or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.apixabanSerious - Use Alternative (1)levomilnacipran, apixaban. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.aripiprazoleMonitor Closely (1)levomilnacipran, 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)levomilnacipran, 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)levomilnacipran, aspirin. 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.aspirin rectalMonitor Closely (1)levomilnacipran, aspirin rectal. 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.aspirin/citric acid/sodium bicarbonateMonitor Closely (1)levomilnacipran, aspirin/citric acid/sodium bicarbonate. 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.atazanavirMonitor Closely (1)atazanavir 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 inhibitorsbenzhydrocodone/acetaminophenMonitor Closely (1)benzhydrocodone/acetaminophen, 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.bumetanideMinor (1)bumetanide, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.buprenorphine subdermal implantMonitor Closely (1)levomilnacipran, 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)levomilnacipran, 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.buspironeSerious - Use Alternative (1)levomilnacipran and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.cariprazineMonitor Closely (1)levomilnacipran, 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).celecoxibMonitor Closely (1)levomilnacipran, celecoxib. 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.cenobamateMonitor Closely (1)cenobamate will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.ceritinibSerious - Use Alternative (1)ceritinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.chloramphenicolSerious - Use Alternative (1)chloramphenicol will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.choline magnesium trisalicylateMonitor Closely (1)levomilnacipran, choline magnesium trisalicylate. 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.citalopramSerious - Use Alternative (1)citalopram and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.clarithromycinMonitor Closely (1)clarithromycin 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 inhibitorsclomipramineSerious - Use Alternative (1)levomilnacipran and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.clonidineMonitor Closely (1)levomilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor. Because levomilnacipran decreases reuptake of NE, it may antagonize clonidine antihypertensive effect.clopidogrelMonitor Closely (1)levomilnacipran 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)levomilnacipran, 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).cobicistatSerious - Use Alternative (1)cobicistat will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not esceed 80 mg levominacipram dose once daily if coadministration necessarycocaine topicalMonitor Closely (1)levomilnacipran and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.conivaptanMonitor Closely (1)conivaptan 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 inhibitorscyclobenzaprineSerious - Use Alternative (1)levomilnacipran and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyclophosphamideMinor (1)cyclophosphamide will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyproheptadineMonitor Closely (1)cyproheptadine decreases effects of levomilnacipran by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.darunavirMonitor Closely (1)darunavir 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 inhibitorsdesipramineSerious - Use Alternative (1)levomilnacipran and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.desvenlafaxineSerious - Use Alternative (1)levomilnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.dexfenfluramineMonitor Closely (1)levomilnacipran and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.dexmethylphenidateSerious - Use Alternative (1)dexmethylphenidate and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.dextroamphetamineMonitor Closely (1)levomilnacipran and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.dextromethorphanSerious - Use Alternative (1)levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.diazepam intranasalMonitor Closely (1)diazepam intranasal, levomilnacipran. 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)levomilnacipran, diclofenac. 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.diflunisalMonitor Closely (1)levomilnacipran, diflunisal. 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.dihydroergotamineMonitor Closely (1)levomilnacipran and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.dihydroergotamine intranasalMonitor Closely (1)levomilnacipran and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.dolasetronSerious - Use Alternative (1)dolasetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.dosulepinSerious - Use Alternative (1)levomilnacipran and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.doxepinSerious - Use Alternative (1)levomilnacipran and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.duloxetineSerious - Use Alternative (1)duloxetine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.duvelisibMonitor Closely (1)duvelisib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.elagolixMonitor Closely (1)elagolix decreases levels of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.eletriptanMonitor Closely (1)eletriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.elvitegravir/cobicistat/emtricitabine/tenofovir DFMonitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF 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 inhibitorsencorafenibMonitor Closely (1)encorafenib, levomilnacipran. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.epinephrineSerious - Use Alternative (1)levomilnacipran increases levels of epinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.epinephrine racemicSerious - Use Alternative (1)levomilnacipran increases levels of epinephrine racemic by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.ergotamineMonitor Closely (1)levomilnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.escitalopramSerious - Use Alternative (1)escitalopram and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.ethacrynic acidMinor (1)ethacrynic acid, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.ethanolContraindicated (1)ethanol will increase the level or effect of levomilnacipran by enhancing GI absorption. Applies only to oral form of both agents. Contraindicated. Alcohol interacts with the extended-release properties of levomilnacipran capsules resulting in a pronounced accelerated drug release etodolacMonitor Closely (1)levomilnacipran, etodolac. 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.fedratinibMonitor Closely (1)fedratinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.fenfluramineMonitor Closely (2)fenfluramine, levomilnacipran. 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. levomilnacipran and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.fenoprofenMonitor Closely (1)levomilnacipran, fenoprofen. 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.fexinidazoleSerious - Use Alternative (1)fexinidazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.fish oil triglyceridesMonitor Closely (1)fish oil triglycerides will increase the level or effect of levomilnacipran 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 (1)fluoxetine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.fluphenazineMonitor Closely (1)levomilnacipran, 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)levomilnacipran, flurbiprofen. 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.fluvoxamineSerious - Use Alternative (1)fluvoxamine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.fosamprenavirMonitor Closely (1)fosamprenavir 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 inhibitorsfrovatriptanMonitor Closely (1)frovatriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.furosemideMinor (1)furosemide, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.gabapentinMonitor Closely (1)gabapentin, 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.gabapentin enacarbilMonitor Closely (1)gabapentin enacarbil, 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