Dosing & Uses
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
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (3)
- amisulpride
amisulpride, olanzapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndromeIncreases risk of neuroleptic malignant syndrome.
- dronedarone
olanzapine and dronedarone both increase QTc interval. Contraindicated.
- thioridazine
olanzapine and thioridazine both increase QTc interval. Contraindicated.
Serious - Use Alternative (113)
- adagrasib
adagrasib, olanzapine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
- amiodarone
olanzapine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.
- amisulpride
amisulpride and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- anagrelide
olanzapine and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.
- apomorphine
olanzapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
apomorphine and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - arsenic trioxide
olanzapine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.
- artemether
artemether and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- artemether/lumefantrine
olanzapine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine
olanzapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- bromocriptine
olanzapine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- buprenorphine
olanzapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. If concurrent use of olanzapine and buprenorphine is necessary, consider dose reduction of one or both drugs.
- buprenorphine buccal
buprenorphine buccal 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
- buprenorphine subdermal implant
buprenorphine subdermal implant 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
- buprenorphine transdermal
buprenorphine transdermal 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
- buprenorphine, long-acting injection
buprenorphine, long-acting injection 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
- cabergoline
olanzapine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.
- calcium/magnesium/potassium/sodium oxybates
olanzapine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- ceritinib
ceritinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- chlorpromazine
olanzapine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.
- ciprofloxacin
olanzapine and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- citalopram
citalopram and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- clarithromycin
clarithromycin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- clozapine
clozapine and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- crizotinib
crizotinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- degarelix
degarelix and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- desflurane
desflurane and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- diazepam intranasal
diazepam intranasal, samidorphan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- disopyramide
olanzapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.
- dopamine
olanzapine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.
- droperidol
olanzapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.
- eliglustat
olanzapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.
- encorafenib
encorafenib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- entrectinib
olanzapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.
- erdafitinib
olanzapine will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.
- eribulin
eribulin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- erythromycin base
olanzapine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
olanzapine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin lactobionate
olanzapine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin stearate
olanzapine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
- fedratinib
olanzapine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.
- fexinidazole
fexinidazole and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.
- fluvoxamine
fluvoxamine will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
olanzapine and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug. - foscarnet
olanzapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.
- givosiran
givosiran will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- glasdegib
olanzapine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.
- goserelin
olanzapine and goserelin both increase QTc interval. Avoid or Use Alternate Drug.
- histrelin
olanzapine and histrelin both increase QTc interval. Avoid or Use Alternate Drug.
- hydrocodone
hydrocodone, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate and olanzapine both increase QTc interval. Avoid or Use Alternate Drug.
- ibutilide
olanzapine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.
- iloperidone
olanzapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.
- inotuzumab
olanzapine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- isoflurane
isoflurane and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- ivosidenib
ivosidenib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.
- lefamulin
lefamulin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug.
- leniolisib
leniolisib will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid leniolisib with CYP1A2 substrates that have a narrow therapeutic index
- lenvatinib
olanzapine and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.
- leuprolide
olanzapine and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.
- levodopa
olanzapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- levodopa inhaled
olanzapine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Atypical (2nd generation) antipsychotics inhibit dopamine D2 receptors in varying degrees (clozapine and quetiapine are lower risk). .
- lisuride
olanzapine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.
- lonafarnib
olanzapine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
- lopinavir
olanzapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.
- macimorelin
macimorelin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.
- maprotiline
olanzapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.
- mefloquine
mefloquine increases toxicity of olanzapine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.
- methadone
olanzapine and methadone both increase QTc interval. Avoid or Use Alternate Drug.
- methyldopa
olanzapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.
- metoclopramide intranasal
samidorphan increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.
olanzapine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.
olanzapine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient. - midostaurin
olanzapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- olopatadine intranasal
samidorphan and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- mobocertinib
mobocertinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.
- moxifloxacin
olanzapine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- olopatadine intranasal
olanzapine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- ondansetron
olanzapine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.
- oxaliplatin
olanzapine and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.
oxaliplatin and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - paliperidone
olanzapine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.
- panobinostat
olanzapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.
- paroxetine
olanzapine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.
- pazopanib
olanzapine and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.
- pefloxacin
pefloxacin will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
- pentamidine
olanzapine and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.
- pimavanserin
olanzapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.
- pimozide
olanzapine and pimozide both increase QTc interval. Contraindicated.
- pitolisant
olanzapine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.
- ponesimod
olanzapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.
- pramipexole
olanzapine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.
- procainamide
olanzapine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.
- propafenone
olanzapine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.
- quetiapine
olanzapine and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.
- quinidine
olanzapine and quinidine both increase QTc interval. Avoid or Use Alternate Drug.
- ranolazine
olanzapine and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.
- ribociclib
ribociclib increases toxicity of olanzapine by QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
- ropinirole
olanzapine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.
- safinamide
olanzapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.
- saquinavir
olanzapine and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.
- selinexor
selinexor, samidorphan. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
selinexor, olanzapine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion. - sevoflurane
sevoflurane and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- siponimod
olanzapine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.
olanzapine and siponimod both increase QTc interval. Avoid or Use Alternate Drug. - sodium oxybate
olanzapine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- sotalol
olanzapine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.
- sufentanil SL
sufentanil SL, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- tetrabenazine
olanzapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.
- thiothixene
olanzapine and thiothixene both increase QTc interval. Avoid or Use Alternate Drug.
- toremifene
olanzapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.
- trazodone
olanzapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
- triptorelin
olanzapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.
- umeclidinium bromide/vilanterol inhaled
olanzapine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
- vandetanib
olanzapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.
- vemurafenib
olanzapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- vilanterol/fluticasone furoate inhaled
olanzapine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
- ziprasidone
olanzapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.
Monitor Closely (392)
- 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. - acrivastine
acrivastine and olanzapine both increase sedation. Use Caution/Monitor.
- albiglutide
olanzapine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- albuterol
olanzapine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
albuterol and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - alfentanil
alfentanil and olanzapine both increase sedation. Use Caution/Monitor.
- alfuzosin
olanzapine and alfuzosin both increase QTc interval. Use Caution/Monitor.
alfuzosin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - almotriptan
almotriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- alprazolam
alprazolam and olanzapine both increase sedation. Use Caution/Monitor.
- amifostine
amifostine, olanzapine. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Due to its alpha adrenergic antagonism, atypical antipsychotic agents has the potential to enhance the effect of certain antihypertensive agents. Monitor blood pressure and adjust dose accordingly.
- amitriptyline
olanzapine and amitriptyline both increase sedation. Use Caution/Monitor.
olanzapine and amitriptyline both increase QTc interval. Use Caution/Monitor. - amobarbital
amobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
amobarbital and olanzapine both increase sedation. Use Caution/Monitor. - amoxapine
olanzapine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and amoxapine both increase sedation. Use Caution/Monitor.
olanzapine and amoxapine both increase QTc interval. Use Caution/Monitor. - anticholinergic/sedative combos
anticholinergic/sedative combos decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
anticholinergic/sedative combos decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - apomorphine
olanzapine and apomorphine both increase sedation. Use Caution/Monitor.
- arformoterol
olanzapine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
arformoterol and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - aripiprazole
aripiprazole and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
aripiprazole and olanzapine both increase sedation. Use Caution/Monitor.
aripiprazole and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - armodafinil
armodafinil will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
olanzapine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - asenapine
asenapine and olanzapine both increase sedation. Use Caution/Monitor.
- asenapine transdermal
asenapine transdermal and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
asenapine transdermal and olanzapine both increase sedation. 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.
avapritinib and olanzapine both increase sedation. 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. - benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen 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.
- brexpiprazole
brexpiprazole and olanzapine both increase sedation. Use Caution/Monitor.
- brimonidine
brimonidine and olanzapine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and olanzapine both increase 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 subdermal implant
buprenorphine subdermal implant and olanzapine both increase sedation. Use Caution/Monitor.
- buprenorphine transdermal
buprenorphine transdermal 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.
buprenorphine, long-acting injection and olanzapine both increase sedation. Use Caution/Monitor. - butabarbital
butabarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
butabarbital and olanzapine both increase sedation. Use Caution/Monitor. - butalbital
butalbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
butalbital and olanzapine both increase sedation. Use Caution/Monitor. - butorphanol
butorphanol and olanzapine both increase sedation. Use Caution/Monitor.
- caffeine
olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cannabidiol
cannabidiol, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.
- captopril
olanzapine, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.
- carbamazepine
carbamazepine will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- carbinoxamine
carbinoxamine and olanzapine both increase sedation. Use Caution/Monitor.
- carisoprodol
carisoprodol and olanzapine both increase sedation. Use Caution/Monitor.
- chloral hydrate
chloral hydrate and olanzapine both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
chlordiazepoxide and olanzapine both increase sedation. Use Caution/Monitor.
- chloroquine
chloroquine increases toxicity of olanzapine by QTc interval. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor.
- chlorpromazine
chlorpromazine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
chlorpromazine and olanzapine both increase sedation. Use Caution/Monitor. - chlorpropamide
olanzapine, chlorpropamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- chlorzoxazone
chlorzoxazone and olanzapine both increase sedation. Use Caution/Monitor.
- cigarette smoking
cigarette smoking will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- cimetidine
cimetidine will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- cinnarizine
cinnarizine and olanzapine both increase sedation. Use Caution/Monitor.
- ciprofloxacin
ciprofloxacin will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Olanzapine plasma concentrations may be elevated, increasing the risk of adverse reactions such as orthostatic hypotension or sedation. It is important to use caution and observe patient and adjust the olanzapine dosage as needed.
- cisatracurium
cisatracurium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
cisatracurium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - clemastine
clemastine and olanzapine both increase sedation. Use Caution/Monitor.
- clobazam
olanzapine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
- clomipramine
olanzapine and clomipramine both increase sedation. Use Caution/Monitor.
olanzapine and clomipramine both increase QTc interval. Use Caution/Monitor. - clonazepam
clonazepam and olanzapine both increase sedation. Use Caution/Monitor.
- clonidine
clonidine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.
- clorazepate
clorazepate and olanzapine both increase sedation. Use Caution/Monitor.
- clozapine
clozapine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
clozapine and olanzapine both increase sedation. Use Caution/Monitor. - codeine
codeine and olanzapine both increase sedation. Use Caution/Monitor.
- cyclizine
cyclizine and olanzapine both increase sedation. Use Caution/Monitor.
cyclizine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
cyclizine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - cyclobenzaprine
cyclobenzaprine and olanzapine both increase sedation. Use Caution/Monitor.
cyclobenzaprine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
cyclobenzaprine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - cyproheptadine
cyproheptadine and olanzapine both increase sedation. Use Caution/Monitor.
- dantrolene
dantrolene and olanzapine both increase sedation. Use Caution/Monitor.
- daridorexant
olanzapine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
samidorphan and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. - darifenacin
darifenacin decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
darifenacin decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - difelikefalin
difelikefalin and samidorphan both increase sedation. Use Caution/Monitor.
- dasatinib
dasatinib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- deferasirox
deferasirox will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- desipramine
olanzapine and desipramine both increase sedation. Use Caution/Monitor.
olanzapine and desipramine both increase QTc interval. Use Caution/Monitor. - deutetrabenazine
olanzapine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.
olanzapine and deutetrabenazine both increase sedation. Use Caution/Monitor.
deutetrabenazine and olanzapine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation). - dexchlorpheniramine
dexchlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor.
- dexfenfluramine
olanzapine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexmedetomidine
dexmedetomidine and olanzapine both increase sedation. Use Caution/Monitor.
- dexmethylphenidate
olanzapine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dextroamphetamine
olanzapine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dextromethorphan
dextromethorphan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- dextromoramide
dextromoramide and olanzapine both increase sedation. Use Caution/Monitor.
- diamorphine
diamorphine and olanzapine both increase sedation. Use Caution/Monitor.
- diazepam
diazepam and olanzapine both increase sedation. Use Caution/Monitor.
- dicyclomine
dicyclomine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
dicyclomine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - diethylpropion
olanzapine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- difelikefalin
difelikefalin and olanzapine both increase sedation. Use Caution/Monitor.
- difenoxin hcl
difenoxin hcl and olanzapine both increase sedation. Use Caution/Monitor.
- dihydroergotamine
dihydroergotamine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- dimenhydrinate
dimenhydrinate and olanzapine both increase sedation. Use Caution/Monitor.
- diphenhydramine
diphenhydramine and olanzapine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - diphenoxylate hcl
diphenoxylate hcl and olanzapine both increase sedation. Use Caution/Monitor.
- dipipanone
dipipanone and olanzapine both increase sedation. Use Caution/Monitor.
- dobutamine
olanzapine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dofetilide
dofetilide increases toxicity of olanzapine by QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
- dolasetron
dolasetron and olanzapine both increase QTc interval. Use Caution/Monitor.
- donepezil
donepezil and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- dopamine
olanzapine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopexamine
olanzapine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dosulepin
olanzapine and dosulepin both increase sedation. Use Caution/Monitor.
- doxepin
olanzapine and doxepin both increase sedation. Use Caution/Monitor.
doxepin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - doxylamine
doxylamine and olanzapine both increase sedation. Use Caution/Monitor.
- droperidol
droperidol and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
droperidol and olanzapine both increase sedation. Use Caution/Monitor. - efavirenz
efavirenz and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- eletriptan
eletriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- elranatamab
elranatamab will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.
- epcoritamab
epcoritamab, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- 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).
- 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).
fentanyl and olanzapine both increase sedation. Use Caution/Monitor. - 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.
- fentanyl intranasal
fentanyl intranasal and olanzapine both increase sedation. Use Caution/Monitor.
- fentanyl iontophoretic transdermal system
fentanyl iontophoretic transdermal system and olanzapine both increase sedation. Use Caution/Monitor.
- fentanyl transdermal
fentanyl transdermal and olanzapine both increase sedation. Use Caution/Monitor.
- fesoterodine
fesoterodine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
fesoterodine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - fexinidazole
fexinidazole will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- finerenone
olanzapine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.
- fingolimod
fingolimod and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- flavoxate
flavoxate decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
flavoxate decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - flecainide
olanzapine and flecainide both increase QTc interval. Use Caution/Monitor.
- flibanserin
olanzapine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
flibanserin, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - fluconazole
olanzapine and fluconazole both increase QTc interval. Use Caution/Monitor.
- fluoxetine
olanzapine and fluoxetine both increase QTc interval. Use Caution/Monitor.
- fluphenazine
fluphenazine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
fluphenazine and olanzapine both increase sedation. Use Caution/Monitor.
olanzapine and fluphenazine both increase QTc interval. Use Caution/Monitor. - flurazepam
flurazepam and olanzapine both increase sedation. Use Caution/Monitor.
- formoterol
olanzapine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- fostemsavir
olanzapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- frovatriptan
frovatriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- gabapentin enacarbil
gabapentin enacarbil, samidorphan. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gadobenate
gadobenate and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- ganaxolone
samidorphan and ganaxolone both increase sedation. Use Caution/Monitor.
olanzapine and ganaxolone both increase sedation. Use Caution/Monitor. - gemifloxacin
gemifloxacin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- lasmiditan
lasmiditan, samidorphan. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- gemtuzumab
olanzapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.
- gepirone
gepirone and olanzapine both increase QTc interval. Modify Therapy/Monitor Closely.
- gilteritinib
gilteritinib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- glimepiride
olanzapine, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- glipizide
olanzapine, glipizide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- glofitamab
glofitamab, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- glyburide
olanzapine, glyburide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- glycopyrrolate
olanzapine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
- glycopyrrolate inhaled
glycopyrrolate inhaled decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
glycopyrrolate inhaled decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - granisetron
granisetron and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- guanfacine
guanfacine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.
- haloperidol
haloperidol and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
haloperidol and olanzapine both increase sedation. Use Caution/Monitor.
haloperidol and olanzapine both increase QTc interval. Use Caution/Monitor. - henbane
henbane decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
henbane decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - homatropine
homatropine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
homatropine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - hydromorphone
hydromorphone and olanzapine both increase sedation. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and olanzapine both increase sedation. Use Caution/Monitor.
hydroxyzine and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - hyoscyamine
hyoscyamine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
hyoscyamine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - hyoscyamine spray
olanzapine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
hyoscyamine spray decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
hyoscyamine spray decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor. - iloperidone
iloperidone and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
iloperidone and olanzapine both increase sedation. Use Caution/Monitor. - imipramine
olanzapine and imipramine both increase sedation. Use Caution/Monitor.
olanzapine and imipramine both increase QTc interval. Use Caution/Monitor. - incobotulinumtoxinA
olanzapine increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
- insulin aspart
olanzapine, insulin aspart. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- insulin degludec
olanzapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.
- insulin degludec/insulin aspart
olanzapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.
- insulin detemir
olanzapine, insulin detemir. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- insulin glargine
olanzapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- insulin glulisine
olanzapine, insulin glulisine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- insulin inhaled
olanzapine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.
- insulin lispro
olanzapine, insulin lispro. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- insulin NPH
olanzapine, insulin NPH. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- insulin regular human
olanzapine, insulin regular human. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- ipratropium
ipratropium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
ipratropium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - isavuconazonium sulfate
olanzapine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isoproterenol
olanzapine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- isradipine
olanzapine and isradipine both increase QTc interval. Use Caution/Monitor.
- itraconazole
itraconazole and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- ivacaftor
olanzapine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .
- ketotifen, ophthalmic
olanzapine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- lapatinib
olanzapine and lapatinib both increase QTc interval. Use Caution/Monitor.
- lasmiditan
lasmiditan, olanzapine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
lemborexant, samidorphan. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
lemborexant, olanzapine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
olanzapine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification. - levalbuterol
olanzapine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- oliceridine
oliceridine, samidorphan. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- levofloxacin
olanzapine and levofloxacin both increase QTc interval. Use Caution/Monitor.
- levomilnacipran
levomilnacipran, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- levorphanol
levorphanol and olanzapine both increase sedation. Use Caution/Monitor.
- linezolid
linezolid, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- liraglutide
olanzapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- lisdexamfetamine
olanzapine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lithium
lithium, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
lithium and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances - lofepramine
olanzapine and lofepramine both increase sedation. Use Caution/Monitor.
- lofexidine
olanzapine and lofexidine both increase sedation. Use Caution/Monitor.
olanzapine and lofexidine both increase QTc interval. Use Caution/Monitor. - lomitapide
olanzapine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
- lonapegsomatropin
lonapegsomatropin will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- loperamide
olanzapine and loperamide both increase QTc interval. Use Caution/Monitor.
- loprazolam
loprazolam and olanzapine both increase sedation. Use Caution/Monitor.
- lorazepam
lorazepam and olanzapine both increase sedation. Use Caution/Monitor.
- lorcaserin
lorcaserin, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- lormetazepam
lormetazepam and olanzapine both increase sedation. Use Caution/Monitor.
- loxapine
loxapine and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
loxapine and olanzapine both increase sedation. Use Caution/Monitor. - loxapine inhaled
loxapine inhaled and olanzapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
loxapine inhaled and olanzapine both increase sedation. Use Caution/Monitor. - lurasidone
lurasidone, olanzapine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
- maprotiline
olanzapine and maprotiline both increase sedation. Use Caution/Monitor.
- maraviroc
maraviroc, olanzapine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.
- marijuana
olanzapine and marijuana both increase sedation. Use Caution/Monitor.
- mavacamten
olanzapine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.
- meclizine
meclizine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
meclizine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - melatonin
olanzapine and melatonin both increase sedation. Use Caution/Monitor.
- meperidine
meperidine and olanzapine both increase sedation. Use Caution/Monitor.
meperidine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - meprobamate
olanzapine and meprobamate both increase sedation. Use Caution/Monitor.
- metaproterenol
olanzapine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metaxalone
metaxalone and olanzapine both increase sedation. Use Caution/Monitor.
- metformin
olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- methadone
methadone and olanzapine both increase sedation. Use Caution/Monitor.
methadone, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - methamphetamine
olanzapine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- methocarbamol
methocarbamol and olanzapine both increase sedation. Use Caution/Monitor.
- methscopolamine
methscopolamine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
methscopolamine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - methylenedioxymethamphetamine
olanzapine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- methylergonovine
methylergonovine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- methylphenidate
olanzapine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.
- metoclopramide
olanzapine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
- mexiletine
mexiletine will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- midazolam
midazolam and olanzapine both increase sedation. Use Caution/Monitor.
- midazolam intranasal
olanzapine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
midazolam intranasal, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. - midodrine
olanzapine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- mifepristone
mifepristone, olanzapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.
- miglitol
olanzapine, miglitol. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- milnacipran
milnacipran, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- mirtazapine
olanzapine and mirtazapine both increase sedation. Use Caution/Monitor.
mirtazapine and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
olanzapine and mirtazapine both increase QTc interval. Use Caution/Monitor. - modafinil
olanzapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- morphine
morphine and olanzapine both increase sedation. Use Caution/Monitor.
- motherwort
olanzapine and motherwort both increase sedation. Use Caution/Monitor.
- moxonidine
olanzapine and moxonidine both increase sedation. Use Caution/Monitor.
- nabilone
olanzapine and nabilone both increase sedation. Use Caution/Monitor.
- nalbuphine
nalbuphine and olanzapine both increase sedation. Use Caution/Monitor.
- naratriptan
naratriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- nateglinide
olanzapine, nateglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- norepinephrine
olanzapine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- nortriptyline
olanzapine and nortriptyline both increase sedation. Use Caution/Monitor.
olanzapine and nortriptyline both increase QTc interval. Use Caution/Monitor. - ofloxacin
olanzapine and ofloxacin both increase QTc interval. Use Caution/Monitor.
- oliceridine
oliceridine, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- onabotulinumtoxinA
onabotulinumtoxinA decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
onabotulinumtoxinA decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - opium tincture
opium tincture and olanzapine both increase sedation. Use Caution/Monitor.
- orphenadrine
orphenadrine and olanzapine both increase sedation. Use Caution/Monitor.
- osilodrostat
osilodrostat and olanzapine both increase QTc interval. Use Caution/Monitor.
- osimertinib
osimertinib and olanzapine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.
- oxaliplatin
oxaliplatin will increase the level or effect of olanzapine by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.
- oxazepam
oxazepam and olanzapine both increase sedation. Use Caution/Monitor.
- oxybutynin
oxybutynin decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxybutynin decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oxybutynin topical
oxybutynin topical decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxybutynin topical decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oxybutynin transdermal
oxybutynin transdermal decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxybutynin transdermal decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oxycodone
oxycodone and olanzapine both increase sedation. Use Caution/Monitor.
- oxymorphone
oxymorphone and olanzapine both increase sedation. Use Caution/Monitor.
- ozanimod
ozanimod and olanzapine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.
- paliperidone
olanzapine and paliperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and paliperidone both increase sedation. Use Caution/Monitor. - pancuronium
pancuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
pancuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - papaveretum
papaveretum and olanzapine both increase sedation. Use Caution/Monitor.
- papaverine
olanzapine and papaverine both increase sedation. Use Caution/Monitor.
- paroxetine
paroxetine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- pasireotide
olanzapine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.
- peginterferon alfa 2a
peginterferon alfa 2a will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- pentazocine
pentazocine and olanzapine both increase sedation. Use Caution/Monitor.
- pentobarbital
pentobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
pentobarbital and olanzapine both increase sedation. Use Caution/Monitor. - perphenazine
olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and perphenazine both increase sedation. Use Caution/Monitor.
olanzapine and perphenazine both increase QTc interval. Use Caution/Monitor. - phendimetrazine
olanzapine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenelzine
phenelzine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- phenobarbital
phenobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
phenobarbital and olanzapine both increase sedation. Use Caution/Monitor. - phentermine
olanzapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenylephrine
olanzapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenylephrine PO
olanzapine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
- pholcodine
olanzapine and pholcodine both increase sedation. Use Caution/Monitor.
- pimozide
olanzapine and pimozide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and pimozide both increase sedation. Use Caution/Monitor. - pioglitazone
olanzapine, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- pipemidic acid
pipemidic acid will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- pirbuterol
olanzapine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- posaconazole
olanzapine and posaconazole both increase QTc interval. Use Caution/Monitor.
- pralidoxime
pralidoxime decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
pralidoxime decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - pramlintide
olanzapine, pramlintide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- pregabalin
pregabalin, samidorphan. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- primaquine
olanzapine and primaquine both increase QTc interval. Use Caution/Monitor.
- primidone
primidone will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
primidone and olanzapine both increase sedation. Use Caution/Monitor. - procarbazine
procarbazine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- prochlorperazine
olanzapine and prochlorperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and prochlorperazine both increase sedation. Use Caution/Monitor.
olanzapine and prochlorperazine both decrease QTc interval. Use Caution/Monitor. - promethazine
olanzapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
promethazine and olanzapine both increase sedation. Use Caution/Monitor.
promethazine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
olanzapine and promethazine both decrease QTc interval. Use Caution/Monitor. - propantheline
propantheline decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
propantheline decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - propofol
propofol and olanzapine both increase sedation. Use Caution/Monitor.
- propylhexedrine
olanzapine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- protriptyline
olanzapine and protriptyline both increase sedation. Use Caution/Monitor.
olanzapine and protriptyline both increase QTc interval. Use Caution/Monitor. - quazepam
quazepam and olanzapine both increase sedation. Use Caution/Monitor.
- quetiapine
olanzapine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and quetiapine both increase sedation. Use Caution/Monitor. - quinine
olanzapine and quinine both increase QTc interval. Use Caution/Monitor.
- quizartinib
quizartinib, olanzapine. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.
- ramelteon
olanzapine and ramelteon both increase sedation. Use Caution/Monitor.
- rapacuronium
rapacuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
rapacuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - remimazolam
remimazolam, samidorphan. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
remimazolam, olanzapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics. - repaglinide
olanzapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases effects of samidorphan by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.
- rifampin
rifampin will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- rilpivirine
olanzapine and rilpivirine both increase QTc interval. Use Caution/Monitor.
- rimabotulinumtoxinB
olanzapine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.
- risperidone
olanzapine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and risperidone both increase sedation. Use Caution/Monitor.
olanzapine and risperidone both increase QTc interval. Use Caution/Monitor. - ritlecitinib
ritlecitinib will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP1A2 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP1A2 substrates.
- ritonavir
ritonavir decreases levels of olanzapine by increasing metabolism. Use Caution/Monitor.
- rocuronium
rocuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
rocuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - romidepsin
olanzapine and romidepsin both increase QTc interval. Use Caution/Monitor.
- rosiglitazone
olanzapine, rosiglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- rucaparib
rucaparib will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.
- salmeterol
olanzapine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- saxagliptin
olanzapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- scopolamine
scopolamine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
scopolamine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - scullcap
olanzapine and scullcap both increase sedation. Use Caution/Monitor.
- secobarbital
secobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
secobarbital and olanzapine both increase sedation. Use Caution/Monitor. - selegiline
selegiline, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- selpercatinib
selpercatinib increases toxicity of olanzapine by QTc interval. Use Caution/Monitor.
- sertraline
olanzapine and sertraline both increase QTc interval. Use Caution/Monitor.
- shepherd's purse
olanzapine and shepherd's purse both increase sedation. Use Caution/Monitor.
- sitagliptin
olanzapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- smoking
smoking will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases effects of olanzapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases effects of samidorphan by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.
sodium sulfate/potassium sulfate/magnesium sulfate increases effects of olanzapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant. - solifenacin
solifenacin decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
solifenacin decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
olanzapine and solifenacin both increase QTc interval. Use Caution/Monitor. - somapacitan
somapacitan will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- somatrogon
somatrogon will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- somatropin
somatropin will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- sorafenib
sorafenib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- stiripentol
stiripentol, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.
stiripentol, olanzapine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. - sufentanil
sufentanil and olanzapine both increase sedation. Use Caution/Monitor.
- sumatriptan
sumatriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- sumatriptan intranasal
sumatriptan intranasal, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- sunitinib
olanzapine and sunitinib both increase QTc interval. Use Caution/Monitor.
- tacrolimus
olanzapine and tacrolimus both increase QTc interval. Use Caution/Monitor.
- talquetamab
talquetamab will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.
- tapentadol
tapentadol and olanzapine both increase sedation. Use Caution/Monitor.
- tazemetostat
olanzapine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- telavancin
olanzapine and telavancin both increase QTc interval. Use Caution/Monitor.
- temazepam
temazepam and olanzapine both increase sedation. Use Caution/Monitor.
- terbutaline
olanzapine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- teriflunomide
teriflunomide decreases levels of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- tetrabenazine
olanzapine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.
- thioridazine
olanzapine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and thioridazine both increase sedation. Use Caution/Monitor. - thiothixene
olanzapine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and thiothixene both increase sedation. Use Caution/Monitor. - tinidazole
olanzapine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tiotropium
tiotropium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
tiotropium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - tobacco use
tobacco use will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- tolazamide
olanzapine, tolazamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- tolbutamide
olanzapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- tolterodine
tolterodine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
tolterodine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - topiramate
olanzapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- tramadol
tramadol and olanzapine both increase sedation. Use Caution/Monitor.
- tranylcypromine
tranylcypromine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- trazodone
olanzapine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
triazolam and olanzapine both increase sedation. Use Caution/Monitor.
- triclabendazole
triclabendazole and olanzapine both increase QTc interval. Use Caution/Monitor.
- triclofos
triclofos and olanzapine both increase sedation. Use Caution/Monitor.
- trifluoperazine
olanzapine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and trifluoperazine both increase sedation. Use Caution/Monitor.
olanzapine and trifluoperazine both decrease QTc interval. Use Caution/Monitor. - trihexyphenidyl
olanzapine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.
- trimipramine
olanzapine and trimipramine both increase sedation. Use Caution/Monitor.
olanzapine and trimipramine both increase QTc interval. Use Caution/Monitor. - triprolidine
triprolidine and olanzapine both increase sedation. Use Caution/Monitor.
- trospium chloride
trospium chloride decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
trospium chloride decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - valbenazine
valbenazine and olanzapine both increase QTc interval. Use Caution/Monitor.
- vardenafil
olanzapine and vardenafil both increase QTc interval. Use Caution/Monitor.
- vecuronium
vecuronium decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vecuronium decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - venlafaxine
venlafaxine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
olanzapine and venlafaxine both decrease QTc interval. Use Caution/Monitor. - verapamil
verapamil will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- vilazodone
vilazodone, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- voclosporin
voclosporin, olanzapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.
- voriconazole
olanzapine and voriconazole both increase QTc interval. Use Caution/Monitor.
- vorinostat
olanzapine and vorinostat both increase QTc interval. Use Caution/Monitor.
- xylometazoline
olanzapine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- yohimbine
olanzapine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ziconotide
olanzapine and ziconotide both increase sedation. Use Caution/Monitor.
- zileuton
zileuton will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- ziprasidone
olanzapine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and ziprasidone both increase sedation. Use Caution/Monitor. - zolmitriptan
zolmitriptan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- zotepine
olanzapine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
olanzapine and zotepine both increase sedation. Use Caution/Monitor.
Minor (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.
- ruxolitinib
olanzapine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
olanzapine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
olanzapine and sage both increase sedation. Minor/Significance Unknown.
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)
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
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
- Monitors pregnancy outcomes in women exposed to atypical antipsychotics during pregnancy
- Encourage patients to register by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/
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
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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
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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
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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.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
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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%)
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
Images
Formulary
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