both increase serotonin levels. Avoid or Use Alternate Drug.olanzapineMonitor Closely (1)levomilnacipran, 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)levomilnacipran, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.ondansetronSerious - Use Alternative (1)ondansetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.oxaprozinMonitor Closely (1)levomilnacipran, oxaprozin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.ozanimodSerious - Use Alternative (1)ozanimod increases toxicity of levomilnacipran 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)levomilnacipran, 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, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.paroxetineSerious - Use Alternative (1)levomilnacipran and paroxetine both increase serotonin levels. Avoid or Use Alternate Drug.pentazocineMonitor Closely (1)levomilnacipran and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.perphenazineMonitor Closely (1)levomilnacipran, perphenazine. 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).phenelzineContraindicated (1)phenelzine and levomilnacipran both increase serotonin levels. Contraindicated. Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndromephentermineSerious - Use Alternative (1)levomilnacipran and phentermine both increase serotonin levels. Avoid or Use Alternate Drug.pimavanserinMonitor Closely (1)levomilnacipran, pimavanserin. 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).pimozideMonitor Closely (1)levomilnacipran, pimozide. 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).piroxicamMonitor Closely (1)levomilnacipran, piroxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.posaconazoleMonitor Closely (1)posaconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitorspregabalinMonitor Closely (1)pregabalin, levomilnacipran. 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.procarbazineContraindicated (1)procarbazine and levomilnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.protriptylineSerious - Use Alternative (1)levomilnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.pseudoephedrineSerious - Use Alternative (1)levomilnacipran increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.quetiapineMonitor Closely (1)levomilnacipran, quetiapine. 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).quinidineMonitor Closely (1)quinidine will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitorsrasagilineContraindicated (1)rasagiline and levomilnacipran both increase serotonin levels. Contraindicated. Concomitant use with MAOIs or within 14 days of discontinuing treatment with an MAOI is contraindicated.remifentanilMonitor Closely (1)remifentanil increases toxicity of levomilnacipran by serotonin levels. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.remimazolamMonitor Closely (1)remimazolam, levomilnacipran. 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.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.risperidoneMonitor Closely (1)levomilnacipran, risperidone. 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).ritonavirMonitor Closely (1)ritonavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitorsrizatriptanMonitor Closely (1)rizatriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.safinamideContraindicated (1)levomilnacipran, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.salsalateMonitor Closely (1)levomilnacipran, salsalate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.SAMeMonitor Closely (1)levomilnacipran and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.saquinavirMonitor Closely (1)saquinavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitorsselegilineContraindicated (1)selegiline and levomilnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI useselegiline transdermalContraindicated (1)selegiline transdermal and levomilnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use serdexmethylphenidate/dexmethylphenidateSerious - Use Alternative (1)serdexmethylphenidate/dexmethylphenidate and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of levomilnacipran by decreasing metabolism. Minor/Significance Unknown.sertralineSerious - Use Alternative (1)levomilnacipran and sertraline both increase serotonin levels. Avoid or Use Alternate Drug.sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycolMonitor Closely (1)levomilnacipran, sodium sulfate/potassium chloride/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.St John's WortSerious - Use Alternative (1)levomilnacipran and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.stiripentolMonitor Closely (1)stiripentol, levomilnacipran. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.sufentanil SLMonitor Closely (1)sufentanil SL, levomilnacipran. 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.sulfasalazineMonitor Closely (1)levomilnacipran, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.sulindacMonitor Closely (1)levomilnacipran, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.sumatriptanMonitor Closely (1)sumatriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.sumatriptan intranasalMonitor Closely (1)sumatriptan intranasal and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.tapentadolMonitor Closely (1)levomilnacipran and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.tedizolidSerious - Use Alternative (1)tedizolid, levomilnacipran. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.thiothixeneMonitor Closely (1)levomilnacipran, 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).tipranavirMonitor Closely (1)tipranavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitorstolmetinMonitor Closely (1)levomilnacipran, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.torsemideMinor (1)torsemide, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.tramadolMonitor Closely (1)levomilnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.tranylcypromineContraindicated (1)tranylcypromine and levomilnacipran both increase serotonin levels. Contraindicated. Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndrometrazodoneSerious - Use Alternative (1)levomilnacipran and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.trifluoperazineMonitor Closely (1)levomilnacipran, 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).trimipramineSerious - Use Alternative (1)levomilnacipran and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valerianMonitor Closely (1)valerian and levomilnacipran both increase sedation. Use Caution/Monitor.venlafaxineSerious - Use Alternative (1)levomilnacipran and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.vilazodoneSerious - Use Alternative (1)levomilnacipran, 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. .vorapaxarMonitor Closely (1)levomilnacipran, 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 .voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitorsvortioxetineSerious - Use Alternative (1)levomilnacipran, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.warfarinMonitor Closely (1)levomilnacipran, 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. .ziprasidoneMonitor Closely (1)levomilnacipran, ziprasidone. unspecified interaction mechanism.