Dosing & Uses
Dosage 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 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)
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (10)
- 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.
- fezolinetant
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 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)
- 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.
- leniolisib
leniolisib will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid leniolisib with CYP1A2 substrates that have a narrow therapeutic index
- 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 (436)
- 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. - avapritinib
avapritinib and clozapine both increase sedation. 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. - benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen 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.
brexpiprazole and clozapine both increase sedation. Use Caution/Monitor. - brimonidine
brimonidine and clozapine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and clozapine both increase sedation. Use Caution/Monitor.
- 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 subdermal implant
buprenorphine subdermal implant and clozapine both increase sedation. Use Caution/Monitor.
- buprenorphine transdermal
buprenorphine transdermal 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.
buprenorphine, long-acting injection and clozapine both increase sedation. Use Caution/Monitor. - 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).
- elranatamab
elranatamab will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.
- epcoritamab
epcoritamab, clozapine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab 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. .
- 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.
- glofitamab
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. .
- 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.
- lonapegsomatropin
lonapegsomatropin 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 substrates
- 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.
- quizartinib
quizartinib, clozapine. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.
- 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. - ritlecitinib
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.
- 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. - somapacitan
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 substrates
- somatrogon
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 substrates
- somatropin
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 substrates
- 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.
- talquetamab
talquetamab will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.
- 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.
Adverse Effects
>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 cholinergic rebound adverse reactions, tardive dyskinesia, neuroleptic malignant syndrome, restless leg syndrome
Cardiovascular: Atrial or ventricular tachycardia or fibrillation, periorbital edema, myocardial infarction, cardiac arrest, QT prolongation, Torsades de pointes, hypertension, mitral valve incompetence, bradycardia, cardiomyopathy, myocarditis
Endocrine system: Pseudopheochromocytoma
Gastrointestinal system: Acute pancreatitis, dysphagia, salivary gland swelling, colitis, hypersalivation, dry mouth, megacolon, intestinal obstruction, ischemia, infarction, perforation, ulceration or necrosis
Hepatobiliary: Hepatotoxicity, hepatic steatosis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, liver injury (hepatic, cholestatic, and mixed), and liver failure
Immune system disorders: Angioedema, leukocytoclastic vasculitis
Urogenital: Renal failure, nocturnal enuresis, acute interstitial nephritis, priapism, retrograde ejaculation
Hemic and lymphatic system: DVT; elevated hemoglobin/hematocrit, ESR; sepsis, pulmonary embolism, thrombocytosis, thrombocytopenia, angioedema, leukocytoclastic vasculitis, eosinophilia
Vision disorders: Narrow-angle glaucoma
Miscellaneous: CPK elevation, hyperuricemia, hyponatremia, weight loss, polyserositis
Warnings
Black Box Warnings
Agranulocytosis
- Available only through a restricted program called the Clozapine REMS
- Severe neutropenia, defined as an absolute neutrophil count (ANC) <500/mm3, has been reported
- Severe neutropenia can lead to serious infection and death
- Before initiating, baseline ANC must be ≥1500/mm3 for the general population and ≥1000/mm3 for patients with documented benign ethnic neutropenia
- Regularly monitor ANC during treatment
- Advise patients to immediately report symptoms consistent with severe neutropenia or infection (eg, fever, weakness, lethargy, sore throat)
Seizures
- Caution with history of seizure or other factors predisposing to seizure
- Risk is dose-related
Myocarditis, cardiomyopathy, and mitral valve incompetence
- Fatal myocarditis and cardiomyopathy reported; discontinue and obtain cardiac evaluation if suspected
- Measuring brain NP levels may offer a means of monitoring to detect early, asymptomatic myocarditis
- Generally, patients with a history of clozapine-associated myocarditis or cardiomyopathy should not be rechallenged; however, if benefit of treatment is judged to outweigh potential risks of recurrent myocarditis or cardiomyopathy, the clinician may consider rechallenging in consultation with a cardiologist, after a complete cardiac evaluation, and under close monitoring
Orthostatic hypotension, bradycardia, syncope
- Orthostatic hypotension, bradycardia, syncope, and cardiac arrest may occur
- Risk is highest during initial titration period, particularly with rapid dose escalation
- May occur with the first dose, and with doses as low as 12.5 mg/day or when restarting patients who have had even a brief interruption in treatment; initiate treatment at 12.5 mg once or twice daily; titrate slowly; and use divided dosages to minimize risk
- Caution with history of cardiovascular or cerebrovascular disease or conditions predisposing to hypotension
Increased mortality in elderly with dementia-related psychosis
- Not approved for dementia-related psychosis; patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
Contraindications
Hypersensitivity (eg, photosensitivity, vasculitis, erythema multiforme, Stevens-Johnson syndrome)
Cautions
Increased risk of dose-related seizures
Eosinophilia (blood eosinophil count >700/mm3) reported; associated in some patients with myocarditis, pancreatitis, hepatitis, colitis, and nephritis; organ involvement could be consistent with a drug reaction with eosinophilia and systemic symptoms syndrome (DRESS)
Increased risk of cerebrovascular adverse events reported with some atypical antipsychotics (mechanism unknown)
FDA warning regarding off-label use for dementia-related psychosis in elderly patients; increased risk of death
Antipsychotic drugs can cause the potentially fatal symptom complex referred to as neuroleptic malignant syndrome (NMS); if NMS occurs, immediately discontinue antipsychotic drug, and other drugs not essential to therapy; implement intensive symptomatic treatment and medical monitoring
Possible QT prolongation; use with caution in patients with history of long QT syndrome or other conditions that may increase risk (eg, hypokalemia, hypomagnesemia)
Severe, life threatening, and in some cases fatal hepatotoxicity including hepatic failure, hepatic necrosis, and hepatitis reported in post marketing studies; monitor for appearance of signs and symptoms of hepatotoxicity such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, coagulopathy, and hepatic encephalopathy; perform serum tests for liver injury and consider permanently discontinuing treatment if hepatitis or transaminase elevations combined with other systemic symptoms are due to clozapine
Transient fever reported; peak incidence is within first 3 weeks of treatment; although this fever is generally benign and self-limited, it may necessitate discontinuing treatment since fever can be associated with an increase or decrease in WBC count; evaluate patients with fever to rule out severe neutropenia or infection; consider possibility of NMS
Treatment must begin at maximum dose of 12.5 mg once daily or twice daily; total daily dose can be increased in increments of 25 mg to 50 mg per day, if well-tolerated, to a target dose of 300 mg to 450 mg per day (administered in divided doses) by end of 2 weeks; subsequently, the dose can be increased weekly or twice weekly, in increments of up to 100 mg; the maximum dose is 900 mg per day; use cautious titration and a divided dosage schedule to minimize risk of serious cardiovascular reactions
Consider reducing the dose if hypotension occurs; when restarting therapy in patients who have had even a brief interruption in treatment, the dosage must be reduced; this is necessary to minimize the risk of hypotension, bradycardia, and syncope
Pulmonary embolism (PE) and DVT reported; unclear whether PE and DVT can be attributed to clozapine
Myocarditis, cardiomyopathy and mitral valve incompetence
- Myocarditis, cardiomyopathy, and mitral valve incompetence reported, including fatalities; discontinue and obtain cardiac evaluation upon suspicion of myocarditis or cardiomyopathy
- Consider the possibility of myocarditis or cardiomyopathy in patients receiving therapy who present with chest pain, dyspnea, persistent tachycardia at rest, palpitations, fever, flu-like symptoms, hypotension, other signs or symptoms of heart failure, or electrocardiographic findings (low voltages, ST-T abnormalities, arrhythmias, right axis deviation, and poor R wave progression)
- Myocarditis most frequently presents within first two months of clozapine treatment; symptoms generally occur later than clozapine-associated myocarditis and usually after 8 weeks of treatment
- However, myocarditis and cardiomyopathy can occur at any period during treatment; it is common for nonspecific flu- like symptoms such as malaise, myalgia, pleuritic chest pain, and low-grade fevers to precede more overt signs of heart failure
- Typical laboratory findings include elevated troponin I or T, elevated creatinine kinase-MB, peripheral eosinophilia, and elevated C-reactive protein (CRP)
- Chest roentgenogram may demonstrate cardiac silhouette enlargement, and cardiac imaging (echocardiogram, radionucleotide studies, or cardiac catheterization) may reveal evidence of left ventricular dysfunction
- In patients who are diagnosed with cardiomyopathy while taking clozapine mitral valve incompetence has been reported; these cases reported either mild or moderate mitral regurgitation on two-dimensional echocardiography
- In patients with suspected cardiomyopathy, consider a 2D-echo Doppler examination to identify mitral valve incompetence
Neutropenia
- Only available through a restricted access program because of risk for neutropenia (ie, low ANC); patients must be registered, prescriber must enroll and complete training, and pharmacies dispensing clozapine must be certified and complete training
- Severe neutropenia (ANC <500/mm³) occurs in a small percentage of patients and is associated with increased risk of serious and potentially fatal infections; risk is greatest during the first 18 weeks of treatment and then declines; see prescribing information for detailed information regarding monitoring ANC, including patients with benign ethnic neutropenia
- Benign transient elevation of temperature reported, peaking within first 3 weeks of treatment (rule out agranulocytosis, infection, NMS)
Metabolic changes
- Increased risk of hyperglycemia and diabetes; in some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with esophageal dysmotility, ketoacidosis, hyperosmolar coma, or death; monitor blood glucose of high-risk patients
- Dyslipidemia and weight gain reported with atypical antipsychotics
Anticholinergic effects
- Potent anticholinergic effects can occur that can result in CNS and peripheral anticholinergic toxicity
- Caution with narrow-angle glaucoma, concomitant anticholinergic medications, prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions
- Impaired core body temperature regulation may occur; caution with strenuous exercise, dehydration, heat exposure, and concomitant medication possessing anticholinergic effects
- Gastrointestinal adverse reactions, including increased frequency of constipation, risk of severe complications of gastrointestinal hypomotility, which can result in fecal impaction, megacolon, and intestinal obstruction, ischemia, infarction, perforation, ulceration or necrosis reported; such reactions can be fatal
- Constipation should be initially treated by ensuring adequate hydration and use of ancillary therapy (eg, bulk laxatives); consult with gastroenterologist in more serious cases
- Evaluate bowel function before initiating treatment
- Instruct patients on preventive measures and to seek medical help if constipation occurs
Cognitive and motor abilities
- May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; for patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long- term antipsychotic therapy
- May cause CNS depression, which may impair physical or mental abilities; caution patients about performing tasks that require mental alertness
Tardive dyskinesia
- Tardive dyskinesia (TD) has occurred with antipsychotic drugs
- Syndrome consists of potentially irreversible, involuntary, dyskinetic movements
- Risk of TD and the likelihood that it will become irreversible are believed to increase with greater durations of treatment and higher total cumulative doses; however, the syndrome can develop after relatively brief treatment periods at low doses
- Prescribe drug in a manner that is most likely to minimize TD risk
- Use the lowest effective dose and the shortest duration necessary to control symptoms
- Periodically assess need for continued treatment; consider discontinuing treatment if TD occurs
- Some patients may require treatment despite the presence of the syndrome
- There is no known treatment for TD; however, the syndrome may remit partially or completely if treatment is discontinued
Drug interaction overview
-
CYP inhibitors and inducers
- Clozapine is a substrate for many cytochrome P450 isozymes, in particular CYP1A2, CYP2D6, and CYP3A4
- Clozapine dosage modification may be required if coadministered with drugs that inhibit or induce metabolism of clozapine (eg, CYP 1A2, 2D6, and 3A4 inhibitors)
-
QT prolongation
- Clozapine associated with QT prolongation
- Caution if coadministered with other drugs that prolong QT interval
-
CYP2D6 substrates
- Clozapine inhibits CYP2D6
- Coadministration with CYP2D6 substrates can increase levels of these substrate; lower dose of CYP2D6 substrate may be required
-
Anticholinergic drugs
- Caution if coadministered with other drugs that elicit anticholinergic effects
- Monitor carefully for additive anticholinergic effects
Pregnancy & Lactation
Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including clozapine, during pregnancy; health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmental health.org/clinical-and-research-programs/pregnancyregistry/
Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery; overall, available data from published epidemiologic studies of pregnant women exposed to clozapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, during pregnancy
Animal data
- In animal reproduction studies, no adverse developmental effects were observed with drug administered to pregnant rats or rabbits during period of organogenesis, or to pregnant rats during pregnancy and lactation, at doses up to approximately 0.4 and 0.9 times the maximum recommended human dose (MRHD) of 900 mg/day, for rats and rabbits respectively, based on mg/m2 body surface area
- There is risk to mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide; schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth; it is not known if this is a direct result of the illness or other comorbid factors
- Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder reported in neonates exposed to antipsychotic drugs during third trimester of pregnancy; these symptoms have varied in severity; monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately; some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization
Lactation
Clozapine is present in human milk; there are reports of sedation and a report of agranulocytosis in an infant exposed to clozapine through human milk; there is no information on effects of clozapine on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed-child from drug or from underlying maternal condition
Infants exposed to drug should be monitored for excess sedation
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Demonstrates weak D2-receptor and D1-receptor blocking activity, but noradrenolytic, anticholinergic, antihistaminic, and arousal reaction inhibiting effects are significant; also possesses antiserotoninergic (5-HT1C, 5-HT2, 5-HT3) properties
Affinity for mesolimbic dopamine D4 receptor accounts for striking effects in control of behavioral and psychiatric symptoms with low incidence of EPS; histamine receptor blockade accounts for increased incidence of sleep disturbances
Absorption
Bioavailability: 50-60%
Onset: 15 min
Duration: 4-12 hr
Peak plasma time: 1.5-2.5 hr
Peak plasma concentration: 102-771 ng/mL
Distribution
Protein bound: 97%
Vd: 4.67 L/kg
Metabolism
Metabolized by hepatic P450 enzyme CYP1A2, N-demethylation, N-oxidation, 3'-carbon oxidation, epoxidation of chlorine-containing aromatic ring, substitution of chlorine by hydroxyl or thiomethyl groups, and sulfur oxidation; also CYP2D6 and CYP3A4
Metabolites: Norclozapine
Elimination
Half-life: 12 hr
Blood clearance: 250 mL/min
Total plasma clearance: 217 mL/min
Excretion: Urine (50%), feces (30%)
Administration
Oral Administration
May take with or without food
Minimize risk of orthostatic hypotension, bradycardia, and syncope by using low starting dose, gradual titration schedule, and divided dosages
Storage
Store at temperature not exceeding 30ºC (86ºF)
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
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Clozaril oral - | 200 mg tablet | ![]() | |
Clozaril oral - | 100 mg tablet | ![]() | |
Clozaril oral - | 50 mg tablet | ![]() | |
Clozaril oral - | 25 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 50 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 50 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 12.5 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 50 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 150 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 150 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 150 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 50 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 200 mg tablet | ![]() | |
clozapine oral - | 100 mg tablet | ![]() | |
clozapine oral - | 25 mg tablet | ![]() | |
clozapine oral - | 50 mg tablet | ![]() | |
Versacloz oral - | 50 mg/mL suspension | ![]() |
Copyright © 2010 First DataBank, Inc.
Patient Handout
clozapine oral
CLOZAPINE - ORAL
(KLOE-za-peen)
COMMON BRAND NAME(S): Clozaril, Versacloz
WARNING: While clozapine can provide great benefits, it can rarely cause serious, possibly fatal side effects. For this reason, clozapine is used when other treatments have not worked or you cannot take them.To receive this medication in the United States, you must understand, agree to, and carefully follow the requirements of the Clozapine REMS Program. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.This medication can cause a serious decrease of a certain type of white blood cells (neutropenia). To make sure you have enough white blood cells, your doctor will order lab tests before starting and while your are taking clozapine. Neutropenia may lower your ability to fight infections. Get medical help right away if you have any signs of severe neutropenia or infection (such as sore throat that doesn't go away, fever, swollen lymph nodes, unusual tiredness, weakness).Clozapine can also cause seizures, especially in higher doses. Let your doctor or pharmacist know if you have ever had seizures. While taking this medication, avoid driving or other activities during which a sudden loss of consciousness could be dangerous (such as operating heavy machinery, swimming).This medication may rarely cause an inflammation of the heart muscle (myocarditis) or heart failure. Get medical help right away if you develop chest pain, fast/irregular heartbeat, shortness of breath, swelling ankles/feet, unusual tiredness, or unusual/sudden weight gain.Clozapine can cause low blood pressure or a slow heartbeat, which can make you dizzy or cause you to faint when you stand up. The risk is higher when you first start or increase your dose of medication. Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from a sitting or lying position.There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
USES: See also Warning section.This medication is used to treat certain mental/mood disorders (schizophrenia, schizoaffective disorders). Clozapine is a psychiatric medication (anti-psychotic type) that works by helping to restore the balance of certain natural substances (neurotransmitters) in the brain.Clozapine decreases hallucinations and helps prevent suicide in people who are likely to try to harm themselves. It helps you to think more clearly and positively about yourself, feel less nervous, and take part in everyday life.
HOW TO USE: If you are using the liquid form of this medication, read the Patient Information Leaflet if available from your pharmacist before you start taking clozapine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food, as directed by your doctor. If you are taking the tablets that dissolve in the mouth, carefully remove each tablet from the blister pack immediately before taking your dose. Allow the tablets to dissolve on your tongue and swallow. You do not need to take the dissolving tablets with water. Discard any dissolving tablets that have been previously exposed to air due to opened/damaged packaging. Do not save them for your next dose.If you are using the liquid form of this medication, shake the bottle well for 10 seconds before each use. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.It is important to begin taking this drug at a low dose, increasing your dose slowly, to lessen side effects such as dizziness, drowsiness and seizures. Follow your doctor's instructions exactly. Your dosage is based on your medical condition and response to therapy. Since clozapine can cause a decrease in white blood cells, you will need to get blood tests done regularly as directed. Be sure to keep all appointments for these lab tests. (See also Notes section.)If you miss your doses for longer than a day or two, consult your doctor for a new schedule to get back to the dose you were on (see Missed Dose section). Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day.Do not stop taking clozapine without consulting your doctor. Some conditions may become worse when the drug is suddenly stopped. Also, you may experience symptoms such as severe sweating, headache, nausea, vomiting, and diarrhea. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.It may take several weeks before the full benefit of this drug takes effect. Tell your doctor if your condition lasts or gets worse.
SIDE EFFECTS: See also Warning section.Drooling, drowsiness, dizziness, lightheadedness, headache, shaking (tremor), vision problems (such as blurred vision), constipation, and weight gain may occur. Many of these effects (especially drowsiness) lessen as your body gets used to the medication. If any of these effects last or get worse, tell your doctor or pharmacist promptly.To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may rarely make your blood sugar rise, which can cause or worsen diabetes. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. If you already have diabetes, check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.This drug may also cause significant weight gain and a rise in your cholesterol (or triglyceride) levels. These effects, along with diabetes, may increase your risk for developing heart disease. Discuss the risks and benefits of treatment with your doctor.Tell your doctor right away if you have any serious side effects, including: facial/muscle twitching, seizures, uncontrollable movements, interrupted breathing during sleep, trouble urinating, severe constipation.Get medical help right away if you have any very serious side effects, including: nausea/vomiting that doesn't stop, severe dizziness, fainting, mental/mood changes, difficulty breathing with exercise, sudden weakness, pain/redness/swelling of the arms/legs, stomach/abdominal pain, yellowing of eyes/skin.This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, signs of kidney problems (such as change in the amount of urine).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: See also Warning and Side Effects sections.Before taking clozapine, tell your doctor or pharmacist if you are allergic to it or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of blood disorders (such as leukemia, low white blood cell count), bowel problems (such as paralytic ileus, irritable bowel syndrome ), breathing problems, diabetes/family history of diabetes, high cholesterol/triglyceride levels, glaucoma, heart problems, kidney problems, liver problems, obesity/family history of obesity, seizures, difficulty urinating (for example, due to enlarged prostate), breathing trouble during sleep (sleep apnea).Clozapine may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm. Before using clozapine, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using clozapine safely.This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Tell your doctor if you are a descendent of Ashkenazi Jews because you may be at a higher risk for a drop in your white blood cells.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Liquid products or dissolving tablets may contain sugar and/or aspartame. Liquid products may also contain alcohol. Caution is advised if you have diabetes, liver disease, phenylketonuria (PKU), or any other condition that requires you to limit/avoid these substances in your diet. Ask your doctor or pharmacist about using this product safely.Older adults may be more sensitive to the side effects of this drug, especially constipation, trouble urinating, drowsiness, dizziness, lightheadedness, and QT prolongation (see above). Drowsiness, dizziness, and lightheadedness can increase the risk of falling.During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.Since untreated mental/mood problems (such as schizophrenia, schizoaffective disorders) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.This medication may pass into breast milk and have undesirable effects on a nursing infant. Breast feeding is not recommended while taking clozapine. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: metoclopramide.Other medications can affect the removal of clozapine from your body, which may affect how clozapine works. Examples include fluvoxamine, saquinavir, St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others.Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as complete blood count, liver function, blood sugar, weight, cholesterol/triglyceride levels) must be done before you start taking this medication and while you are taking it. Clozapine blood levels may also be checked. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. If you miss doses for longer than a day or two, consult your doctor for a new schedule to get back to the dose you were taking. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Store the dissolving tablets in their blister packets, and do not remove each dose until just before taking. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised August 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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