What Is Midazolam and How Does It Work?
Midazolam is a prescription medication used to treat the symptoms of Status Epilepticus, sedation of intubated or ventilated patients, anesthesia and preoperative sedation or Anxiolysis with Anterograde Amnesia.
- Midazolam is available under the following different brand names: Seizalam, Versed (DSC)
What Are Dosages of Midazolam?
Adult and Pediatric dosage
Oral syrup: Schedule IV
- 2mg/mL (generic)
- Injectable solution: Schedule IV
- 1mg/mL (generic)
- 5mg/mL (generic, Seizalam)
Preoperative Sedation/Anxiolysis with Anterograde Amnesia
- 70-80 mcg/kg (dose range ~5 mg) 30-60 minutes before surgery (reduce 50% for chronically ill or geriatric patients)
- 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 over 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 every 2-3 minutes as needed; 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 as needed by slow titration; reduce 30% if premedicated with opiate (50% in elderly/chronically ill)
- Younger than 55 years of age 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 as needed to complete induction; may use up to 0.6 mg/kg total dose in resistant cases, but such dosing may prolong recovery.
- Older than 55 years without premedication and with no systemic disease, in a patient who is not weak: 300 mcg/kg over 20-30 second initially; wait 2-3 minutes to evaluate sedative effect after each dose adjustment
- Older than 55 years without premedication but presence of system 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
- Older than 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
- May administer increments of 25% of induction dose as needed when there are signs that anesthetic effects are lightening
- Loading dose: 50-150 mcg/kg IV over 2-3 minutes as needed to achieve desired effect
- Continuous infusion: 1-2 mcg/kg/min IV infusion
- IV loading dose should not be used in neonates
- Continuous infusion: 0.5 mcg/kg/min IV infusion
- 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 every 5-15 min as needed
- Maintenance: Initial, 20-100 mcg/kg/hr infusion: titrate up or down 25-50% as needed
- 500-750 mcg/kg orally 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
- Younger than 6 months: Initial, 50 mcg/kg IV over 2-3 minutes; titrate with small increments to clinical effect; monitor closely; data are limited in non-intubated infants
- 6 months-6 years: Initial, 50-100 mcg/kg IV over 2-3 minutes; repeat every 2-3 minutes as needed; 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 every 2-3 minutes as needed; may require up to 400 mcg/kg; not to exceed 10 mg total dose
- Seizalam: Indicated for treatment of status epilepticus in adults
- 10 mg IM
Dosage Considerations – Should be Given as Follows:
- See "Dosages."
What Are Side Effects Associated with Using Midazolam?
Common side effects of Midazolam include:
- amnesia or forgetfulness after the procedure,
- vomiting, and
- pain, redness, or tenderness at the injection site
Serious side effects of Midazolam include:
- difficulty breathing,
- swelling of the face, lips, tongue, or throat,
- trouble breathing,
- weak or shallow breathing,
- slow heart rate,
- uncontrolled muscle movements,
- unusual thoughts or behavior
Rare side effects of Midazolam include:
What Other Drugs Interact with Midazolam?
If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.
- Midazolam has severe interactions with the following drugs:
- Midazolam has serious interactions with at least 45 other drugs.
- Midazolam has moderate interactions with at least 272 other drugs.
- Midazolam has minor interactions with at least 17 other drugs.
This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.
What Are Warnings and Precautions for Midazolam?
- 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
Effects of drug abuse
- See “What are Side Effects Associated with Using Midazolam?”
- See “What Are Side Effects Associated with Using Midazolam?”
- 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
- 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 and Lactation
- 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/
- 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