midazolam (Rx)

Brand and Other Names:Seizalam, Versed (DSC)
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

oral syrup: Schedule IV

  • 2mg/mL (generic)

injectable solution: Schedule IV

  • 1mg/mL (generic)
  • 5mg/mL (generic, Seizalam)

Preoperative Sedation/Anxiolysis With Anterograde Amnesia

IM

  • 70-80 mcg/kg (dose range ~5 mg) 30-60 minutes before surgery (reduce 50% for chronically ill or geriatric patients)  

IV

  • Initial: Usually 0.5-1 mg given over 2 minutes (not to exceed 2.5 mg/dose); wait 2-3 minutes to evaluate sedative effect after each dose adjustment; total dose >5 mg usually not necessary to reach desired sedation; use 30% less midazolam if patient premedicated with narcotics or other CNS depressants
  • Debilitated or chronically ill patients: 1.5 mg IV initially; may repeat with 1 mg/dose IV q2-3 min PRN; not to exceed cumulative dose of 3.5 mg; peak effect may be delayed in elderly, so increments should be smaller and rate of injection slower
  • Maintenance: 25% of initial effective dose PRN by slow titration; reduce 30% if premedicated with opiate (50% in elderly/chronically ill)

Anesthesia

Induction

  • <55 years without premedication: 300-350 mcg/kg IV injection over 20-30 seconds; wait 2-3 minutes to evaluate sedative effect after each dose adjustment; may use increments of 25% of initial dose PRN to complete induction; may use up to 0.6 mg/kg total dose in resistant cases, but such dosing may prolong recovery  
  • >55 years without premedication and with no systemic disease, in a patient who is not weak: 300 mcg/kg over 20-30 seconds initially; wait 2-3 minutes to evaluate sedative effect after each dose adjustment
  • >55 years without premedication but presence of systemic disease or weak patient: 200-250 mcg/kg over 20-30 seconds usually enough; 0.15 mg/kg enough in some cases; wait 2-3 minutes to evaluate sedative effect after each dose adjustment
  • >55 years with premedication: 150-350 mcg/kg IV injection over 20-30 seconds; wait 2-3 minutes to evaluate sedative effect after each dose adjustment; a dose of 250 mcg/kg usually enough to achieve desired effect

Maintenance

  • May administer increments of 25% of induction dose PRN when there are signs that anesthetic effects are lightening

Sedation of Intubated/Ventilated Patients

Load: 10-50 mcg/kg (dose range 0.5-4 mg) slow IV injection or infusion over several minutes; repeat q5-15min PRN  

Maintenance: Initial, 20-100 mcg/kg/hr infusion; titrate up or down 25-50% PRN

Status Epilepticus

Seizalam: Indicated for treatment of status epilepticus in adults

10 mg IM

Dosing Considerations

Because it is water soluble, takes approximately 3 times longer than diazepam to peak EEG effects; thus, clinician must wait 2-3 minutes to fully evaluate sedative effects before initiating procedure or repeating dose

Has twice the affinity for benzodiazepine receptors that diazepam has

May be administered IM if unable to obtain vascular access

Anesthesia: Typical adult induction and maintenance doses may need to be decreased in some elderly patients by 20-50%, because the elderly overall are more susceptible to CNS depressants than is the general population

Organophophorous Poisoning (Orphan)

Orphan designation for treatment of seizures induced by organophosphorous insecticide poisoning

Sponsor

  • Meridian Medical Technologies, Inc., A Pfizer Company; 6350 Stevens Forest Road; Columbia, Maryland 21046

Dosage Forms & Strengths

syrup: Schedule IV

  • 2mg/mL (generic)

injectable solution: Schedule IV

  • 1mg/mL (generic)
  • 5mg/mL (generic)

Sedation

500-750 mcg/kg PO once diluted by juice 20-30 minutes prior to procedure; not to exceed 20 mg  

100-150 mcg/kg IM; up to 500 mcg/kg used; not to exceed 10 mg

IV

  • <6 months: Initial, 50 mcg/kg IV over 2-3 minutes; titrate with small increments to clinical effect; monitor closely; data are limited in nonintubated infants
  • 6 months-6 years: Initial, 50-100 mcg/kg IV over 2-3 minutes; repeat q2-3min PRN; may require up to 600 mcg/kg total dose; not to exceed 6 mg total dose
  • 6-12 years: Initial, 25-50 mcg/kg IV over 2-3 minutes; repeat q2-3min PRN; may require up to 400 mcg/kg; not to exceed 10 mg total dose

Anesthesia (Non-neonatal)

Loading dose: 50-150 mcg/kg IV over 2-3 minutes PRN to achieve desired effect  

Continuous infusion: 1-2 mcg/kg/min IV infusion

Anesthesia (Neonatal)

IV loading dose should not be used in neonates

Continuous infusion: 0.5 mcg/kg/min IV infusion  

Preoperative Sedation/Anxiolysis with Anterograde Amnesia

IM: 2-3 mg (~20-50 mcg/kg) 30-60 minutes before surgery; some elderly patients may respond to as little as 1 mg; onset is 15 minutes (peaking at 30-60 min)

IV (>60 years): 1-1.5 mg initially; not to exceed >1.5 mg in 2 min period; may repeat with 1 mg/dose q2-3min PRN; not to exceed cumulative dose of 3.5 mg; peak effect may be delayed in elderly, so increments should be smaller and rate of injection slower

IV maintenance: 25% of initial effective dose PRN by slow titration

Dosing Considerations

Because geriatric patients may have altered drug distribution and diminished hepatic and/or renal function, reduced doses of midazolam are recommended

IV and IM doses of midazolam should be decreased for elderly and for debilitated patients, and patients aged ≥70 yr may be particularly sensitive

Anesthesia: Typical adult induction and maintenance doses may need to be decreased in some geriatric patients by 20-50%, because they are more susceptible to CNS depressants than is the general population

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Interactions

Interaction Checker

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            Contraindicated (6)

            • cobicistat

              cobicistat will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Triazolam and midazolam (PO) are extensively metabolized by CYP3A. Coadministration of triazolam or midazolam (PO) may cause large increases in the concentrations of these benzodiazepines. Potential for serious and/or life-threatening events (eg, prolonged or increased sedation or respiratory depression).

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events; contraindication applies to oral midazolam; consider dose reduction for parenteral midazolam.

            • itraconazole

              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.

            • lonafarnib

              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.

            • nelfinavir

              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).

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir 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 midazolam

            Serious - Use Alternative (45)

            • abametapir

              abametapir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • apalutamide

              apalutamide will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • atazanavir

              atazanavir increases levels of midazolam by decreasing metabolism. Contraindicated.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, midazolam. 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.

            • bremelanotide

              bremelanotide will decrease the level or effect of midazolam by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • brigatinib

              brigatinib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

            • calcium/magnesium/potassium/sodium oxybates

              midazolam, 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 midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cyclosporine

              cyclosporine will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darunavir

              darunavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Triazolam and midazolam (PO) are extensively metabolized by CYP3A. Coadministration of triazolam or midazolam (PO) with darunavir/ritonavir may cause large increases in the concentrations of these benzodiazepines. Potential for serious and/or life-threatening events (eg, prolonged or increased sedation or respiratory depression)

            • enzalutamide

              enzalutamide will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erdafitinib

              erdafitinib, midazolam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with erdafitinib and sensitive CYP3A4 substrates with narrow therapeutic indices. Erdafitinib may altered plasma concentrations of CYP3A4 substrates, leading to either loss of activity or increased toxicity of the substrate.

            • erythromycin base

              erythromycin base will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosamprenavir

              fosamprenavir increases levels of midazolam by decreasing metabolism. Contraindicated.

            • hydrocodone

              hydrocodone, midazolam. 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.

            • idelalisib

              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 midazolam

            • indinavir

              indinavir increases levels of midazolam by decreasing metabolism. Contraindicated.

            • ivosidenib

              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.

            • ketoconazole

              ketoconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              ketoconazole increases levels of midazolam by decreasing metabolism. Contraindicated.

            • lopinavir

              lopinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lorlatinib

              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.

            • lumacaftor/ivacaftor

              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.

            • metoclopramide intranasal

              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.

            • mobocertinib

              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.

            • nefazodone

              nefazodone will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pexidartinib

              pexidartinib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 inducer) with sensitive CYP3A substrates may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.

            • rifabutin

              rifabutin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir increases levels of midazolam by decreasing metabolism. Contraindicated.

            • saquinavir

              saquinavir increases levels of midazolam by decreasing metabolism. Contraindicated.

              saquinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, midazolam. 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.

            • sodium oxybate

              midazolam, 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.

            • sotorasib

              sotorasib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • St John's Wort

              St John's Wort will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sufentanil SL

              sufentanil SL, midazolam. 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.

            • tipranavir

              tipranavir increases levels of midazolam by decreasing metabolism. Contraindicated.

              tipranavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • valerian

              valerian and midazolam both increase sedation. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (273)

            • albuterol

              midazolam increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfentanil

              midazolam and alfentanil both increase sedation. Use Caution/Monitor.

            • alprazolam

              alprazolam and midazolam both increase sedation. Use Caution/Monitor.

            • amitriptyline

              midazolam and amitriptyline both increase sedation. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              amobarbital and midazolam both increase sedation. Use Caution/Monitor.

            • amoxapine

              midazolam and amoxapine both increase sedation. Use Caution/Monitor.

            • apomorphine

              midazolam and apomorphine both increase sedation. Use Caution/Monitor.

            • aprepitant

              aprepitant will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • arformoterol

              midazolam increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aripiprazole

              midazolam and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              armodafinil will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              midazolam 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 midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atazanavir

              atazanavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atogepant

              midazolam will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • avapritinib

              midazolam will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • axitinib

              midazolam increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azelastine

              azelastine and midazolam both increase sedation. Use Caution/Monitor.

            • baclofen

              midazolam and baclofen both increase sedation. Use Caution/Monitor.

            • belladonna and opium

              midazolam and belladonna and opium both increase sedation. Use Caution/Monitor.

            • benperidol

              midazolam and benperidol both increase sedation. Use Caution/Monitor.

            • benzphetamine

              midazolam increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • berotralstat

              berotralstat will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

            • bosentan

              bosentan will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexanolone

              brexanolone, midazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and midazolam both increase sedation. Use Caution/Monitor.

            • budesonide

              budesonide will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine

              midazolam and buprenorphine both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              midazolam and buprenorphine buccal both increase sedation. Use Caution/Monitor.

            • buprenorphine subdermal implant

              midazolam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

            • buprenorphine, long-acting injection

              midazolam 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.

            • butabarbital

              butabarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              butabarbital and midazolam both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              butalbital and midazolam both increase sedation. Use Caution/Monitor.

            • butorphanol

              midazolam and butorphanol both increase sedation. Use Caution/Monitor.

            • caffeine

              midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and midazolam both increase sedation. Use Caution/Monitor.

            • carisoprodol

              midazolam and carisoprodol both increase sedation. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • chloral hydrate

              midazolam and chloral hydrate both increase sedation. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of strong CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • chlordiazepoxide

              chlordiazepoxide and midazolam both increase sedation. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and midazolam both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              midazolam and chlorpromazine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              midazolam and chlorzoxazone both increase sedation. Use Caution/Monitor.

            • cholic acid

              midazolam increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

            • cinnarizine

              cinnarizine and midazolam both increase sedation. Use Caution/Monitor.

            • clemastine

              clemastine and midazolam both increase sedation. Use Caution/Monitor.

            • clomipramine

              midazolam and clomipramine both increase sedation. Use Caution/Monitor.

            • clonazepam

              clonazepam and midazolam both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate and midazolam both increase sedation. Use Caution/Monitor.

            • clozapine

              midazolam and clozapine both increase sedation. Use Caution/Monitor.

            • codeine

              midazolam and codeine both increase sedation. Use Caution/Monitor.

            • conivaptan

              conivaptan will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cortisone

              cortisone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • crofelemer

              crofelemer increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclizine

              cyclizine and midazolam both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              midazolam and cyclobenzaprine both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and midazolam both increase sedation. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dantrolene

              midazolam and dantrolene both increase sedation. Use Caution/Monitor.

            • darifenacin

              darifenacin will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasatinib

              dasatinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deferasirox

              deferasirox will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • desflurane

              desflurane and midazolam both increase sedation. Use Caution/Monitor.

            • desipramine

              midazolam and desipramine both increase sedation. Use Caution/Monitor.

            • deutetrabenazine

              midazolam and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dexamethasone

              dexamethasone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine and midazolam both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              midazolam increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmedetomidine

              midazolam and dexmedetomidine both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              midazolam increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              midazolam increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextromoramide

              midazolam and dextromoramide both increase sedation. Use Caution/Monitor.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diamorphine

              midazolam and diamorphine both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and midazolam both increase sedation. Use Caution/Monitor.

            • diazepam intranasal

              diazepam intranasal, midazolam. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • diethylpropion

              midazolam increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difenoxin hcl

              midazolam and difenoxin hcl both increase sedation. Use Caution/Monitor.

            • diltiazem

              diltiazem will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Midazolam dose adjustments may be necessary in patients receiving concomitant diltiazem and midazolam. Monitor for signs of midazolam toxicity (eg, sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma).

            • dimenhydrinate

              dimenhydrinate and midazolam both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and midazolam both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              midazolam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dipipanone

              midazolam and dipipanone both increase sedation. Use Caution/Monitor.

            • dobutamine

              midazolam increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopamine

              midazolam increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              midazolam increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              midazolam and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

              midazolam and doxepin both increase sedation. Use Caution/Monitor.

            • doxylamine

              midazolam and doxylamine both increase sedation. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • droperidol

              midazolam and droperidol both increase sedation. Use Caution/Monitor.

            • duvelisib

              duvelisib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • efavirenz

              efavirenz will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix decreases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing oral midazolam dose if needed.

            • eluxadoline

              eluxadoline increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

            • encorafenib

              encorafenib, midazolam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ephedrine

              midazolam increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              midazolam increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              midazolam increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • esketamine intranasal

              esketamine intranasal, midazolam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estazolam

              estazolam and midazolam both increase sedation. Use Caution/Monitor.

            • ethanol

              midazolam and ethanol both increase sedation. Use Caution/Monitor.

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of midazolam by Mechanism: decreasing metabolism. Use Caution/Monitor. Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.

            • etomidate

              etomidate and midazolam both increase sedation. Use Caution/Monitor.

            • etravirine

              etravirine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              midazolam increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • finerenone

              midazolam will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flibanserin

              midazolam and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

              midazolam will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • fluconazole

              fluconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluphenazine

              midazolam and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam and midazolam both increase sedation. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May increase risk of hypoventilation, airway obstruction, or apnea and may contribute to profound and/or prolonged drug effect

            • formoterol

              midazolam 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 midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • gabapentin

              gabapentin, midazolam. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, midazolam. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • glycerol phenylbutyrate

              glycerol phenylbutyrate will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index. Cmax and AUC were 25% and 32% lower for a single dose of midazolam after multiple doses of glycerol phenylbutyrate.

            • grapefruit

              grapefruit will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • griseofulvin

              griseofulvin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • guselkumab

              guselkumab, midazolam. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • haloperidol

              midazolam and haloperidol both increase sedation. Use Caution/Monitor.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydromorphone

              midazolam and hydromorphone both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and midazolam both increase sedation. Use Caution/Monitor.

            • iloperidone

              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.

            • imipramine

              midazolam and imipramine both increase sedation. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoproterenol

              midazolam increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • istradefylline

              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.

            • ketamine

              ketamine and midazolam both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              midazolam and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • lapatinib

              lapatinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lasmiditan

              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.

            • lemborexant

              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.

            • letermovir

              letermovir increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levalbuterol

              midazolam increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              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.

            • levorphanol

              midazolam and levorphanol both increase sedation. Use Caution/Monitor.

            • lisdexamfetamine

              midazolam increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lofepramine

              midazolam and lofepramine both increase sedation. Use Caution/Monitor.

            • lofexidine

              midazolam and lofexidine both increase sedation. Use Caution/Monitor.

            • lomitapide

              midazolam increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • loprazolam

              loprazolam and midazolam both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and midazolam both increase sedation. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and midazolam both increase sedation. Use Caution/Monitor.

            • loxapine

              midazolam and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              midazolam and loxapine inhaled both increase sedation. Use Caution/Monitor.

            • lumefantrine

              lumefantrine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lurasidone

              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.

            • maprotiline

              midazolam and maprotiline both increase sedation. Use Caution/Monitor.

            • marijuana

              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.

            • melatonin

              midazolam and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              midazolam and meperidine both increase sedation. Use Caution/Monitor.

            • meprobamate

              midazolam and meprobamate both increase sedation. Use Caution/Monitor.

            • metaproterenol

              midazolam increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              midazolam and metaxalone both increase sedation. Use Caution/Monitor.

            • methadone

              midazolam and methadone both increase sedation. Use Caution/Monitor.

            • methamphetamine

              midazolam increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              midazolam and methocarbamol both increase sedation. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              midazolam increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • metronidazole

              metronidazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • midazolam intranasal

              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.

            • midodrine

              midazolam increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mirtazapine

              midazolam and mirtazapine both increase sedation. Use Caution/Monitor.

            • mitotane

              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.

            • modafinil

              modafinil will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              midazolam increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • morphine

              midazolam and morphine both increase sedation. Use Caution/Monitor.

            • motherwort

              midazolam and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              midazolam and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              midazolam and nabilone both increase sedation. Use Caution/Monitor.

            • nafcillin

              nafcillin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nalbuphine

              midazolam and nalbuphine both increase sedation. Use Caution/Monitor.

            • nelfinavir

              nelfinavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nifedipine

              nifedipine will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norepinephrine

              midazolam increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nortriptyline

              midazolam and nortriptyline both increase sedation. Use Caution/Monitor.

            • olanzapine

              midazolam and olanzapine both increase sedation. Use Caution/Monitor.

            • oliceridine

              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.

            • opium tincture

              midazolam and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

              midazolam and orphenadrine both increase sedation. Use Caution/Monitor.

            • oxazepam

              midazolam and oxazepam both increase sedation. Use Caution/Monitor.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxycodone

              midazolam and oxycodone both increase sedation. Use Caution/Monitor.

            • oxymorphone

              midazolam and oxymorphone both increase sedation. Use Caution/Monitor.

            • palbociclib

              palbociclib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib

            • paliperidone

              midazolam and paliperidone both increase sedation. Use Caution/Monitor.

            • papaveretum

              midazolam and papaveretum both increase sedation. Use Caution/Monitor.

            • papaverine

              midazolam and papaverine both increase sedation. Use Caution/Monitor.

            • pazopanib

              pazopanib increases levels of midazolam by decreasing metabolism. Use Caution/Monitor.

            • pentazocine

              midazolam and pentazocine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              pentobarbital and midazolam both increase sedation. Use Caution/Monitor.

            • perampanel

              perampanel and midazolam both increase sedation. Use Caution/Monitor.

            • perphenazine

              midazolam and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              midazolam increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenobarbital

              phenobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              phenobarbital and midazolam both increase sedation. Use Caution/Monitor.

            • phentermine

              midazolam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              midazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine PO

              midazolam 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 midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pholcodine

              midazolam and pholcodine both increase sedation. Use Caution/Monitor.

            • pimozide

              midazolam and pimozide both increase sedation. Use Caution/Monitor.

            • pirbuterol

              midazolam increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pitolisant

              pitolisant will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

            • posaconazole

              posaconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prednisone

              prednisone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pregabalin

              pregabalin, midazolam. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              primidone and midazolam both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              midazolam and prochlorperazine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and midazolam both increase sedation. Use Caution/Monitor.

            • propofol

              propofol and midazolam both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              midazolam increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              midazolam and protriptyline both increase sedation. Use Caution/Monitor.

            • quazepam

              midazolam and quazepam both increase sedation. Use Caution/Monitor.

            • quetiapine

              midazolam and quetiapine both increase sedation. Use Caution/Monitor.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ramelteon

              midazolam and ramelteon both increase sedation. Use Caution/Monitor.

            • remimazolam

              remimazolam, midazolam. 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.

            • ribociclib

              ribociclib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • rifapentine

              rifapentine will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              midazolam and risperidone both increase sedation. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ropeginterferon alfa 2b

              ropeginterferon alfa 2b will increase the level or effect of midazolam by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

            • rucaparib

              rucaparib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • rufinamide

              rufinamide will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • salmeterol

              midazolam increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • schisandra

              schisandra will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • scullcap

              midazolam and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              secobarbital and midazolam both increase sedation. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and midazolam both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              midazolam and shepherd's purse both increase sedation. Use Caution/Monitor.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

            • spironolactone

              spironolactone will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. midazolam dose may need to be adjusted

            • stiripentol

              stiripentol, midazolam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, midazolam. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

              midazolam and sufentanil both increase sedation. Use Caution/Monitor.

            • suvorexant

              suvorexant and midazolam both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • tapentadol

              midazolam and tapentadol both increase sedation. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              midazolam will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • teduglutide

              teduglutide increases levels of midazolam by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.

            • temazepam

              midazolam and temazepam both increase sedation. Use Caution/Monitor.

            • terbutaline

              midazolam increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thioridazine

              midazolam and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              midazolam and thiothixene both increase sedation. Use Caution/Monitor.

            • tinidazole

              midazolam will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • topiramate

              topiramate will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              midazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              midazolam and tramadol both increase sedation. Use Caution/Monitor.

            • trazodone

              midazolam and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              midazolam and triazolam both increase sedation. Use Caution/Monitor.

            • triclofos

              midazolam and triclofos both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              midazolam and trifluoperazine both increase sedation. Use Caution/Monitor.

            • trimipramine

              midazolam and trimipramine both increase sedation. Use Caution/Monitor.

            • triprolidine

              triprolidine and midazolam both increase sedation. Use Caution/Monitor.

            • ustekinumab

              ustekinumab, midazolam. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • verapamil

              verapamil will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voriconazole

              voriconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • xylometazoline

              midazolam increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              midazolam 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 midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ziconotide

              midazolam and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              midazolam and ziprasidone both increase sedation. Use Caution/Monitor.

            • zotepine

              midazolam and zotepine both increase sedation. Use Caution/Monitor.

            Minor (17)

            • brimonidine

              brimonidine increases effects of midazolam by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • cilostazol

              midazolam increases levels of cilostazol by decreasing metabolism. Minor/Significance Unknown.

            • ciprofloxacin

              ciprofloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • esomeprazole

              esomeprazole increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • eucalyptus

              midazolam and eucalyptus both increase sedation. Minor/Significance Unknown.

            • fleroxacin

              fleroxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • gemifloxacin

              gemifloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • green tea

              green tea decreases effects of midazolam by pharmacodynamic antagonism. Minor/Significance Unknown. Caffeine component of green tea may decrease sedative effects of benzodiazepines.

            • levofloxacin

              levofloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • moxifloxacin

              moxifloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • ofloxacin

              ofloxacin increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • omeprazole

              omeprazole increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • rifabutin

              rifabutin decreases levels of midazolam by increasing metabolism. Minor/Significance Unknown.

            • ruxolitinib

              midazolam will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              midazolam and sage both increase sedation. Minor/Significance Unknown.

            • vinpocetine

              midazolam increases effects of vinpocetine by unspecified interaction mechanism. Minor/Significance Unknown. Desirable interaction enhanced memory improvement (based on preliminary trial).

            • zolpidem

              zolpidem, midazolam. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

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            Adverse Effects

            >10%

            Decreased respiratory rate (23%)

            Apnea (15%)

            1-10%

            Drowsiness (1-5%)

            Seizure-like activity (1%)

            Nausea/vomiting (3%)

            Cough (1%)

            Pain at injection site (4-5%)

            Frequency Not Defined

            Headache

            Sedation

            Hiccoughs

            Delirium

            Euphoria

            Pediatric

            • Desaturation
            • Hypotension
            • Seizurelike activity
            • Nystagmus
            • Paradoxical reactions
            • Hiccoughs
            • Apnea
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            Warnings

            Black Box Warnings

            Respiratory depression/arrest has been associated with use, especially when used for sedation in noncritical care settings

            Use lower end of dosing range in debilitated patients, including the elderly

            Do not administer by rapid IV injection in neonates (hypotension and seizures reported, especially when used concomitantly with fentanyl)

            Should be used only in settings (eg, hospital, ambulatory care settings, including physicians' or dentists' offices) that can provide continuous monitoring of respiratory and cardiac function; immediate availability of resuscitative drugs and age- and size-appropriate equipment for ventilation and intubations, as well as personnel trained in their use and skilled in airway management, should be ensured

            For deeply sedated patients, a dedicated individual other than the practitioner performing the procedure should monitor the patient throughout the procedure

            Use of the 1 mg/mL formulation or dilution of the 1 mg/mL or 5 mg/mL formulation is recommended to facilitate slower injection

            Adult dosing

            • The initial IV dose for sedation in adult patients may be as little as 1 mg but should not exceed 2.5 mg in a normal, healthy adult; lower doses are necessary for older (>60 years) or debilitated patients and for patients receiving concomitant narcotics or other CNS depressants; the initial dose and all subsequent doses should always be titrated slowly; administer over at least 2 minutes and allow an additional 2 or more minutes to fully evaluate the sedative effect

            Pediatric dosing

            • Doses of sedative medications in pediatric patients must be calculated on a mg/kg basis, and initial doses and all subsequent doses should always be titrated slowly; the initial pediatric dose of midazolam for sedation/anxiolysis/amnesia is age, procedure, and route dependent.

            Neonates

            • Midazolam should not be administered by rapid injection in the neonatal population; severe hypotension and seizures have been reported following rapid IV administration, particularly with concomitant use of fentanyl

            General anesthetics and sedation drugs in young children and pregnant women

            • Brain development
              • Prolonged or repeated exposure may result in negative effects on fetal or young children’s brain development
              • Caution with use during surgeries or procedures in children younger than 3 yr or in pregnant women during their third trimester
              • Assess the risk:benefit ratio in these populations, especially for prolonged procedures (ie, >3 hr) or multiple procedures

            Risks from concomitant use with opioids

            Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death

            Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

            Limit dosages and durations to the minimum required

            Follow patients for signs and symptoms of respiratory depression and sedation

            Inform patients and caregivers that potentially fatal additive effects may occur if drug is used with opioids and that such drugs should not be used concomitantly unless supervised by a health care provider

            Prescribers should advise caregivers that they expect to be informed immediately if a patient develops any new findings which are not typical of the patient’s characteristic seizure episode

            Addiction, abuse, and misuse

            On September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death

            Physical dependence can occur when taken steadily for several days to weeks, even as prescribed

            Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening

            Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction

            Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions

            Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk

            Contraindications

            Documented hypersensitivity

            Acute alcohol intoxication

            Acute narrow angle glaucoma

            Intrathecal/epidural use (formulations containing preservatives, such as, benzyl alcohol)

            Potent inhibitors of CYP3A4 including amprenavir, atazanavir, darunavir, indinavir, lopinavir, ritonavir, nelfinavir, ritonavir, saquinavir, tipranavir or oral or injectable midazolam with fosamprenavir

            Cautions

            Use caution in COPD, sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), depression, suicidal ideation, impaired gag reflex, heart failure, patients at risk of falls, or obese patients

            Anterograde amnesia reported with benzodiazepines

            Use caution in myasthenia gravis (allowable in limited circumstances)

            Use in narrow-angle glaucoma questionable

            May cause hypotension; may occur more frequently in patients receiving opioid analgesics

            Use caution in patient receiving other CNS depressants or psychoactive medications

            IV use in shock, coma, depressed respiration, patients who recently received other respiratory depressants not recommended

            Paradoxical reactions, including hyperactive or aggressive behavior reported

            Avoid extravasation of arterial formulation

            Does not protect against increases in heart rate or blood pressure

            May cause CNS depression and impair ability to perform hazardous tasks

            Not for use as antidepressant, analgesic, or antipsychotic agent

            Not for use in acute alcohol intoxication, shock, or coma

            Use of drug, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency

            Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate

            For patients treated more frequently than recommended, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose), to reduce risk of withdrawal reactions

            Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use

            In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months

            Do not inject by rapid bolus to neonates or for sedation

            IV

            • Associated with risk of potentially fatal respiratory depression and arrest
            • Wait 2-3 min to evaluate sedation before repeating dose
            • Monitor respiratory and cardiac function
            • Have resuscitative drugs and equipment available; must monitor respiratory and cardiovascular status while administering the drug IV
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            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled studies of midazolam intranasal in pregnant women

            Available data suggest benzodiazepines are not associated with marked increases in risk for congenital anomalies

            Clinical considerations

            • Exposure to benzodiazepines during the second and third trimesters of pregnancy or immediately prior to or during childbirth may increase risk for decreased fetal movement and/or fetal heart rate variability, floppy infant syndrome, dependence, and withdrawal
            • Clinical manifestations of withdrawal or neonatal abstinence syndrome may include hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting

            Pregnancy registry

            • Encourage women prescribed midazolam intranasal during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or register at http://www.aedpregnancyregistry.org/

            Animal studies

            • Administration of midazolam to rats and rabbits during the period of organogenesis or to rats during late pregnancy and throughout lactation at doses greater than those used clinically did not result in any apparent adverse effects on development
            • However, published data for benzodiazepines suggest potential of neuronal cell death and long-term effects on neurobehavioral and immunological function in animals following prenatal or early postnatal exposure at clinically relevant doses

            Lactation

            Midazolam is excreted in human milk

            Studies assessing effects in the breastfed infant or on milk production/excretion have not been performed

            Postmarketing experience suggests that breastfed infants of mothers taking benzodiazepines may experience lethargy, somnolence, and poor sucking

            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.

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            Pharmacology

            Mechanism of Action

            Binds receptors at several sites within the CNS, including the limbic system and reticular formation; effects may be mediated through GABA receptor system; increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA; the shift in chloride ions causes hyperpolarization (less excitability) and stabilization of the neuronal membrane

            Absorption

            Bioavailability: 36% (children); 40-50% (PO); >90% (IM)

            Onset: 15-20 min (IM, PO); 3-5 min (IV)

            Duration: 1-6 hr (IM)

            Duration of anterograde amnesia: 1 hr (IM); 20-40 min (IV)

            Peak plasma concentration: 90 ng/mL (IM)

            Peak effect: 0.5 hr (IM)

            Peak sedation: 30-60 min

            Distribution

            Protein bound: 97%

            Vd: 1.0-3.1 L/kg

            Metabolism

            Metabolized by liver via CYP3A4

            Metabolites: 1-hydroxymethylmidazolam

            Elimination

            Half-life: 2-6 hr

            Total body clearance: 0.25-0.54 L/hr/kg

            Excretion: Urine (90%); feces (2%)

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            Administration

            IV Incompatibilities

            Additive: Aminophylline(?), amoxicillin

            Syringe: Dimenhydrinate, heparin, pentobarbital, perphenazine, prochlorperazine, ranitidine

            Y-site: Albumin, amoxicillin, amphotericin B cholSO4, ampicillin, bumetanide, butorphanol, ceftazidime, cefuroxime, clonidine, dexamethasone, dobutamine(?), foscarnet, fosphenytoin, furosemide, hydrocortisone, imipenem-cilastatin, methotrexate, nafcillin, omeprazole, Na-bicarbonate, thiopental, TMP-SMX

            IV Compatibilities

            Solution: D5W, D5/NS, NS

            Additive: Cefuroxime, cimetidine, ciprofloxacin, furosemide, gentamicin, hydrocortisone, hydromorphone, metronidazole, ranitidine

            Syringe: Alfentanil, atracurium, atropine, buprenorphine, butorphanol, chlorpromazine, cimetidine, diamorphine, diphenhydramine, droperidol, fentanyl, glycopyrrolate, hydromorphone, hydroxyzine, meperidine, metoclopramide, morphine, nalbuphine, ondansetron, promazine, promethazine, scopolamine, sufentanil, thiethylperazine, trimethobenzamide

            Y-site: Abciximab, amikacin, amiodarone, argatroban, atracurium, bivalirudin, Ca-gluconate, cefazolin, cefotaxime, cimetidine, ciprofloxacin, cisatracurium, clindamycin, digoxin, diltiazem, dopamine, epinephrine, erythromycin, esmolol, etomidate, famotidine, fenoldopam, fentanyl, fluconazole, gatifloxacin, gentamicin, haloperidol, heparin, hetastarch, hydromorphone, insulin, labetalol, linezolid, lorazepam, methadone, methylprednisolone, metronidazole, milrinone, morphine, nicardipine, nitroglycerin, norepinephrine, pancuronium, piperacillin, KCl, propofol, ranitidine, remifentanil, sodium nitroprusside, sufentanil, theophylline, tirofiban, tobramycin, vancomycin, vecuronium

            IV Preparation

            Solution: 100 mg in 250 mL D5W or NS

            IV Administration

            Administered via infusion pump

            Give slowly over at least 2 min

            And wait at least 2 min when adjusting doses to desired effect

            Excessive dose or too rapid infusion may cause respiratory arrest

            Have resuscitation equipment available and monitor patient closely until effects of IV administration are known

            May dilute 1 mg/mL or 5 mg/mL in D5W or NS to facilitate slow injection

            IVP: Administer through side port of free-flowing IV

            Pediatric patients

            • As a group, pediatric patients generally require higher dosages of midazolam (mg/kg) than do adults
            • Younger (age <6 yr) may require higher dosages (mg/kg) than older pediatric patients, and may require close monitoring
            • Obese pediatric patients: Calculate dose based on ideal body weight

            Neonates

            • Do not administer by rapid injection; severe hypotension and seizures reported, particularly with concomitant fentanyl use

            IV monitoring

            • Monitor for irritation and infiltration
            • Extravasation can cause tissue damage and necrosis

            IM Administration

            Deep into large muscle mass

            Seizalam: For IM injection only; inject in mid-outer thigh (vastus lateralis muscle)

            Storage

            Unopened vials: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            midazolam oral
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            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Select a drug:
            Patient Education
            midazolam oral

            MIDAZOLAM - ORAL SYRUP

            (mid-AZE-oh-lam)

            COMMON BRAND NAME(S): Versed

            WARNING: Midazolam has a risk for abuse and addiction, which can lead to overdose and death. Taking this medication with alcohol or other drugs that can cause drowsiness or breathing problems (especially opioid medications such as codeine, hydrocodone) may cause very serious side effects, including death. To lower your risk, your doctor should have you take the smallest dose of midazolam that works, and take it for the shortest possible time. Be sure you know how to take midazolam and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if any of these very serious side effects occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness, difficulty waking up.Suddenly stopping this medication may cause serious (possibly fatal) withdrawal, especially if you have used it for a long time or in high doses. To prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist right away if you have any withdrawal symptoms such as headaches, trouble sleeping, restlessness, hallucinations/confusion, depression, nausea, or seizures. Withdrawal symptoms may sometimes last weeks to months.

            USES: This medication is used by children before a procedure or anesthesia to cause drowsiness, decrease anxiety, and cause forgetfulness of the surgery or procedure. It should be used while the child is under the care of a health professional. It is not for home or long-term use.Midazolam belongs to a class of medications called benzodiazepines, which produce a calming effect on the brain and nerves (central nervous system). It is thought to work by increasing the effect of a certain natural chemical (GABA) in the brain.

            HOW TO USE: See also Warning section.A healthcare professional will prepare and measure your dose. Take this medication by mouth as directed by your doctor. It is usually given as a single dose before a procedure or anesthesia.The dosage is based on your medical condition, response to therapy, weight, and other medications you may be taking.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Do not increase your dose, take it more often, or use it for a longer time than prescribed. Talk with the doctor if this medication stops working well. Properly stop the medication when so directed.Avoid eating grapefruit or drinking grapefruit juice while being treated with this medication unless the doctor instructs you otherwise. Grapefruit can increase the amount of certain medications in the bloodstream. Consult the doctor or pharmacist for more details.

            SIDE EFFECTS: See also Warning section.Nausea, vomiting, dizziness, or drowsiness may occur. If any of these effects persist or worsen, notify the doctor or pharmacist promptly.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.Tell your doctor right away if you have any serious side effects, including: mental/mood changes (e.g., agitation, aggressive behavior), uncontrollable movements (e.g., shaking/tremor), slow/fast heartbeat, vision changes (e.g., blurred vision).Get medical help right away if you have any very serious side effects, including: fainting, rapid/slow/shallow breathing.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 the 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: Before taking midazolam, tell the doctor or pharmacist if you are allergic to it; or to other benzodiazepines (e.g., diazepam); or if you have any other allergies. This product may contain inactive ingredients (such as cherry flavoring), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: glaucoma (narrow-angle).Before using this medication, tell the doctor or pharmacist your medical history, especially of: kidney disease, liver disease, breathing problems (e.g., chronic obstructive pulmonary disease-COPD, sleep apnea), heart disease (e.g., congestive heart failure), glaucoma (open-angle), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol).This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell the doctor or dentist that you are using this medication.Infants and children younger than 3 years using anesthesia or drugs for sedation (including midazolam) for procedures/surgeries may be at risk for slower brain growth. Talk to the doctor about the risks and benefits of this medication.This medication is not recommended for use during pregnancy. It may harm an unborn baby. Infants born to mothers who used similar medications for an extended time have had withdrawal symptoms such as irritability, abnormal/persistent crying, vomiting, or diarrhea. Consult your doctor for more details.This medication passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also Warning section.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.Some products that may interact with this drug include: delavirdine, HIV protease inhibitors (e.g., ritonavir, saquinavir, atazanavir), lonafarnib, sodium oxybate.Other medications can affect the removal of midazolam from your body, which may affect how midazolam works. Examples include azole antifungals (such as itraconazole, ketoconazole), macrolide antibiotics (such as erythromycin), cimetidine, rifamycins (such as rifabutin, rifampin), St. John's wort, certain anti-seizure medicines (such as carbamazepine, phenytoin), calcium channel blockers (such as diltiazem, verapamil), certain SSRIs (such as fluoxetine, fluvoxamine), nefazodone, conivaptan, among others.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are taking other products 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.

            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. Symptoms of overdose may include: drowsiness, confusion, loss of coordination.

            NOTES: Do not share this medication with others. Sharing it is against the law.This medication has been prescribed for your current procedure only. Do not use it later for another condition or procedure unless told to do so by the doctor. A different medication may be necessary in that case.Laboratory and/or medical tests (e.g., breathing, blood pressure, heartbeat) should be performed periodically to monitor your progress or check for side effects. Consult the doctor for more details.

            MISSED DOSE: Not applicable.

            STORAGE: Not applicable. This medication is given in a hospital, clinic, or doctor's office and will not be stored at home.

            Information last revised July 2021. Copyright(c) 2021 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.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.