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 chlorideMonitor 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 sulfateMonitor 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.solifenacinMonitor 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.somapacitanMonitor Closely (1)somapacitan will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatrogonMonitor Closely (1)somatrogon will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatropinMonitor Closely (1)somatropin will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessorafenibMonitor Closely (1)sorafenib and clozapine both increase QTc interval. Use Caution/Monitor.sotalolSerious - Use Alternative (1)clozapine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.St John's WortSerious - 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.stiripentolMonitor 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.sufentanilMonitor Closely (1)sufentanil and clozapine both increase sedation. Use Caution/Monitor.sufentanil SLSerious - 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.sulfamethoxypyridazineMonitor Closely (1)sulfamethoxypyridazine increases toxicity of clozapine by unspecified interaction mechanism. Use Caution/Monitor. Possibly increased neutropenic effects.sumatriptanMonitor 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 intranasalMonitor 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).sunitinibMonitor Closely (1)clozapine and sunitinib both increase QTc interval. Use Caution/Monitor.suvorexantMonitor 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 inhibitorstacrolimusMonitor Closely (1)clozapine and tacrolimus both increase QTc interval. Use Caution/Monitor.tamsulosinMonitor Closely (1)clozapine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tapentadolMonitor Closely (1)tapentadol and clozapine both increase sedation. Use Caution/Monitor.telavancinMonitor Closely (1)clozapine and telavancin both increase QTc interval. Use Caution/Monitor.temazepamMonitor Closely (1)temazepam and clozapine both increase sedation. Use Caution/Monitor.terbutalineMonitor Closely (1)clozapine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.teriflunomideMonitor Closely (1)teriflunomide decreases levels of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tetrabenazineMonitor 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.thioridazineContraindicated (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.thiothixeneMonitor 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.tiotropiumMonitor 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 useMonitor Closely (1)tobacco use will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tolazamideMonitor 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.tolbutamideMonitor 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.tolterodineMonitor 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.topiramateMonitor 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.toremifeneSerious - Use Alternative (1)clozapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.tramadolMonitor Closely (1)tramadol and clozapine both increase sedation. Use Caution/Monitor.tranylcypromineMonitor 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).trazodoneMonitor 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.triazolamMonitor Closely (1)triazolam and clozapine both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (1)clozapine and triclabendazole both increase QTc interval. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and clozapine both increase sedation. Use Caution/Monitor.trifluoperazineMonitor 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.trihexyphenidylMonitor Closely (1)clozapine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.trimipramineMonitor Closely (2)clozapine and trimipramine both increase QTc interval. Use Caution/Monitor. clozapine and trimipramine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and clozapine both increase sedation. Use Caution/Monitor.triptorelinMonitor Closely (1)triptorelin increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.trospium chlorideMonitor 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 inhaledSerious - 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.valbenazineMonitor Closely (1)valbenazine and clozapine both increase QTc interval. Use Caution/Monitor.valproic acidMinor (1)valproic acid decreases levels of clozapine by plasma protein binding competition. Minor/Significance Unknown.vandetanibSerious - Use Alternative (1)clozapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.vardenafilMonitor Closely (1)clozapine and vardenafil both increase QTc interval. Use Caution/Monitor.vecuroniumMonitor 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.vemurafenibSerious - Use Alternative (1)clozapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.venlafaxineMonitor 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).verapamilMonitor 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 inhaledSerious - 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.vilazodoneMonitor 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).voclosporinMonitor Closely (1)voclosporin, clozapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleMonitor 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.vorinostatSerious - Use Alternative (1)clozapine and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.xylometazolineMonitor Closely (1)clozapine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)clozapine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ziconotideMonitor Closely (1)clozapine and ziconotide both increase sedation. Use Caution/Monitor.zidovudineSerious - Use Alternative (1)clozapine, zidovudine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of myelosuppression.zileutonMonitor Closely (1)zileuton will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.ziprasidoneMonitor 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.zolmitriptanMonitor 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).zotepineMonitor 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. >10% Hypersalivation (13-48%) Sedation/somnolence (21-46%) Weight gain (4-31%) Dizziness (14-27%) Tachycardia (17-25%) Constipation (14-25%) Insomnia (2-20%) Dizziness/vertigo (19%) Nausea (17%) Vomiting (17%) Dyspepsia (14%) Hypotension (9-13%) Fever (5-13%) 1-10% Headache (7-10%) Tremor (6%) Syncope (6%) Sweating (6%) Dry mouth (5-6%) Visual disturbances (5%) Disturbed sleep/nightmares (4%) Restlessness (4%) Hypokinesia/akinesia (4%) Agitation (4%) Hypertension (4%) Abdominal discomfort/heartburn (4%) Seizures (3%) Rigidity (3%) Akathisia (3%) Confusion (3%) Leukopenia/neutropenia (3%) Fatigue (2%) Diarrhea (2%) Urinary abnormalities (2%) Rash (2%) Postmarketing Reports Skin: Hypersensitivity reactions: photosensitivity, vasculitis, erythema multiforme, and Stevens-Johnson Syndrome, skin pigmentation disorder Musculoskeletal system: Myasthenic syndrome, rhabdomyolysis, systemic lupus erythematosus Respiratory system: Aspiration, pleural effusion, pneumonia and lower respiratory tract infection (LRTI), which may be fatal, sleep apnea Central nervous system: Delirium, EEG abnormal, myoclonus, paresthesia, possible cataplexy, status epilepticus, obsessive compulsive symptoms, and post-discontinuation