Midazolam Hydrochloride

Class: Benzodiazepines
VA Class: CN302
Chemical Name: 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine monohydrochloride
Molecular Formula: C₁₈H₁₃ClFN₃•HCl
CAS Number: 59467-96-8

• 
  

  Use only when adequate treatment facilities for appropriate management of therapy and complications are available.^{1 250}

  
  


• 
  

  For deeply sedated pediatric patients, an individual other than the clinician performing the procedure should be dedicated to monitoring the patient throughout the procedure.^{1 250}

  
  

• Respiratory Effects


• 
  

  Associated with respiratory depression and respiratory arrest, especially when used for sedation in non-critical-care settings.^{1 250} (See Respiratory and Cardiovascular Effects under Cautions.)

  
  


• 
  

  Death or hypoxic encephalopathy has resulted when respiratory depression was not recognized promptly and treated effectively.^{1 250}

  
  

• Dosage and Administration Considerations for Procedural Sedation


• 
  

  Initial IV dose for healthy adults should not exceed 2.5 mg.^{1 250} (See Dosage under Dosage and Administration.)

  
  


• 
  

  Lower dosages are necessary in patients >60 years of age, debilitated patients, and patients receiving concomitant opiates or other CNS depressants.^{1 250} (See Dosage and also Special Populations, under Dosage and Administration.)

  
  


• 
  

  Titrate initial and subsequent dosages slowly; administer the appropriate dose over ≥2 minutes and wait an additional 2 or more minutes to fully evaluate the sedative effect.¹

  
  


• 
  

  Administer by direct IV injection as the 1-mg/mL solution or dilute the 1- or 5-mg/mL solution to facilitate slower administration.¹

  
  

• Pediatric Dosage and Administration Considerations


• 
  

  Calculate pediatric dosage on a mg/kg basis.¹ Initial dose is dependent on age, procedure, and route; titrate subsequent dosages slowly.¹ (See Dosage: Pediatric Patients, under Dosage and Administration.)

  
  


• 
  

  Do not administer by rapid IV injection in neonates.¹ Severe hypotension and seizures have been reported following rapid IV administration, particularly with concomitant administration of fentanyl.¹

  
  

Introduction

Benzodiazepine;^{2 3 4 5 6 7 17 157} sedative, anxiolytic, amnesic,^{1 3 157 219} and hypnotic.^{2 4 7 70 84 86 104 177 178}

Uses for Midazolam Hydrochloride

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

Preoperatively, to produce sedation, relieve anxiety, and provide anterograde amnesia.^{1 3 157 219}

Some clinicians consider midazolam the benzodiazepine of choice for preoperative use for short surgical procedures because of its relatively rapid onset and short duration of effect and improved local tolerance at the site of injection compared with other currently available parenteral benzodiazepines.^{2 4 7 14 32 173 174 181}

Procedural Sedation

For procedural sedation, anxiolysis, and amnesia (alone or in combination with an opiate agonist)^{1 3 157} when administered prior to dental^{2 4 7 14 35 66 130 131 176} or minor surgical procedures or diagnostic, therapeutic, or endoscopic procedures such as upper GI endoscopy,^{1 2 3 7 71 72 73 74 75 76 77 78 79} bronchoscopy,^{1 2 3 80 157} cystoscopy,^{1 2 7 115 157} cardiac catheterization,^{1 2 7 35 85 157} coronary angiography,^{1 50 85 157} oncology procedures,¹ radiologic procedures¹ (e.g., computerized tomography),^{1 89} or suture of lacerations.¹

Some clinicians consider midazolam the benzodiazepine of choice for moderate sedation (formerly known as conscious sedation) prior to short procedures^{14 181} because of its relatively rapid onset^{2 4 7 14 74 75 79 86 178} and short duration of action,^{4 7 26 46 74 75 86 87 176 178} pronounced amnesic effect,^{7 25 73 74 75 78 79 115 178} and improved local tolerance at the site of injection^{2 7 14 25 74 75 76 78 79 86 87 176 177 178} compared with other currently available IV benzodiazepines.

Induction and Maintenance of Anesthesia

Induction of general anesthesia prior to administration of other anesthetic agents.^{1 2 3 4 7 14 25 35 70 84 87 95 99 100 101 102 103 104 105 106 107 108 125 157} Induction with midazolam provides anxiolysis, anterograde amnesia, and dose-related hypnotic effects (progressing from sedation to loss of consciousness), but not analgesia.^{2 4 7 70 84 86 104 177 178}

An acceptable alternative to thiopental for induction of anesthesia; midazolam’s slow onset and long duration of action and variability in response relative to those of thiopental preclude it from becoming the drug of choice for induction of anesthesia in most patients, particularly outpatients and patients undergoing short surgical procedures.^{2 4 7 181 182}

Maintenance of anesthesia during short surgical procedures,^{1 2 3 4 14 27 100 113 114} usually in conjunction with inhalation anesthetic agents, balanced anesthesia (e.g., nitrous oxide and oxygen), and/or opiate agonists (e.g., fentanyl).^{1 70 112 113 184} Should not be used alone for maintenance of anesthesia.^{2 27 70 184}

Use for maintenance of anesthesia during relatively long surgical procedures has not been fully evaluated to date.^{1 3 27 70 157 181}

Sedation in Critical-care Settings

Sedation of intubated and mechanically ventilated patients in a critical-care setting.^{1 220 221 222 223}

A preferred drug for sedation of acutely agitated patients in critical-care settings because of its rapid onset and short duration of action.²³⁵

As effective as propofol and appears to have a better adverse effect profile (e.g., less hypotension) than propofol;^{220 221 223} however, midazolam appears to have a more variable effect on recovery of consciousness and time to recovery of function after cessation of therapy than propofol.^{220 223}

Recommended for short-term (≤24 hours) sedation only, since the effects of the drug on awakening and the time to extubation are unpredictable when midazolam infusions are administered over longer periods (e.g., exceeding 48–72 hours).²³⁵

Insomnia

Has been used for short-term management of insomnia†.^{4 7 116 117 118 119 120 121 122 123}

Agitation

Has been used for management of acute agitation†.^{53 90 146 147 148 181}

Midazolam Hydrochloride Dosage and Administration

General

• 
  

  Adjust dosage according to individual requirements and response, age, body weight, physical and clinical status, underlying pathologic condition(s), type and amount of premedication or concomitant medication, and the nature and duration of the surgical or other procedure; however, individual response also may vary independent of these factors.^{1 3 157 163 193}

  
  


• 
  

  Facilities for administration of oxygen and controlled respiration should be readily available during and immediately following IV administration.^{1 3 193}

  
  


• 
  

  Oral solution is intended for use in monitored settings (e.g., hospital, ambulatory care settings including physician and dental offices) only; is not intended for chronic or home use.²¹⁹

  
  

Administration

Administer orally,²¹⁹ by IM injection, or by slow IV injection ^{1 2 3 4 7 14 157 193} or continuous IV infusion.^{1 36 90 150 181 219} Avoid intra-arterial injection or extravasation of the drug.¹ Do not administer intrathecally or epidurally.¹

Oral Administration

Consult manufacturer’s labeling for instruction on use of the special press-in bottle adapter and oral dispensers for administration of the oral solution.²¹⁹

Administer from the individual oral dispenser directly into the child’s mouth; do not mix the oral solution with any other liquid (e.g., grapefruit juice) prior to administration.²¹⁹

Effect of food on absorption of the oral solution has not been determined, but food intake generally is precluded prior to procedural sedation in pediatric patients.²¹⁹

IM Administration

Administer deeply into a large muscle mass.^{1 3 157}

IV Administration

For solution and drug compatibility, see Compatibility under Stability.

Direct IV injection should be made in incremental doses.^{1 3 157 163}

Use of the 1-mg/mL injection is recommended to facilitate slow direct IV injection of the drug;^{1 193} the 1- and 5-mg/mL injections may be diluted with a compatible diluent (see Solution Compatibility under Stability) to facilitate slower injection.¹

Dilution

For administration as a continuous IV infusion, dilute the 5-mg/mL injection to a concentration of 0.5 mg/mL with a compatible diluent (see Solution Compatibility under Stability).¹

Rate of Administration: General

Rapid IV administration may result in respiratory depression, airway obstruction, and/or respiratory arrest.¹

Rate of Administration: Pediatric Patients

IV injection for preoperative or procedural sedation: Administer IV midazolam over 2–3 minutes; wait an additional 2–3 minutes to fully evaluate the sedative effect before initiating a procedure or repeating a dose.¹

Do not administer by rapid IV injection in neonates.¹ (See Boxed Warning.)

Continuous IV infusion: Individualize the infusion rate.¹ (See General and also Pediatric Patients: Sedation in Critical-care Settings, under Dosage and Administration.)

Rate of Administration: Adults

IV injection for procedural sedation: Administer the appropriate dose as a 1-mg/mL solution over ≥2 minutes; allow ≥2 minutes to evaluate the sedative effect.^{1 163 193}

IV injection for induction of anesthesia: Administer the appropriate dose as a 1-mg/mL solution over 20–30 seconds; supplemental doses may be given at 2-minute intervals.^{1 3 157}

Continuous IV infusion: Individualize the infusion rate.¹ (See General and also Adults: Sedation in Critical-care Settings, under Dosage and Administration.)

Dosage

Available as midazolam hydrochloride; dosage expressed in terms of midazolam.^{1 3}

Pediatric Patients

The depth of sedation/anxiolysis needed depends on the type of procedure being performed.¹ It is vital to titrate the midazolam dose and the dose of other concomitant drugs slowly to achieve the desired clinical effect.¹

Unlike adult patients, pediatric patients generally receive increments of midazolam on a mg/kg basis; calculate dosage in obese children on the basis of ideal body weight.^{1 219} Pediatric patients generally require higher dosages on a mg/kg basis than adults;¹ patients <6 years of age generally require higher drug dosages on a mg/kg basis than older children and may require closer monitoring.^{1 219}

It is essential to wait 2–3 minutes to fully evaluate the sedative effect before starting the procedure or administering a repeat dose; peak EEG effects are not achieved as quickly as with diazepam, since midazolam is water soluble.¹

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

Oral

Children 6 months to 16 years of age: 250–500 mcg/kg as a single dose, depending on the status of the patient and the desired effect (maximum 20 mg).²¹⁹

250 mcg/kg may be sufficient for children 6–16 years of age or for cooperative patients, especially if the anticipated intensity and duration of sedation is less critical.²¹⁹

Younger children (e.g., 6 months to <6 years of age) and less cooperative patients may require a higher than usual dose of up to 1 mg/kg (maximum 20 mg).²¹⁹

Consider an initial dose of 250 mcg/kg for patients 6 months to 16 years of age with cardiac or respiratory compromise, other higher-risk surgical patients, and those who have received concomitant opiates or other CNS depressants.²¹⁹

IV

Nonintubated patients <6 months of age: Limited dosing information is available.¹ Dosing recommendations are unclear because of uncertainty about when a patient transfers from a neonatal to pediatric physiology; however, titration of the dose in small increments to clinical effect and careful monitoring are essential, since patients <6 months of age are vulnerable to airway obstruction and hypoventilation.¹

Children 6 months to 5 years of age: Initially, 50–100 mcg/kg; a total dose of up to 600 mcg/kg may be required to reach the desired endpoint, but total dose usually does not exceed 6 mg.¹

Children 6–12 years of age: Initially, 25–50 mcg/kg; a total dose of up to 400 mcg/kg may be required to reach the desired endpoint, but total dose usually does not exceed 10 mg.¹

Adolescents 12–16 years of age: Dose as adults; although some patients in this age range may require higher than recommended adult doses, total dose usually does not exceed 10 mg.¹

Dosage must be reduced in pediatric patients receiving opiates or other sedatives as premedications; higher-risk or debilitated patients may require lower dosages regardless of whether premedication was administered.¹

IM

Pediatric patients ≥1 month of age: 100–150 mcg/kg; doses up to 500 mcg/kg have been used for more anxious patients.¹ Total dose usually does not exceed 10 mg, although this has not been systematically studied.¹

If midazolam is administered with an opiate, reduce the initial dose of each drug.¹

Procedural Sedation

Oral

Children 6 months to 16 years of age: 250–500 mcg/kg as a single dose, depending on the status of the patient and the desired effect (maximum 20 mg).²¹⁹

250 mcg/kg may be sufficient for children 6–16 years of age or for cooperative patients, especially if the anticipated intensity and duration of sedation is less critical.²¹⁹

Younger children (e.g., 6 months to <6 years of age) and less cooperative patients may require a higher than usual dose of up to 1 mg/kg (maximum 20 mg).²¹⁹

Consider an initial dose of 250 mcg/kg for patients 6 months to 16 years of age with cardiac or respiratory compromise, other higher-risk surgical patients, and those who have received concomitant opiates or other CNS depressants.²¹⁹

IV

Nonintubated patients <6 months of age: Limited dosing information is available.¹ Dosing recommendations are unclear because of uncertainty about when a patient transfers from a neonatal to pediatric physiology; however, titration of the dose in small increments to clinical effect and careful monitoring are essential, since patients <6 months of age are vulnerable to airway obstruction and hypoventilation.¹

Children 6 months to 5 years of age: Initially, 50–100 mcg/kg; a total dose of up to 600 mcg/kg may be required to reach the desired endpoint, but total dose usually does not exceed 6 mg.¹

Children 6–12 years of age: Initially, 25–50 mcg/kg; a total dose of up to 400 mcg/kg may be required to reach the desired endpoint, but total dose usually does not exceed 10 mg.¹

Adolescents 12–16 years of age: Dose as adults;¹ some patients may require higher than recommended adult doses, but total dose usually does not exceed 10 mg.¹

Dosage must be reduced in pediatric patients receiving opiates or other sedatives as premedications; higher-risk or debilitated patients may require lower dosages regardless of whether premedication was administered.¹

IM

Children ≥1 month of age: 100–150 mcg/kg; doses up to 500 mcg/kg have been used for more anxious patients.¹ Total dose usually does not exceed 10 mg, although this has not been systematically studied.¹

If midazolam is administered with an opiate, reduce the initial dose of each drug.¹

Sedation in Critical-care Settings

Neonates

IV

IV loading doses should not be used in neonates; rather, the infusion may be administered more rapidly for the first several hours to establish therapeutic plasma drug concentrations.¹

Preterm neonates (<32 weeks’ gestation): Initially, 30 mcg/kg per hour (0.5 mcg/kg per minute).¹

Term neonates (≥32 weeks’ gestation): Initially, 60 mcg/kg per hour (1 mcg/kg per minute).¹

Reassess the infusion rate carefully and frequently, particularly after approximately the first 24 hours, to administer the lowest possible effective dosage and to reduce the potential for drug accumulation.¹ This is particularly important because of the potential for adverse effects related to benzyl alcohol metabolism.¹ (See Pediatric Use under Cautions.)

Non-neonatal Pediatric Patients (Intubated)

IV

Initially, 50–200 mcg/kg as a loading dose, followed by a continuous IV infusion initiated at a rate of 60–120 mcg/kg per hour (1–2 mcg/kg per minute) to maintain the clinical effect.¹

Increase or decrease the infusion rate as required, generally by 25% of the initial or subsequent infusion rate, or administer supplemental IV doses to increase or maintain the desired effect.¹ Perform frequent patient assessments at regular intervals using standard pain/sedation scales.¹

Midazolam infusions have been used in children whose trachea was intubated but who were allowed to breathe spontaneously; however, assisted ventilation is recommended in those who are receiving other CNS depressants (e.g., opiates).¹

In hemodynamically compromised children, initiate therapy by titrating the usual loading dose in small increments; monitor the patient closely for hemodynamic instability (e.g., hypotension).¹

Adults

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

IM

70–80 mcg/kg (about 5 mg) administered approximately 30–60 minutes prior to surgery.^{1 3 14 180 181} If administered concomitantly with an opiate agonist or other CNS depressant, the midazolam dosage must be individualized and reduced.¹

Procedural Sedation

IV

Initial dose of ≤2.5 mg in healthy adults <60 years of age; some patients may respond to as little as 1 mg.^{1 193} Total dose of ≤5 mg generally is adequate.¹

If a thorough clinical evaluation clearly indicates a need for additional doses to maintain the desired level of sedation, administer additional doses in increments of approximately 25% of the initial dose.^{1 3}

A total dose up to 200 mcg/kg has been used rarely, particularly if an opiate agonist was not used concomitantly;^{3 157 191 192} avoid such doses, if possible.¹⁸⁰

Some clinicians recommend initiating dosing with 0.5–2 mg and repeating doses, as necessary, at 2- to 3-minute intervals up to a total dose of 100–150 mcg/kg.^{14 181}

When used concomitantly with an opiate agonist or other CNS depressant, reduce midazolam dosage by about 30%.^{1 3 14 157}

Induction and Maintenance of Anesthesia

IV

Individual response is variable, especially when opiate agonist premedication is not used; therefore, titrate dosage carefully to the desired clinical effect, taking into consideration the patient’s age and clinical status.^{1 2 3 70}

When used prior to other anesthetic agents for the induction of general anesthesia,^{1 3} the initial dose of each of these agents may be substantially reduced, in some instances to as low as 25% of the usual initial dose of the individual agents.¹

Without Opiate Premedication

IV

Initial dose of 300–350 mcg/kg administered IV over 20–30 seconds in patients <55 years of age; allow approximately 2 minutes for clinical effect.^{1 3 157 180} Alternatively, some clinicians recommend an initial dose of 200 mcg/kg.^{14 144 181}

Supplemental doses of about 25% of the initial dose may be given as necessary to complete induction or for maintenance of sedation or anesthesia.^{1 3 14 157} Alternatively, induction of anesthesia may be completed with inhalation agents.^{1 3 157}

Total IV induction doses of up to 600 mcg/kg may be required in some resistant patients, but such doses may prolong recovery from anesthesia.^{1 3 4 100 157}

With Opiate or Sedative Premedication

IV

Initial dose of 150–350 mcg/kg as an induction dose in patients <55 years of age.^{1 3 157} Usual induction dose is 250 mcg/kg administered IV over 20–30 seconds; allow approximately 2 minutes for clinical effects.^{1 3 157}

For maintenance of anesthesia (as a component of balanced anesthesia) during short surgical procedures: Following premedication with an opiate agonist,^{1 3} administer in incremental IV doses of approximately 25% of the initial induction dose when lightening of anesthesia is evident.^{1 3} Repeat as necessary according to patient’s response to maintain the required level of anesthesia.^{1 3}

Sedation in Critical-care Settings

IV

If a loading dose is necessary to initiate sedation rapidly, 10–50 mcg/kg (approximately 0.5–4 mg) administered slowly or infused over several minutes.¹ Repeat this dose at 10- to 15-minute intervals until adequate sedation is achieved.¹ Usual initial infusion rate for maintenance of sedation is 20–100 mcg/kg per hour (approximately 1–7 mg per hour).¹ Higher loading doses or maintenance infusion rates occasionally may be required.¹

In patients with residual effects from anesthetic agents or in those currently receiving other sedatives or opiates, use the lowest recommended dosage.¹

Infuse at the lowest rate that produces the desired level of sedation.¹ Assess sedation at regular intervals and adjust the infusion rate up or down by 25–50% of the initial infusion rate to ensure adequate titration of the sedation level.¹ Larger adjustments or even a small, incremental dose may be necessary if rapid changes in the level of sedation are required.¹ Decrease infusion rate by 10–25% every few hours to find the minimum effective infusion rate.¹

Consider administering an opiate concomitantly in patients experiencing agitation, hypertension, or tachycardia in response to noxious stimuli but who otherwise are adequately sedated.¹ Addition of an opiate generally will reduce the minimum effective midazolam infusion rate.¹

Prescribing Limits

Pediatric Patients

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia or Procedural Sedation

Oral

Children 6 months to 16 years of age: Maximum 20 mg.²¹⁹

IV

Manufacturer states that the total dose usually does not exceed 6 mg in pediatric patients 6 months to 5 years of age or 10 mg in those 6–16 years of age.¹

IM

Manufacturer states that the total dose usually does not exceed 10 mg in pediatric patients ≥1 month of age, although this has not been systematically studied.¹

Procedural Sedation

IV

Manufacturer states that the total dose usually does not exceed 6 mg in pediatric patients 6 months to 5 years of age or 10 mg in those 6–16 years of age.¹

Adults

Procedural Sedation

IV

Initial dose for sedation should not exceed 2.5 mg.¹

Special Populations

Renal Impairment

Use with caution and individualize dosage carefully.^{1 2 4 7 31 33 34 42 70 163} (See Renal Impairment under Cautions.)

CHF

Use with caution and individualize dosage carefully.^{1 3 35 50 163} (See Special Populations under Pharmacokinetics and also Other Populations under Dosage and Administration.)

Geriatric Patients

Reduce initial dose, since some degree of impairment in 1 or more organ systems frequently is present.^{1 3 157 163 193} Dosage requirements in this age group generally appear to decrease with increasing age;^{1 163} consider the possibility of profound and/or prolonged effects in older and/or debilitated patients.¹ Low doses usually are required when midazolam is administered with or without premedication.^{1 3 157 163 193}

Dosage titration should be more gradual in patients ≥60 years of age receiving midazolam for procedural sedation and in those ≥55 years of age receiving the drug for induction of anesthesia.^{1 157 163 180}

Use the smallest effective dose.^{1 3} Excessive doses or rapid or single large IV injections may result in respiratory depression and/or arrest.^{1 3 157 163 193}

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia in Patients ≥60 Years of Age

IM: In patients ≥60 years of age who did not receive concomitant opiate agonist therapy, doses of 2–3 mg (20–50 mcg/kg) have produced adequate preoperative sedation;¹ 1 mg may be sufficient in some geriatric patients if the anticipated intensity and duration of sedation is less critical.¹

Procedural Sedation in Patients ≥60 Years of Age

IV: Initial dose of ≤1.5 mg ^{1 193} over ≥2 minutes; wait ≥2 minutes to fully evaluate the clinical response.¹ If further sedation is required, the dosage may be further titrated in small increments (≤1 mg) of the initial dose to the desired effect (e.g., onset of slurred speech).¹ Total dose of ≤3.5 mg usually is adequate.¹

If a thorough clinical evaluation clearly indicates a need for additional doses to maintain the desired level of sedation, administer additional doses that are^{1 3} reduced by ≥25%.¹⁴

When used concomitantly with an opiate or other CNS depressant, reduce midazolam dosage to about 50% of that used in young, unpremedicated adults.¹

Induction and Maintenance of Anesthesia in Patients ≥55 Years of Age

IV: Manufacturer recommends an initial IV induction dose of 300 mcg/kg if premedication has not been given.^{1 3 157}

If premedication has been given, manufacturer recommends an initial induction dose of 200 mcg/kg if the patient is a good risk (e.g., ASA I and II) surgical patient.^{1 3}

Other Populations

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia in Patients with COPD or Other Higher-risk Surgical Patients

IM: Individualize and reduce dosage in patients with COPD and in other higher-risk surgical patients.¹

Procedural Sedation in Chronically Ill or Debilitated Patients

IV: Smaller increments in dosage and slower rate of injection recommended in patients with chronic debilitating illnesses (e.g., CHF) or decreased pulmonary reserve because of the increased risk of underventilation or apnea and because the peak drug effect may occur later.^{1 3 157 163 180 193}

Administer initial dose of ≤1.5 mg ^{1 193} over ≥2 minutes; wait ≥2 minutes to fully evaluate the clinical response.¹ If further sedation is required, the dosage may be further titrated in small increments (≤1 mg) of the initial dose to the desired effect (e.g., onset of slurred speech).¹ Total dose of ≤3.5 mg usually is adequate.¹

If a thorough clinical evaluation clearly indicates a need for additional doses to maintain the desired level of sedation, administer additional doses that are^{1 3} reduced by ≥25%.¹⁴

When used concomitantly with an opiate or other CNS depressant, reduce midazolam dosage to about 50% of that used in young, unpremedicated adults.¹

Induction and Maintenance of Anesthesia in Patients with Severe Systemic Disease or Other Debilitation

IV: Unpremedicated patients: Initial dose of 200–250 mcg/kg usually is adequate; doses as low as 150 mcg/kg may be adequate for induction in some patients.^{1 3 157}

Premedicated patients: Doses as low as 150 mcg/kg may be adequate for induction in some patients.^{1 3 157}

Cautions for Midazolam Hydrochloride

Contraindications

• 
  

  Known hypersensitivity to midazolam or any ingredient in the formulation; oral solution contraindicated in patients with allergies to cherries.^{1 219}

  
  


• 
  

  Acute angle-closure glaucoma (but may be administered to patients with open-angle glaucoma who are receiving appropriate therapy).¹

  
  


• 
  

  Midazolam hydrochloride injection contains benzyl alcohol and is not intended for intrathecal or epidural administration.¹

  
  

Warnings/Precautions

Warnings

Respiratory and Cardiovascular Effects

Possible serious and occasionally fatal adverse effects, including respiratory depression, airway obstruction, oxygen desaturation, apnea, respiratory arrest, and/or cardiac arrest,^{1 2 37 137 139 157 163 175 193} particularly in patients receiving midazolam concomitantly with other CNS depressants^{1 250} and in those undergoing procedures involving the airway without the protective effect of an endotracheal tube, in geriatric or severely ill patients, or in patients with limited pulmonary reserve or unstable cardiovascular status, or if the drug is administered IV too rapidly.¹

Possible hypotensive episodes requiring treatment during or following diagnostic or surgical manipulation.¹ Concomitant administration of an opiate agonist may increase the risk of severe hypotension.^{1 4 14 112}

Do not administer parenterally to patients with shock, those who are comatose, or those with acute alcohol intoxication and accompanying depression of vital signs.¹ Exercise caution if administered IV to patients with uncompensated acute illnesses, including severe fluid or electrolyte imbalances.¹

Slow administration and individualized titration of dosage is required.¹

Administer orally or IV only in settings in which continuous monitoring of respiratory and cardiac function (i.e., pulse oximetry) is possible.^{1 250} Potential for hypoxia and/or cardiac arrest if early signs of hypoventilation, airway obstruction, or apnea are not corrected immediately.¹ Monitoring of vital signs should continue during recovery period.¹

Should be administered as an induction agent only by individuals who are experienced in the use of general anesthesia.^{1 163 193 219}

Should be used for procedural sedation only in the presence of personnel experienced in early detection of underventilation, maintenance of an adequate airway, and respiratory support.^{1 163 193 219} When the complexity of the procedure prohibits adequate monitoring by the attending clinician, additional personnel competent in monitoring and managing potential complications should be in attendance.^{1 163 175} For deeply sedated pediatric patients, an individual other than the clinician performing the procedure should be dedicated to monitoring the patient throughout the procedure.^{1 250}

Facilities, age- and size-appropriate equipment for bag/mask/valve ventilation and intubation, drugs, skilled personnel necessary for ventilation an