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Pronunciation: meh-DAZE-oh-lam HIGH-droe-KLOR-ide
Class: General anesthetic
- Syrup 2 mg/mL
- Injection 1 mg (as hydrochloride)/mL
- Injection 5 mg (as hydrochloride)/mL
Depresses all levels of CNS, including limbic and reticular formation, probably through increased action of GABA, which is major inhibitory neurotransmitter in brain.
Midazolam is rapidly absorbed. The oral AUC ratio of metabolite to midazolam is higher than IV. Mean T max is 0.17 to 2.65 h and the absolute bioavailability is 36%.
Midazolam exhibits linear pharmacokinetics (dose 0.25 to 1 mg/kg). Approximately 97% is protein bound (mainly to albumin). The mean steady-state Vd is 1.24 to 2.02 L/kg in children 6 mo to younger than 16 yr of age receiving 0.15 mg/kg IV.
Midazolam is subject to substantial intestinal and hepatic first-pass metabolism by CYP-450 3A4. Active metabolite is alpha-hydroxymidazolam.
Onset is 10 to 20 min.
Special PopulationsHepatic Function Impairment
Following oral administration (15 mg), C max and bioavailability were 43% and 100% higher, respectively. Cl was reduced 40% and t ½ increased 90%. Doses should be titrated.CHF
Following oral administration (7.5 mg), t ½ increased 43%.
Indications and Usage
Preoperative sedative; conscious sedation prior to diagnostic, therapeutic or endoscopic procedures; induction of general anesthesia; supplement to nitrous oxide and oxygen for short surgical procedures; infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in critical care setting.
Treatment of epileptic seizures; alternative for the termination of refractory status epilepticus.
Hypersensitivity to benzodiazepines; uncontrolled pain; existing CNS depression; shock; acute narrow-angle glaucoma; acute alcohol intoxication; coma.
Dosage and AdministrationPreoperative Sedative
IM 0.07 to 0.08 mg/kg approximately 1 h before surgery.Conscious Sedation
IV 1 to 2.5 mg as 1 mg/mL dilution over 2 min. Increase by small increments to total dose of no more than 5 mg in at least 2 min intervals; use less if patient is premedicated with other CNS depressants.Children
IM 0.1 to 0.15mg/kg. Doses up to 0.5 mg/kg have been used for more anxious patients. Total dose usually does not exceed 10 mg.Children (younger than 6 mo of age)
IV Titrate in small increments to clinical effect and monitor carefully.Children (6 mo to 5 yr of age)
IV 0.05 to 0.1 mg/kg. Total dose up to 0.6 mg/kg may be necessary. Do not exceed 6 mg.Children (6 to 12 yr of age)
IV 0.025 to 0.05 mg/kg. Total dose up to 0.4 mg/kg. Do not exceed 10 mg.Children (12 to 16 yr of age)
IV Dose as adults.Induction of General Anesthesia
IV 0.3 to 0.35 mg/kg as 1 mg/mL dilution over 20 to 30 sec, allowing 2 min for effect; may use increments of approximately 25% of initial dose.Premedicated Adults
IV 0.15 to 0.35 mg/kg over 20 to 30 sec.Continuous Infusion
Adults Loading dose
0.01 to 0.05 mg/kg given slowly over several minutes. May be repeated at 10- to 15-min intervals until adequate sedation is achieved.Maintenance
0.02 to 0.1 mg/kg/h (1 to 7 mg/h).Children (non-neonatal)
IV 0.05 to 0.2 mg/kg over at least 2 to 3 min in patients whose trachea is intubated. Loading dose may be followed by continuous IV infusion at 0.06 to 0.12 mg/kg/h (1 to 2 mcg/kg/min). Increase or decrease approximately 25% of the initial infusion rate or subsequent infusion rate.Intubated preterm and term newborns (younger than 32 wk of age)
0.03 mg/kg/h (0.5 mcg/kg/min).Intubated preterm and term newborns (younger than 32 wk of age)
0.06 mg/kg/h (1 mcg/kg/min).Maintenance Of Anesthesia
IV Increments of approximately 25% of induction dose in response to signs of lightening of anesthesia and repeat as necessary.
Store at room temperature (59° to 86°F).
Drug InteractionsAnesthetics, inhalation
Inhalation anesthetics may need to be reduced if midazolam is used as an induction agent. IV administration decreases minimum alveolar concentration of halothane required for general anesthesia.Azole antifungal agents
Serum concentration of certain benzodiazepines may be increased and prolonged, producing enhanced CNS depression and prolonged effects.Barbiturates, alcohol, other CNS depressants
May prolong effect and increase risk of underventilation or apnea.Cimetidine
May increase midazolam levels.Contraceptives, oral
Coadministration may result in prolongation of benzodiazepine t ½ .Droperidol, narcotics, secobarbital
May accentuate hypnotic effect of midazolam.Ethanol
Increased CNS effects with acute ethanol ingestion.Fluvoxamine
Reduced clearance, prolonged t ½ and increased serum concentrations of certain benzodiazepines may occur. Sedation or ataxia may be increased.Indinavir
Possibly severe sedation and respiratory depression.Propofol
Pharmacologic effects of propofol may be increased.Rifamycins
Pharmacokinetic parameters of benzodiazepines may be altered.Ritonavir
Possibly severe sedation and respiratory depression.Theophyllines
Sedative effects of benzodiazepines may be antagonized.Thiopental
Moderate reduction in induction dosage requirements has been noted following use of IM midazolam for premedication.Valproic acid
Pharmacokinetic parameters of benzodiazepines may be increased. Liver metabolism may be decreased.Verapamil
Effects of certain benzodiazepines may be increased, producing increased CNS depression and prolonged effects.
Dimenhydrinate, pentobarbital, perphenazine, prochlorperazine, ranitidine.
Laboratory Test Interactions
None well documented.
Bigeminy; hypotension; PVCs; tachycardia; cardiac arrest; vasovagal episode; bradycardia; nodal rhythm.
Headache; oversedation; retrograde amnesia; euphoria or dysphoria; confusion; argumentativeness; anxiety; emergence delirium and dreaming; nightmares; tonic/clonic movements; tremor; athetoid movements; ataxia; dizziness; slurred speech; paresthesia; weakness; loss of balance; drowsiness; nervousness; agitation; restlessness; prolonged emergence from anesthesia; insomnia; dysphonia.
Hives; hive-like elevation at injection site; swelling or feeling of burning; warmth or coldness at injection site; rash; pruritus.
Vision disturbances; nystagmus; pinpoint pupils; cyclic eyelid movements; blocked ears; blurred vision; diplopia; difficulty focusing; loss of balance.
Nausea; vomiting; acid taste; excessive salivation; retching.
Respiratory depression or arrest; decreased tidal volume, decreased respiratory rate; apnea, coughing; laryngospasm; bronchospasm; dyspnea; hyperventilation; wheezing; shallow respirations; airway obstruction; tachypnea.
Pain, tenderness and induration at injection site; yawning; chills; lethargy; weakness; toothache; faint feeling; hematoma; desaturation, apnea, hypotension, paradoxical reactions, hiccough, seizure-like activity, nystagmus (children).
Respiratory depression/arrest has been reported with use for sedation in noncritical care settings and occurs most often with concurrent CNS depressants. Midazolam should only be used in settings that can provide continuous monitoring for respiratory and cardiac function. Severe hypotension and seizures have been reported in neonates after rapid IV injection, particularly with concurrent fentanyl. Do not administer via rapid injection in this population.
Category D .
Midazolam is excreted in breast milk. Exercise caution when administering to a breast-feeding woman.
As a group, children generally require higher dosages of midazolam (mg/kg) than do adults. Children (younger than 6 yr of age) may require higher dosages (mg/kg) than older children and may require closer monitoring. In obese children, calculate the dose based on ideal body weight.
May need to decrease dosage. Titration should be more gradual.
Labor and Delivery
Drug not recommended because of transplacental transfer.
Patients with renal function impairment may have longer t ½ for midazolam, which may result in slower recovery.
Special Risk Patients
High-risk surgical patients require lower doses. Patients with COPD are unusually sensitive to respiratory depressant effects. In renal or heart failure patients, give less frequently. Exercise care when administering to patients with uncompensated acute illness (eg, severe fluid or electrolyte disturbances).
No patient should operate hazardous machinery or a motor vehicle until the adverse reactions of the drug have subsided or until the day after anesthesia and surgery, whichever is longer.
Withdrawal symptoms (convulsions, hallucinations, tremor, abdominal and muscle cramps, vomiting, and sweating) may occur following abrupt discontinuation.
The midazolam injection contains benzyl alcohol, which has been associated with a fatal “gasping syndrome” in premature infants.
May need to decrease dosage. Titration should be more gradual.
Serious cardiorespiratory events
Have occurred, including respiratory depression, airway obstruction, desaturation, permanent neurologic injury, apnea, respiratory arrest or cardiac arrest, sometimes resulting in death.
Reactions such as agitation, involuntary movements, hyperactivity, and combativeness have been reported.
Moderate lowering of IOP following induction with midazolam.
Intracranial pressure/circulatory side effects
Does not protect against the increase in intracranial pressure or circulatory effects associated with endotracheal intubation under light general anesthesia.
Sedation, impaired coordination and reflexes, hypotension, hypoventilation, somnolence, coma, confusion.
- Inform patient and family pre-operatively about possibility of temporary postoperative amnesia.
- Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until drowsiness has subsided or until day after administration, whichever is longer.
- Advise patient to avoid alcohol and other CNS depressants for 24 h following administration.
- Patients receiving continuous infusion in critical care settings over an extended period of time may experience symptoms of withdrawal following abrupt discontinuation.
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