Benzodiazepines and Non-Benzodiazepine Sedatives

alprazolam (Xanax ®):

Short half-life
Dosing (Adults):  Initial: 0.25 to 0.5 mg orally 2 to 3 times daily. Usual maximum: 4 mg/day.
Supplied:   [0.25, 0.5, 1, 2 mg tabs]

buspirone  (BuSpar ® ):

Non-Benzodiazepine (Anxiolytic)
Dosing (Adults):   Anxiety disorders (GAD): 15 mg/day (7.5 mg twice daily). May increase in increments of 5 mg/day every 2-4 days to a maximum of 60 mg/day. Target dose for most people is 30 mg/day (15 mg twice daily).

Supplied: 5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg tablet.

chlordiazepoxide (Librium ®):

Long half-life
Dosing (Adults): Anxiety: 5 to 25 mg orally or 25-50mg IM/IV 3 to 4 times a day. Alcohol withdrawal: 50-100mg oral, IM or IV every 3 to 4 hours as needed. Normally, do not exceed 300mg / day.

chlorazepate (Tranxene ®):

Long half-life
Dosing (Adults): 7.5 to 15 mg orally 1 to 3 times per day.

clonazepam (Klonopin ®):

Long half-life
Dosing (Adults): Start 0.25 to 0.5 mg orally three times daily.
Maximum: 20mg/day.

diazepam (Valium ®):

Long half-life
Dosing (Adults): Anxiety: 2-10 mg orally 2 to 4 times per day. Status epilepticus: 5-10 mg IV q10-20min, up to 30 mg in an 8 hour period. Muscle relaxant: 2 to 5 mg orally 2 to 4 times per day.

estazolam (ProSom ®):

Intermediate half-life

Dosing (Adults): 1-2 mg orally at bedtime.

eszcpiclone (Lunesta ® ):

Non-Benzodiazepine (Sedative)
Dosing (Adults): Insomnia: Initial: 2 mg before bedtime (maximum dose: 3 mg). Concurrent use with strong CYP3A4 inhibitor: 1 mg before bedtime; if needed, dose may be increased to 2 mg.
Supplied: 1 mg, 2 mg, 3 mg tablet.

flurazepam (Dalmane ®):

Long half-life
Dosing (Adults): 15-30mg orally at bedtime.

lorazepam (Ativan ®):

Intermediate half-life
Prolonged infusions have been associated with toxicity from propylene glycol and/or polyethylene glycol.

IV: Do not exceed 2 mg/minute
Dosing (Adults):
Anxiety/sedation: 1-10 mg orally in 2-3 divided doses. Usual dose: 2-6 mg/day in divided doses. Initial dose should not exceed 2 mg in debilitated patients.
Insomnia: 2-4 mg orally at bedtime.
Operative amnesia: I.V.: Up to 0.05 mg/kg; maximum: 4 mg/dose.
Status epilepticus: 4 mg IV over 2 to 5 min. May repeat in 10-15 minutes. usual maximum dose: 8 mg.
Continuous infusion: (ICU): 1 to 20 mg/hr (0.01-0.1 mg/kg/hour).

PHARMACODYNAMICS / KINETICS
Onset of action:
Hypnosis: I.M.: 20-30 minutes
Sedation: I.V.: 5-20 minutes
Anticonvulsant: I.V.: 5 minutes, oral: 30-60 minutes.
Severe Hyperosmolar Metabolic Acidosis Due to a Large Dose of Intravenous Lorazepam.
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Previous cases of propylene glycol toxicity secondary to high-dose lorazepam infusion have occurred in patients with compromised renal function. Our patient's renal function remained stable throughout the hospital course, which caused us to look further for an explanation for the propylene glycol-induced lactic acidosis. Based on the Naranjo probability scale, propylene glycol was determined to be the probable cause of lactic acidosis. Since this case occurred, our intensive care unit has instituted recommendations for the prevention of lorazepam-associated propylene glycol toxicity.
CONCLUSIONS: Our case highlights the development of propylene glycol-induced lactic acidosis secondary to high-dose lorazepam infusion not associated with renal dysfunction.
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The lorazepam solvents polyethylene glycol (PEG) and propylene glycol (PG) have been implicated as the cause of reversible acute tubular necrosis, lactic acidosis, and hyperosmolar states after prolonged high-dose infusions. The dosing threshold for this effect has not been prospectively defined, but these case reports described doses that exceeded 18 mg/hr and continued for longer than four weeks and higher doses (>25 mg/hr) continuing for hours to days.119–121 It seems prudent to avoid doses of this magnitude. Alternatively, lorazepam and diazepam may be administered via the enteral route in tablet or liquid form.122 Large doses of liquid lorazepam (i.e., 60 mg of 2 mg/mL every six hours) may lead to diarrhea because of the high PEG and PG content.

midazolam  (Versed ®)

Intermediate half-life
Intubated patients (Continuous infusion): 1 to 7 mg/hr.
Dosing (Adults): 
Preoperative sedation:
I.M.: 0.07-0.08 mg/kg 30-60 minutes prior to surgery/procedure; usual dose: 5 mg; Note: Reduce dose in patients with COPD, high-risk patients, patients >/= 60 years of age, and patients receiving other narcotics or CNS depressants
I.V.: 0.02-0.04 mg/kg; repeat every 5 minutes as needed to desired effect or up to 0.1-0.2 mg/kg
Intranasal (not an approved route): 0.2 mg/kg (up to 0.4 mg/kg in some studies); administer 30-45 minutes prior to surgery/procedure.

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: Initial: 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. Maintenance: 25% of dose used to reach sedative effect.

Anesthesia: I.V.: Induction: Unpremedicated patients: 0.3-0.35 mg/kg (up to 0.6 mg/kg in resistant cases)
Premedicated patients: 0.15-0.35 mg/kg.
Maintenance: 0.05-0.3 mg/kg as needed, or continuous infusion 0.25-1.5 mcg/kg/minute.

Sedation in mechanically-ventilated 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: 0.02-0.08 mg/kg (~1 mg to 5 mg in 70 kg adult) initially and either repeated at 5-15 minute intervals until adequate sedation is achieved or continuous infusion rates of 0.04-0.2 mg/kg/hour and titrate to reach desired level of sedation.

DOSING: ELDERLY — 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. 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.

Supplied: Injection, solution: 1 mg/mL (2 mL, 5 mL, 10 mL); 5 mg/mL (1 mL, 2 mL, 5 mL, 10 mL)
PHARMACODYNAMICS / KINETICS
Onset of action: I.M.: Sedation: ~15 minutes; I.V.: 1-5 min.
Peak effect: I.M.: 0.5-1 hour.
Duration: I.M.: Up to 6 hours; Mean: 2 hours.
Half-life elimination: 1-4 hours; prolonged with cirrhosis, congestive heart failure, obesity, and elderly.

Oxazepam  (Serax ®):

Short half-life
Dosing (Adults):  10-30 mg orally 3 to 4 times daily.
Supplied:  [10, 15, 30 mg]

ramelteon (Rozerem ® ):

Non-Benzodiazepine (Sedative)
Melatonin receptor agonist.
Dosing (Adults):  Insomnia: 8 mg orally taken within 30 min of bedtime.
Supplied: 8 mg tablet.

temazepam (Restoril ®):

Intermediate half-life
Dosing (Adults):  7.5 to 30 mg orally at bedtime

triazolam (Halcion ®):

Short half-life
Dosing (Adults): 0.125 to 0.5 mg orally at bedtime

zaleplon (Sonata ® ):

Non-Benzodiazepine (Sedative)
Dosing (Adults):  Insomnia: 5-10mg orally at bedtime as needed.

zolpidem  (Ambien ®):

Non-Benzodiazepine (Sedative)
Dosing (Adults):  Insomnia:  5-10 mg orally at bedtime.
 

Disclaimer
Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.

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