CYP3A4 metabolism. Use Caution/Monitor. pentobarbital and clozapine both increase sedation. Use Caution/Monitor.perphenazineMonitor 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.phendimetrazineMonitor Closely (1)clozapine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.phenelzineMonitor 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).phenobarbitalMonitor 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.phentermineMonitor Closely (1)clozapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.phenylephrineMonitor Closely (1)clozapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.phenylephrine POMonitor Closely (1)clozapine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .phenytoinMonitor 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.pholcodineMonitor Closely (1)clozapine and pholcodine both increase sedation. Use Caution/Monitor.pimavanserinSerious - Use Alternative (1)clozapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.pimozideMonitor 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.pioglitazoneMonitor 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 acidMonitor Closely (1)pipemidic acid will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.pirbuterolMonitor Closely (1)clozapine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.pitolisantSerious - Use Alternative (1)clozapine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.ponesimodSerious - Use Alternative (1)clozapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.posaconazoleMonitor 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.pralidoximeMonitor 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.pramipexoleSerious - Use Alternative (1)clozapine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.prednisoneMonitor Closely (1)prednisone will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.primaquineMonitor Closely (1)clozapine and primaquine both increase QTc interval. Use Caution/Monitor.primidoneMonitor 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.procainamideSerious - Use Alternative (1)clozapine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.procarbazineMonitor 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).prochlorperazineMonitor 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.promethazineMonitor 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.propafenoneSerious - Use Alternative (1)clozapine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.propanthelineMonitor 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.propofolMonitor Closely (1)propofol and clozapine both increase sedation. Use Caution/Monitor.propylhexedrineMonitor Closely (1)clozapine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.propylthiouracilSerious - Use Alternative (1)propylthiouracil, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of agranulocytosis.protriptylineMonitor Closely (2)clozapine and protriptyline both increase QTc interval. Use Caution/Monitor. clozapine and protriptyline both increase sedation. Use Caution/Monitor.quazepamMonitor Closely (1)quazepam and clozapine both increase sedation. Use Caution/Monitor.quetiapineMonitor 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.quinidineSerious - Use Alternative (1)clozapine and quinidine both increase QTc interval. Contraindicated.quinineMonitor Closely (1)clozapine and quinine both increase QTc interval. Use Caution/Monitor.quinupristin/dalfopristinMonitor Closely (1)quinupristin/dalfopristin will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ramelteonMonitor Closely (1)clozapine and ramelteon both increase sedation. Use Caution/Monitor.ranolazineSerious - Use Alternative (1)clozapine and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.rapacuroniumMonitor 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.remimazolamMonitor 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.repaglinideMonitor 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.ribociclibSerious - 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.rifabutinSerious - Use Alternative (1)rifabutin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.rifampinMonitor 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.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rilpivirineMonitor Closely (1)clozapine and rilpivirine both increase QTc interval. Use Caution/Monitor.rimabotulinumtoxinBMonitor Closely (1)clozapine increases effects of rimabotulinumtoxinB by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.risperidoneMonitor 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.ritlecitinibMonitor Closely (1)ritlecitinib will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP1A2 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP1A2 substrates. ritonavirMonitor Closely (1)ritonavir will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rocuroniumMonitor 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.romidepsinSerious - Use Alternative (1)clozapine and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.ropeginterferon alfa 2bSerious - 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.ropiniroleSerious - Use Alternative (1)clozapine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.rucaparibMonitor 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.rufinamideMonitor Closely (1)rufinamide will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.safinamideSerious - 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.sageMinor (1)clozapine and sage both increase sedation. Minor/Significance Unknown.salmeterolMonitor 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.saquinavirContraindicated (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.saxagliptinMonitor 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.scopolamineMonitor 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.scullcapMonitor Closely (1)clozapine and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor 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.selegilineMonitor 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).selinexorSerious - 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.selpercatinibMonitor Closely (1)selpercatinib increases toxicity of clozapine by QTc interval. Use Caution/Monitor.sertralineMonitor 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.sevofluraneMonitor 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 purseMonitor Closely (1)clozapine and shepherd's purse both increase sedation. Use Caution/Monitor.siponimodSerious - Use Alternative (1)clozapine and siponimod both increase QTc interval. Avoid or Use Alternate Drug.sitagliptinMonitor 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.smokingMonitor Closely (1)smoking will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.sodium oxybateSerious - 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