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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              Serious - Use Alternative (38)

              • 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.

              • 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

              • 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

              • 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.

              • 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

              • 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.

              • dopamine

                olanzapine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              Monitor Closely (342)

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

              • 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.

              • 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.

              • 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).

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

                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.

              • 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.

              • 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).

              • lofepramine

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

              • lofexidine

                olanzapine and lofexidine both increase sedation. 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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).

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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).

              • 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.

              • 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.

              • 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.

              • 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.

              • 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).

              • 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.

              • 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 (7)

              • 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.

              • 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.