Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.tolterodineMonitor Closely (3)olanzapine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. tolterodine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. tolterodine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.Serious - Use Alternative (1)fluoxetine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.topiramateMonitor Closely (1)olanzapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.toremifeneMonitor Closely (1)toremifene and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)olanzapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.torsemideMinor (1)torsemide, fluoxetine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.tramadolMonitor Closely (2)tramadol and olanzapine both increase sedation. Use Caution/Monitor. fluoxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.tranylcypromineContraindicated (1)tranylcypromine and fluoxetine both increase serotonin levels. Contraindicated.Monitor Closely (1)tranylcypromine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).trazodoneMonitor Closely (2)trazodone and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely. olanzapine and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)fluoxetine and trazodone both increase serotonin levels. Avoid or Use Alternate Drug. olanzapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.triazolamMonitor Closely (1)triazolam and olanzapine both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (2)triclabendazole and olanzapine both increase QTc interval. Use Caution/Monitor. triclabendazole and fluoxetine both increase QTc interval. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and olanzapine both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (5)olanzapine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. trifluoperazine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely. fluoxetine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. olanzapine and trifluoperazine both increase sedation. Use Caution/Monitor. olanzapine and trifluoperazine both decrease QTc interval. Use Caution/Monitor.trihexyphenidylMonitor Closely (1)olanzapine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.trimethoprimMonitor Closely (1)fluoxetine and trimethoprim both increase QTc interval. Use Caution/Monitor.trimipramineMonitor Closely (3)olanzapine and trimipramine both increase QTc interval. Use Caution/Monitor. trimipramine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely. olanzapine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fluoxetine and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.triprolidineMonitor Closely (1)triprolidine and olanzapine both increase sedation. Use Caution/Monitor.triptorelinSerious - Use Alternative (2)olanzapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug. triptorelin increases toxicity of fluoxetine by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.tropisetronMonitor Closely (2)fluoxetine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. fluoxetine and tropisetron both increase QTc interval. Use Caution/Monitor.trospium chlorideMonitor Closely (3)trospium chloride decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. trospium chloride decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor. olanzapine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.umeclidinium bromide/vilanterol inhaledMonitor Closely (1)fluoxetine and umeclidinium bromide/vilanterol inhaled both increase QTc interval. Modify Therapy/Monitor Closely. Fluoxetine prolongs the QT interval; the prescribing information for fluoxetine recommends avoiding concurrent use of other drugs that may prolong the QT interval; risk may be increased with higher doses and/or when associated with hypokalemia; drugs that prolong the QTc interval may potentiate the effects of beta2 agonists on the cardiovascular systemSerious - Use Alternative (1)olanzapine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.valbenazineMonitor Closely (3)valbenazine and olanzapine both increase QTc interval. Use Caution/Monitor. fluoxetine will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Consider reducing valbenazine dose based on tolerability if coadministered with a strong CYP2D6 inhibitor. valbenazine and fluoxetine both increase QTc interval. Use Caution/Monitor.valerianMonitor Closely (1)valerian and fluoxetine both increase sedation. Use Caution/Monitor.vandetanibSerious - Use Alternative (2)olanzapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug. fluoxetine, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.vardenafilMonitor Closely (2)olanzapine and vardenafil both increase QTc interval. Use Caution/Monitor. vardenafil and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.vecuroniumMonitor Closely (3)vecuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. vecuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor. olanzapine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.vemurafenibSerious - Use Alternative (2)olanzapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. vemurafenib and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.venlafaxineMonitor Closely (3)fluoxetine and venlafaxine both increase QTc interval. Use Caution/Monitor. olanzapine and venlafaxine both decrease QTc interval. Use Caution/Monitor. venlafaxine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)fluoxetine and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)venlafaxine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.verapamilMonitor Closely (1)verapamil will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.vilanterol/fluticasone furoate inhaledMonitor Closely (1)fluoxetine and vilanterol/fluticasone furoate inhaled both increase QTc interval. Modify Therapy/Monitor Closely. Fluoxetine prolongs the QT interval; the prescribing information for fluoxetine recommends avoiding concurrent use of other drugs that may prolong the QT interval; risk may be increased with higher doses and/or when associated with hypokalemia; drugs that prolong the QTc interval may potentiate the effects of beta2 agonists on the cardiovascular systemSerious - Use Alternative (1)olanzapine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vilazodoneMonitor Closely (1)vilazodone, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)fluoxetine, 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. .voclosporinMonitor Closely (2)voclosporin, olanzapine. Either increases effects of the other by QTc interval. Use Caution/Monitor. voclosporin, fluoxetine. Either increases effects of the other by QTc interval. Use Caution/Monitor.vorapaxarMonitor Closely (1)fluoxetine, 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 .voriconazoleMonitor Closely (3)fluoxetine will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. fluoxetine and voriconazole both increase QTc interval. Use Caution/Monitor. olanzapine and voriconazole both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)fluoxetine will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.vorinostatMonitor Closely (2)olanzapine and vorinostat both increase QTc interval. Use Caution/Monitor. vorinostat and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.vortioxetineSerious - Use Alternative (1)fluoxetine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.warfarinMonitor Closely (1)fluoxetine, 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. .xylometazolineMonitor Closely (1)olanzapine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)olanzapine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zanubrutinibMonitor Closely (1)fluoxetine, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.ziconotideMonitor Closely (1)olanzapine and ziconotide both increase sedation. Use Caution/Monitor.zileutonMonitor Closely (1)zileuton will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.ziprasidoneMonitor Closely (3)olanzapine and ziprasidone both increase sedation. Use Caution/Monitor. fluoxetine and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely. olanzapine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Serious - Use Alternative (1)olanzapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (2)zolmitriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). zolmitriptan and fluoxetine both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)fluoxetine, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.zotepineMonitor Closely (3)olanzapine and zotepine both increase sedation. Use Caution/Monitor. olanzapine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. fluoxetine increases levels of zotepine by decreasing metabolism. Use Caution/Monitor. Frequency Not Defined Rhabdomyolysis and venous thromboembolic events (including pulmonary embolism and deep venous thrombosis) Fluoxetine Aplastic anemia, cholestatic jaundice, eosinophilic pneumonia, erythema multiforme, violent behavior, atrial fibrillation, cataract, cerebrovascular accident, epidermal necrolysis, erythema nodosum, heart arrest, hepatic failure/necrosis, hypoglycemia, kidney failure, memory impairment, optic neuritis, pulmonary hypertension, Stevens-Johnson syndrome. Olanzapine Diabetic coma, jaundice, random triglyceride levels of greater than or equal to 1000 mg/dL, restless legs syndrome, stuttering, salivary hypersecretion, allergic reaction (eg, anaphylactoid reaction, angioedema, pruritus or urticaria), diabetic ketoacidosis, discontinuation reaction (diaphoresis, nausea or vomiting), drug reaction with eosinophilia and systemic symptoms (DRESS) Black Box Warnings Children and antidepressants In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses This increase was not seen in patients >24 years of age A slight decrease in suicidal thinking was seen in adults >65 years Risks must be weighed in children and young adults against the benefits of taking antidepressants Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during the initial 1-2 months of therapy and dosage adjustments The patient’s family should communicate to the healthcare provider any abrupt changes in behavior; worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy This drug is not approved for children <10 years Antipsychotics & Dementia Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials The deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature This drug is not approved for the treatment of patients with dementia-related psychosis (See WARNINGS in package insert) Contraindications Hypersensitivity to any component Concomitant thioridazine, pimozide Coadministration with MAOIs Within 14 days of taking MAOIs Increased risk of serotonin syndrome when MAOIs coadministered MAOIs coadministered with fluoxetine or within 5 weeks of discontinuing fluoxetine/olanzapine Starting fluoxetine in a patient who is being treated with linezolid or IV methylene blue Cautions This drug combination has potential to impair judgment, thinking, or motor skills; patients should be cautioned about operating hazardous machinery, including automobiles until they are reasonably certain that therapy