c






c

- 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.

c  

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.

   

   

 
sollowing 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.

=

sollowing oral administration (7.5 mg), t ½ increased 43%.


 
 

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.

 

  
 



  
 

 IM 0.07 to 0.08 mg/kg approximately 1 h before surgery.

= 
 


 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.

= 

 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.

  
   






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.







IV 0.15 to 0.35 mg/kg over 20 to 30 sec.

=  

 !



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.

c  

0.02 to 0.1 mg/kg/h (1 to 7 mg/h).

= 

"# $

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.






 %
" 
&'% $

0.03 mg/kg/h (0.5 mcg/kg/min).






 %
" 
&'% $

0.06 mg/kg/h (1 mcg/kg/min).

c      

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°s).



 

   )  

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.




Pharmacologic effects of propofol may be increased.

    

Dimenhydrinate, pentobarbital, perphenazine, prochlorperazine, ranitidine.



 *  

=




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.
mm


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.

c   

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.


  , = 
-

! 

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.

m

  ,c 


 
 -

 
 


-

!

  
,

 

  
 

-

*  

Patients with renal function impairment may have longer t ½ for midazolam, which may
result in slower recovery.

  *  

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 ³gasping syndrome´ in premature infants.
   
 

May need to decrease dosage. Titration should be more gradual.







  

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.


#

 /  

Unknown.



 

(


  

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.