Closely (1)green tea, milnacipran. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.haloperidolMonitor Closely (1)milnacipran, haloperidol. 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).hydrocodoneMonitor Closely (1)hydrocodone, 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.ibrutinibMonitor Closely (1)ibrutinib will increase the level or effect of milnacipran 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. ibuprofenMonitor Closely (1)milnacipran, 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 IVMonitor Closely (1)milnacipran, 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.iloperidoneMonitor Closely (1)milnacipran, iloperidone. 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).imipramineSerious - Use Alternative (1)milnacipran and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.indomethacinMonitor Closely (1)milnacipran, 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.iobenguane I 123Contraindicated (1)milnacipran 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.iobenguane I 131Serious - Use Alternative (1)milnacipran 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.isocarboxazidContraindicated (1)isocarboxazid and milnacipran both increase serotonin levels. Contraindicated.isoniazidMonitor Closely (1)milnacipran and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.ketoprofenMonitor Closely (1)milnacipran, 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.ketorolacMonitor Closely (1)milnacipran, 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 intranasalMonitor Closely (1)milnacipran, 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-tryptophanMonitor Closely (1)milnacipran and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.lasmiditanMonitor Closely (2)lasmiditan, milnacipran. 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. milnacipran increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.lemborexantMonitor Closely (1)lemborexant, milnacipran. 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.levomilnacipranSerious - Use Alternative (1)levomilnacipran and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.linezolidSerious - Use Alternative (1)linezolid and milnacipran 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.lisdexamfetamineMonitor Closely (1)milnacipran, 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).lithiumMonitor Closely (1)milnacipran and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)milnacipran, lithium. Mechanism: unknown. Minor/Significance Unknown. Risk of neurotoxicity.lofepramineSerious - Use Alternative (1)milnacipran and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.lorcaserinSerious - Use Alternative (1)milnacipran and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.lornoxicamMonitor Closely (1)milnacipran, 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.loxapineMonitor Closely (1)milnacipran, loxapine. 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).loxapine inhaledMonitor Closely (1)milnacipran, loxapine inhaled. 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).lsdMonitor Closely (1)milnacipran and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.lurasidoneMonitor Closely (2)milnacipran, lurasidone. 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). lurasidone increases effects of milnacipran by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .maprotilineSerious - Use Alternative (1)milnacipran and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.meclofenamateMonitor Closely (1)milnacipran, 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 acidMonitor Closely (1)milnacipran, 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.meloxicamMonitor Closely (1)milnacipran, 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.meperidineSerious - Use Alternative (1)milnacipran and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.methylene blueSerious - Use Alternative (1)methylene blue and milnacipran 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.metoclopramideSerious - Use Alternative (1)metoclopramide and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Additive effects; increased risk for serotonin syndrome, neuroleptic malignant syndrome, dystonia, or other extrapyramidal reactionsmirtazapineMonitor Closely (1)milnacipran and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.molindoneMonitor Closely (1)milnacipran, molindone. 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).morphineMonitor Closely (1)milnacipran and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.nabumetoneMonitor Closely (1)milnacipran, 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.naproxenMonitor Closely (1)milnacipran, 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.naratriptanMonitor Closely (1)naratriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)milnacipran, naratriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.nefazodoneSerious - Use Alternative (1)milnacipran and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.netupitant/palonosetronSerious - Use Alternative (1)netupitant/palonosetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.norepinephrineSerious - Use Alternative (1)milnacipran increases levels of norepinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.nortriptylineSerious - Use Alternative (1)milnacipran and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.olanzapineMonitor Closely (1)milnacipran, olanzapine. 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).oliceridineMonitor Closely (1)milnacipran, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.ondansetronSerious - Use Alternative (1)ondansetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.oxaprozinMonitor Closely (1)milnacipran, 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.ozanimodSerious - Use Alternative (1)ozanimod increases toxicity of milnacipran 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.paliperidoneMonitor Closely (1)milnacipran, paliperidone. 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).palonosetronSerious - Use Alternative (1)palonosetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.panax ginsengMinor (1)panax ginseng increases effects of milnacipran by pharmacodynamic synergism. Minor/Significance Unknown.parecoxibMonitor Closely (1)milnacipran, 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.paroxetineSerious - Use Alternative (1)milnacipran and paroxetine both increase serotonin levels. Avoid or Use Alternate