other by serotonin levels. Avoid or Use Alternate Drug.fentanyl transdermalSerious - Use Alternative (1)fentanyl transdermal, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.fentanyl transmucosalSerious - Use Alternative (1)fentanyl transmucosal, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.fexinidazoleSerious - Use Alternative (1)fexinidazole will increase the level or effect of vortioxetine 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 oilMonitor Closely (1)fish oil, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.fish oil triglyceridesMonitor Closely (1)fish oil triglycerides will increase the level or effect of vortioxetine 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, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.flurbiprofenMonitor Closely (1)flurbiprofen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.fluvoxamineSerious - Use Alternative (1)fluvoxamine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.fondaparinuxMonitor Closely (1)vortioxetine and fondaparinux both increase anticoagulation. Use Caution/Monitor.fosphenytoinMonitor Closely (1)fosphenytoin decreases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.frovatriptanSerious - Use Alternative (1)frovatriptan, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.gabapentinMonitor Closely (1)gabapentin, vortioxetine. 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, vortioxetine. 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)vortioxetine and ganaxolone both increase sedation. Use Caution/Monitor.garlicMonitor Closely (1)garlic, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.givosiranSerious - Use Alternative (1)givosiran will decrease the level or effect of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.heparinMonitor Closely (1)vortioxetine and heparin both increase anticoagulation. Use Caution/Monitor.hydromorphoneSerious - Use Alternative (1)hydromorphone, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.ibrutinibMonitor Closely (1)ibrutinib will increase the level or effect of vortioxetine 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)ibuprofen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.ibuprofen IVMonitor Closely (1)ibuprofen IV, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.idelalisibSerious - Use Alternative (1)idelalisib will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substratesimipramineSerious - Use Alternative (1)imipramine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.indinavirMonitor Closely (1)indinavir will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.indomethacinMonitor Closely (1)indomethacin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.isocarboxazidContraindicated (1)isocarboxazid, vortioxetine. Either increases effects of the other by serotonin levels. Contraindicated.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.ivosidenibSerious - Use Alternative (1)ivosidenib will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.ketoprofenMonitor Closely (1)ketoprofen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.ketorolacMonitor Closely (1)ketorolac, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.ketorolac intranasalMonitor Closely (1)ketorolac intranasal, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.larotrectinibMinor (1)larotrectinib will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (1)lasmiditan, vortioxetine. 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.lenacapavirMonitor Closely (1)lenacapavir will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.levoketoconazoleMinor (1)levoketoconazole will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.levomilnacipranSerious - Use Alternative (1)levomilnacipran, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.linezolidContraindicated (1)linezolid increases toxicity of vortioxetine by serum potassium. Contraindicated. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be urgently administered, discontinue vortioxetine immediately and monitor for serotonin syndrome. Monitor for serotonin syndrome for 3 weeks or 24 hr after last linezolid dose, whichever comes first. Vortioxetine may be resumed 24 hr after last linezolid dose.lithiumSerious - Use Alternative (1)lithium, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.lonafarnibSerious - Use Alternative (1)lonafarnib will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.lopinavirSerious - Use Alternative (1)lopinavir increases levels of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Decrease vortioxetine dose by 50% when coadministered with strong CYP2D6 inhibitors.lorcaserinSerious - Use Alternative (1)lorcaserin increases levels of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Decrease vortioxetine dose by 50% when coadministered with strong CYP2D6 inhibitors.lorlatinibMonitor Closely (1)lorlatinib will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.meclofenamateMonitor Closely (1)meclofenamate, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.mefenamic acidMonitor Closely (1)mefenamic acid, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.meloxicamMonitor Closely (1)meloxicam, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.meperidineSerious - Use Alternative (1)meperidine, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.metforminMonitor Closely (1)vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.methylene blueContraindicated (1)methylene blue increases toxicity of vortioxetine by serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be urgently administered, discontinue vortioxetine immediately and monitor for serotonin syndrome. Monitor for serotonin syndrome for 3 weeks or 24 hr after last methylene blue dose, whichever comes first. Vortioxetine may be resumed 24 hr after last methylene blue dose.mifepristoneMonitor Closely (1)mifepristone will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.milnacipranSerious - Use Alternative (1)milnacipran, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.mirtazapineSerious - Use Alternative (1)mirtazapine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.mitotaneMonitor Closely (1)mitotane decreases levels of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.morphineSerious - Use Alternative (1)morphine, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.nabumetoneMonitor Closely (1)nabumetone, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.nafcillinMonitor Closely (2)nafcillin decreases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose. nafcillin will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.naproxenMonitor Closely (1)naproxen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.naratriptanSerious - Use Alternative (1)naratriptan, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.nefazodoneSerious - Use Alternative (1)nefazodone, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.nevirapineMonitor Closely (1)nevirapine decreases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.nortriptylineSerious - Use Alternative (1)nortriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.olopatadine intranasalSerious - Use Alternative (1)vortioxetine 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. omega 3 carboxylic acidsMonitor Closely (1)omega 3 carboxylic acids, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.omega 3 fatty acidsMonitor Closely (1)omega 3 fatty acids, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.oxaprozinMonitor Closely (1)oxaprozin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.oxcarbazepineMonitor Closely (1)oxcarbazepine increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.paroxetineSerious - Use Alternative (1)paroxetine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.pentobarbitalMonitor Closely (1)pentobarbital increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.pentosan polysulfate sodiumMonitor Closely (1)pentosan polysulfate sodium, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.phenelzineContraindicated (1)phenelzine increases toxicity of vortioxetine by serotonin levels. Contraindicated.phenobarbitalMonitor Closely (1)phenobarbital increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.phenytoinMonitor Closely (1)phenytoin increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.Serious - Use Alternative (1)phenytoin will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.piroxicamMonitor Closely (1)piroxicam, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.prasugrelMonitor Closely (1)prasugrel increases effects of vortioxetine by anticoagulation. Use Caution/Monitor.pregabalinMonitor Closely (1)pregabalin, vortioxetine. 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.primidoneMonitor Closely (1)primidone increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.Serious - Use Alternative (1)primidone will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.protein C concentrateMonitor Closely (1)protein C concentrate, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.protriptylineSerious - Use Alternative (1)protriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.quinidineSerious - Use Alternative (1)quinidine increases levels of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Decrease vortioxetine dose by 50% when coadministered with strong CYP2D6 inhibitors.quinineSerious - Use Alternative (1)quinine increases levels of vortioxetine by affecting hepatic