by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ruxolitinib topicalMinor (1)desvenlafaxine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.safinamideContraindicated (1)desvenlafaxine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.SAMeSerious - Use Alternative (1)SAMe and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.selegilineContraindicated (1)selegiline and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drugselegiline transdermalContraindicated (1)selegiline transdermal and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drugsertralineSerious - Use Alternative (1)sertraline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycolMonitor Closely (1)desvenlafaxine, 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)St John's Wort and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.sufentanilSerious - Use Alternative (1)desvenlafaxine and sufentanil both decrease serotonin levels. Avoid or Use Alternate Drug. May cause serotonin syndromesufentanil SLMonitor Closely (1)sufentanil SL, desvenlafaxine. 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.sumatriptanSerious - Use Alternative (1)sumatriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.sumatriptan intranasalSerious - Use Alternative (1)sumatriptan intranasal and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.tapentadolMonitor Closely (1)desvenlafaxine and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.tazemetostatMonitor Closely (1)desvenlafaxine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tedizolidSerious - Use Alternative (1)tedizolid, desvenlafaxine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.thioridazineMonitor Closely (1)desvenlafaxine will increase the level or effect of thioridazine 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 mgtimololMonitor Closely (1)desvenlafaxine will increase the level or effect of timolol 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 mgtinidazoleMonitor Closely (1)desvenlafaxine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tolterodineMonitor Closely (1)desvenlafaxine will increase the level or effect of tolterodine 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 mgtramadolMonitor Closely (1)desvenlafaxine will increase the level or effect of tramadol 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)tramadol and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.tranylcypromineContraindicated (1)tranylcypromine and desvenlafaxine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with a serotonergic drugtrazodoneSerious - Use Alternative (1)trazodone and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.trifluoperazineMonitor Closely (1)desvenlafaxine will increase the level or effect of trifluoperazine 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 mgtrimipramineSerious - Use Alternative (1)trimipramine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.valerianMonitor Closely (1)valerian and desvenlafaxine both increase sedation. Use Caution/Monitor.vilazodoneSerious - Use Alternative (1)desvenlafaxine, 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)desvenlafaxine, 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 .vortioxetineSerious - Use Alternative (1)desvenlafaxine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.warfarinMonitor Closely (1)desvenlafaxine, 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. .zolmitriptanSerious - Use Alternative (1)zolmitriptan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug. Adverse drug reactions (ADRs) shown occur with 50 mg/day dosage at rate higher than seen with placebo >10% Nausea (22-41%) Dry mouth (11-25%) Hyperhidrosis (10-21%) Dizziness (10-16%) Insomnia (9-15%) Constipation (9-14%) Somnolence (4-12%) Fatigue (7-10%) 1-10% Increased total cholesterol of ≥50 mg/dL and an absolute value of ≥261 mg/dL (3-10%) Decreased appetite (5-10%) Vomiting (3-9%) Tremor (2-9%) Anorgasmia (3-8%) Ejaculation delayed (1-7%) Libido decreased (3-6%) Triglycerides, fasting ≥327 mg/dL (2-6%) Mydriasis (2-6%) Vertigo (2-5%) Anxiety (3-5%) Blurred vision (3-4%) Chills (1-4%) Yawning (1-4%) Abnormal dreams (2-3%) Feeling jittery (1-3%) Orgasm abnormal (1-3%) Nervousness (<2%) Tachycardia (<2%) Asthenia (<2%) Weight increased, liver function test abnormal, blood prolactin increased (<2%) Musculoskeletal stiffness (<2%) Syncope, convulsion, dystonia (<2%) Depersonalization, bruxism (<2%) Urinary retention (<2%) Rash, alopecia, photosensitivity reaction, angioedema (<2%) Urinary hesitation (1-2%) Ejaculation failure (1-2% Sexual dysfunction (1-3%) Tinnitus (1-2%) Dysgeusia (1-2%) Hot flush (1-2%) Blood pressure increased (1-2%) Increased LDL ≥50 mg/dL and an absolute value of ≥190 mg/dl (1-2%) Frequency Not Defined Ischemic cardiac events in patients with multiple underlying cardiac risk factors Gastrointestinal (GI) bleeding, hallucinations, photosensitivity reactions and severe cutaneous reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have occurred with other serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) Suicidal thoughts and behaviors in adolescents and young adults Hyponatremia Interstitial lung disease and eosinophilic pneumonia Serotonin syndrome Elevated blood pressure Abnormal bleeding Narrow-angle glaucoma Activation of mania or hypomania Discontinuance syndrome Seizure Postmarketing Reports Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome Gastrointestinal disorders: Pancreatitis acute Cardiovascular system: Takotsubo cardiomyopathy Black Box Warnings Suicidal thoughts and behaviors Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years In children and young adults, initiate only if benefits greatly outweigh risks Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments Patient’s family should communicate any abrupt behavioral changes to healthcare provider Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy Not approved for use in pediatric patients Contraindications Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine formulation Coadministration with serotonergic drugs Coadministration with MAOIs increases risk of serotonin syndrome Use of MAOIs concomitantly within 14 days before initiating desvenlafaxine or within 7 days after discontinuing desvenlafaxine Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome (NMS), seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma Starting desvenlafaxine in patient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome If linezolid or IV methylene blue must be administered, discontinue desvenlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first Cautions Suicidality; monitor for clinical worsening and suicide risk (especially in children, adolescents, and young adults aged 18-24 years), during early phases of treatment and alterations in dosages Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy; avoid use of antidepressants, including desvenlafaxine, in patients with untreated anatomically narrow angles Use caution in patients with history of seizure disorders Screen for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants May precipitate shift to mania or hypomania in patients with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen for bipolar disorder patients presenting with depressive symptoms Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein and triglycerides is increased Hyponatremia due to syndrome of inappropriate antidiuretic hormone; cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy May impair cognitive abilities; use caution operating heavy machinery Discontinuation syndrome There have been postmarketing reports of serious discontinuation symptoms which can be protracted and severe; completed suicide, suicidal thoughts, aggression and violent behavior reported in patients during reduction in dosage, including during discontinuation Other postmarketing reports describe visual changes (such as blurred vision or trouble focusing) and increased blood pressure after stopping or reducing dose If intolerable symptoms occur following a decrease in dose or upon discontinuation of treatment, then resuming previously prescribed dose may be considered Subsequently, the healthcare provider may continue decreasing the dose, but at a more gradual rate; in some patients, discontinuation may need to occur over a period of several months Sexual dysfunction Use may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider Use of SSRIs, may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm Important for prescribers to inquire about sexual function before initiating and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder Discuss potential management strategies to support patients in making informed decisions about treatment Serotonin syndrome Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding Monitor for the emergence of serotonin syndrome Discontinue desvenlafaxine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment If concomitant use of desvenlafaxine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms Risk of bleeding SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage Concomitant use of aspirin, NSAIDs,