metabolism. Use Caution/Monitor.hydromorphoneMonitor Closely (1)midazolam and hydromorphone both increase sedation. Use Caution/Monitor.hydroxyzineMonitor Closely (1)hydroxyzine and midazolam both increase sedation. Use Caution/Monitor.idelalisibSerious - Use Alternative (1)idelalisib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Applies to chronic use with PO midazolamiloperidoneMonitor Closely (2)midazolam and iloperidone both increase sedation. Use Caution/Monitor. iloperidone increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.imipramineMonitor Closely (1)midazolam and imipramine both increase sedation. Use Caution/Monitor.indinavirMonitor Closely (1)indinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)indinavir increases levels of midazolam by decreasing metabolism. Contraindicated.isavuconazonium sulfateMonitor Closely (1)isavuconazonium sulfate will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.isoniazidMonitor Closely (1)isoniazid will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.isoproterenolMonitor Closely (1)midazolam increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.itraconazoleContraindicated (1)itraconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of oral midazolam and itraconazole is contraindicated during and 2 weeks after itraconazole treatment. Use IV midazolam with great caution in patients receiving itraconazole, consider reduced initial doses whenever possible and closely monitor.ivosidenibSerious - Use Alternative (1)ivosidenib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.ketamineMonitor Closely (1)ketamine and midazolam both increase sedation. Use Caution/Monitor.ketoconazoleSerious - Use Alternative (2)ketoconazole increases levels of midazolam by decreasing metabolism. Contraindicated. ketoconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ketotifen, ophthalmicMonitor Closely (1)midazolam and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.lapatinibMonitor Closely (1)lapatinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.larotrectinibMinor (1)larotrectinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (1)lasmiditan, midazolam. 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.lemborexantMonitor Closely (2)midazolam will increase the level or effect 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, midazolam. 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.lenacapavirMonitor Closely (1)lenacapavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.letermovirMonitor Closely (1)letermovir increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levalbuterolMonitor Closely (1)midazolam increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.levofloxacinMinor (1)levofloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.levoketoconazoleSerious - Use Alternative (2)levoketoconazole increases levels of midazolam by decreasing metabolism. Contraindicated. levoketoconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.levonorgestrel oral/ethinylestradiol/ferrous bisglycinateMonitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will increase the level or effect of midazolam by decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.levorphanolMonitor Closely (1)midazolam and levorphanol both increase sedation. Use Caution/Monitor.lisdexamfetamineMonitor Closely (1)midazolam increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.lofepramineMonitor Closely (1)midazolam and lofepramine both increase sedation. Use Caution/Monitor.lofexidineMonitor Closely (1)midazolam and lofexidine both increase sedation. Use Caution/Monitor.lomitapideMonitor Closely (1)midazolam increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.lonafarnibContraindicated (1)lonafarnib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration is contraindicated; temporarily discontinue lonafarnib for 10-14 days before and 2 days after administration of midazolam.lonapegsomatropinMonitor Closely (1)lonapegsomatropin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrateslopinavirSerious - Use Alternative (1)lopinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.loprazolamMonitor Closely (1)loprazolam and midazolam both increase sedation. Use Caution/Monitor.lorazepamMonitor Closely (1)lorazepam and midazolam both increase sedation. Use Caution/Monitor.lorlatinibSerious - Use Alternative (1)lorlatinib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.lormetazepamMonitor Closely (1)lormetazepam and midazolam both increase sedation. Use Caution/Monitor.loxapineMonitor Closely (1)midazolam and loxapine both increase sedation. Use Caution/Monitor.loxapine inhaledMonitor Closely (1)midazolam and loxapine inhaled both increase sedation. Use Caution/Monitor.lumacaftor/ivacaftorSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.lumefantrineMonitor Closely (1)lumefantrine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lurasidoneMonitor Closely (1)lurasidone, midazolam. 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.maprotilineMonitor Closely (1)midazolam and maprotiline both increase sedation. Use Caution/Monitor.marijuanaMonitor Closely (2)marijuana will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. midazolam and marijuana both increase sedation. Use Caution/Monitor.melatoninMonitor Closely (1)midazolam and melatonin both increase sedation. Use Caution/Monitor.meperidineMonitor Closely (1)midazolam and meperidine both increase sedation. Use Caution/Monitor.meprobamateMonitor Closely (1)midazolam and meprobamate both increase sedation. Use Caution/Monitor.metaproterenolMonitor Closely (1)midazolam increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.metaxaloneMonitor Closely (1)midazolam and metaxalone both increase sedation. Use Caution/Monitor.methadoneMonitor Closely (1)midazolam and methadone both increase sedation. Use Caution/Monitor.methamphetamineMonitor Closely (1)midazolam increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.methocarbamolMonitor Closely (1)midazolam and methocarbamol both increase sedation. Use Caution/Monitor.methylenedioxymethamphetamineMonitor Closely (1)midazolam increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.methylphenidate transdermalMonitor Closely (1)methylphenidate transdermal will increase the level or effect of midazolam by decreasing metabolism. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate. methylprednisoloneMonitor Closely (1)methylprednisolone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.metoclopramide intranasalSerious - Use Alternative (1)midazolam, 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.metronidazoleMonitor Closely (1)metronidazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.miconazole vaginalMonitor Closely (1)miconazole vaginal will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.midazolam intranasalMonitor Closely (1)midazolam intranasal, midazolam. 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)midazolam increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.mirtazapineMonitor Closely (1)midazolam and mirtazapine both increase sedation. Use Caution/Monitor.mitotaneMonitor Closely (1)mitotane decreases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.mobocertinibSerious - Use Alternative (1)mobocertinib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.modafinilMonitor Closely (1)midazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.morphineMonitor Closely (1)midazolam and morphine both increase sedation. Use Caution/Monitor.motherwortMonitor Closely (1)midazolam and motherwort both increase sedation. Use Caution/Monitor.moxifloxacinMinor (1)moxifloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.moxonidineMonitor Closely (1)midazolam and moxonidine both increase sedation. Use Caution/Monitor.nabiloneMonitor Closely (1)midazolam and nabilone both increase sedation. Use Caution/Monitor.nafcillinMonitor Closely (1)nafcillin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nalbuphineMonitor Closely (1)midazolam and nalbuphine both increase sedation. Use Caution/Monitor.nefazodoneSerious - Use Alternative (1)nefazodone will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.nelfinavirContraindicated (1)nelfinavir increases levels of midazolam by decreasing metabolism. Contraindicated. Potential for serious and/or life threatening reactions (eg, prolonged or increased sedation, or respiratory depression).Monitor Closely (1)nelfinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nevirapineMonitor Closely (1)nevirapine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nifedipineMonitor Closely (1)nifedipine will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nilotinibMonitor Closely (1)nilotinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nirmatrelvirContraindicated (1)nirmatrelvir will increase the level or effect of midazolam 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/ritonavirContraindicated (1)nirmatrelvir/ritonavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with oral midazolam. If IV midazolam required, reduce midazolam dose and administer in setting that ensures close monitoring and appropriate medical management if respiratory depression occurs.norepinephrineMonitor Closely (1)midazolam increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.nortriptylineMonitor Closely (1)midazolam and nortriptyline both increase sedation. Use Caution/Monitor.ofloxacinMinor (1)ofloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.olanzapineMonitor Closely (1)midazolam and olanzapine both increase sedation. Use Caution/Monitor.oliceridineMonitor Closely (1)oliceridine, midazolam. 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.olopatadine intranasalSerious - Use Alternative (1)midazolam 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. olutasidenibSerious - Use Alternative (1)olutasidenib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.omaveloxoloneMonitor Closely (1)omaveloxolone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed. ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)Contraindicated (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with benzodiazepines that are extensively metabolized by CYP3A4 may cause large increases in the concentration of these benzodiazepines, possibly leading to serious and/or life -hreatening events (eg, prolonged or increased sedation or respiratory depression); applies to repeat dosing with PO