increased frequency of glucose monitoring may be required.insulin degludec/insulin aspartMonitor Closely (1)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 detemirMonitor Closely (1)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 glargineMonitor Closely (1)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 glulisineMonitor Closely (1)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 inhaledMonitor Closely (1)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 lisproMonitor Closely (1)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 NPHMonitor Closely (1)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 humanMonitor Closely (1)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.ipratropiumMonitor Closely (3)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.irinotecanContraindicated (2)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 liposomalContraindicated (2)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.isofluraneSerious - Use Alternative (1)clozapine and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.isoniazidMonitor Closely (2)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.isoproterenolMonitor Closely (1)clozapine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.isradipineMonitor Closely (1)clozapine and isradipine both increase QTc interval. Use Caution/Monitor.itraconazoleSerious - Use Alternative (2)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.ivosidenibSerious - Use Alternative (1)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.ketamineMonitor Closely (1)ketamine and clozapine both increase sedation. Use Caution/Monitor.ketoconazoleSerious - Use Alternative (1)ketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ketotifen, ophthalmicMonitor Closely (1)clozapine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.lapatinibMonitor Closely (1)clozapine and lapatinib both increase QTc interval. Use Caution/Monitor.lasmiditanMonitor Closely (1)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.lefamulinSerious - Use Alternative (1)lefamulin and clozapine both increase QTc interval. Avoid or Use Alternate Drug.lemborexantMonitor Closely (1)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.leniolisibSerious - Use Alternative (1)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 indexlenvatinibMonitor Closely (1)clozapine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.letermovirMonitor Closely (1)letermovir increases levels of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.leuprolideMonitor Closely (1)leuprolide increases toxicity of clozapine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.levalbuterolMonitor Closely (2)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.levodopaSerious - Use Alternative (1)clozapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.levodopa inhaledSerious - Use Alternative (1)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). .levofloxacinMonitor Closely (1)clozapine and levofloxacin both increase QTc interval. Use Caution/Monitor.levoketoconazoleSerious - Use Alternative (1)levoketoconazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.levomilnacipranMonitor Closely (1)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).levorphanolMonitor Closely (1)levorphanol and clozapine both increase sedation. Use Caution/Monitor.linezolidMonitor Closely (1)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).liraglutideMonitor Closely (1)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.lisdexamfetamineMonitor Closely (1)clozapine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.lisurideSerious - Use Alternative (1)clozapine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.lithiumMonitor Closely (1)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).Serious - Use Alternative (1)clozapine and lithium both increase QTc interval. Avoid or Use Alternate Drug.lofepramineMonitor Closely (1)clozapine and lofepramine both increase sedation. Use Caution/Monitor.lofexidineMonitor Closely (1)clozapine and lofexidine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.lomustineMonitor Closely (1)lomustine, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Monitor for neutropenia when taking clozapine and another myelosuppressive agent.lonapegsomatropinMonitor Closely (1)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 substratesloperamideSerious - Use Alternative (1)clozapine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.lopinavirSerious - Use Alternative (1)clozapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.loprazolamMonitor Closely (1)loprazolam and clozapine both increase sedation. Use Caution/Monitor.lorazepamMonitor Closely (2)lorazepam, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Possible risk of cardiorespiratory collapse. lorazepam and clozapine both increase sedation. Use Caution/Monitor.lorcaserinMonitor Closely (1)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).lormetazepamMonitor Closely (1)lormetazepam and clozapine both increase sedation. Use Caution/Monitor.loxapineMonitor Closely (2)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 inhaledMonitor Closely (2)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.lumateperoneMonitor Closely (2)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.lumefantrineMonitor Closely (1)lumefantrine will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lurasidoneMonitor Closely (1)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.macimorelinSerious - Use Alternative (1)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.maprotilineMonitor Closely (1)clozapine and maprotiline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.marijuanaMonitor Closely (2)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.mavacamtenMonitor Closely (1)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. mechlorethamineMonitor Closely (1)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.meclizineMonitor Closely (3)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.mefloquineMonitor Closely (1)clozapine and mefloquine both increase QTc interval. Use Caution/Monitor.melatoninMonitor Closely (1)clozapine and melatonin both increase sedation. Use Caution/Monitor.meperidineMonitor Closely (2)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). meperidine and clozapine both increase sedation. Use Caution/Monitor.meprobamateMonitor Closely (1)clozapine and meprobamate both increase sedation. Use Caution/Monitor.metaproterenolMonitor Closely (1)clozapine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.metaxaloneMonitor Closely (1)metaxalone and clozapine both increase sedation. Use Caution/Monitor.metforminMonitor Closely (1)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.methadoneMonitor Closely (2)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). methadone and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and methadone both increase QTc interval. Avoid or Use Alternate Drug.methamphetamineMonitor Closely (1)clozapine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.methimazoleSerious - Use Alternative (1)methimazole, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased