cognitive and/or neuropsychiatric adverse reactions. desvenlafaxine increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.lemborexantMonitor Closely (2)desvenlafaxine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification. lemborexant, desvenlafaxine. 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.levodopaSerious - Use Alternative (1)levodopa and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.levomilnacipranSerious - Use Alternative (1)levomilnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.levorphanolSerious - Use Alternative (1)desvenlafaxine and levorphanol both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndromelinezolidContraindicated (1)linezolid and desvenlafaxine both increase serotonin levels. Contraindicated. 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 firstlisdexamfetamineMonitor Closely (1)desvenlafaxine, 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).lithiumSerious - Use Alternative (1)lithium and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.lomitapideMonitor Closely (1)desvenlafaxine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.lonafarnibSerious - Use Alternative (1)desvenlafaxine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.lopinavirMonitor Closely (1)lopinavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.loratadineMonitor Closely (1)desvenlafaxine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mglorcaserinSerious - Use Alternative (1)desvenlafaxine and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.lsdSerious - Use Alternative (1)lsd and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.lurasidoneMonitor Closely (1)lurasidone, desvenlafaxine. 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.maprotilineSerious - Use Alternative (1)maprotiline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.meperidineSerious - Use Alternative (1)meperidine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.methamphetamineMonitor Closely (1)desvenlafaxine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgmethylene blueContraindicated (1)methylene blue and desvenlafaxine both increase serotonin levels. Contraindicated. 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 firstmetoclopramideSerious - Use Alternative (1)metoclopramide and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug. Additive effects; increased risk for serotonin syndrome, neuroleptic malignant syndrome, dystonia, or other extrapyramidal reactionsmetoclopramide intranasalSerious - Use Alternative (1)desvenlafaxine, 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.metoprololMonitor Closely (1)desvenlafaxine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgmexiletineMonitor Closely (1)desvenlafaxine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgmidazolam intranasalMonitor Closely (2)desvenlafaxine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation. midazolam intranasal, desvenlafaxine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.milnacipranSerious - Use Alternative (1)milnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.mirtazapineSerious - Use Alternative (1)mirtazapine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.morphineMonitor Closely (1)desvenlafaxine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgSerious - Use Alternative (1)morphine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.nalbuphineSerious - Use Alternative (1)desvenlafaxine and nalbuphine both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndromenaratriptanSerious - Use Alternative (1)naratriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.nebivololMonitor Closely (1)desvenlafaxine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgnefazodoneSerious - Use Alternative (1)nefazodone and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.nelfinavirMonitor Closely (1)nelfinavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .netupitant/palonosetronSerious - Use Alternative (1)netupitant/palonosetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.nortriptylineMonitor Closely (1)desvenlafaxine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgSerious - Use Alternative (1)nortriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.oliceridineMonitor Closely (1)desvenlafaxine, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.olopatadine intranasalSerious - Use Alternative (1)desvenlafaxine 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. ondansetronSerious - Use Alternative (1)ondansetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.opium tinctureSerious - Use Alternative (1)desvenlafaxine and opium tincture both increase serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndromeoxycodoneMonitor Closely (1)desvenlafaxine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgoxymorphoneMonitor Closely (1)desvenlafaxine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgozanimodSerious - Use Alternative (1)ozanimod increases toxicity of desvenlafaxine 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.palonosetronSerious - Use Alternative (1)palonosetron, desvenlafaxine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.paroxetineMonitor Closely (1)desvenlafaxine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgSerious - Use Alternative (1)paroxetine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.pentazocineSerious - Use Alternative (1)pentazocine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.perphenazineMonitor Closely (1)desvenlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgphenelzineContraindicated (1)phenelzine and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drugpregabalinMonitor Closely (1)pregabalin, desvenlafaxine. 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 desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drugprochlorperazineMonitor Closely (1)desvenlafaxine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgpromethazineMonitor Closely (1)desvenlafaxine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgpropafenoneMonitor Closely (1)desvenlafaxine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgpropranololMonitor Closely (1)desvenlafaxine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgprotriptylineSerious - Use Alternative (1)protriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.pseudoephedrineSerious - Use Alternative (1)desvenlafaxine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.rasagilineContraindicated (1)rasagiline and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drugremifentanilSerious - Use Alternative (1)desvenlafaxine and remifentanil both decrease serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndromeremimazolamMonitor Closely (1)remimazolam, desvenlafaxine. 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.risperidoneMonitor Closely (1)desvenlafaxine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgritonavirMonitor Closely (1)ritonavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .rizatriptanSerious - Use Alternative (1)rizatriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.ropeginterferon alfa 2bSerious - Use Alternative (1)ropeginterferon alfa 2b and desvenlafaxine both increase Other (see comment). Avoid or Use Alternate Drug. Narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity.ruxolitinibMinor (1)desvenlafaxine will increase the level or effect of ruxolitinib