Dosing & Uses
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
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (8)
- 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).
- nirmatrelvir
nirmatrelvir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with oral midazolam. If IV midazolam required, reduce midazolam dose and administer in setting that ensures close monitoring and appropriate medical management if respiratory depression occurs.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with benzodiazepines that are extensively metabolized by CYP3A4 may cause large increases in the concentration of these benzodiazepines, possibly leading to serious and/or life -hreatening events (eg, prolonged or increased sedation or respiratory depression); applies to repeat dosing with PO midazolam
Serious - Use Alternative (47)
- 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. - levoketoconazole
levoketoconazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
levoketoconazole 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.
- pacritinib
pacritinib 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 (277)
- 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.
- daridorexant
midazolam and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- darifenacin
darifenacin will increase the level or effect of 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.
- difelikefalin
difelikefalin and midazolam both increase sedation. 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.
- ganaxolone
midazolam and ganaxolone both increase sedation. Use Caution/Monitor.
- 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.
- methylphenidate transdermal
methylphenidate transdermal will increase the level or effect of midazolam by decreasing metabolism. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.
- 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
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 (18)
- 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.
- ruxolitinib topical
midazolam will increase the level or effect of ruxolitinib topical 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.
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
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
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.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%)
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)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 5 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam injection - | 1 mg/mL vial |  | |
| midazolam oral - | 2 mg/mL syrup |  | |
| midazolam oral - | 2 mg/mL syrup |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
midazolam injection
MIDAZOLAM - INJECTION
(mi-DAZ-oh-lam)
COMMON BRAND NAME(S): Versed
WARNING: Giving midazolam by injection into a vein can sometimes cause severe breathing problems which could rarely lead to brain damage or be fatal. The risk of serious breathing problems is higher with high doses or if midazolam is given too quickly into a vein. Midazolam must be used only under close medical supervision.Infants, children, older adults, or weak patients are more sensitive to the effects of midazolam. Lower doses should be used for these patients. Lower doses of midazolam should be used if a patient is also receiving other medications that cause drowsiness. Newborns must not be given midazolam by rapid injection because of the risk of very serious side effects.Midazolam has a risk for abuse and addiction, which can lead to overdose and death. Using 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 use the smallest dose of midazolam that works, and use it for the shortest possible time. Be sure you know how to use 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: Midazolam is used before surgery or a procedure. It helps to cause drowsiness, decrease anxiety, and to decrease your memory of the surgery or procedure. This medication may also be used to help with anesthesia or to sedate people who need a tube or machine to help with breathing. Midazolam works by calming the brain and nerves. It belongs to a class of drugs known as benzodiazepines.
HOW TO USE: See also Warning section.This medication is given by slow injection into a vein or muscle as directed by your doctor. It is usually given by a health care professional. The dosage is based on your medical condition, type of procedure you are having, other medications you are receiving, age, weight, and response to treatment.If you are using this medication at home, learn all preparation and usage instructions from your health care professional. Giving this medication too fast into a vein can cause serious side effects. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.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). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.
SIDE EFFECTS: See also Warning section.Pain/redness at the injection site or dizziness may occur. If any of these effects last or get worse, tell your 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 (such as agitation, aggressive behavior), shaking, uncontrolled movements, low blood pressure.Get medical help right away if you have any very serious side effects, including: slow/shallow breathing, seizures.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: See also Warning section.Before using midazolam, tell your doctor or pharmacist if you are allergic to it; or to other benzodiazepines (such as diazepam, lorazepam); or if you have any other allergies. This product may contain inactive ingredients which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: glaucoma, heart failure, kidney disease, liver disease, breathing problems (such as chronic obstructive lung disease-COPD, sleep apnea), 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, or until 24 hours after anesthesia and surgery, whichever is longer. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).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.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using midazolam. Midazolam may harm an unborn baby. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.This drug 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 are: conivaptan, delavirdine, HIV protease inhibitors (such as atazanavir), lonafarnib, ritonavir, sodium oxybate.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is used 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), other drugs for sleep or anxiety (such as alprazolam, diazepam, 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: confusion, slow reflexes, clumsiness, slow/shallow breathing, deep sleep, coma.
NOTES: Do not share this medication with others. Sharing it is against the law.Medical tests (such as breathing rate, blood pressure, oxygen saturation) should be done while you are using this medication. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule. Do not double the dose to catch up.
STORAGE: Check the product package for instructions on how to store this medication, or ask your pharmacist. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised August 2022. Copyright(c) 2022 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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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.
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- Compare formulary status to other drugs in the same class.
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