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Pharmacologic class: Benzodiazepine
Therapeutic class: Anxiolytic, sedative-hypnotic, adjunct for general anesthesia induction
Controlled substance schedule IV
Pregnancy risk category D
FDA Box Warning
• I.V. form is linked to respiratory depression and respiratory arrest, especially when used for sedation in non-critical care settings. In some cases, where this wasn't recognized promptly and treated effectively, death or hypoxic encephalopathy resulted. Use I.V. form only in hospital or ambulatory care setting that provides continuous monitoring of respiratory and cardiac function. Ensure immediate availability of resuscitative drugs and equipment as well as personnel trained in their use and skilled in airway management. For deeply sedated pediatric patient, dedicated individual should monitor patient throughout procedure.
• Patients who are debilitated, older than age 60, or receiving concurrent opioids or other CNS depressants require lower dosages. Slowly titrate initial dose and all subsequent doses; give over at least 2 minutes and allow 2 or more additional minutes to fully evaluate sedative effect. In pediatric patients, calculate dosage on mg/kg basis, and titrate slowly.
• Don't give by rapid injection to neonates. Severe hypotension and seizures may result.
Unknown. Thought to suppress CNS stimulation at limbic and subcortical levels by enhancing the effects of gamma-aminobutyric acid, an inhibitory neurotransmitter.
Injection: 1 mg/ml, 5 mg/ml
Syrup: 2 mg/ml
Indications and dosages
➣ To induce general anesthesia
Adults younger than age 55: 0.3 to 0.35 mg/kg I.V. over 20 to 30 seconds if patient hasn't received premedication, or 0.15 to 0.35 mg/kg (usual dosage of 0.25 mg/kg) I.V. over 20 to 30 seconds if patient has received premedication. Wait 2 minutes to evaluate effect. Additional increments of 25% of initial dosage may be needed to complete induction.
➣ Continuous infusion to initiate sedation
Adults: When rapid sedation is required, give loading dose of 0.01 to 0.05 mg/kg I.V. slowly; repeat dose q 10 to 15 minutes until adequate sedation occurs. To maintain sedation, infuse at initial rate of 0.02 to 0.10 mg/kg/hour (1 to 7 mg/hour). Adjust infusion rate as needed.
➣ Preoperative sedation, anxiolysis, and amnesia
Adults: 0.07 to 0.08 mg/kg I.M. 30 minutes to 1 hour before surgery. For I.V. administration in healthy adults younger than age 60, give initial dose of 1 mg and titrate slowly to effect. Some patients may respond adequately to 1-mg dose. Don't give more than 2.5 mg over a 2-minute period. Total dosage above 5 mg is rarely necessary. Wait at least 2 minutes after additional doses to assess effect.
➣ Anxiolysis and amnesia before diagnostic, therapeutic, and endoscopic procedures or anesthesia induction
Children: 0.25 to 0.5 mg/kg P.O. as a single dose. Maximum dosage is 20 mg.
• Elderly patients
• Children or neonates
• Hypersensitivity to drug, its components, or other benzodiazepines
• Acute closed-angle glaucoma
• Allergy to cherries (syrup preparation)
Use cautiously in:
• pulmonary disease, heart failure, renal impairment, severe hepatic impairment
• obese pediatric patients
• elderly or debilitated patients
• pregnant or breastfeeding patients
• children and neonates.
☞ Keep oxygen and resuscitation equipment at hand in case severe respiratory depression occurs.
• Inject I.M. deep into large muscle mass.
• Know that drug may be mixed in same syringe as meperidine, atropine, scopolamine, or morphine.
• Dilute concentrate for I.V. infusion to 0.5 mg/ml using dextrose 5% in water or normal saline solution. Infuse over at least 2 minutes; then wait at least 2 minutes before giving second dose. Be aware that excessive dosage or rapid I.V. delivery may cause severe respiratory depression.
• Give oral form with liquid, but never with grapefruit juice.
CNS: headache, oversedation, drowsiness, agitation and excitement (in children)
CV: hypotension, irregular pulse, bradycardia, arrhythmias, cardiac arrest
GI: nausea, vomiting
Respiratory: decreased respiratory rate, hiccups, apnea, respiratory arrest
Other: pain and tenderness at injection site
Drug-drug. CNS depressants (such as some antidepressants, antihistamines, barbiturates, opioids, tranquilizers), respiratory depressants: potentiation of CNS effects of these drugs
Diltiazem, verapamil: increased midazolam blood level
Erythromycin: decreased midazolam clearance
Hormonal contraceptives: prolonged midazolam half-life
Rifampin: decreased midazolam blood level
Theophylline: increased sedative effect of midazolam
Drug-food. Grapefruit juice: increased bioavailability of oral midazolam
Drug-herbs. Chamomile, kava, skullcap, valerian: increased CNS depression
Drug-behaviors. Alcohol use: potentiation of midazolam effects
• Monitor vital signs, ECG, respiratory status, and oxygen saturation.
• Assess neurologic status closely, especially in pediatric patient.
• Watch for nausea and vomiting.
• Advise patient that drug causes perioperative amnesia.
• If patient will use oral drug at home, instruct him to take it with liquid but never grapefruit juice.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Tell female patient to inform prescriber is she is pregnant or breastfeeding.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, foods, herbs, and behaviors mentioned above.