platelets.sulindacMonitor Closely (1)duloxetine, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.sumatriptanMonitor Closely (1)sumatriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)duloxetine, sumatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.sumatriptan intranasalMonitor Closely (1)sumatriptan intranasal and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)duloxetine, sumatriptan intranasal. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.tamoxifenMonitor Closely (1)duloxetine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.tamsulosinMonitor Closely (1)duloxetine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tapentadolMonitor Closely (1)duloxetine and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.tedizolidSerious - Use Alternative (1)tedizolid, duloxetine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.terbinafineMonitor Closely (1)terbinafine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.teriflunomideMonitor Closely (1)teriflunomide decreases levels of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.thioridazineSerious - Use Alternative (2)duloxetine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. thioridazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.timololMonitor Closely (1)duloxetine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tipranavirSerious - Use Alternative (1)tipranavir will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.tobacco useSerious - Use Alternative (1)tobacco use will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.tolfenamic acidMonitor Closely (1)duloxetine, tolfenamic 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.tolmetinMonitor Closely (1)duloxetine, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.tolterodineMinor (1)duloxetine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.torsemideMinor (1)torsemide, duloxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.tramadolMonitor Closely (1)duloxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)duloxetine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.tranylcypromineContraindicated (1)tranylcypromine and duloxetine both increase serotonin levels. Contraindicated.trazodoneSerious - Use Alternative (1)duloxetine and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.trifluoperazineMinor (1)duloxetine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.trimipramineSerious - Use Alternative (1)duloxetine and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.tropisetronMinor (1)duloxetine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.valerianMonitor Closely (1)valerian and duloxetine both increase sedation. Use Caution/Monitor.venlafaxineMonitor Closely (1)venlafaxine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)duloxetine and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.verapamilSerious - Use Alternative (1)verapamil will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.vilazodoneSerious - Use Alternative (1)duloxetine, 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)duloxetine, 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)duloxetine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.warfarinMonitor Closely (1)duloxetine, 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. .zileutonSerious - Use Alternative (1)zileuton will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)zolmitriptan and duloxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)duloxetine, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain. >10% Nausea (23-25%) Dry mouth (13-15%) Headache (13-14%) Somnolence (10-12%) Fatigue (9-11%) 1-10% Constipation (9-10%) Dizziness (9-10%) Insomnia (9-10%) Diarrhea (9-10%) Anorexia (8%) Decreased appetite (7-8%) Abdominal pain (4-6%) Hyperhidrosis (6%) Agitation (5%) Nasopharyngitis (5%) Vomiting (3-5%) Male sexual dysfunction (2-5%) Erectile dysfunction (4%) Decreased libido (4%) Musculoskeletal pain (4%) Upper respiratory tract infection (URTI) (4%) Decreased libido (3-4%) Musculoskeletal pain (3-4%) Abnormal orgasm (2-3%) Agitation (3%) Anxiety (3%) Blurred vision (3%) Cough (3%) Influenza (3%) Muscle spasms (2-3%) Tremor (3%) Abnormal dreams (2%) Dyspepsia (2%) Hot flushes (2%) Oropharyngeal pain (2%) Palpitations (2%) Paresthesia (2%) Weight loss (2%) Yawning (2%) Blood pressure increase (2%) Ejaculation delayed (2%) Dysuria (>1%) Gastritis (>1%) Rash (>1%) Postmarketing Reports General: Anaphylactic reaction, angioneurotic edema, hypersensitivity, chills/rigors, falls, feeling abnormal, feeling hot and/or cold, malaise, thirst Cardiovascular: Hypertensive crisis, supraventricular arrhythmia, myocardial infarction, tachycardia, Takotsubo cardiomyopathy Endocrine: Galactorrhea, gynecologic bleeding, hyperglycemia, hyperprolactinemia, hypothyroidism Neurologic: Restless legs syndrome, seizures upon treatment discontinuance, extrapyramidal disorders, dysgeusia, lethargy, and paraesthesia/hypoesthesia, disturbance in attention, dyskinesia, myoclonus, poor quality sleep Ophthalmic: Glaucoma, blurred vision, diplopia, dry eyes, visual impairment Otic: Tinnitus (upon treatment discontinuance), ear pain, vertigo Psychiatric: Aggression and anger (particularly early in treatment or after treatment discontinuance), hallucinations; abnormal dreams and sleep disorder; apathy, bruxism, disorientation/confusional state, irritability, mood swings, and suicide attempt; completed suicide (rare) Musculoskeletal: Trismus, muscle spasm, muscle tightness, muscle twitching Skin: Serious skin reactions (eg, erythema multiforme and Stevens-Johnson syndrome) necessitating drug discontinuance or hospitalization, urticaria, rash, pruritus, dermatitis, cold sweat, erythema, increased tendency to bruise, night sweats, photosensitivity reaction Gastrointestinal: Colitis (microscopic or unspecified), cutaneous vasculitis (sometimes associated with systemic involvement), acute pancreatitis Infection: Gastroenteritis, laryngitis Investigations: Increased/decreased weight, increased blood cholesterol Black Box Warnings Suicidal thoughts and behaviors Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients >24 yr There was a reduction in risk with antidepressant use in patients ≥65 yr In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors Advise families and caregivers of the need for close observation and communication with the prescriber Contraindications Concomitant use of duloxetine with MAOIs intended to treat psychiatric disorders Use of duloxetine within 14 days of MAOI discontinuation Initiating duloxetine in patients who are being treated with linezolid or IV methylene blue Cautions Prior to initiating treatment with, screen patients for any personal or family history of bipolar disorder, mania, or hypomania Suicidality; monitor for clinical worsening and suicide risk, especially in children, adolescents and young adults (18-24 years) during early phases of treatment and alterations in dosage (see Black Box Warnings) Serotonin syndrome or neuroleptic malignant syndrome-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics and serotonin precursors Neonates exposed to serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding Increased risk of hepatotoxicity, sometimes fatal; monitor for abdominal pain, hepatomegaly, elevated AST/ALT exceeding 20x ULN, and jaundice; cholestatic jaundice with minimal elevations of hepatic transaminases have also been reported; not recommended in patients with substantial alcohol use or chronic liver disease 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, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk Severe skin reactions (eg, erythema multiforme and Stevens-Johnson syndrome); discontinue at first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified Orthostatic hypotension and syncope, especially during week 1 of therapy; monitor patients taking drugs that increase risk of orthostatic hypotension; consider dose reduction or discontinue therapy in patients who experience symptomatic orthostatic hypotension, falls and/or syncope Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium <110 mmol/L have been reported to be reversible upon discontinuance Diabetes due to worsening of glycemic control in some patients; monitor increases in fasting blood glucose and hemoglobin A1c Monitor weight and growth in adolescents and children; decrease in appetite and weight loss reported Urinary hesitation and retention Cognitive or motor function impairment; use with caution when operating heavy machinery Bone fractures reported with antidepressant treatment; consider possibility of bone fracture if patient complains of unexplained bone pain or joint tenderness or experiences bruising or swelling Use caution in gastroparesis, hypertension, controlled narrow-angle glaucoma, renal impairment, or seizure disorders May lower seizure threshold when administered on currently with other drugs that lower seizure threshold Risk of mydriasis; may trigger angle closure attack in patients with angle-closure glaucoma with anatomically narrow angles without a patent iridectomy Headache, dizziness, nausea, diarrhea, paresthesia, vomiting, irritability, insomnia, hyperhidrosis, anxiety, and fatigue reported in patients following abrupt discontinuation of duloxetine Therapy may increase blood pressure; measure blood prior to initiating treatment and periodically throughout treatment Use with caution in patients with conditions that slow gastric emptying 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 Changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of psychiatric disorders or diabetes, but may also be a consequence of pharmacologic treatment Use of SNRIs, may cause symptoms of sexual dysfunction; in male patients, SNRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction; in female patients, SNRI use may result in decreased libido and delayed or absent orgasm It is important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment; 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 the underlying psychiatric disorder Discuss potential management strategies to support patients in making informed decisions about treatment Increased risk of bleeding postpartum Drugs that interfere with serotonin reuptake inhibition, may increase risk of bleeding; case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and occurrence of gastrointestinal bleeding A postmarketing study showed a higher incidence of postpartum hemorrhage in mothers receiving therapy; Other bleeding events related to SSRI and SNRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages; concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk Inform about risk of bleeding associated with concomitant use of drug and NSAIDs, aspirin, or other drugs that affect coagulation Drug interaction overview Use caution when administering concomitantly with CNS depressants Duloxetine is CYP1A2 and CYP2D6 substrate; moderate CYP2D6 inhibitor CYP2D6 Inhibitors Concomitant use of duloxetine with potent CYP2D6 inhibitors may result in higher concentrations (on average of 60%) of duloxetine Coadministration of duloxetine with drugs that are extensively metabolized by CYP2D6 with a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs]), phenothiazines and Type 1C antiarrhythmics (eg, propafenone, flecainide), should be used with caution Avoid coadministration with Drizalma Sprinkle and potent CYP2D6 Alcohol Cymbalta: Three treated patients had liver injury as manifested by ALT and total bilirubin elevations, with evidence of obstruction; substantial intercurrent ethanol use was present in each of these cases, and this may have contributed to the abnormalities seen Drizalma Sprinkle: An in vitro study showed significant increases of duloxetine hydrochloride release at 2 hr to ~86% and 56% of the drug release in the