affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong CYP3A inhibitors.lemborexantMonitor Closely (1)lemborexant, nefazodone. 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.Serious - Use Alternative (1)nefazodone will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.lenacapavirMonitor Closely (1)lenacapavir will increase the level or effect of nefazodone 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.leniolisibSerious - Use Alternative (1)nefazodone will increase the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.letermovirSerious - Use Alternative (1)nefazodone will increase the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.levamlodipineMonitor Closely (1)nefazodone will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.levoketoconazoleMonitor Closely (2)levoketoconazole will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. nefazodone will increase the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levomilnacipranMonitor Closely (1)nefazodone 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 inhibitorsSerious - Use Alternative (1)levomilnacipran and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.levonorgestrel oralSerious - Use Alternative (1)nefazodone will increase the level or effect of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.levonorgestrel oral/ethinylestradiol/ferrous bisglycinateMonitor Closely (1)nefazodone will increase the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase the plasma hormone concentrations. Use of a nonhormonal contraceptive is recommended.linagliptinMonitor Closely (1)nefazodone will increase the level or effect of linagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.linezolidSerious - Use Alternative (1)linezolid and nefazodone 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.lithiumMonitor Closely (1)nefazodone and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)nefazodone, lithium. Mechanism: unknown. Minor/Significance Unknown. Risk of neurotoxicity.lofepramineSerious - Use Alternative (1)nefazodone and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.lomitapideContraindicated (1)nefazodone increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.lonafarnibContraindicated (1)nefazodone will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated. loperamideMonitor Closely (1)nefazodone will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.lopinavirMonitor Closely (2)nefazodone will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. lopinavir will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.loratadineMonitor Closely (1)nefazodone will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nefazodone will increase the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lorcaserinMonitor Closely (1)lorcaserin will increase the level or effect of nefazodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.lorlatinibSerious - Use Alternative (2)lorlatinib will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. nefazodone will increase the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering lorlatinib with strong CYP3A inhibitors. If unavoidable, reduce lorlatinib dose by 25 mg/day. If strong CYP3A inhibitor discontinued, increase to previous lorlatinib (dose after 3 plasma half-lives of strong CYP3A inhibitor). See monograph for further details.lornoxicamMonitor Closely (1)nefazodone, 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.losartanMonitor Closely (1)nefazodone will increase the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lovastatinContraindicated (1)nefazodone will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors increase systemic statin exposure and risk of myopathy, including rhabdomyolysisMonitor Closely (1)nefazodone will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.lsdMonitor Closely (1)nefazodone and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.lumacaftor/ivacaftorMonitor Closely (1)nefazodone increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.lumateperoneMonitor Closely (1)nefazodone will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.lumefantrineSerious - Use Alternative (1)nefazodone will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.lurasidoneContraindicated (1)nefazodone increases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lurasidone and strong CYP3A4 inhibitors is contraindicated.Monitor Closely (1)lurasidone, nefazodone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.lurbinectedinSerious - Use Alternative (1)nefazodone will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.macitentanSerious - Use Alternative (1)nefazodone will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors maprotilineSerious - Use Alternative (1)nefazodone and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.maravirocMonitor Closely (2)nefazodone will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors nefazodone will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.marijuanaMonitor Closely (1)nefazodone will increase the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mavacamtenContraindicated (1)nefazodone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction. meclofenamateMonitor Closely (1)nefazodone, 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.medroxyprogesteroneMonitor Closely (1)nefazodone will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.mefenamic acidMonitor Closely (1)nefazodone, 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.mefloquineSerious - Use Alternative (1)nefazodone will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. Avoid coadministration during and for 15 weeks after discontinuing mefloquine.meloxicamMonitor Closely (1)nefazodone, 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)nefazodone and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.mestranolMonitor Closely (1)nefazodone will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.metaxaloneMonitor Closely (1)nefazodone will increase the level or effect of metaxalone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.methadoneSerious - Use Alternative (1)nefazodone will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.methylene blueSerious - Use Alternative (1)methylene blue and nefazodone 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.methylergonovineContraindicated (1)nefazodone will increase the level or effect of methylergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.methylprednisoloneMonitor Closely (1)nefazodone will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.metoclopramide intranasalSerious - Use Alternative (1)nefazodone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.midazolamSerious - Use Alternative (1)nefazodone will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.midazolam intranasalMonitor Closely (1)midazolam intranasal, nefazodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.Serious - Use Alternative (1)nefazodone will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.midostaurinSerious - Use Alternative (1)nefazodone will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.mifepristoneMonitor Closely (2)nefazodone will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Do not exceed mifepristone 300 mg/day for Cushing syndrome when coadministered with strong CYP3A4 inhibitors mifepristone will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.milnacipranSerious - Use Alternative (1)milnacipran and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.mirabegronMonitor Closely (1)mirabegron will increase the level or effect of nefazodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.mirtazapineMonitor Closely (1)nefazodone and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)nefazodone will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.mirvetuximab soravtansineMonitor Closely (1)nefazodone will increase the level or effect of mirvetuximab soravtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong CYP3A4 inhibitors may increase unconjugated DM4 (a CYP3A4 substrate and the cytotoxic component of the antibody drug conjugate for mirvetuximab soravtansine) exposure, which may increase the risk of adverse reactions. mitotaneMonitor Closely (1)mitotane decreases levels of nefazodone 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.mobocertinibSerious - Use Alternative (1)nefazodone will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.modafinilMonitor Closely (1)nefazodone will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism.