interval. Use Caution/Monitor.esketamine intranasalMonitor Closely (1)esketamine intranasal, clozapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.eslicarbazepine acetateMinor (1)eslicarbazepine acetate will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.esomeprazoleMonitor Closely (1)esomeprazole will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.estazolamMonitor Closely (1)estazolam and clozapine both increase sedation. Use Caution/Monitor.ethanolMonitor 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.etomidateMonitor Closely (1)etomidate and clozapine both increase sedation. Use Caution/Monitor.etravirineMonitor Closely (1)etravirine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.eucalyptusMinor (1)clozapine and eucalyptus both increase sedation. Minor/Significance Unknown.exenatide injectable solutionMonitor 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 suspensionMonitor 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.fedratinibSerious - 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.fenfluramineMonitor 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.fentanylMonitor 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).fesoterodineMonitor 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.fexinidazoleMonitor 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.fezolinetantContraindicated (1)clozapine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitorsfingolimodMonitor Closely (1)fingolimod and clozapine both increase QTc interval. Use Caution/Monitor.flavoxateMonitor 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.flecainideSerious - Use Alternative (1)clozapine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.flibanserinMonitor 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).fluconazoleMonitor 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.fludrocortisoneMonitor Closely (1)fludrocortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fluoxetineMonitor 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.fluphenazineMonitor 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.flurazepamMonitor Closely (1)flurazepam and clozapine both increase sedation. Use Caution/Monitor.fluvoxamineMonitor 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.formoterolMonitor Closely (1)clozapine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.fosamprenavirMonitor Closely (1)fosamprenavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fosaprepitantMonitor Closely (1)fosaprepitant will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.foscarnetSerious - Use Alternative (1)clozapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.fosphenytoinMonitor Closely (1)fosphenytoin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fostemsavirMonitor Closely (1)clozapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir. frovatriptanMonitor 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).gadobenateMonitor Closely (1)clozapine and gadobenate both increase QTc interval. Use Caution/Monitor.ganaxoloneMonitor Closely (1)clozapine and ganaxolone both increase sedation. Use Caution/Monitor.gemifloxacinMonitor Closely (1)clozapine and gemifloxacin both increase QTc interval. Use Caution/Monitor.gemtuzumabMonitor Closely (1)clozapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.gilteritinibMonitor Closely (1)clozapine and gilteritinib both increase QTc interval. Use Caution/Monitor.givosiranSerious - 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.glasdegibSerious - 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.glimepirideMonitor 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.glipizideMonitor 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.glofitamabMonitor Closely (1)glofitamab, clozapine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .glyburideMonitor 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.glycopyrrolateMonitor Closely (1)clozapine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.glycopyrrolate inhaledMonitor 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.goserelinMonitor Closely (1)goserelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.granisetronMonitor Closely (1)clozapine and granisetron both increase QTc interval. Use Caution/Monitor.grapefruitMonitor Closely (1)grapefruit will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.green teaMonitor 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. .griseofulvinMonitor Closely (1)griseofulvin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.guanfacineMonitor Closely (1)guanfacine, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.haloperidolMonitor 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.henbaneMonitor 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.histrelinMonitor Closely (1)histrelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.homatropineMonitor 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.hydrocodoneSerious - 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.hydrocortisoneMonitor Closely (1)hydrocortisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.hydromorphoneMonitor Closely (1)hydromorphone and clozapine both increase sedation. Use Caution/Monitor.hydroxychloroquine sulfateSerious - Use Alternative (1)hydroxychloroquine sulfate and clozapine both increase QTc interval. Avoid or Use Alternate Drug.hydroxyureaMonitor Closely (1)clozapine, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Avoid combination. Combination may increase risk of myelosuppression.hydroxyzineMonitor 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.hyoscyamineMonitor 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 sprayMonitor 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.ibutilideSerious - Use Alternative (1)clozapine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.ifosfamideMonitor 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.iloperidoneMonitor 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.imipramineMonitor Closely (1)clozapine and imipramine both increase sedation. Use Caution/Monitor.incobotulinumtoxinAMonitor 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, inhaledMonitor Closely (1)clozapine and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.indinavirMonitor Closely (1)indinavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.inotuzumabSerious - 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 aspartMonitor 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 degludecMonitor 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