of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification. lemborexant, ziprasidone. 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.lenvatinibMonitor Closely (1)ziprasidone 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 ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.leuprolideContraindicated (1)leuprolide increases toxicity of ziprasidone by QTc interval. Contraindicated. Increases risk of torsades de pointes.levalbuterolMonitor Closely (1)ziprasidone increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.levodopaSerious - Use Alternative (1)ziprasidone decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.levodopa inhaledSerious - Use Alternative (1)ziprasidone 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)levofloxacin and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.levoketoconazoleMonitor Closely (1)levoketoconazole will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)levoketoconazole and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.levomilnacipranMonitor Closely (1)levomilnacipran, ziprasidone. 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 ziprasidone both increase sedation. Use Caution/Monitor.linezolidMonitor Closely (1)linezolid, ziprasidone. 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)ziprasidone, 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)ziprasidone increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.lisurideSerious - Use Alternative (1)ziprasidone decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.lithiumMonitor Closely (1)lithium, ziprasidone. 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)lithium and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.lofepramineMonitor Closely (1)ziprasidone and lofepramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)lofepramine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.lofexidineMonitor Closely (2)ziprasidone and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended. ziprasidone and lofexidine both increase sedation. Use Caution/Monitor.lomitapideMonitor Closely (1)ziprasidone increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.lonafarnibSerious - Use Alternative (1)ziprasidone will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.loprazolamMonitor Closely (1)loprazolam and ziprasidone both increase sedation. Use Caution/Monitor.lorazepamMonitor Closely (1)lorazepam and ziprasidone both increase sedation. Use Caution/Monitor.lorcaserinMonitor Closely (1)lorcaserin, ziprasidone. 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)ziprasidone and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.lormetazepamMonitor Closely (1)lormetazepam and ziprasidone both increase sedation. Use Caution/Monitor.loxapineMonitor Closely (2)loxapine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. loxapine and ziprasidone both increase sedation. Use Caution/Monitor.loxapine inhaledMonitor Closely (2)loxapine inhaled and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. loxapine inhaled and ziprasidone both increase sedation. Use Caution/Monitor.lumefantrineSerious - Use Alternative (1)lumefantrine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)lumefantrine will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lurasidoneMonitor Closely (1)lurasidone, ziprasidone. 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 ziprasidone 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)ziprasidone and maprotiline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)maprotiline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.maravirocMonitor Closely (1)maraviroc, ziprasidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.marijuanaMonitor Closely (1)ziprasidone and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.meclizineMonitor Closely (3)meclizine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. meclizine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor. ziprasidone increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.mefloquineSerious - Use Alternative (1)mefloquine increases toxicity of ziprasidone by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.melatoninMonitor Closely (1)ziprasidone and melatonin both increase sedation. Use Caution/Monitor.meperidineMonitor Closely (2)meperidine, ziprasidone. 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 ziprasidone both increase sedation. Use Caution/Monitor.meprobamateMonitor Closely (1)ziprasidone and meprobamate both increase sedation. Use Caution/Monitor.metaproterenolMonitor Closely (1)ziprasidone increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.metaxaloneMonitor Closely (1)metaxalone and ziprasidone both increase sedation. Use Caution/Monitor.metforminMonitor Closely (1)ziprasidone, 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 (3)methadone, ziprasidone. 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 ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely. methadone and ziprasidone both increase sedation. Use Caution/Monitor.methamphetamineMonitor Closely (1)ziprasidone increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.methocarbamolMonitor Closely (1)methocarbamol and ziprasidone both increase sedation. Use Caution/Monitor.methscopolamineMonitor Closely (3)methscopolamine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. methscopolamine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor. ziprasidone increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.methyldopaSerious - Use Alternative (1)ziprasidone decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.methylenedioxymethamphetamineMonitor Closely (1)ziprasidone increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.methylergonovineMonitor Closely (1)methylergonovine, ziprasidone. 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).methylphenidateMonitor Closely (1)ziprasidone 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.methylprednisoloneMinor (1)methylprednisolone will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.metoclopramideMonitor Closely (1)ziprasidone and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.metoclopramide intranasalSerious - Use Alternative (2)ziprasidone, 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. ziprasidone 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.metronidazoleMinor (1)metronidazole will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.miconazole vaginalMinor (1)miconazole vaginal will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.midazolamMonitor Closely (1)midazolam and ziprasidone both increase sedation. Use Caution/Monitor.midazolam intranasalMonitor Closely (1)midazolam intranasal, ziprasidone. Either increases toxicity 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.midodrineMonitor Closely (1)ziprasidone increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.mifepristoneMonitor Closely (1)mifepristone, ziprasidone. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.miglitolMonitor Closely (1)ziprasidone, 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.milnacipranMonitor Closely (1)milnacipran, ziprasidone. 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).mirtazapineMonitor Closely (1)ziprasidone and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.mobocertinibSerious - Use Alternative (1)mobocertinib and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.modafinilMonitor Closely (1)ziprasidone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.morphineMonitor Closely (1)morphine and ziprasidone both increase sedation. Use Caution/Monitor.motherwortMonitor Closely (1)ziprasidone and motherwort both increase sedation. Use Caution/Monitor.moxifloxacinSerious - Use Alternative (1)moxifloxacin and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.moxonidineMonitor Closely (1)ziprasidone and moxonidine both increase sedation. Use Caution/Monitor.nabiloneMonitor Closely (1)ziprasidone and nabilone both increase sedation. Use Caution/Monitor.nafcillinMinor (1)nafcillin will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nalbuphineMonitor Closely (1)nalbuphine and ziprasidone both increase sedation. Use Caution/Monitor.naratriptanMonitor Closely (1)naratriptan, ziprasidone. 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).nateglinideMonitor Closely (1)ziprasidone, 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.nefazodoneMonitor Closely (1)nefazodone will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nelfinavirMinor (1)nelfinavir will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nevirapineMinor (1)nevirapine will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme