No

Benzodiazepine

Dental: Sedation component in I.V. conscious sedation in oral surgery patients; syrup formulation is used for children to help alleviate anxiety before a dental procedure

Medical: Preoperative sedation and provides conscious sedation prior to diagnostic or radiographic procedures

Unlabeled use: Anxiety, status epilepticus

C-IV

D

Hypersensitivity to this drug or any component of its formulation, including benzyl alcohol (cross-sensitivity with other benzodiazepines may exist); parenteral form is not for intrathecal or epidural injection; narrow-angle glaucoma (not in product labeling, however, benzodiazepines are contraindicated); pregnancy; concurrent use with protease inhibitors like amprenavir and ritonavir

May cause severe respiratory depression, respiratory arrest, or apnea. Use with extreme caution, particularly in noncritical care settings. Appropriate resuscitative equipment and qualified personnel must be available for administration and monitoring. Initial dosing must be cautiously titrated and individualized, particularly in elderly or debilitated patients, patients with hepatic impairment (including alcoholics), or in renal impairment, particularly if other CNS depressants (including opiates) are used concurrently. Initial doses in elderly or debilitated patients should not exceed 2.5 mg. Use with caution in patients with respiratory disease or impaired gag reflex. Use during upper airway procedures may increase risk of hypoventilation. Prolonged responses have been noted following extended administration by continuous infusion (possibly due to metabolite accumulation) or in the presence of drugs which inhibit midazolam metabolism.

Causes CNS depression (dose-related) resulting in sedation, dizziness, confusion, or ataxia which may impair physical and mental capabilities. Patients must be cautioned about performing tasks which require mental alertness (ie, operating machinery or driving). A minimum of 1 day should elapse after midazolam administration before attempting these tasks. Use with caution in patients receiving other CNS depressants or psychoactive agents. Effects with other sedative drugs or ethanol may be potentiated. Benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially the elderly).

Midazolam causes anterograde amnesia. Paradoxical reactions, including hyperactive or aggressive behavior have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Does not have analgesic, antidepressant, or antipsychotic properties.

Benzodiazepines have been associated with dependence and acute withdrawal symptoms on discontinuation or reduction in dose. Acute withdrawal, including seizures, may be precipitated after administration of flumazenil to patients receiving long-term benzodiazepine therapy.

>10%: Respiratory: Decreased tidal volume and/or respiratory rate decrease, apnea

1% to 10%:

Central nervous system: Drowsiness, oversedation, headache

Gastrointestinal: Nausea, vomiting

Local: Pain and local reactions at injection site (severity less than diazepam)

Respiratory: Coughing

Miscellaneous: Physical and psychological dependence with prolonged use, hiccups

<1%: PVC, bradycardia, tachycardia, bigeminy, acid taste, excessive salivation, amnesia, euphoria, hallucinations, confusion, emergence delirium, agitation, rash, wheezing, laryngospasm, bronchospasm, dyspnea, hyperventilation

Symptoms of overdose include respiratory depression, hypotension, coma, stupor, confusion, apnea

Treatment for benzodiazepine overdose is supportive. Rarely is mechanical ventilation required. Flumazenil has been shown to selectively block the binding of benzodiazepines to CNS receptors, resulting in a reversal of benzodiazepine-induced CNS depression; respiratory reaction to hypoxia may not be restored.

CYP3A3/4 enzyme substrate

Verapamil, troleandomycin, miconazole, itraconazole, nifedipine, grapefruit juice, diltiazem, fluconazole, ketoconazole, clarithromycin, and erythromycin, protease inhibitors like amprenavir and ritonavir may increase the serum concentrations and effects of midazolam via CYP3A4 inhibition

If narcotics or other CNS depressants are administered concomitantly, the midazolam dose should be reduced by 30% if <65 years of age, or by at least 50% if >65 years of age

Stable for 24 hours at room temperature/refrigeration; admixtures do not require protection from light for short-term storage; compatible with NS, D₅W

Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.

I.M.:

Onset of sedation: Within 15 minutes

Peak effect: 0.5-1 hour

Duration: 2 hours mean, up to 6 hours

I.V.: Onset of action: Within 1-5 minutes

Absorption: Oral: Rapid

Distribution: V_d: 0.8-2.5 L/kg; increased with congestive heart failure (CHF) and chronic renal failure

Protein binding: 95%

Metabolism: Extensively in the liver (microsomally)

Bioavailability: 45% mean

Half-life, elimination: 1-4 hours, increased with cirrhosis, CHF, obesity, elderly

Elimination: As glucuronide conjugated metabolites in urine, ~2% to 10% excreted in feces

The dose of midazolam needs to be individualized based on the patient's age, underlying diseases, and concurrent medications. Decrease dose (by ~30%) if narcotics or other CNS depressants are administered concomitantly. Personnel and equipment needed for standard respiratory resuscitation should be immediately available during midazolam administration.

Infants <2 months and Children: Status epilepticus refractory to standard therapy: I.V.: Loading dose: 0.15 mg/kg followed by a continuous infusion of 1 mcg/kg/minute; titrate dose upward every 5 minutes until clinical seizure activity is controlled; mean infusion rate required in 24 children was 2.3 mcg/kg/minute with a range of 1-18 mcg/kg/minute

Children:

Preoperative sedation:

I.M.: 0.07-0.08 mg/kg 30-60 minutes presurgery

I.V.: 0.035 mg/kg/dose, repeat over several minutes as required to achieve the desired sedative effect up to a total dose of 0.1-0.2 mg/kg

Conscious sedation during mechanical ventilation: I.V.: Loading dose: 0.05-0.2 mg/kg then follow with initial continuous infusion: 1-2 mcg/kg/minute; titrate to the desired effect; usual range: 0.4-6 mcg/kg/minute

Conscious sedation for procedures:

Oral, Intranasal: 0.2-0.4 mg/kg (maximum: 15 mg) 30-45 minutes before the procedure

I.V.: 0.05 mg/kg 3 minutes before procedure

Adolescents >12 years: I.V.: 0.5 mg every 3-4 minutes until effect achieved

Adults:

Preoperative sedation: I.M.: 0.07-0.08 mg/kg 30-60 minutes presurgery; usual dose: 5 mg

Conscious sedation: I.V.: Initial: 0.5-2 mg slow I.V. over at least 2 minutes; slowly titrate to effect by repeating doses every 2-3 minutes if needed; usual total dose: 2.5-5 mg; use decreased doses in elderly

Healthy Adults <60 years: Some patients respond to doses as low as 1 mg; no more than 2.5 mg should be administered over a period of 2 minutes. Additional doses of midazolam may be administered after a 2-minute waiting period and evaluation of sedation after each dose increment. A total dose >5 mg is generally not needed. If narcotics or other CNS depressants are administered concomitantly, the midazolam dose should be reduced by 30%.

Elderly: I.V.: Conscious sedation: Initial: 0.5 mg slow I.V.; give no more than 1.5 mg in a 2-minute period; if additional titration is needed, give no more than 1 mg over 2 minutes, waiting another 2 or more minutes to evaluate sedative effect; a total dose >3.5 mg is rarely necessary

Sedation in mechanically intubated patients: I.V. continuous infusion: 100 mg in 250 mL D₅W or NS, (if patient is fluid-restricted, may concentrate up to a maximum of 0.5 mg/mL); initial dose: 1 mg/hour; titrate to reach desired level of sedation

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics

No data reported

Oral: Do not mix with any liquid (such as grapefruit juice) prior to administration

Parenteral: Administer by slow I.V. injection over at least 2-5 minutes at a concentration of 1-5 mg/mL or by I.V. infusion

Respiratory and cardiovascular status, blood pressure, blood pressure monitor required during I.V. administration

No information available to require special precautions

No effects or complications reported

Avoid use of alcohol or prescription or OTC sedatives or hypnotics for a minimum of 24 hours after administration. Avoid driving or engaging in any tasks that require alertness for 24 hours following administration. You may experience some loss of memory following administration. Pregnancy/breast-feeding precautions: Advise prescriber if you are pregnant; this medication is contraindicated for pregnant women. Breast-feeding is not recommended.

Midazolam is a short-acting benzodiazepine; recovery occurs within 2 hours in most patients, however, may require up to 6 hours in some cases

Injection, as hydrochloride: 1 mg/mL (2 mL, 5 mL, 10 mL); 5 mg/mL (1 mL, 2 mL, 5 mL, 10 mL)

Syrup: 2 mg/mL (118 mL)

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