Avoid or Use Alternate Drug.triazolamMonitor Closely (1)triazolam and olanzapine both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (1)triclabendazole and olanzapine both increase QTc interval. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and olanzapine both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (3)olanzapine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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.trimipramineMonitor Closely (2)olanzapine and trimipramine both increase sedation. Use Caution/Monitor. olanzapine and trimipramine both increase QTc interval. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and olanzapine both increase sedation. Use Caution/Monitor.triptorelinSerious - Use Alternative (1)olanzapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.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 inhaledSerious - 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 (1)valbenazine and olanzapine both increase QTc interval. Use Caution/Monitor.vandetanibSerious - Use Alternative (1)olanzapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.vardenafilMonitor Closely (1)olanzapine and vardenafil both increase QTc interval. Use Caution/Monitor.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 (1)olanzapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.venlafaxineMonitor Closely (2)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). olanzapine and venlafaxine both decrease QTc interval. Use Caution/Monitor.verapamilMonitor Closely (1)verapamil will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.vilanterol/fluticasone furoate inhaledSerious - 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).voclosporinMonitor Closely (1)voclosporin, olanzapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (1)olanzapine and voriconazole both increase QTc interval. Use Caution/Monitor.vorinostatMonitor Closely (1)olanzapine and vorinostat both increase QTc interval. Use Caution/Monitor.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.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 (2)olanzapine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. olanzapine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)olanzapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)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).zotepineMonitor Closely (2)olanzapine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. olanzapine and zotepine both increase sedation. Use Caution/Monitor. >10% Schizophrenia Glucose levels increase >10 mg/dL (66%) Shift from hemoglobin (Hgb) A1c normal (<5.7%) to impaired (≥5.7 to < 6.5%) (42%) Weight increased (19-25%) Somnolence (21%) Shifts in fasting triglycerides from normal to high (14%) Increased appetite (11%) 1-10% Schizophrenia Shift from Hgb A1c impaired (≥5.7 to < 6.5%) to high (≥6.5%) (9.5%) Somnolence (9%) Dry mouth (7%) Waist circumference increased (6%) Headache (4-6%) Blood creatine phosphokinase increased (5%) Lethargy (4%) Sedation (2-4%) Dizziness (2-3%) Akathisia (3%) ALT increased (3%) AST increased (3%) Constipation (3%) Fatigue (3%) Nausea (3%) Blood pressure (BP) increased (3%) Neutrophil count decreased (2-3%) Blood insulin increased (2-3%) Weight decreased (2%) Dyslipidemia (2%) Schizophrenia (1%) Abnormal liver function tests (1%) <1% Schizophrenia Shift from Hgb A1c normal (<5.76%) to high (≥6.5%) (0.5%) Frequency Not Defined Schizophrenia Dystonia symptoms including spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue Bipolar I disorder (monotherapy) ** Relies on studies of olanzapine tablets I bipolar I disorder** Somnolence Dry mouth Dizziness Asthenia Constipation Dyspepsia Increased appetite Tremor Bipolar I disorder (adjunctive therapy) ** Relies on studies of olanzapine tablets I bipolar I disorder** Dry mouth Weight gain Increased appetite Dizziness Back pain Constipation Speech disorder Increased salivation Amnesia Paresthesia Postmarketing Reports Allergic reactions (eg, anaphylactoid reaction, angioedema, pruritus or urticaria) Cholestatic or mixed liver injury, hepatitis, jaundice Diabetic coma, diabetic ketoacidosis Discontinuation reaction (diaphoresis, nausea, or vomiting) Drug reaction with eosinophilia and systemic symptoms (DRESS) Hyperlipidemia (random cholesterol levels ≥240 mg/dL and random triglyceride levels ≥1000 mg/dL reported) Neutropenia Pancreatitis Priapism Rash Restless legs syndrome Rhabdomyolysis Salivary hypersecretion Stuttering Venous thromboembolic events (including pulmonary embolism and deep venous thrombosis) Black Box Warnings Increased mortality in elderly patients with dementia-related psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death Not approved for treatment of patients with dementia-related psychosis Contraindications Patients using opioids Patients undergoing acute opioid withdrawal If administered with lithium or valproate, refer to lithium or valproate prescribing information for contraindications for these products Cautions Significantly greater increase of death reported in elderly patients with dementia-related psychosis treated with olanzapine; majority of deaths were either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) Cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, reported in olanzapine trials in elderly patients with dementia-related psychosis DRESS reported with exposure to olanzapine; may present with a cutaneous reaction (eg, rash, exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications (eg, hepatitis, nephritis, pneumonitis, myocarditis, pericarditis); discontinue treatment if DRESS is suspected Antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls, fractures, or other injuries; complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Olanzapine was associated with constipation, dry mouth, and tachycardia, and all adverse reactions related to cholinergic antagonism; use with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related condition Atypical antipsychotics may disrupt the ability to reduce core body temperature; strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use with caution in patients who may experience these conditions May cause somnolence and has the potential to impair judgment, thinking, or motor skills; advise patients to exercise caution when operating hazardous machinery, including motor vehicles May cause seizures; use caution in patients with a history of seizures or with conditions that lower the seizure threshold Esophageal dysmotility and aspiration have been associated with antipsychotic drug use; use with caution in patients at risk for aspiration Refer to lithium or valproate prescribing information for a description of the risks for these products if used Hyperprolactinemia Olanzapine elevates prolactin levels and elevation can persist during long-term administration Hyperprolactinemia may suppress hypothalamic gonadotropin-releasing hormone, resulting in reduced pituitary gonadotropin secretion; may inhibit reproductive function by impairing gonadal steroidogenesis in both females and males Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported Long-standing hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone density in both females and males Tardive dyskinesia Tardive dyskinesia may develop in patients treated with antipsychotic drugs; elderly patients appear to be at highest risk Prescribe in a manner that is most likely to reduce the risk of tardive dyskinesia. Reserve long-term antipsychotic treatment for patients Who have a chronic illness that is responsive to antipsychotic drugs For whom alternative, effective, but potentially less harmful treatments are unavailable or inappropriate If long-term treatment is necessary, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response; periodically reassess the need to continue treatment If signs and symptoms of tardive dyskinesia appear, consider discontinuation Opioids Contraindicated Olanzapine/samidorphan increases the risk of precipitation of acute opioid withdrawal in patients who are opioid-dependent Emergency situations: If treated patient requires opioid treatment for anesthesia or analgesia, discontinue olanzapine/samidorphan; opioid should be administered by properly trained individual(s), and properly monitor patient in a setting equipped and staffed for cardiopulmonary resuscitation Nonemergency situations: If treated patient is expected to require opioid treatment (eg, for analgesia during or after an elective surgical procedure), discontinue olanzapine/samidorphan at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed Samidorphan is an opioid antagonist; opioid treatment may be less effective or ineffective shortly after discontinuing olanzapine/samidorphan Explain the risks associated with precipitated withdrawal and the importance of giving an accurate account of last opioid use to patients and caregivers Patients with a history of long-term opioid use before treatment with olanzapine/samidorphan have decreased opioid tolerance if therapy is interrupted or discontinued Advise that decreased tolerance may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage Neuroleptic malignant syndrome (NMS) NMS reported in association with administration of antipsychotic drugs Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, delirium, and autonomic instability Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure If NMS is suspected, immediately discontinue therapy, provide intensive symptomatic treatment, and monitor Metabolic changes Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics Monitor for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose (FBG) testing Hyperglycemia may resolve once the atypical antipsychotic is discontinued; however, some patients required antidiabetic treatment despite discontinuation Test FBG and fasting lipid profile at the beginning of treatment and periodically during treatment Monitor weight prior to initiation and frequently thereafter Leukopenia, neutropenia, and agranulocytosis Leukopenia and neutropenia reported during treatment Agranulocytosis (including fatal cases) has been reported with other agents in this class Possible risk factors for leukopenia and neutropenia include preexisting low white blood cell (WBC) count or absolute neutrophil count (ANC) and history of drug-induced leukopenia or neutropenia Perform a complete blood cell count frequently during the first few months of therapy Consider discontinuation at the first sign of a clinically significant decline in WBC count in the absence of other causative factors Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur Discontinue therapy in patients with severe neutropenia (ANC <1000/mm3) and follow their WBC count until recovery Drug interaction overview Strong CYP3A4 inducers Not recommended Strong CYP3A4 inducers decrease AUC and efficacy of olanzapine/samidorphan Strong CYP1A2 inhibitors Consider dosage reduction of olanzapine component Strong CYP1A2 inhibitors increase olanzapine plasma concentrations and risk of adverse reactions of olanzapine/samidorphan CYP1A2 inducers Consider dosage increase of olanzapine component Strong CYP1A2 inducers decrease effects of olanzapine and efficacy of olanzapine/samidorphan CNS acting drugs Use with caution