clozapine (Rx)

Schizophrenia

Indicated for reducing risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder in patients who are judged to be at chronic risk to re-experience suicidal behavior

Also indicated for treatment-resistant schizophrenia in patients who fail to respond adequately to standard antipsychotic treatment

12.5 mg PO once daily or q12hr initially; increase in increments of 25-50 mg/day, if well tolerated, to achieve target dosage of 300-450 mg/day (administered in divided doses) by end of 2 weeks

Subsequently, may increase dose once or twice weekly in increments of up to 100 mg; not to exceed 900 mg/day

Maintenance: Generally, patients who respond should continue maintenance treatment on their effective dose beyond the acute episode

Reinitiation of therapy

• If therapy interrupted for ≥48 hr, must reinitiate dose at 12.5 mg qDay or BID to minimize risk of hypotension, bradycardia, and syncope; if dose well tolerated, may increase more rapidly than with initial titration, unless cardiopulmonary arrest occurred during initial titration, then titrate with extreme caution

Discontinuation of therapy

• Method of treatment discontinuation depends on patient’s last ANC
• Reduce dose gradually over a period of 1-2 weeks if termination not related to neutropenia; taper gradually to avoid withdrawal symptoms and minimize risk of relapse; for schizophrenia, guidelines recommend gradual taper over 6-24 months (American Psychiatric Association guidelines recommend reducing dose 10% each month)
• For abrupt clozapine discontinuation for a reason unrelated to neutropenia, continue existing ANC monitoring until ANC is ≥1500/mm³
• If benign patient has benign ethnic neutropenia (BEN); monitor until ANC is ≥1000/mm³ or above baseline
• Additional ANC monitoring required for onset of fever during the 2 weeks after discontinuation
• Monitor all patients carefully for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound (eg, profuse sweating, headache, nausea, vomiting, diarrhea)

Dosage Modifications

Coadministration with CYP inhibitors

• Strong CYP1A2 inhibitors: Use one-third clozapine dose
• Moderate or weak CYP1A2 inhibitors: Monitor for adverse reactions; consider reducing clozapine dose if needed
• CYP2D6 or CYP3A4 inhibitors: Monitor for adverse reactions; consider reducing clozapine dose if needed
• CYP2D6 poor metabolizers: Clozapine dose reduction may be needed

Coadministration with CYP inducers

• Strong CYP3A4 inducers: Coadministration not recommended; if the inducer is necessary, clozapine dose may need to be increased
• Moderate or weak CYP1A2 or CYP3A4 inducers: Monitor for decreased effectiveness; consider increasing clozapine dose if necessary

Renal or hepatic impairment

• Dose reduction may be necessary with significant renal or hepatic impairment

Dosing Considerations

Required laboratory monitoring

• Before initiating, obtain CBC count with differential for baseline ANC; to continue treatment, ANC must be monitored regularly
• In order to initiate treatment, ANC must be ≥1500/mm³ for the general population and ≥1000/mm³ for patients with documented benign ethnic neutropenia

Safety and efficacy not established

Lower initial dosage of 12.5-25 mg/day indicated; may be titrated more slowly than in younger adults

Elderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to orthostatic hypotension and tachycardia; anticholinergic effects are also common (constipation, confusion, urinary retention)

Contraindicated (9)

• amisulpride

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

• dronedarone

  clozapine and dronedarone both increase QTc interval. Contraindicated.

• eliglustat

  clozapine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• irinotecan

  clozapine, irinotecan. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administraiton increases risk of agranulocytosis.
  
  irinotecan, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administration increases risk of agranulocytosis.

• irinotecan liposomal

  irinotecan liposomal, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administration increases risk of agranulocytosis.
  
  clozapine, irinotecan liposomal. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administraiton increases risk of agranulocytosis.

• nirmatrelvir

  nirmatrelvir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.

• saquinavir

  clozapine and saquinavir both increase QTc interval. Contraindicated.

• thioridazine

  clozapine and thioridazine both increase QTc interval. Contraindicated.

Serious - Use Alternative (130)

• abametapir

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

• adagrasib

  adagrasib, clozapine. 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

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

• amisulpride

  clozapine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• apomorphine

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

• aripiprazole

  aripiprazole and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• arsenic trioxide

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

• artemether

  artemether and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

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

• asenapine

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

• asenapine transdermal

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

• azithromycin

  clozapine and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, clozapine. 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

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

• buprenorphine

  clozapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  buprenorphine buccal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine transdermal

  buprenorphine transdermal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• bupropion

  clozapine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

• cabergoline

  clozapine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• calcium/magnesium/potassium/sodium oxybates

  clozapine, 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.

• carbamazepine

  carbamazepine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  carbamazepine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.

• ceritinib

  ceritinib and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• chlorpromazine

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

• cimetidine

  cimetidine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ciprofloxacin

  ciprofloxacin will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use caution when administering ciprofloxacin in patients receiving drugs that prolong the QT interval. At elevated serum concentrations, clozapine may produce clinically significant prolongation of the QTc interval.
  
  clozapine and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• cisapride

  clozapine and cisapride both increase QTc interval. Avoid or Use Alternate Drug.

• citalopram

  citalopram and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  clarithromycin will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clarithromycin and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• crizotinib

  clozapine and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

• dasatinib

  clozapine and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.

• deferiprone

  deferiprone, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

• desflurane

  desflurane and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• disopyramide

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

• dofetilide

  dofetilide increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug.

• dopamine

  clozapine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

• droperidol

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

• eliglustat

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

• encorafenib

  clozapine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

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

• eribulin

  clozapine and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin base

  erythromycin base will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• fedratinib

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

• flecainide

  clozapine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

• fluconazole

  clozapine and fluconazole both increase QTc interval. Contraindicated.

• fluvoxamine

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

• foscarnet

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

• givosiran

  givosiran will increase the level or effect of clozapine 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

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

• hydrocodone

  hydrocodone, clozapine. 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 clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  hydroxyzine increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.

• ibutilide

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

• iloperidone

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

• inotuzumab

  inotuzumab and clozapine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

• isoflurane

  clozapine and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• itraconazole

  itraconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  ivosidenib and clozapine 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.

• ketoconazole

  ketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lefamulin

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

• levodopa

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

• levodopa inhaled

  clozapine 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). .

• levoketoconazole

  levoketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lisuride

  clozapine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• lithium

  clozapine and lithium both increase QTc interval. Avoid or Use Alternate Drug.

• lofexidine

  clozapine and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

• loperamide

  clozapine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

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

• macimorelin

  macimorelin and clozapine 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

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

• methadone

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

• methimazole

  methimazole, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.

• methyldopa

  clozapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• metoclopramide intranasal

  clozapine, 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.
  
  clozapine 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.

• midostaurin

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

• mobocertinib

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

• moxifloxacin

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

• olanzapine

  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

• olopatadine intranasal

  clozapine 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

  clozapine 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

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

• paliperidone

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

• panobinostat

  clozapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

• pazopanib

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

• pefloxacin

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

• pentamidine

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

• pimavanserin

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

• pimozide

  clozapine and pimozide both increase QTc interval. Contraindicated.

• pitolisant

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

• ponesimod

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

• posaconazole

  clozapine and posaconazole both increase QTc interval. Contraindicated.

• pramipexole

  clozapine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• procainamide

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

• propafenone

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

• propylthiouracil

  propylthiouracil, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.

• quetiapine

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

• quinidine

  clozapine and quinidine both increase QTc interval. Contraindicated.

• ranolazine

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

• ribociclib

  ribociclib will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ribociclib increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

  rifabutin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  rifampin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• romidepsin

  clozapine and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b, clozapine. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.

• ropinirole

  clozapine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• safinamide

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

• saquinavir

  saquinavir increases levels of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. Increased risk of QT prolongation and cardiac arrhythmias.

• selinexor

  selinexor, clozapine. 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

  clozapine and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• siponimod

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

• sodium oxybate

  clozapine, 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

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

• St John's Wort

  St John's Wort will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sufentanil SL

  sufentanil SL, clozapine. 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

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

• thiothixene

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

• toremifene

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

• trazodone

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

• umeclidinium bromide/vilanterol inhaled

  clozapine 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

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

• vemurafenib

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

• vilanterol/fluticasone furoate inhaled

  clozapine 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.

• voriconazole

  clozapine and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

• vorinostat

  clozapine and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.

• zidovudine

  clozapine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of myelosuppression.

• ziprasidone

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

Monitor Closely (420)

• abobotulinumtoxinA

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

• acalabrutinib

  acalabrutinib, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.

• acarbose

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

• acrivastine

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

• albiglutide

  clozapine, 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

  clozapine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and clozapine both increase QTc interval. Use Caution/Monitor.

• alfentanil

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

• alfuzosin

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

• almotriptan

  almotriptan, clozapine. 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 clozapine both increase sedation. Use Caution/Monitor.

• amifampridine

  clozapine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amifostine

  amifostine, clozapine. 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

  clozapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• amobarbital

  amobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital and clozapine both increase sedation. Use Caution/Monitor.

• amoxapine

  clozapine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and amoxapine both increase sedation. Use Caution/Monitor.
  
  clozapine and amoxapine both increase QTc interval. Use Caution/Monitor.

• anagrelide

  clozapine and anagrelide both increase QTc interval. Use Caution/Monitor.

• anticholinergic/sedative combos

  anticholinergic/sedative combos decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  anticholinergic/sedative combos decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• apomorphine

  clozapine and apomorphine both increase sedation. Use Caution/Monitor.
  
  apomorphine and clozapine both increase QTc interval. Use Caution/Monitor.

• aprepitant

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

• arformoterol

  clozapine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and clozapine both increase QTc interval. Use Caution/Monitor.

• aripiprazole

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

• armodafinil

  armodafinil will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  armodafinil will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• artemether/lumefantrine

  artemether/lumefantrine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• asenapine

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

• asenapine transdermal

  asenapine transdermal and clozapine both increase sedation. Use Caution/Monitor.

• atazanavir

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

• atomoxetine

  atomoxetine and clozapine both increase QTc interval. Use Caution/Monitor.

• atracurium

  atracurium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atracurium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• atropine

  atropine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• atropine IV/IM

  clozapine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atropine IV/IM decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine IV/IM decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.

• azelastine

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

• baclofen

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

• bedaquiline

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

• belladonna alkaloids

  belladonna alkaloids decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• belladonna and opium

  belladonna and opium and clozapine both increase sedation. Use Caution/Monitor.
  
  belladonna and opium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna and opium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• benazepril

  clozapine increases toxicity of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.
  
  benazepril increases toxicity of clozapine by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

• benperidol

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

• benzphetamine

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

• benztropine

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

• bosentan

  bosentan will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexanolone

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

• brexpiprazole

  clozapine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• brompheniramine

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

• budesonide

  budesonide will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine, long-acting injection

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

• butabarbital

  butabarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butabarbital and clozapine both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and clozapine both increase sedation. Use Caution/Monitor.

• butorphanol

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

• caffeine

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

• captopril

  clozapine increases toxicity of captopril by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbamazepine

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

• carbinoxamine

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

• carisoprodol

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

• cenobamate

  cenobamate, clozapine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

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

• chlorpheniramine

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

• chlorpromazine

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

• chlorpropamide

  clozapine, 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 clozapine both increase sedation. Use Caution/Monitor.

• cigarette smoking

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

• cimetidine

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

• cinnarizine

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

• cisatracurium

  cisatracurium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cisatracurium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• citalopram

  citalopram increases effects of clozapine by pharmacodynamic synergism. Use Caution/Monitor. Increased risk for serotonin syndrome.

• clemastine

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

• clobazam

  clozapine, 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

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

• clonazepam

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

• clonidine

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

• clorazepate

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

• codeine

  codeine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• conivaptan

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

• cortisone

  cortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyclizine

  cyclizine and clozapine both increase sedation. Use Caution/Monitor.
  
  cyclizine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclizine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• cyclobenzaprine

  cyclobenzaprine and clozapine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• cyclosporine

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

• cyproheptadine

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

• dantrolene

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

• daridorexant

  clozapine 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 will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darifenacin decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  darifenacin decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• darunavir

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

• dasatinib

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

• deferasirox

  deferasirox increases levels of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• degarelix

  clozapine and degarelix both increase QTc interval. Use Caution/Monitor.

• desflurane

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

• desipramine

  clozapine and desipramine both increase sedation. Use Caution/Monitor.
  
  clozapine and desipramine both increase QTc interval. Use Caution/Monitor.

• deutetrabenazine

  clozapine 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.
  
  clozapine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  clozapine and deutetrabenazine 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).

• dexamethasone

  dexamethasone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextromethorphan

  dextromethorphan, clozapine. 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 clozapine both increase sedation. Use Caution/Monitor.

• DHEA, herbal

  DHEA, herbal will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diamorphine

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

• diazepam

  diazepam and clozapine both increase sedation. Use Caution/Monitor.
  
  diazepam, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Possible risk of cardiorespiratory collapse.

• dicyclomine

  dicyclomine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  dicyclomine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• dihydroergotamine

  dihydroergotamine, clozapine. 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).

• diltiazem

  diltiazem will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant treatment with clozapine and CYP2D6 or CYP3A4 inhibitors can increase clozapine levels and lead to adverse reactions. Use caution and monitor patients closely when using such inhibitors. Consider reducing clozapine dose.

• dimenhydrinate

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

• diphenhydramine

  diphenhydramine and clozapine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

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

• dolasetron

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

• donepezil

  donepezil and clozapine both increase QTc interval. Use Caution/Monitor.

• dopamine

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

• dopexamine

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

• dosulepin

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

• doxepin

  clozapine and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin and clozapine both increase QTc interval. Use Caution/Monitor.

• doxylamine

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

• dronedarone

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

• droperidol

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

• efavirenz

  efavirenz will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  efavirenz and clozapine both increase QTc interval. Use Caution/Monitor.

• eletriptan

  eletriptan, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• ephedrine

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

• epinephrine

  clozapine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.

• epinephrine racemic

  clozapine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.

• ergoloid mesylates

  ergoloid mesylates, clozapine. 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, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• erythromycin base

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

• erythromycin ethylsuccinate

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

• erythromycin lactobionate

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

• erythromycin stearate

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

• escitalopram

  escitalopram increases levels of clozapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  escitalopram increases toxicity of clozapine by QTc interval. Use Caution/Monitor.

• esketamine intranasal

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

• esomeprazole

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

• estazolam

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

• ethanol

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

• etomidate

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

• etravirine

  etravirine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• exenatide injectable solution

  clozapine, 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

  clozapine, 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

  clozapine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

• fentanyl

  fentanyl, clozapine. 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).

• fesoterodine

  fesoterodine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  fesoterodine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• fexinidazole

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

• fingolimod

  fingolimod and clozapine both increase QTc interval. Use Caution/Monitor.

• flavoxate

  flavoxate decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  flavoxate decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• flibanserin

  flibanserin, clozapine. 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

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

• fludrocortisone

  fludrocortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  fluoxetine increases levels of clozapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  clozapine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

• fluphenazine

  clozapine and fluphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  clozapine and fluphenazine both increase QTc interval. Use Caution/Monitor.

• flurazepam

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

• fluvoxamine

  fluvoxamine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• formoterol

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

• fosamprenavir

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

• fosaprepitant

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

• fosphenytoin

  fosphenytoin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fostemsavir

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

• frovatriptan

  frovatriptan, clozapine. 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).

• gadobenate

  clozapine and gadobenate both increase QTc interval. Use Caution/Monitor.

• ganaxolone

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

• gemifloxacin

  clozapine and gemifloxacin both increase QTc interval. Use Caution/Monitor.

• gemtuzumab

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

• gilteritinib

  clozapine and gilteritinib both increase QTc interval. Use Caution/Monitor.

• glimepiride

  clozapine, 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

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

• glyburide

  clozapine, 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

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

• glycopyrrolate inhaled

  glycopyrrolate inhaled decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  glycopyrrolate inhaled decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• goserelin

  goserelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• granisetron

  clozapine and granisetron both increase QTc interval. Use Caution/Monitor.

• grapefruit

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

• green tea

  green tea decreases effects of clozapine by Other (see comment). Use Caution/Monitor. Comment: (Theoretical, due to caffeine content) High caffeine doses (400 1000mg/day) may increase levels/toxicity of clozapine. Clozapine clearance may decrease during coadministration of caffeine, and a documented increase in clozapine serum concentrations has occurred in selected patients. .

• griseofulvin

  griseofulvin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• guanfacine

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

• haloperidol

  clozapine and haloperidol both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and haloperidol both increase sedation. Use Caution/Monitor.
  
  haloperidol and clozapine both increase QTc interval. Use Caution/Monitor.

• henbane

  henbane decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  henbane decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• histrelin

  histrelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• homatropine

  homatropine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  homatropine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hydrocortisone

  hydrocortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydromorphone

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

• hydroxyurea

  clozapine, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Avoid combination. Combination may increase risk of myelosuppression.

• hydroxyzine

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

• hyoscyamine

  hyoscyamine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hyoscyamine spray

  clozapine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  hyoscyamine spray decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.

• ifosfamide

  ifosfamide, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Ifosfamide may enhance the toxicities of myelosuppressive agents. Monitor for increased risk of myelosuppression.

• iloperidone

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

• imipramine

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

• incobotulinumtoxinA

  clozapine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indacaterol, inhaled

  clozapine and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.

• indinavir

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

• insulin aspart

  clozapine, 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

  clozapine 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

  clozapine 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

  clozapine, 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

  clozapine, 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

  clozapine, 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

  clozapine 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

  clozapine, 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

  clozapine, 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

  clozapine, 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 clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ipratropium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• isoniazid

  isoniazid will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  isoniazid will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isoproterenol

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

• isradipine

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

• ketamine

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

• ketotifen, ophthalmic

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

• lapatinib

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

• lasmiditan

  lasmiditan, clozapine. 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, clozapine. 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.

• lenvatinib

  clozapine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.

• letermovir

  letermovir increases levels of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• leuprolide

  leuprolide increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• levalbuterol

  clozapine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine and levalbuterol both increase QTc interval. Use Caution/Monitor.

• levofloxacin

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

• levomilnacipran

  levomilnacipran, clozapine. 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 clozapine both increase sedation. Use Caution/Monitor.

• linezolid

  linezolid, clozapine. 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

  clozapine, 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

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

• lithium

  lithium, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• lofepramine

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

• lofexidine

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

• lomustine

  lomustine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Monitor for neutropenia when taking clozapine and another myelosuppressive agent.

• loprazolam

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

• lorazepam

  lorazepam and clozapine both increase sedation. Use Caution/Monitor.
  
  lorazepam, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Possible risk of cardiorespiratory collapse.

• lorcaserin

  lorcaserin, clozapine. 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 clozapine both increase sedation. Use Caution/Monitor.

• loxapine

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

• loxapine inhaled

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

• lumateperone

  clozapine and lumateperone both increase sedation. Use Caution/Monitor. Concomitant use of clozapine and lumaterperone may exacerbate such effects as somnolence, postural hypotension, and motor/sensory instability; complete fall risk assessment when initiating treatment and periodically during long-term use.
  
  clozapine and lumateperone both increase pharmacodynamic synergism. Use Caution/Monitor. Concomitant use of clozapine and lumaterperone may exacerbate such effects as somnolence, postural hypotension, and motor/sensory instability; complete fall risk assessment when initiating treatment and periodically during long-term use.

• lumefantrine

  lumefantrine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

  lurasidone, clozapine. 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

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

• marijuana

  marijuana will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine and marijuana both increase sedation. Use Caution/Monitor.

• mavacamten

  clozapine 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.

• mechlorethamine

  mechlorethamine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Mechlorethamine may enhance the toxicities of myelosuppressive agents. Monitor for increased risk of myelosuppression.

• meclizine

  meclizine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  meclizine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• mefloquine

  clozapine and mefloquine both increase QTc interval. Use Caution/Monitor.

• melatonin

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

• meperidine

  meperidine and clozapine both increase sedation. Use Caution/Monitor.
  
  meperidine, clozapine. 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

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

• metaproterenol

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

• metaxalone

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

• metformin

  clozapine, 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 clozapine both increase sedation. Use Caution/Monitor.
  
  methadone, clozapine. 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

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

• methocarbamol

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

• methscopolamine

  methscopolamine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  methscopolamine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• methylenedioxymethamphetamine

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

• methylergonovine

  methylergonovine, clozapine. 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

  clozapine 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.

• methylprednisolone

  methylprednisolone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metoclopramide

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

• metronidazole

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

• mexiletine

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

• miconazole vaginal

  miconazole vaginal will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• midazolam

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

• midazolam intranasal

  midazolam intranasal, clozapine. Either increases effects 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

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

• mifepristone

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

• miglitol

  clozapine, 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, clozapine. 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

  clozapine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  clozapine and mirtazapine both increase QTc interval. Use Caution/Monitor.

• modafinil

  modafinil will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  clozapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

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

• motherwort

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

  naratriptan, clozapine. 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

  clozapine, 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.

• nefazodone

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

• nelfinavir

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

• nevirapine

  nevirapine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

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

• nilotinib

  nilotinib will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine and nilotinib both increase QTc interval. Use Caution/Monitor.

• norepinephrine

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

• nortriptyline

  clozapine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• octreotide

  clozapine and octreotide both increase QTc interval. Use Caution/Monitor.

• ofloxacin

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

• olanzapine

  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.

• oliceridine

  clozapine will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
  
  oliceridine, clozapine. 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.

• olodaterol inhaled

  clozapine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.

• omeprazole

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

• onabotulinumtoxinA

  onabotulinumtoxinA decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  onabotulinumtoxinA decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• opium tincture

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

• orphenadrine

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

• osilodrostat

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

• osimertinib

  osimertinib and clozapine 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 and clozapine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Use of oxaliplatin with concomitant immunosuppressants or with impaired immune systems may increased risk for serious infections.
  
  oxaliplatin will increase the level or effect of clozapine 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 clozapine both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxybutynin

  oxybutynin decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oxybutynin topical

  oxybutynin topical decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin topical decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oxybutynin transdermal

  oxybutynin transdermal decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin transdermal decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oxycodone

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

• oxymorphone

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

• ozanimod

  ozanimod and clozapine 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

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

• pancuronium

  pancuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pancuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• papaveretum

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

• papaverine

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

• paroxetine

  paroxetine increases levels of clozapine by decreasing metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  paroxetine, clozapine. 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

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

• peginterferon alfa 2a

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

• pentazocine

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

• pentobarbital

  pentobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  pentobarbital and clozapine both increase sedation. Use Caution/Monitor.

• perphenazine

  clozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and perphenazine both increase sedation. Use Caution/Monitor.
  
  clozapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• phendimetrazine

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

• phenelzine

  phenelzine, clozapine. 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 clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and clozapine both increase sedation. Use Caution/Monitor.

• phentermine

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

• phenylephrine

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

• phenylephrine PO

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

• phenytoin

  phenytoin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When adding phenytoin therapy to patients stabilized on clozapine, monitor patient closely for worsening of psychotic symptoms. If needed, increase the clozapine dose cautiously on basis of psychotic symptoms. Conversely, when phenytoin is discontinued, levels of clozapine may significantly increase.

• pholcodine

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

• pimozide

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

• pioglitazone

  clozapine, 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 clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• pirbuterol

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

• posaconazole

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

• pralidoxime

  pralidoxime decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pralidoxime decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• prednisone

  prednisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primaquine

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

• primidone

  primidone will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  primidone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  primidone and clozapine both increase sedation. Use Caution/Monitor.

• procarbazine

  procarbazine, clozapine. 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

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

• promethazine

  clozapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and clozapine both increase sedation. Use Caution/Monitor.
  
  promethazine, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• propantheline

  propantheline decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  propantheline decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• propofol

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

• propylhexedrine

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

• protriptyline

  clozapine and protriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and protriptyline both increase QTc interval. Use Caution/Monitor.

• quazepam

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

• quetiapine

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

• quinine

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

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ramelteon

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

• rapacuronium

  rapacuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rapacuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• remimazolam

  remimazolam, clozapine. 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

  clozapine, 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.

• rifampin

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

• rifapentine

  rifapentine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

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

• rimabotulinumtoxinB

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

• risperidone

  clozapine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and risperidone both increase sedation. Use Caution/Monitor.
  
  clozapine and risperidone both increase QTc interval. Use Caution/Monitor.

• ritonavir

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

• rocuronium

  rocuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rocuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• rucaparib

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

• rufinamide

  rufinamide will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• salmeterol

  clozapine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine and salmeterol both increase QTc interval. Use Caution/Monitor.

• saxagliptin

  clozapine, 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 clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  scopolamine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• scullcap

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

• secobarbital

  secobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  secobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  secobarbital and clozapine both increase sedation. Use Caution/Monitor.

• selegiline

  selegiline, clozapine. 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 clozapine by QTc interval. Use Caution/Monitor.

• sertraline

  sertraline increases levels of clozapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  clozapine and sertraline both increase QTc interval. Use Caution/Monitor.

• sevoflurane

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

• shepherd's purse

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

• sitagliptin

  clozapine, 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 clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases effects of clozapine 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 clozapine 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 clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  solifenacin decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  clozapine and solifenacin both increase QTc interval. Use Caution/Monitor.

• sorafenib

  sorafenib and clozapine both increase QTc interval. Use Caution/Monitor.

• stiripentol

  stiripentol, clozapine. 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.

• sufentanil

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

• sulfamethoxypyridazine

  sulfamethoxypyridazine increases toxicity of clozapine by unspecified interaction mechanism. Use Caution/Monitor. Possibly increased neutropenic effects.

• sumatriptan

  sumatriptan, clozapine. 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, clozapine. 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

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

• suvorexant

  clozapine will increase the level or effect of suvorexant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

• tacrolimus

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

• tamsulosin

  clozapine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tapentadol

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

• telavancin

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

• temazepam

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

• terbutaline

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

• teriflunomide

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

• tetrabenazine

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

• thioridazine

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

• thiothixene

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

• tiotropium

  tiotropium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tiotropium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine 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 clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tolazamide

  clozapine, 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

  clozapine, 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 clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tolterodine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• topiramate

  topiramate will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

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

• tranylcypromine

  tranylcypromine, clozapine. 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

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

• triazolam

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

• triclabendazole

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

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimipramine

  clozapine and trimipramine both increase sedation. Use Caution/Monitor.
  
  clozapine and trimipramine both increase QTc interval. Use Caution/Monitor.

• triprolidine

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

• triptorelin

  triptorelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• trospium chloride

  trospium chloride decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  trospium chloride decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• valbenazine

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

• vardenafil

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

• vecuronium

  vecuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  vecuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• venlafaxine

  venlafaxine, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• verapamil

  verapamil will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  verapamil will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilazodone

  vilazodone, clozapine. 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, clozapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

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

• xylometazoline

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

• yohimbine

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

• zafirlukast

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

• ziconotide

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

• zileuton

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

• ziprasidone

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

• zolmitriptan

  zolmitriptan, clozapine. 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

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

Minor (9)

• azithromycin

  azithromycin increases toxicity of clozapine by unspecified interaction mechanism. Minor/Significance Unknown. Enhanced CNS toxicity.

• brimonidine

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

• chasteberry

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

• cilostazol

  clozapine increases levels of cilostazol by decreasing metabolism. Minor/Significance Unknown.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ethanol

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

• eucalyptus

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

• sage

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

• valproic acid

  valproic acid decreases levels of clozapine by plasma protein binding competition. Minor/Significance Unknown.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

• abobotulinumtoxinA

  Monitor Closely (1)abobotulinumtoxinA increases effects of clozapine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• acalabrutinib

  Monitor Closely (1)acalabrutinib, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.

• acarbose

  Monitor Closely (1)acarbose, clozapine. 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

  Monitor Closely (2)aclidinium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• acrivastine

  Monitor Closely (1)acrivastine and clozapine both increase sedation. Use Caution/Monitor.

• adagrasib

  Serious - Use Alternative (1)adagrasib, clozapine. 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.

• albiglutide

  Monitor Closely (1)clozapine, 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

  Monitor Closely (2)clozapine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and clozapine both increase QTc interval. Use Caution/Monitor.

• alfentanil

  Monitor Closely (1)alfentanil and clozapine both increase sedation. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (2)clozapine and alfuzosin both increase QTc interval. Use Caution/Monitor.
  
  alfuzosin and clozapine both increase QTc interval. Use Caution/Monitor.

• almotriptan

  Monitor Closely (1)almotriptan, clozapine. 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

  Monitor Closely (1)alprazolam and clozapine both increase sedation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)clozapine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amifostine

  Monitor Closely (1)amifostine, clozapine. 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.

• amiodarone

  Serious - Use Alternative (1)clozapine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  Contraindicated (1)amisulpride, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndromeIncreases risk of neuroleptic malignant syndrome.Serious - Use Alternative (1)clozapine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amitriptyline

  Monitor Closely (2)clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  Monitor Closely (3)amobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital and clozapine both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (3)clozapine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and amoxapine both increase sedation. Use Caution/Monitor.
  
  clozapine and amoxapine both increase QTc interval. Use Caution/Monitor.

• anagrelide

  Monitor Closely (1)clozapine and anagrelide both increase QTc interval. Use Caution/Monitor.

• anticholinergic/sedative combos

  Monitor Closely (3)anticholinergic/sedative combos decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  anticholinergic/sedative combos decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• apomorphine

  Monitor Closely (2)clozapine and apomorphine both increase sedation. Use Caution/Monitor.
  
  apomorphine and clozapine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)clozapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  Monitor Closely (2)clozapine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and clozapine both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  Monitor Closely (2)aripiprazole and clozapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  aripiprazole and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)aripiprazole and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• armodafinil

  Monitor Closely (3)armodafinil will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  armodafinil will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• arsenic trioxide

  Serious - Use Alternative (1)clozapine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Serious - Use Alternative (1)artemether and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• asenapine

  Monitor Closely (1)asenapine and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine transdermal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• atazanavir

  Monitor Closely (1)atazanavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atomoxetine

  Monitor Closely (1)atomoxetine and clozapine both increase QTc interval. Use Caution/Monitor.

• atracurium

  Monitor Closely (3)atracurium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atracurium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• atropine

  Monitor Closely (3)atropine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• atropine IV/IM

  Monitor Closely (3)clozapine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atropine IV/IM decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine IV/IM decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.

• azelastine

  Monitor Closely (1)azelastine and clozapine both increase sedation. Use Caution/Monitor.

• azithromycin

  Serious - Use Alternative (1)clozapine and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)azithromycin increases toxicity of clozapine by unspecified interaction mechanism. Minor/Significance Unknown. Enhanced CNS toxicity.

• baclofen

  Monitor Closely (1)baclofen and clozapine both increase sedation. Use Caution/Monitor.

• bedaquiline

  Monitor Closely (1)clozapine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

  Monitor Closely (3)belladonna alkaloids decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• belladonna and opium

  Monitor Closely (4)belladonna and opium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna and opium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna and opium and clozapine both increase sedation. Use Caution/Monitor.

• benazepril

  Monitor Closely (2)clozapine increases toxicity of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.
  
  benazepril increases toxicity of clozapine by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

• benperidol

  Monitor Closely (2)benperidol and clozapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  benperidol and clozapine both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (1)benzhydrocodone/acetaminophen, clozapine. 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.

• benzphetamine

  Monitor Closely (1)clozapine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benztropine

  Monitor Closely (1)clozapine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexanolone

  Monitor Closely (1)brexanolone, clozapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (1)clozapine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• brimonidine

  Minor (1)brimonidine increases effects of clozapine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• bromocriptine

  Serious - Use Alternative (1)clozapine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• brompheniramine

  Monitor Closely (1)brompheniramine and clozapine both increase sedation. Use Caution/Monitor.

• budesonide

  Monitor Closely (1)budesonide will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (1)buprenorphine and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  Monitor Closely (1)buprenorphine buccal and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine transdermal

  Serious - Use Alternative (1)buprenorphine transdermal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  Monitor Closely (1)clozapine 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.Serious - Use Alternative (1)buprenorphine, long-acting injection and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• bupropion

  Serious - Use Alternative (1)clozapine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

• butabarbital

  Monitor Closely (3)butabarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butabarbital and clozapine both increase sedation. Use Caution/Monitor.

• butalbital

  Monitor Closely (3)butalbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and clozapine both increase sedation. Use Caution/Monitor.

• butorphanol

  Monitor Closely (1)butorphanol and clozapine both increase sedation. Use Caution/Monitor.

• cabergoline

  Serious - Use Alternative (1)clozapine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• caffeine

  Monitor Closely (1)clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)clozapine, 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.

• captopril

  Monitor Closely (1)clozapine increases toxicity of captopril by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)carbamazepine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  carbamazepine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and clozapine both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)carisoprodol and clozapine both increase sedation. Use Caution/Monitor.

• cenobamate

  Monitor Closely (1)cenobamate, clozapine. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  Serious - Use Alternative (1)ceritinib and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• chasteberry

  Minor (1)chasteberry decreases effects of clozapine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

• chloral hydrate

  Monitor Closely (1)chloral hydrate and clozapine both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and clozapine both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine increases toxicity of clozapine by QTc interval. Use Caution/Monitor.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and clozapine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (2)chlorpromazine and clozapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  chlorpromazine and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

• chlorpropamide

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)chlorzoxazone and clozapine both increase sedation. Use Caution/Monitor.

• cigarette smoking

  Monitor Closely (1)cigarette smoking will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• cilostazol

  Minor (1)clozapine increases levels of cilostazol by decreasing metabolism. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)cimetidine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cinnarizine

  Monitor Closely (1)cinnarizine and clozapine both increase sedation. Use Caution/Monitor.

• ciprofloxacin

  Serious - Use Alternative (2)ciprofloxacin will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use caution when administering ciprofloxacin in patients receiving drugs that prolong the QT interval. At elevated serum concentrations, clozapine may produce clinically significant prolongation of the QTc interval.
  
  clozapine and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• cisapride

  Serious - Use Alternative (1)clozapine and cisapride both increase QTc interval. Avoid or Use Alternate Drug.

• cisatracurium

  Monitor Closely (3)cisatracurium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cisatracurium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• citalopram

  Monitor Closely (1)citalopram increases effects of clozapine by pharmacodynamic synergism. Use Caution/Monitor. Increased risk for serotonin syndrome.Serious - Use Alternative (1)citalopram and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  Serious - Use Alternative (2)clarithromycin will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clarithromycin and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• clemastine

  Monitor Closely (1)clemastine and clozapine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

  Monitor Closely (1)clonazepam and clozapine both increase sedation. Use Caution/Monitor.

• clonidine

  Monitor Closely (1)clonidine, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• clorazepate

  Monitor Closely (1)clorazepate and clozapine both increase sedation. Use Caution/Monitor.

• codeine

  Monitor Closely (2)codeine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cortisone

  Monitor Closely (1)cortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crizotinib

  Serious - Use Alternative (1)clozapine and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

• cyclizine

  Monitor Closely (4)cyclizine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclizine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclizine and clozapine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (4)cyclobenzaprine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclobenzaprine and clozapine both increase sedation. Use Caution/Monitor.

• cyclosporine

  Monitor Closely (1)cyclosporine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and clozapine both increase sedation. Use Caution/Monitor.

• dantrolene

  Monitor Closely (1)dantrolene and clozapine both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)clozapine 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

  Monitor Closely (4)darifenacin will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darifenacin decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  darifenacin decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dasatinib

  Monitor Closely (1)dasatinib will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.

• deferasirox

  Monitor Closely (1)deferasirox increases levels of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• deferiprone

  Serious - Use Alternative (1)deferiprone, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

• degarelix

  Monitor Closely (1)clozapine and degarelix both increase QTc interval. Use Caution/Monitor.

• desflurane

  Monitor Closely (1)desflurane and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)desflurane and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• desipramine

  Monitor Closely (2)clozapine and desipramine both increase sedation. Use Caution/Monitor.
  
  clozapine and desipramine both increase QTc interval. Use Caution/Monitor.

• deutetrabenazine

  Monitor Closely (3)clozapine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  clozapine and deutetrabenazine 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).
  
  clozapine 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.

• dexamethasone

  Monitor Closely (1)dexamethasone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and clozapine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (1)clozapine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine and clozapine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)clozapine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (1)clozapine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextromethorphan

  Monitor Closely (1)dextromethorphan, clozapine. 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

  Monitor Closely (1)dextromoramide and clozapine both increase sedation. Use Caution/Monitor.

• DHEA, herbal

  Monitor Closely (1)DHEA, herbal will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)diamorphine and clozapine both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)diazepam, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Possible risk of cardiorespiratory collapse.
  
  diazepam and clozapine both increase sedation. Use Caution/Monitor.

• dicyclomine

  Monitor Closely (3)dicyclomine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  dicyclomine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• diethylpropion

  Monitor Closely (1)clozapine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (1)difelikefalin and clozapine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)difenoxin hcl and clozapine both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)dihydroergotamine, clozapine. 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).

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant treatment with clozapine and CYP2D6 or CYP3A4 inhibitors can increase clozapine levels and lead to adverse reactions. Use caution and monitor patients closely when using such inhibitors. Consider reducing clozapine dose.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and clozapine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (4)diphenhydramine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and clozapine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (1)diphenoxylate hcl and clozapine both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)dipipanone and clozapine both increase sedation. Use Caution/Monitor.

• disopyramide

  Serious - Use Alternative (1)clozapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• dobutamine

  Monitor Closely (1)clozapine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dofetilide

  Serious - Use Alternative (1)dofetilide increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (1)clozapine and dolasetron both increase QTc interval. Use Caution/Monitor.

• donepezil

  Monitor Closely (1)donepezil and clozapine both increase QTc interval. Use Caution/Monitor.

• dopamine

  Monitor Closely (1)clozapine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)clozapine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

• dopexamine

  Monitor Closely (1)clozapine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  Monitor Closely (1)clozapine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  Monitor Closely (2)clozapine and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin and clozapine both increase QTc interval. Use Caution/Monitor.

• doxylamine

  Monitor Closely (1)doxylamine and clozapine both increase sedation. Use Caution/Monitor.

• dronedarone

  Contraindicated (1)clozapine and dronedarone both increase QTc interval. Contraindicated.Monitor Closely (1)dronedarone will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• droperidol

  Monitor Closely (2)clozapine and droperidol both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and droperidol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• efavirenz

  Monitor Closely (2)efavirenz will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  efavirenz and clozapine both increase QTc interval. Use Caution/Monitor.

• eletriptan

  Monitor Closely (1)eletriptan, clozapine. 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).

• eliglustat

  Contraindicated (1)clozapine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.Serious - Use Alternative (1)clozapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

• encorafenib

  Serious - Use Alternative (1)clozapine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Serious - Use Alternative (1)clozapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• ephedrine

  Monitor Closely (1)clozapine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (2)clozapine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
  
  clozapine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (2)clozapine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
  
  clozapine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ergoloid mesylates

  Monitor Closely (1)ergoloid mesylates, clozapine. 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

  Monitor Closely (1)ergotamine, clozapine. 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).

• eribulin

  Serious - Use Alternative (1)clozapine and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)erythromycin base will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)erythromycin ethylsuccinate will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)erythromycin lactobionate will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)erythromycin stearate will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (2)escitalopram increases levels of clozapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  escitalopram increases toxicity of clozapine by QTc interval. Use Caution/Monitor.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, clozapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Minor (1)eslicarbazepine acetate will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  Monitor Closely (1)esomeprazole will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• estazolam

  Monitor Closely (1)estazolam and clozapine both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (1)clozapine and ethanol both increase sedation. Use Caution/Monitor.Minor (1)ethanol, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• etomidate

  Monitor Closely (1)etomidate and clozapine both increase sedation. Use Caution/Monitor.

• etravirine

  Monitor Closely (1)etravirine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eucalyptus

  Minor (1)clozapine and eucalyptus both increase sedation. Minor/Significance Unknown.

• exenatide injectable solution

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, 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.

• fedratinib

  Serious - Use Alternative (1)clozapine 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.

• fenfluramine

  Monitor Closely (2)clozapine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.
  
  clozapine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fentanyl

  Monitor Closely (1)fentanyl, clozapine. 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).

• fesoterodine

  Monitor Closely (3)fesoterodine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  fesoterodine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)fexinidazole and clozapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

• fingolimod

  Monitor Closely (1)fingolimod and clozapine both increase QTc interval. Use Caution/Monitor.

• flavoxate

  Monitor Closely (3)flavoxate decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  flavoxate decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• flecainide

  Serious - Use Alternative (1)clozapine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

• flibanserin

  Monitor Closely (1)flibanserin, clozapine. 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

  Monitor Closely (1)fluconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and fluconazole both increase QTc interval. Contraindicated.

• fludrocortisone

  Monitor Closely (1)fludrocortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  Monitor Closely (2)fluoxetine increases levels of clozapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  clozapine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

• fluphenazine

  Monitor Closely (3)clozapine and fluphenazine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and fluphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (1)flurazepam and clozapine both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (1)clozapine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fosamprenavir

  Monitor Closely (1)fosamprenavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• foscarnet

  Serious - Use Alternative (1)clozapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

• fosphenytoin

  Monitor Closely (1)fosphenytoin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fostemsavir

  Monitor Closely (1)clozapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  Monitor Closely (1)frovatriptan, clozapine. 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).

• gadobenate

  Monitor Closely (1)clozapine and gadobenate both increase QTc interval. Use Caution/Monitor.

• ganaxolone

  Monitor Closely (1)clozapine and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)clozapine and gemifloxacin both increase QTc interval. Use Caution/Monitor.

• gemtuzumab

  Monitor Closely (1)clozapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.

• gilteritinib

  Monitor Closely (1)clozapine and gilteritinib both increase QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of clozapine 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

  Serious - Use Alternative (1)clozapine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

• glimepiride

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, glipizide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• glyburide

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• glycopyrrolate inhaled

  Monitor Closely (3)glycopyrrolate inhaled decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  glycopyrrolate inhaled decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• goserelin

  Monitor Closely (1)goserelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• granisetron

  Monitor Closely (1)clozapine and granisetron both increase QTc interval. Use Caution/Monitor.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• green tea

  Monitor Closely (1)green tea decreases effects of clozapine by Other (see comment). Use Caution/Monitor. Comment: (Theoretical, due to caffeine content) High caffeine doses (400 1000mg/day) may increase levels/toxicity of clozapine. Clozapine clearance may decrease during coadministration of caffeine, and a documented increase in clozapine serum concentrations has occurred in selected patients. .

• griseofulvin

  Monitor Closely (1)griseofulvin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• guanfacine

  Monitor Closely (1)guanfacine, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• haloperidol

  Monitor Closely (3)clozapine and haloperidol both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and haloperidol both increase sedation. Use Caution/Monitor.
  
  haloperidol and clozapine both increase QTc interval. Use Caution/Monitor.

• henbane

  Monitor Closely (3)henbane decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  henbane decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• histrelin

  Monitor Closely (1)histrelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• homatropine

  Monitor Closely (3)homatropine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  homatropine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hydrocodone

  Serious - Use Alternative (1)hydrocodone, clozapine. 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.

• hydrocortisone

  Monitor Closely (1)hydrocortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydromorphone

  Monitor Closely (1)hydromorphone and clozapine both increase sedation. Use Caution/Monitor.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyurea

  Monitor Closely (1)clozapine, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Avoid combination. Combination may increase risk of myelosuppression.

• hydroxyzine

  Monitor Closely (1)hydroxyzine and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)hydroxyzine increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.

• hyoscyamine

  Monitor Closely (3)hyoscyamine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hyoscyamine spray

  Monitor Closely (3)clozapine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  hyoscyamine spray decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.

• ibutilide

  Serious - Use Alternative (1)clozapine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

• ifosfamide

  Monitor Closely (1)ifosfamide, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Ifosfamide may enhance the toxicities of myelosuppressive agents. Monitor for increased risk of myelosuppression.

• iloperidone

  Monitor Closely (2)clozapine and iloperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and iloperidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

• imipramine

  Monitor Closely (1)clozapine and imipramine both increase sedation. Use Caution/Monitor.

• incobotulinumtoxinA

  Monitor Closely (1)clozapine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indacaterol, inhaled

  Monitor Closely (1)clozapine and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• inotuzumab

  Serious - Use Alternative (1)inotuzumab and clozapine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

• insulin aspart

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine 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

  Monitor Closely (1)clozapine 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (3)ipratropium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ipratropium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• irinotecan

  Contraindicated (2)clozapine, irinotecan. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administraiton increases risk of agranulocytosis.
  
  irinotecan, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administration increases risk of agranulocytosis.

• irinotecan liposomal

  Contraindicated (2)irinotecan liposomal, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administration increases risk of agranulocytosis.
  
  clozapine, irinotecan liposomal. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administraiton increases risk of agranulocytosis.

• isoflurane

  Serious - Use Alternative (1)clozapine and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• isoniazid

  Monitor Closely (2)isoniazid will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  isoniazid will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isoproterenol

  Monitor Closely (1)clozapine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• isradipine

  Monitor Closely (1)clozapine and isradipine both increase QTc interval. Use Caution/Monitor.

• itraconazole

  Serious - Use Alternative (2)itraconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clozapine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib and clozapine 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.

• ketamine

  Monitor Closely (1)ketamine and clozapine both increase sedation. Use Caution/Monitor.

• ketoconazole

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (1)clozapine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lapatinib

  Monitor Closely (1)clozapine and lapatinib both increase QTc interval. Use Caution/Monitor.

• lasmiditan

  Monitor Closely (1)lasmiditan, clozapine. 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.

• lefamulin

  Serious - Use Alternative (1)lefamulin and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• lemborexant

  Monitor Closely (1)lemborexant, clozapine. 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.

• lenvatinib

  Monitor Closely (1)clozapine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.

• letermovir

  Monitor Closely (1)letermovir increases levels of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• leuprolide

  Monitor Closely (1)leuprolide increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• levalbuterol

  Monitor Closely (2)clozapine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine and levalbuterol both increase QTc interval. Use Caution/Monitor.

• levodopa

  Serious - Use Alternative (1)clozapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• levodopa inhaled

  Serious - Use Alternative (1)clozapine 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). .

• levofloxacin

  Monitor Closely (1)clozapine and levofloxacin both increase QTc interval. Use Caution/Monitor.

• levoketoconazole

  Serious - Use Alternative (1)levoketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, clozapine. 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

  Monitor Closely (1)levorphanol and clozapine both increase sedation. Use Caution/Monitor.

• linezolid

  Monitor Closely (1)linezolid, clozapine. 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lisuride

  Serious - Use Alternative (1)clozapine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• lithium

  Monitor Closely (1)lithium, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)clozapine and lithium both increase QTc interval. Avoid or Use Alternate Drug.

• lofepramine

  Monitor Closely (1)clozapine and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  Monitor Closely (1)clozapine and lofexidine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

• lomustine

  Monitor Closely (1)lomustine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Monitor for neutropenia when taking clozapine and another myelosuppressive agent.

• loperamide

  Serious - Use Alternative (1)clozapine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

  Serious - Use Alternative (1)clozapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

• loprazolam

  Monitor Closely (1)loprazolam and clozapine both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (2)lorazepam, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Possible risk of cardiorespiratory collapse.
  
  lorazepam and clozapine both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin, clozapine. 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

  Monitor Closely (1)lormetazepam and clozapine both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (2)clozapine and loxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (2)clozapine and loxapine inhaled both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumateperone

  Monitor Closely (2)clozapine and lumateperone both increase sedation. Use Caution/Monitor. Concomitant use of clozapine and lumaterperone may exacerbate such effects as somnolence, postural hypotension, and motor/sensory instability; complete fall risk assessment when initiating treatment and periodically during long-term use.
  
  clozapine and lumateperone both increase pharmacodynamic synergism. Use Caution/Monitor. Concomitant use of clozapine and lumaterperone may exacerbate such effects as somnolence, postural hypotension, and motor/sensory instability; complete fall risk assessment when initiating treatment and periodically during long-term use.

• lumefantrine

  Monitor Closely (1)lumefantrine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)lurasidone, clozapine. 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.

• macimorelin

  Serious - Use Alternative (1)macimorelin and clozapine 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

  Monitor Closely (1)clozapine and maprotiline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

• marijuana

  Monitor Closely (2)marijuana will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine and marijuana both increase sedation. Use Caution/Monitor.

• mavacamten

  Monitor Closely (1)clozapine 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.

• mechlorethamine

  Monitor Closely (1)mechlorethamine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Mechlorethamine may enhance the toxicities of myelosuppressive agents. Monitor for increased risk of myelosuppression.

• meclizine

  Monitor Closely (3)meclizine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  meclizine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• mefloquine

  Monitor Closely (1)clozapine and mefloquine both increase QTc interval. Use Caution/Monitor.

• melatonin

  Monitor Closely (1)clozapine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (2)meperidine, clozapine. 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).
  
  meperidine and clozapine both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (1)clozapine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (1)clozapine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)metaxalone and clozapine both increase sedation. Use Caution/Monitor.

• metformin

  Monitor Closely (1)clozapine, 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

  Monitor Closely (2)methadone, clozapine. 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).
  
  methadone and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

• methamphetamine

  Monitor Closely (1)clozapine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methimazole

  Serious - Use Alternative (1)methimazole, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.

• methocarbamol

  Monitor Closely (1)methocarbamol and clozapine both increase sedation. Use Caution/Monitor.

• methscopolamine

  Monitor Closely (3)methscopolamine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  methscopolamine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• methyldopa

  Serious - Use Alternative (1)clozapine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• methylenedioxymethamphetamine

  Monitor Closely (1)clozapine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylergonovine

  Monitor Closely (1)methylergonovine, clozapine. 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

  Monitor Closely (1)clozapine 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.

• methylprednisolone

  Monitor Closely (1)methylprednisolone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metoclopramide

  Monitor Closely (1)clozapine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• metoclopramide intranasal

  Serious - Use Alternative (2)clozapine, 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.
  
  clozapine 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.

• metronidazole

  Monitor Closely (1)metronidazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mexiletine

  Monitor Closely (1)mexiletine will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• miconazole vaginal

  Monitor Closely (1)miconazole vaginal will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• midazolam

  Monitor Closely (1)midazolam and clozapine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, clozapine. Either increases effects 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

  Monitor Closely (1)clozapine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• midostaurin

  Serious - Use Alternative (1)clozapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

• mifepristone

  Monitor Closely (1)mifepristone, clozapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)milnacipran, clozapine. 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

  Monitor Closely (2)clozapine and mirtazapine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and mirtazapine both increase sedation. Use Caution/Monitor.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib and clozapine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• modafinil

  Monitor Closely (2)modafinil will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  clozapine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

  Monitor Closely (1)morphine and clozapine both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (1)clozapine and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (1)clozapine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxonidine

  Monitor Closely (1)clozapine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)clozapine and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)nalbuphine and clozapine both increase sedation. Use Caution/Monitor.

• naratriptan

  Monitor Closely (1)naratriptan, clozapine. 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

  Monitor Closely (1)clozapine, 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.

• nefazodone

  Monitor Closely (1)nefazodone will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  Monitor Closely (1)nelfinavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)nifedipine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nilotinib

  Monitor Closely (2)nilotinib will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine and nilotinib both increase QTc interval. Use Caution/Monitor.

• nirmatrelvir

  Contraindicated (1)nirmatrelvir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.

• nirmatrelvir/ritonavir

  Contraindicated (1)nirmatrelvir/ritonavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.

• norepinephrine

  Monitor Closely (1)clozapine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (2)clozapine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  clozapine and nortriptyline both increase sedation. Use Caution/Monitor.

• octreotide

  Monitor Closely (1)clozapine and octreotide both increase QTc interval. Use Caution/Monitor.

• ofloxacin

  Monitor Closely (1)clozapine and ofloxacin both increase QTc interval. Use Caution/Monitor.

• olanzapine

  Monitor Closely (2)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.Serious - Use Alternative (1)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

• oliceridine

  Monitor Closely (2)clozapine will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
  
  oliceridine, clozapine. 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.

• olodaterol inhaled

  Monitor Closely (1)clozapine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.

• olopatadine intranasal

  Serious - Use Alternative (1)clozapine 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.

• omeprazole

  Monitor Closely (1)omeprazole will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• onabotulinumtoxinA

  Monitor Closely (3)onabotulinumtoxinA decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  onabotulinumtoxinA decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ondansetron

  Serious - Use Alternative (1)clozapine 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.

• opium tincture

  Monitor Closely (1)opium tincture and clozapine both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (1)orphenadrine and clozapine both increase sedation. Use Caution/Monitor.

• osilodrostat

  Monitor Closely (1)osilodrostat and clozapine both increase QTc interval. Use Caution/Monitor.

• osimertinib

  Monitor Closely (1)osimertinib and clozapine 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

  Monitor Closely (2)oxaliplatin and clozapine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Use of oxaliplatin with concomitant immunosuppressants or with impaired immune systems may increased risk for serious infections.
  
  oxaliplatin will increase the level or effect of clozapine by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.Serious - Use Alternative (1)clozapine and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

• oxazepam

  Monitor Closely (1)oxazepam and clozapine both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxybutynin

  Monitor Closely (3)oxybutynin decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oxybutynin topical

  Monitor Closely (3)oxybutynin topical decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin topical decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oxybutynin transdermal

  Monitor Closely (3)oxybutynin transdermal decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin transdermal decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oxycodone

  Monitor Closely (1)oxycodone and clozapine both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (1)oxymorphone and clozapine both increase sedation. Use Caution/Monitor.

• ozanimod

  Monitor Closely (1)ozanimod and clozapine 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

  Monitor Closely (2)clozapine and paliperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and paliperidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

• pancuronium

  Monitor Closely (3)pancuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pancuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• panobinostat

  Serious - Use Alternative (1)clozapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

• papaveretum

  Monitor Closely (1)papaveretum and clozapine both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)clozapine and papaverine both increase sedation. Use Caution/Monitor.

• paroxetine

  Monitor Closely (2)paroxetine increases levels of clozapine by decreasing metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  paroxetine, clozapine. 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

  Monitor Closely (1)clozapine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Serious - Use Alternative (1)clozapine and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

• pefloxacin

  Serious - Use Alternative (1)pefloxacin will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• peginterferon alfa 2a

  Monitor Closely (1)peginterferon alfa 2a will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• pentamidine

  Serious - Use Alternative (1)clozapine and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

• pentazocine

  Monitor Closely (1)pentazocine and clozapine both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (3)pentobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  pentobarbital and clozapine both increase sedation. Use Caution/Monitor.

• perphenazine

  Monitor Closely (3)clozapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and perphenazine both increase sedation. Use Caution/Monitor.

• phendimetrazine

  Monitor Closely (1)clozapine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  Monitor Closely (1)phenelzine, clozapine. 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

  Monitor Closely (3)phenobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and clozapine both increase sedation. Use Caution/Monitor.

• phentermine

  Monitor Closely (1)clozapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine

  Monitor Closely (1)clozapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (1)clozapine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When adding phenytoin therapy to patients stabilized on clozapine, monitor patient closely for worsening of psychotic symptoms. If needed, increase the clozapine dose cautiously on basis of psychotic symptoms. Conversely, when phenytoin is discontinued, levels of clozapine may significantly increase.

• pholcodine

  Monitor Closely (1)clozapine and pholcodine both increase sedation. Use Caution/Monitor.

• pimavanserin

  Serious - Use Alternative (1)clozapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• pimozide

  Monitor Closely (2)clozapine and pimozide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and pimozide both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and pimozide both increase QTc interval. Contraindicated.

• pioglitazone

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)pipemidic acid will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• pirbuterol

  Monitor Closely (1)clozapine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pitolisant

  Serious - Use Alternative (1)clozapine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• ponesimod

  Serious - Use Alternative (1)clozapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

• posaconazole

  Monitor Closely (1)posaconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and posaconazole both increase QTc interval. Contraindicated.

• pralidoxime

  Monitor Closely (3)pralidoxime decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pralidoxime decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• pramipexole

  Serious - Use Alternative (1)clozapine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• prednisone

  Monitor Closely (1)prednisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primaquine

  Monitor Closely (1)clozapine and primaquine both increase QTc interval. Use Caution/Monitor.

• primidone

  Monitor Closely (3)primidone will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  primidone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  primidone and clozapine both increase sedation. Use Caution/Monitor.

• procainamide

  Serious - Use Alternative (1)clozapine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

• procarbazine

  Monitor Closely (1)procarbazine, clozapine. 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

  Monitor Closely (2)clozapine and prochlorperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  Monitor Closely (3)promethazine, clozapine. 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).
  
  clozapine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and clozapine both increase sedation. Use Caution/Monitor.

• propafenone

  Serious - Use Alternative (1)clozapine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

• propantheline

  Monitor Closely (3)propantheline decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  propantheline decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• propofol

  Monitor Closely (1)propofol and clozapine both increase sedation. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (1)clozapine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• propylthiouracil

  Serious - Use Alternative (1)propylthiouracil, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.

• protriptyline

  Monitor Closely (2)clozapine and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  clozapine and protriptyline both increase sedation. Use Caution/Monitor.

• quazepam

  Monitor Closely (1)quazepam and clozapine both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)clozapine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and quetiapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

• quinidine

  Serious - Use Alternative (1)clozapine and quinidine both increase QTc interval. Contraindicated.

• quinine

  Monitor Closely (1)clozapine and quinine both increase QTc interval. Use Caution/Monitor.

• quinupristin/dalfopristin

  Monitor Closely (1)quinupristin/dalfopristin will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ramelteon

  Monitor Closely (1)clozapine and ramelteon both increase sedation. Use Caution/Monitor.

• ranolazine

  Serious - Use Alternative (1)clozapine and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.

• rapacuronium

  Monitor Closely (3)rapacuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rapacuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• remimazolam

  Monitor Closely (1)remimazolam, clozapine. 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

  Monitor Closely (1)clozapine, 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.

• ribociclib

  Serious - Use Alternative (2)ribociclib will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ribociclib increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

  Serious - Use Alternative (1)rifabutin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)rifampin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)clozapine and rilpivirine both increase QTc interval. Use Caution/Monitor.

• rimabotulinumtoxinB

  Monitor Closely (1)clozapine increases effects of rimabotulinumtoxinB by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• risperidone

  Monitor Closely (3)clozapine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and risperidone both increase sedation. Use Caution/Monitor.
  
  clozapine and risperidone both increase QTc interval. Use Caution/Monitor.

• ritonavir

  Monitor Closely (1)ritonavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rocuronium

  Monitor Closely (3)rocuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rocuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• romidepsin

  Serious - Use Alternative (1)clozapine and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

• ropeginterferon alfa 2b

  Serious - Use Alternative (1)ropeginterferon alfa 2b, clozapine. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.

• ropinirole

  Serious - Use Alternative (1)clozapine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

• rufinamide

  Monitor Closely (1)rufinamide will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• safinamide

  Serious - Use Alternative (1)clozapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• sage

  Minor (1)clozapine and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)clozapine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clozapine and salmeterol both increase QTc interval. Use Caution/Monitor.

• saquinavir

  Contraindicated (1)clozapine and saquinavir both increase QTc interval. Contraindicated.Serious - Use Alternative (1)saquinavir increases levels of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. Increased risk of QT prolongation and cardiac arrhythmias.

• saxagliptin

  Monitor Closely (1)clozapine, 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

  Monitor Closely (3)scopolamine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  scopolamine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• scullcap

  Monitor Closely (1)clozapine and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (3)secobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  secobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  secobarbital and clozapine both increase sedation. Use Caution/Monitor.

• selegiline

  Monitor Closely (1)selegiline, clozapine. 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).

• selinexor

  Serious - Use Alternative (1)selinexor, clozapine. 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.

• selpercatinib

  Monitor Closely (1)selpercatinib increases toxicity of clozapine by QTc interval. Use Caution/Monitor.

• sertraline

  Monitor Closely (2)sertraline increases levels of clozapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Plasma levels of clozapine may be increased, resulting in increased pharmacologic and toxic effects. Adjust clozapine dose as needed when initiating or discontinuing certain SSRIs. .
  
  clozapine and sertraline both increase QTc interval. Use Caution/Monitor.

• sevoflurane

  Monitor Closely (1)sevoflurane and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• shepherd's purse

  Monitor Closely (1)clozapine and shepherd's purse both increase sedation. Use Caution/Monitor.

• siponimod

  Serious - Use Alternative (1)clozapine and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

• sitagliptin

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)smoking will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• sodium oxybate

  Serious - Use Alternative (1)clozapine, 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.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases effects of clozapine 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

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases effects of clozapine 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

  Monitor Closely (4)solifenacin decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  solifenacin decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  clozapine and solifenacin both increase QTc interval. Use Caution/Monitor.

• sorafenib

  Monitor Closely (1)sorafenib and clozapine both increase QTc interval. Use Caution/Monitor.

• sotalol

  Serious - Use Alternative (1)clozapine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

• St John's Wort

  Serious - Use Alternative (1)St John's Wort will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)stiripentol, clozapine. 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.

• sufentanil

  Monitor Closely (1)sufentanil and clozapine both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, clozapine. 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.

• sulfamethoxypyridazine

  Monitor Closely (1)sulfamethoxypyridazine increases toxicity of clozapine by unspecified interaction mechanism. Use Caution/Monitor. Possibly increased neutropenic effects.

• sumatriptan

  Monitor Closely (1)sumatriptan, clozapine. 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

  Monitor Closely (1)sumatriptan intranasal, clozapine. 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

  Monitor Closely (1)clozapine and sunitinib both increase QTc interval. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)clozapine will increase the level or effect of suvorexant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

• tacrolimus

  Monitor Closely (1)clozapine and tacrolimus both increase QTc interval. Use Caution/Monitor.

• tamsulosin

  Monitor Closely (1)clozapine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tapentadol

  Monitor Closely (1)tapentadol and clozapine both increase sedation. Use Caution/Monitor.

• telavancin

  Monitor Closely (1)clozapine and telavancin both increase QTc interval. Use Caution/Monitor.

• temazepam

  Monitor Closely (1)temazepam and clozapine both increase sedation. Use Caution/Monitor.

• terbutaline

  Monitor Closely (1)clozapine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetrabenazine

  Monitor Closely (1)clozapine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)clozapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  Contraindicated (1)clozapine and thioridazine both increase QTc interval. Contraindicated.Monitor Closely (2)clozapine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  Monitor Closely (2)clozapine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and thiothixene both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and thiothixene both increase QTc interval. Avoid or Use Alternate Drug.

• tiotropium

  Monitor Closely (3)tiotropium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tiotropium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• tobacco use

  Monitor Closely (1)tobacco use will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tolazamide

  Monitor Closely (1)clozapine, 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

  Monitor Closely (1)clozapine, 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

  Monitor Closely (3)tolterodine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tolterodine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• topiramate

  Monitor Closely (2)topiramate will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clozapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• toremifene

  Serious - Use Alternative (1)clozapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.

• tramadol

  Monitor Closely (1)tramadol and clozapine both increase sedation. Use Caution/Monitor.

• tranylcypromine

  Monitor Closely (1)tranylcypromine, clozapine. 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

  Monitor Closely (1)clozapine and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

• triazolam

  Monitor Closely (1)triazolam and clozapine both increase sedation. Use Caution/Monitor.

• triclabendazole

  Monitor Closely (1)clozapine and triclabendazole both increase QTc interval. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)triclofos and clozapine both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (2)clozapine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and trifluoperazine both increase sedation. Use Caution/Monitor.

• trihexyphenidyl

  Monitor Closely (1)clozapine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimipramine

  Monitor Closely (2)clozapine and trimipramine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

  Monitor Closely (1)triprolidine and clozapine both increase sedation. Use Caution/Monitor.

• triptorelin

  Monitor Closely (1)triptorelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

• trospium chloride

  Monitor Closely (3)trospium chloride decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  trospium chloride decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• umeclidinium bromide/vilanterol inhaled

  Serious - Use Alternative (1)clozapine 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.

• valbenazine

  Monitor Closely (1)valbenazine and clozapine both increase QTc interval. Use Caution/Monitor.

• valproic acid

  Minor (1)valproic acid decreases levels of clozapine by plasma protein binding competition. Minor/Significance Unknown.

• vandetanib

  Serious - Use Alternative (1)clozapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.

• vardenafil

  Monitor Closely (1)clozapine and vardenafil both increase QTc interval. Use Caution/Monitor.

• vecuronium

  Monitor Closely (3)vecuronium decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  vecuronium decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• vemurafenib

  Serious - Use Alternative (1)clozapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.

• venlafaxine

  Monitor Closely (1)venlafaxine, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• verapamil

  Monitor Closely (2)verapamil will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  verapamil will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (1)clozapine 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.

• vilazodone

  Monitor Closely (1)vilazodone, clozapine. 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

  Monitor Closely (1)voclosporin, clozapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  Monitor Closely (1)voriconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

• vorinostat

  Serious - Use Alternative (1)clozapine and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.

• xylometazoline

  Monitor Closely (1)clozapine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  Monitor Closely (1)clozapine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zafirlukast

  Monitor Closely (1)zafirlukast will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ziconotide

  Monitor Closely (1)clozapine and ziconotide both increase sedation. Use Caution/Monitor.

• zidovudine

  Serious - Use Alternative (1)clozapine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of myelosuppression.

• zileuton

  Monitor Closely (1)zileuton will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (2)clozapine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolmitriptan

  Monitor Closely (1)zolmitriptan, clozapine. 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

  Monitor Closely (2)clozapine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and zotepine both increase sedation. Use Caution/Monitor.