AdultPediatricGeriatricDosage Forms & Strengths tablet 25mg 50mg 100mg 200mg oral suspension (Versacloz) 50mg/mL 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 establishedLower 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)Interaction CheckerEnter a drug name and clozapineNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (10)amisulprideamisulpride, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndromeIncreases risk of neuroleptic malignant syndrome.dronedaroneclozapine and dronedarone both increase QTc interval. Contraindicated.eliglustatclozapine 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.fezolinetantclozapine 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 inhibitorsirinotecanclozapine, 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 liposomalirinotecan 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.nirmatrelvirnirmatrelvir 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/ritonavirnirmatrelvir/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.saquinavirclozapine and saquinavir both increase QTc interval. Contraindicated.thioridazineclozapine and thioridazine both increase QTc interval. Contraindicated.Serious - Use Alternative (131)abametapirabametapir 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.adagrasibadagrasib, 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.amiodaroneclozapine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.amisulprideclozapine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.apomorphineclozapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.aripiprazolearipiprazole and clozapine both increase QTc interval. Avoid or Use Alternate Drug.arsenic trioxideclozapine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.artemetherartemether and clozapine both increase QTc interval. Avoid or Use Alternate Drug.artemether/lumefantrineclozapine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.asenapineclozapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.asenapine transdermalasenapine transdermal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.azithromycinclozapine and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.benzhydrocodone/acetaminophenbenzhydrocodone/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.bromocriptineclozapine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.buprenorphineclozapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine buccalbuprenorphine buccal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine subdermal implantbuprenorphine subdermal implant and clozapine both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine transdermalbuprenorphine transdermal and clozapine both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine, long-acting injectionbuprenorphine, long-acting injection and clozapine both increase QTc interval. Avoid or Use Alternate Drug.bupropionclozapine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.cabergolineclozapine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.calcium/magnesium/potassium/sodium oxybatesclozapine, 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.carbamazepinecarbamazepine 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.ceritinibceritinib and clozapine both increase QTc interval. Avoid or Use Alternate Drug.chlorpromazineclozapine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.cimetidinecimetidine will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ciprofloxacinciprofloxacin 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.cisaprideclozapine and cisapride both increase QTc interval. Avoid or Use Alternate Drug.citalopramcitalopram and clozapine both increase QTc interval. Avoid or Use Alternate Drug.clarithromycinclarithromycin 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.crizotinibclozapine and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.dasatinibclozapine and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.deferipronedeferiprone, 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.desfluranedesflurane and clozapine both increase QTc interval. Avoid or Use Alternate Drug.disopyramideclozapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.dofetilidedofetilide increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug.dopamineclozapine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.droperidolclozapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.eliglustatclozapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.encorafenibclozapine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.entrectinibclozapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.eribulinclozapine and eribulin both increase QTc interval. Avoid or Use Alternate Drug.erythromycin baseerythromycin 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 ethylsuccinateerythromycin 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 lactobionateerythromycin 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 stearateerythromycin 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.fedratinibclozapine 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.fexinidazolefexinidazole 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.flecainideclozapine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.fluconazoleclozapine and fluconazole both increase QTc interval. Contraindicated.fluvoxaminefluvoxamine will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.foscarnetclozapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.givosirangivosiran 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.glasdegibclozapine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.hydrocodonehydrocodone, 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 sulfatehydroxychloroquine sulfate and clozapine both increase QTc interval. Avoid or Use Alternate Drug.hydroxyzinehydroxyzine increases toxicity of clozapine by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.ibutilideclozapine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.iloperidoneclozapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.inotuzumabinotuzumab and clozapine both increase QTc interval. Avoid or Use Alternate Drug.