olanzapine/samidorphan (Rx)

Brand and Other Names:Lybalvi
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

olanzapine/samidorphan

tablet

  • 5mg/10mg
  • 10mg/10mg
  • 15mg/10mg
  • 20mg/10mg

Schizophrenia

Indicated for treatment of schizophrenia in adults

Initial dose: Olanzapine 5 mg/samidorphan 10 mg OR olanzapine 10 mg/samidorphan 10 mg PO qDay

Maintenance dose: May adjust dosage at weekly intervals of 5 mg (based on the olanzapine component) depending on clinical response and tolerability; not to exceed olanzapine 20 mg/samidorphan 10 mg qDay

Bipolar I Disorder

Adjunctive to lithium or valproate

  • Indicated for acute treatment of manic or mixed episodes as an adjunct to lithium or valproate in adults with bipolar I disorder
  • Initial dose: 1 tablet (olanzapine 10 mg/samidorphan 10 mg) PO qDay
  • Maintenance dose: May adjust dosage at weekly intervals of 5 mg (based on the olanzapine component) depending on clinical response and tolerability; not to exceed olanzapine 20 mg/samidorphan 10 mg qDay

Monotherapy

  • Indicated for acute treatment of manic or mixed episodes as monotherapy and maintenance monotherapy in adults with bipolar I disorder
  • Initial dose: Olanzapine 10 mg/samidorphan 10 mg OR olanzapine 15mg/samidorphan 10 mg PO qDay
  • Adjust dose in increments/decrements of 5 mg (based on olanzapine component), if necessary, at intervals ≥24 hr; not to exceed olanzapine 20 mg/samidorphan 10 mg qDay
  • Maintenance monotherapy: Not to exceed olanzapine 20 mg/samidorphan 10 mg qDay

Dosage Modifications

Hypotensive patients

  • Patients who have a higher risk of hypotensive reactions, are at risk of slower olanzapine metabolism, or may be more pharmacodynamically sensitive to olanzapine
  • If dose escalation is necessary, increase dose slowly

Renal impairment

  • Mild-to-severe (eGFR 15-89 mL/min/1.73 m2): No dosage adjustment necessary
  • Severe (eGFR 15 to 29 mL/minute/1.73 m2): Plasma exposure to olanzapine and samidorphan was higher compared with patients with normal renal function
  • End-stage renal disease (eGFR <15 mL/min/1.73 m2): Not studied; not recommended

Hepatic impairment

  • No dosage adjustment necessary
  • Moderate: Olanzapine and samidorphan plasma exposures were found to be higher compared with patients with normal hepatic function, but not clinically relevant
  • Severe: Not studied

Dosing Considerations

Initiation in patients using opioids

  • Contraindicated in patients using opioids or undergoing acute opioid withdrawal
  • Delay initiation if currently using opioids
    • Short-acting opioids: At least for 7 days after last opioid use
    • Long-acting opioids : At least for 14 days after last opioid use

Safety and efficacy not established

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Interactions

Interaction Checker

and olanzapine/samidorphan

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            Contraindicated (3)

            • amisulpride

              amisulpride, olanzapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndromeIncreases risk of neuroleptic malignant syndrome.

            • dronedarone

              olanzapine and dronedarone both increase QTc interval. Contraindicated.

            • thioridazine

              olanzapine and thioridazine both increase QTc interval. Contraindicated.

            Serious - Use Alternative (108)

            • abametapir

              abametapir will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

            • amiodarone

              olanzapine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • amisulpride

              amisulpride and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • anagrelide

              olanzapine and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

            • apomorphine

              olanzapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • arsenic trioxide

              olanzapine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              artemether and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • artemether/lumefantrine

              olanzapine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine

              olanzapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • bromocriptine

              olanzapine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • buprenorphine

              olanzapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. If concurrent use of olanzapine and buprenorphine is necessary, consider dose reduction of one or both drugs.

            • cabergoline

              olanzapine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

            • calcium/magnesium/potassium/sodium oxybates

              olanzapine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ceritinib

              ceritinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • chlorpromazine

              olanzapine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

            • ciprofloxacin

              olanzapine and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • clarithromycin

              clarithromycin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • clozapine

              clozapine and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • crizotinib

              crizotinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • degarelix

              degarelix and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • desflurane

              desflurane and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • diazepam intranasal

              diazepam intranasal, samidorphan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • disopyramide

              olanzapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

            • dopamine

              olanzapine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

            • droperidol

              olanzapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • eliglustat

              olanzapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

            • encorafenib

              encorafenib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • entrectinib

              olanzapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • erdafitinib

              olanzapine will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

            • eribulin

              eribulin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • erythromycin base

              olanzapine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              olanzapine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              olanzapine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              olanzapine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • fedratinib

              olanzapine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fexinidazole

              fexinidazole and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

            • fluvoxamine

              fluvoxamine will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

              olanzapine and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.

            • foscarnet

              olanzapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

            • givosiran

              givosiran will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

            • glasdegib

              olanzapine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

            • goserelin

              olanzapine and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

            • histrelin

              olanzapine and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

            • hydrocodone

              hydrocodone, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and olanzapine both increase QTc interval. Avoid or Use Alternate Drug.

            • ibutilide

              olanzapine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

            • iloperidone

              olanzapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • inotuzumab

              olanzapine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.

            • isoflurane

              isoflurane and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • ivosidenib

              ivosidenib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

            • lefamulin

              lefamulin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug.

            • lenvatinib

              olanzapine and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • leuprolide

              olanzapine and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

            • levodopa

              olanzapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • levodopa inhaled

              olanzapine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Atypical (2nd generation) antipsychotics inhibit dopamine D2 receptors in varying degrees (clozapine and quetiapine are lower risk). .

            • lisuride

              olanzapine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

            • lonafarnib

              olanzapine 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.

            • lopinavir

              olanzapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • macimorelin

              macimorelin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • maprotiline

              olanzapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

            • mefloquine

              mefloquine increases toxicity of olanzapine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

            • methadone

              olanzapine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • methyldopa

              olanzapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

            • metoclopramide intranasal

              samidorphan increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.

              olanzapine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.

              olanzapine, 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.

            • midostaurin

              olanzapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • olopatadine intranasal

              samidorphan 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.

            • mobocertinib

              mobocertinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • moxifloxacin

              olanzapine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • olopatadine intranasal

              olanzapine 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.

            • ondansetron

              olanzapine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

            • oxaliplatin

              olanzapine and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

              oxaliplatin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • paliperidone

              olanzapine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • panobinostat

              olanzapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.

            • paroxetine

              olanzapine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.

            • pazopanib

              olanzapine and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

            • pefloxacin

              pefloxacin will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • pentamidine

              olanzapine and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

            • pimavanserin

              olanzapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

            • pimozide

              olanzapine and pimozide both increase QTc interval. Contraindicated.

            • pitolisant

              olanzapine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              olanzapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

            • pramipexole

              olanzapine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

            • procainamide

              olanzapine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

            • propafenone

              olanzapine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

            • quetiapine

              olanzapine and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

            • quinidine

              olanzapine and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

            • ranolazine

              olanzapine and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib increases toxicity of olanzapine by QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.

            • ropinirole

              olanzapine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

            • safinamide

              olanzapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • saquinavir

              olanzapine and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, samidorphan. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

              selinexor, olanzapine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sevoflurane

              sevoflurane and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • siponimod

              olanzapine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              olanzapine and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

            • sodium oxybate

              olanzapine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sotalol

              olanzapine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

            • sufentanil SL

              sufentanil SL, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tetrabenazine

              olanzapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • thiothixene

              olanzapine and thiothixene both increase QTc interval. Avoid or Use Alternate Drug.

            • toremifene

              olanzapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.

            • trazodone

              olanzapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

            • triptorelin

              olanzapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

            • umeclidinium bromide/vilanterol inhaled

              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.

            • vandetanib

              olanzapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.

            • vemurafenib

              olanzapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • vilanterol/fluticasone furoate inhaled

              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.

            • ziprasidone

              olanzapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (375)

            • abobotulinumtoxinA

              abobotulinumtoxinA increases effects of olanzapine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

            • acarbose

              olanzapine, acarbose. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • aclidinium

              aclidinium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              aclidinium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • albiglutide

              olanzapine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • albuterol

              olanzapine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              albuterol and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • alfentanil

              alfentanil and olanzapine both increase sedation. Use Caution/Monitor.

            • alfuzosin

              olanzapine and alfuzosin both increase QTc interval. Use Caution/Monitor.

              alfuzosin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • almotriptan

              almotriptan, 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).

            • alprazolam

              alprazolam and olanzapine both increase sedation. Use Caution/Monitor.

            • amifostine

              amifostine, olanzapine. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Due to its alpha adrenergic antagonism, atypical antipsychotic agents has the potential to enhance the effect of certain antihypertensive agents. Monitor blood pressure and adjust dose accordingly.

            • amitriptyline

              olanzapine and amitriptyline both increase sedation. Use Caution/Monitor.

              olanzapine and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              amobarbital and olanzapine both increase sedation. Use Caution/Monitor.

            • amoxapine

              olanzapine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and amoxapine both increase sedation. Use Caution/Monitor.

              olanzapine and amoxapine both increase QTc interval. Use Caution/Monitor.

            • anticholinergic/sedative combos

              anticholinergic/sedative combos decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              anticholinergic/sedative combos decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • apomorphine

              olanzapine and apomorphine both increase sedation. Use Caution/Monitor.

            • arformoterol

              olanzapine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              arformoterol and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • aripiprazole

              aripiprazole and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              aripiprazole and olanzapine both increase sedation. Use Caution/Monitor.

              aripiprazole and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • armodafinil

              armodafinil will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              olanzapine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • asenapine transdermal

              asenapine transdermal and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • atomoxetine

              atomoxetine and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • atracurium

              atracurium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atracurium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • atropine

              atropine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • atropine IV/IM

              olanzapine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine IV/IM decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine IV/IM decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

            • avapritinib

              olanzapine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • axitinib

              olanzapine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azelastine

              azelastine and olanzapine both increase sedation. Use Caution/Monitor.

            • azithromycin

              azithromycin increases toxicity of olanzapine by QTc interval. Use Caution/Monitor.

            • baclofen

              baclofen and olanzapine both increase sedation. Use Caution/Monitor.

            • bedaquiline

              olanzapine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

            • belladonna alkaloids

              belladonna alkaloids decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              belladonna alkaloids decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • belladonna and opium

              belladonna and opium and olanzapine both increase sedation. Use Caution/Monitor.

              belladonna and opium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              belladonna and opium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • benazepril

              olanzapine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

            • benperidol

              benperidol and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              benperidol and olanzapine both increase sedation. Use Caution/Monitor.

            • benzphetamine

              olanzapine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benztropine

              olanzapine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

            • brexanolone

              brexanolone, olanzapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and olanzapine both increase sedation. Use Caution/Monitor.

            • buprenorphine

              buprenorphine and olanzapine both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal and olanzapine both increase sedation. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              olanzapine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

            • butabarbital

              butabarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              butabarbital and olanzapine both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              butalbital and olanzapine both increase sedation. Use Caution/Monitor.

            • butorphanol

              butorphanol and olanzapine both increase sedation. Use Caution/Monitor.

            • caffeine

              olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cannabidiol

              cannabidiol, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • captopril

              olanzapine, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

            • carbamazepine

              carbamazepine will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and olanzapine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and olanzapine both increase sedation. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and olanzapine both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and olanzapine both increase sedation. Use Caution/Monitor.

            • chloroquine

              chloroquine increases toxicity of olanzapine by QTc interval. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              chlorpromazine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              chlorpromazine and olanzapine both increase sedation. Use Caution/Monitor.

            • chlorpropamide

              olanzapine, chlorpropamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • chlorzoxazone

              chlorzoxazone and olanzapine both increase sedation. Use Caution/Monitor.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and olanzapine both increase sedation. Use Caution/Monitor.

            • ciprofloxacin

              ciprofloxacin will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Olanzapine plasma concentrations may be elevated, increasing the risk of adverse reactions such as orthostatic hypotension or sedation. It is important to use caution and observe patient and adjust the olanzapine dosage as needed.

            • cisatracurium

              cisatracurium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              cisatracurium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • clemastine

              clemastine and olanzapine both increase sedation. Use Caution/Monitor.

            • clobazam

              olanzapine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              olanzapine and clomipramine both increase sedation. Use Caution/Monitor.

              olanzapine and clomipramine both increase QTc interval. Use Caution/Monitor.

            • clonazepam

              clonazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • clonidine

              clonidine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

            • clorazepate

              clorazepate and olanzapine both increase sedation. Use Caution/Monitor.

            • clozapine

              clozapine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              clozapine and olanzapine both increase sedation. Use Caution/Monitor.

            • codeine

              codeine and olanzapine both increase sedation. Use Caution/Monitor.

            • cyclizine

              cyclizine and olanzapine both increase sedation. Use Caution/Monitor.

              cyclizine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              cyclizine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • cyclobenzaprine

              cyclobenzaprine and olanzapine both increase sedation. Use Caution/Monitor.

              cyclobenzaprine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              cyclobenzaprine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • cyproheptadine

              cyproheptadine and olanzapine both increase sedation. Use Caution/Monitor.

            • dantrolene

              dantrolene and olanzapine both increase sedation. Use Caution/Monitor.

            • daridorexant

              olanzapine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              samidorphan and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darifenacin

              darifenacin decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              darifenacin decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • difelikefalin

              difelikefalin and samidorphan both increase sedation. Use Caution/Monitor.

            • dasatinib

              dasatinib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • deferasirox

              deferasirox will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • desipramine

              olanzapine and desipramine both increase sedation. Use Caution/Monitor.

              olanzapine and desipramine both increase QTc interval. Use Caution/Monitor.

            • deutetrabenazine

              olanzapine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.

              olanzapine and deutetrabenazine both increase sedation. Use Caution/Monitor.

              deutetrabenazine and olanzapine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

            • dexchlorpheniramine

              dexchlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              olanzapine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and olanzapine both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              olanzapine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              olanzapine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextromethorphan

              dextromethorphan, 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).

            • dextromoramide

              dextromoramide and olanzapine both increase sedation. Use Caution/Monitor.

            • diamorphine

              diamorphine and olanzapine both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • dicyclomine

              dicyclomine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              dicyclomine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • diethylpropion

              olanzapine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difelikefalin

              difelikefalin and olanzapine both increase sedation. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and olanzapine both increase sedation. Use Caution/Monitor.

            • dihydroergotamine

              dihydroergotamine, 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).

            • dimenhydrinate

              dimenhydrinate and olanzapine both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and olanzapine both increase sedation. Use Caution/Monitor.

              diphenhydramine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              diphenhydramine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • diphenoxylate hcl

              diphenoxylate hcl and olanzapine both increase sedation. Use Caution/Monitor.

            • dipipanone

              dipipanone and olanzapine both increase sedation. Use Caution/Monitor.

            • dobutamine

              olanzapine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dofetilide

              dofetilide increases toxicity of olanzapine by QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.

            • dolasetron

              dolasetron and olanzapine both increase QTc interval. Use Caution/Monitor.

            • donepezil

              donepezil and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • dopamine

              olanzapine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              olanzapine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              olanzapine and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

              olanzapine and doxepin both increase sedation. Use Caution/Monitor.

              doxepin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • doxylamine

              doxylamine and olanzapine both increase sedation. Use Caution/Monitor.

            • droperidol

              droperidol and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              droperidol and olanzapine both increase sedation. Use Caution/Monitor.

            • efavirenz

              efavirenz and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • eletriptan

              eletriptan, 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).

            • ephedrine

              olanzapine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              olanzapine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              olanzapine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ergoloid mesylates

              ergoloid mesylates, 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).

            • ergotamine

              ergotamine, 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).

            • erythromycin base

              erythromycin base will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • escitalopram

              escitalopram increases toxicity of olanzapine by QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.

            • esketamine intranasal

              esketamine intranasal, olanzapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • estazolam

              estazolam and olanzapine both increase sedation. Use Caution/Monitor.

            • ethanol

              olanzapine and ethanol both increase sedation. Use Caution/Monitor.

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • exenatide injectable solution

              olanzapine, exenatide injectable solution. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • exenatide injectable suspension

              olanzapine, exenatide injectable suspension. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • fenfluramine

              olanzapine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

              olanzapine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              samidorphan decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

            • fentanyl

              fentanyl, 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).

            • gabapentin

              gabapentin, samidorphan. 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.

            • fesoterodine

              fesoterodine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              fesoterodine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • fexinidazole

              fexinidazole will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • finerenone

              olanzapine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fingolimod

              fingolimod and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • flavoxate

              flavoxate decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              flavoxate decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • flecainide

              olanzapine and flecainide both increase QTc interval. Use Caution/Monitor.

            • flibanserin

              olanzapine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

              flibanserin, 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).

            • fluconazole

              olanzapine and fluconazole both increase QTc interval. Use Caution/Monitor.

            • fluoxetine

              olanzapine and fluoxetine both increase QTc interval. Use Caution/Monitor.

            • fluphenazine

              fluphenazine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              fluphenazine and olanzapine both increase sedation. Use Caution/Monitor.

              olanzapine and fluphenazine both increase QTc interval. Use Caution/Monitor.

            • flurazepam

              flurazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • formoterol

              olanzapine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fostemsavir

              olanzapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • frovatriptan

              frovatriptan, 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).

            • gabapentin enacarbil

              gabapentin enacarbil, samidorphan. 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.

            • gadobenate

              gadobenate and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • ganaxolone

              samidorphan and ganaxolone both increase sedation. Use Caution/Monitor.

              olanzapine and ganaxolone both increase sedation. Use Caution/Monitor.

            • gemifloxacin

              gemifloxacin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • lasmiditan

              lasmiditan, samidorphan. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • gemtuzumab

              olanzapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • gilteritinib

              gilteritinib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • glimepiride

              olanzapine, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • glipizide

              olanzapine, glipizide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • glyburide

              olanzapine, glyburide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • glycopyrrolate

              olanzapine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • glycopyrrolate inhaled

              glycopyrrolate inhaled decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              glycopyrrolate inhaled decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • granisetron

              granisetron and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • guanfacine

              guanfacine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

            • haloperidol

              haloperidol and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              haloperidol and olanzapine both increase sedation. Use Caution/Monitor.

              haloperidol and olanzapine both increase QTc interval. Use Caution/Monitor.

            • henbane

              henbane decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              henbane decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • homatropine

              homatropine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • hydromorphone

              hydromorphone and olanzapine both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and olanzapine both increase sedation. Use Caution/Monitor.

              hydroxyzine and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • hyoscyamine

              hyoscyamine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              hyoscyamine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • hyoscyamine spray

              olanzapine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              hyoscyamine spray decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              hyoscyamine spray decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

            • iloperidone

              iloperidone and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              iloperidone and olanzapine both increase sedation. Use Caution/Monitor.

            • imipramine

              olanzapine and imipramine both increase sedation. Use Caution/Monitor.

              olanzapine and imipramine both increase QTc interval. Use Caution/Monitor.

            • incobotulinumtoxinA

              olanzapine increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • insulin aspart

              olanzapine, insulin aspart. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • insulin degludec

              olanzapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

            • insulin degludec/insulin aspart

              olanzapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

            • insulin detemir

              olanzapine, insulin detemir. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • insulin glargine

              olanzapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • insulin glulisine

              olanzapine, insulin glulisine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • insulin inhaled

              olanzapine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

            • insulin lispro

              olanzapine, insulin lispro. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • insulin NPH

              olanzapine, insulin NPH. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • insulin regular human

              olanzapine, insulin regular human. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • ipratropium

              ipratropium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              ipratropium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • isavuconazonium sulfate

              olanzapine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • isoproterenol

              olanzapine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • isradipine

              olanzapine and isradipine both increase QTc interval. Use Caution/Monitor.

            • itraconazole

              itraconazole and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • ivacaftor

              olanzapine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • ketotifen, ophthalmic

              olanzapine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • lapatinib

              olanzapine and lapatinib both increase QTc interval. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, olanzapine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, samidorphan. 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.

              lemborexant, olanzapine. 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.

              olanzapine 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.

            • levalbuterol

              olanzapine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • oliceridine

              oliceridine, samidorphan. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • levofloxacin

              olanzapine and levofloxacin both increase QTc interval. Use Caution/Monitor.

            • levomilnacipran

              levomilnacipran, 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).

            • levorphanol

              levorphanol and olanzapine both increase sedation. Use Caution/Monitor.

            • linezolid

              linezolid, 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).

            • liraglutide

              olanzapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • lisdexamfetamine

              olanzapine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lithium

              lithium, 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).

              lithium and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • lofepramine

              olanzapine and lofepramine both increase sedation. Use Caution/Monitor.

            • lofexidine

              olanzapine and lofexidine both increase sedation. Use Caution/Monitor.

              olanzapine and lofexidine both increase QTc interval. Use Caution/Monitor.

            • lomitapide

              olanzapine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • loperamide

              olanzapine and loperamide both increase QTc interval. Use Caution/Monitor.

            • loprazolam

              loprazolam and olanzapine both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • lorcaserin

              lorcaserin, 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).

            • lormetazepam

              lormetazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • loxapine

              loxapine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              loxapine and olanzapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              loxapine inhaled and olanzapine both increase sedation. Use Caution/Monitor.

            • lurasidone

              lurasidone, olanzapine. 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.

            • maprotiline

              olanzapine and maprotiline both increase sedation. Use Caution/Monitor.

            • maraviroc

              maraviroc, olanzapine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • marijuana

              olanzapine and marijuana both increase sedation. Use Caution/Monitor.

            • mavacamten

              olanzapine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • meclizine

              meclizine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              meclizine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • melatonin

              olanzapine and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              meperidine and olanzapine both increase sedation. Use Caution/Monitor.

              meperidine, 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).

            • meprobamate

              olanzapine and meprobamate both increase sedation. Use Caution/Monitor.

            • metaproterenol

              olanzapine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              metaxalone and olanzapine both increase sedation. Use Caution/Monitor.

            • metformin

              olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • methadone

              methadone and olanzapine both increase sedation. Use Caution/Monitor.

              methadone, 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).

            • methamphetamine

              olanzapine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and olanzapine both increase sedation. Use Caution/Monitor.

            • methscopolamine

              methscopolamine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              methscopolamine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • methylenedioxymethamphetamine

              olanzapine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methylergonovine

              methylergonovine, 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).

            • methylphenidate

              olanzapine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.

            • metoclopramide

              olanzapine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

            • mexiletine

              mexiletine will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • midazolam

              midazolam and olanzapine both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              olanzapine 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, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

              olanzapine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mifepristone

              mifepristone, olanzapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

            • miglitol

              olanzapine, miglitol. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • milnacipran

              milnacipran, 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).

            • mirtazapine

              olanzapine and mirtazapine both increase sedation. Use Caution/Monitor.

              mirtazapine and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

              olanzapine and mirtazapine both increase QTc interval. Use Caution/Monitor.

            • modafinil

              modafinil will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              olanzapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • morphine

              morphine and olanzapine both increase sedation. Use Caution/Monitor.

            • motherwort

              olanzapine and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              olanzapine and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              olanzapine and nabilone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              nalbuphine and olanzapine both increase sedation. Use Caution/Monitor.

            • naratriptan

              naratriptan, 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).

            • nateglinide

              olanzapine, nateglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • norepinephrine

              olanzapine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nortriptyline

              olanzapine and nortriptyline both increase sedation. Use Caution/Monitor.

              olanzapine and nortriptyline both increase QTc interval. Use Caution/Monitor.

            • ofloxacin

              olanzapine and ofloxacin both increase QTc interval. Use Caution/Monitor.

            • oliceridine

              oliceridine, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • onabotulinumtoxinA

              onabotulinumtoxinA decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              onabotulinumtoxinA decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • opium tincture

              opium tincture and olanzapine both increase sedation. Use Caution/Monitor.

            • orphenadrine

              orphenadrine and olanzapine both increase sedation. Use Caution/Monitor.

            • osilodrostat

              osilodrostat and olanzapine both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              osimertinib and olanzapine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxaliplatin

              oxaliplatin will increase the level or effect of olanzapine by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

            • oxazepam

              oxazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • oxybutynin

              oxybutynin decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              oxybutynin decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oxybutynin topical

              oxybutynin topical decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              oxybutynin topical decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oxybutynin transdermal

              oxybutynin transdermal decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              oxybutynin transdermal decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oxycodone

              oxycodone and olanzapine both increase sedation. Use Caution/Monitor.

            • oxymorphone

              oxymorphone and olanzapine both increase sedation. Use Caution/Monitor.

            • ozanimod

              ozanimod and olanzapine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              olanzapine and paliperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and paliperidone both increase sedation. Use Caution/Monitor.

            • pancuronium

              pancuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              pancuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • papaveretum

              papaveretum and olanzapine both increase sedation. Use Caution/Monitor.

            • papaverine

              olanzapine and papaverine both increase sedation. Use Caution/Monitor.

            • paroxetine

              paroxetine, 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).

            • pasireotide

              olanzapine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • peginterferon alfa 2a

              peginterferon alfa 2a will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • pentazocine

              pentazocine and olanzapine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              pentobarbital and olanzapine both increase sedation. Use Caution/Monitor.

            • perphenazine

              olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and perphenazine both increase sedation. Use Caution/Monitor.

              olanzapine and perphenazine both increase QTc interval. Use Caution/Monitor.

            • phendimetrazine

              olanzapine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenelzine

              phenelzine, 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).

            • phenobarbital

              phenobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital and olanzapine both increase sedation. Use Caution/Monitor.

            • phentermine

              olanzapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              olanzapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine PO

              olanzapine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • pholcodine

              olanzapine and pholcodine both increase sedation. Use Caution/Monitor.

            • pimozide

              olanzapine and pimozide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and pimozide both increase sedation. Use Caution/Monitor.

            • pioglitazone

              olanzapine, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • pipemidic acid

              pipemidic acid will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • pirbuterol

              olanzapine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • posaconazole

              olanzapine and posaconazole both increase QTc interval. Use Caution/Monitor.

            • pralidoxime

              pralidoxime decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              pralidoxime decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • pramlintide

              olanzapine, pramlintide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • pregabalin

              pregabalin, samidorphan. 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.

            • primaquine

              olanzapine and primaquine both increase QTc interval. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              primidone and olanzapine both increase sedation. Use Caution/Monitor.

            • procarbazine

              procarbazine, 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).

            • prochlorperazine

              olanzapine and prochlorperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and prochlorperazine both increase sedation. Use Caution/Monitor.

              olanzapine and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

            • promethazine

              olanzapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              promethazine and olanzapine both increase sedation. Use Caution/Monitor.

              promethazine, 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 promethazine both decrease QTc interval. Use Caution/Monitor.

            • propantheline

              propantheline decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              propantheline decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • propofol

              propofol and olanzapine both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              olanzapine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              olanzapine and protriptyline both increase sedation. Use Caution/Monitor.

              olanzapine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • quazepam

              quazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • quetiapine

              olanzapine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and quetiapine both increase sedation. Use Caution/Monitor.

            • quinine

              olanzapine and quinine both increase QTc interval. Use Caution/Monitor.

            • ramelteon

              olanzapine and ramelteon both increase sedation. Use Caution/Monitor.

            • rapacuronium

              rapacuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              rapacuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • remimazolam

              remimazolam, samidorphan. 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.

              remimazolam, olanzapine. 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.

            • repaglinide

              olanzapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of samidorphan by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • rifampin

              rifampin will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • rilpivirine

              olanzapine and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • rimabotulinumtoxinB

              olanzapine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

            • risperidone

              olanzapine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and risperidone both increase sedation. Use Caution/Monitor.

              olanzapine and risperidone both increase QTc interval. Use Caution/Monitor.

            • ritonavir

              ritonavir decreases levels of olanzapine by increasing metabolism. Use Caution/Monitor.

            • rocuronium

              rocuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              rocuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • romidepsin

              olanzapine and romidepsin both increase QTc interval. Use Caution/Monitor.

            • rosiglitazone

              olanzapine, rosiglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • rucaparib

              rucaparib will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

            • salmeterol

              olanzapine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • saxagliptin

              olanzapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • scopolamine

              scopolamine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              scopolamine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • scullcap

              olanzapine and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              secobarbital and olanzapine both increase sedation. Use Caution/Monitor.

            • selegiline

              selegiline, 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).

            • selpercatinib

              selpercatinib increases toxicity of olanzapine by QTc interval. Use Caution/Monitor.

            • sertraline

              olanzapine and sertraline both increase QTc interval. Use Caution/Monitor.

            • shepherd's purse

              olanzapine and shepherd's purse both increase sedation. Use Caution/Monitor.

            • sitagliptin

              olanzapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • smoking

              smoking will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of olanzapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of samidorphan by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of olanzapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • solifenacin

              solifenacin decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              solifenacin decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              olanzapine and solifenacin both increase QTc interval. Use Caution/Monitor.

            • sorafenib

              sorafenib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • stiripentol

              stiripentol, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

              stiripentol, olanzapine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

              sufentanil and olanzapine both increase sedation. Use Caution/Monitor.

            • sumatriptan

              sumatriptan, 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).

            • sumatriptan intranasal

              sumatriptan intranasal, 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).

            • sunitinib

              olanzapine and sunitinib both increase QTc interval. Use Caution/Monitor.

            • tacrolimus

              olanzapine and tacrolimus both increase QTc interval. Use Caution/Monitor.

            • tapentadol

              tapentadol and olanzapine both increase sedation. Use Caution/Monitor.

            • tazemetostat

              olanzapine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • telavancin

              olanzapine and telavancin both increase QTc interval. Use Caution/Monitor.

            • temazepam

              temazepam and olanzapine both increase sedation. Use Caution/Monitor.

            • terbutaline

              olanzapine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • teriflunomide

              teriflunomide decreases levels of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • tetrabenazine

              olanzapine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.

            • thioridazine

              olanzapine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              olanzapine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and thiothixene both increase sedation. Use Caution/Monitor.

            • tinidazole

              olanzapine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tiotropium

              tiotropium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              tiotropium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • tobacco use

              tobacco use will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • tolazamide

              olanzapine, tolazamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • tolbutamide

              olanzapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • tolterodine

              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.

              olanzapine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • topiramate

              olanzapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              tramadol and olanzapine both increase sedation. Use Caution/Monitor.

            • tranylcypromine

              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).

            • trazodone

              olanzapine and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and olanzapine both increase sedation. Use Caution/Monitor.

            • triclabendazole

              triclabendazole and olanzapine both increase QTc interval. Use Caution/Monitor.

            • triclofos

              triclofos and olanzapine both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              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.

            • trihexyphenidyl

              olanzapine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimipramine

              olanzapine and trimipramine both increase sedation. Use Caution/Monitor.

              olanzapine and trimipramine both increase QTc interval. Use Caution/Monitor.

            • triprolidine

              triprolidine and olanzapine both increase sedation. Use Caution/Monitor.

            • trospium chloride

              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.

            • valbenazine

              valbenazine and olanzapine both increase QTc interval. Use Caution/Monitor.

            • vardenafil

              olanzapine and vardenafil both increase QTc interval. Use Caution/Monitor.

            • vecuronium

              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.

            • venlafaxine

              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.

            • verapamil

              verapamil will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • vilazodone

              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).

            • voclosporin

              voclosporin, olanzapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              olanzapine and voriconazole both increase QTc interval. Use Caution/Monitor.

            • vorinostat

              olanzapine and vorinostat both increase QTc interval. Use Caution/Monitor.

            • xylometazoline

              olanzapine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              olanzapine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              olanzapine and ziconotide both increase sedation. Use Caution/Monitor.

            • zileuton

              zileuton will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • ziprasidone

              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.

            • zolmitriptan

              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).

            • zotepine

              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.

            Minor (8)

            • brimonidine

              brimonidine increases effects of olanzapine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • chasteberry

              chasteberry decreases effects of olanzapine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

            • ethanol

              ethanol, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

            • eucalyptus

              olanzapine and eucalyptus both increase sedation. Minor/Significance Unknown.

            • omeprazole

              omeprazole will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • ruxolitinib

              olanzapine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ruxolitinib topical

              olanzapine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              olanzapine and sage both increase sedation. Minor/Significance Unknown.

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            Adverse Effects

            >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)

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            Warnings

            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
              • Diazepam, alcohol, or other CNS-acting drugs may potentiate the orthostatic hypotension observed with olanzapine
            • Anticholinergic drugs
              • Use with caution
              • Olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility
            • Antihypertensive agents
              • Monitor BP and reduce dosage of antihypertensive drug in accordance with its prescribing information
              • Olanzapine/samidorphan may enhance the effects of certain antihypertensive agents
            • Levodopa and dopamine agonists
              • Not recommended
              • Olanzapine/samidorphan may antagonize the effects of levodopa and dopamine agonists
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            Pregnancy & Lactation

            Pregnancy

            No data are available on use of samidorphan or olanzapine/samidorphan in pregnant females to determine drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Olanzapine

            • Neonates exposed to antipsychotic drugs, including olanzapine, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery
            • Overall published epidemiologic studies of pregnant females exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Pregnancy exposure registry

            Infertility

            • Based on the pharmacologic action of olanzapine (D2 antagonism), an increase in serum prolactin levels may occur, which may lead to a reversible reduction in fertility in females of reproductive potential

            Clinical considerations

            • Disease-associated maternal and/or embryofetal risk
              • There is risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide
              • Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth
              • Unknown if a direct result of the illness or other comorbid factors
            • Fetal or neonatal risks
              • Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including the olanzapine, during the third trimester of pregnancy; symptoms vary in severity
              • Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately
              • Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization

            Animal data

            • Oral administration of olanzapine and samidorphan to pregnant rats during organogenesis produced adverse effects on embryofetal development and fetal toxicity at maternally toxic doses that are 6x and >400x the maximum recommended human dose (MRHD) of olanzapine 20mg/samidorphan 10mg, respectively based on AUC
            • Olanzapine
              • Early resorptions and increased numbers of nonviable fetuses were observed at a dose 9x the MRHD based on mg/m2 body surface area (BSA) and gestation was prolonged at 5x the MRHD based on mg/m2 BSA
              • Fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of olanzapine, which is 30x the MRHD based on mg/m2 BSA
            • Samidorphan
              • Oral administration of samidorphan to pregnant rats and rabbits during organogenesis caused fetal toxicities in rats only at maternally toxic doses that are >248x the human exposure at the MRHD of 10 mg/day based on AUC
              • Oral administration of samidorphan to pregnant rats during pregnancy and lactation resulted in lower pup survival and decreased pup weights at 188x the human exposure at the MRHD based on AUC

            Lactation

            Olanzapine

            • Present in human milk
            • There are reports of excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) in infants exposed to olanzapine through breast milk
            • There is no information on the effects of olanzapine on milk production

            Samidorphan

            • There are no data on the presence of samidorphan or olanzapine/samidorphan in human milk, effects on breastfed infants, or effects on milk production
            • When administered to lactating rats, samidorphan and a metabolite were detected in the plasma of nursing pups, likely due to the presence of samidorphan in milk
            • Monitor infants exposed to olanzapine/samidorphan for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements)

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Olanzapine: May act through combination of dopamine and serotonin type 2 receptor site antagonism

            Samidorphan: Opioid antagonist; mitigates weight gain associated with olanzapine

            Absorption

            Steady-state exposure (olanzapine20 mg/samidorphan 10mg)

            Peak plasma concentration

            • Olanzapine: 64.6 ng/mL
            • Samidorphan: 45.1 ng/mL

            Peak plasma time

            • Olanzapine: 4.5-7 hr
            • Samidorphan: 1-2 hr

            AUC

            • Olanzapine: 1,086 ng⋅hr/mL
            • Samidorphan: 364 ng⋅hr/mL

            Time to reach steady-state

            • Olanzapine: 7 days
            • Samidorphan: 5 days

            Accumulation at steady-state

            • Olanzapine: 2-fold
            • Samidorphan: 1.3-fold

            Effect of food

            • High-fat meal: Meal containing ~900-1000 calories and 50% fat content
            • Olanzapine
              • Cmax ratio: 0.88
              • AUC ratio: 0.93
            • Samidorphan
              • Cmax ratio: 0.85
              • AUC ratio: 1.03

            Distribution

            Protein bound

            • Olanzapine: 93%
            • Samidorphan: 23-33%

            Blood-to-plasma

            • Olanzapine: Not determined
            • Samidorphan: 0.8

            Metabolism

            Olanzapine

            • Primary pathways: UGT1A4, CYP1A2
            • Minor pathway: CYP2D6
            • Metabolites: 10-N-glucuronide and 4′-N-desmethyl-olanzapine; both lack pharmacological activity at therapeutic concentrations

            Samidorphan

            • Primary pathway: CYP3A4
            • Minor pathways: CYP3A5, CYP2C19, CYP2C8
            • Metabolites: N-dealkylated and cis-N-oxide metabolites; neither metabolite contributes to the pharmacological effects of samidorphan

            Elimination

            Half-life

            • Olanzapine: 35-52 hr
            • Samidorphan: 7-11 hr

            Clearance

            • Olanzapine: 15-22 L/hr; clearance was ~40% higher in smokers than in nonsmokers
            • Samidorphan: 35-45 L/hr

            Excretion

            • Olanzapine: Urine (57% [7% unchanged]); feces (30%)
            • Samidorphan: Urine (67% [18% unchanged]); feces (16%)
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            Administration

            Oral Administration

            Take with or without food as a single tablet

            Do not divide tablets or combine strengths

            Storage

            Store at room temperature of 20-25ºC (68-77ºF) in original bottle with desiccant; excursions permitted to 15-30ºC (59-86ºF)

            Keep bottle tightly closed and protect from moisture

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.