Benzodiazepine Pharmacokinetics and Routes of Administration

• Benzodiazepines are used for numerous acute states in the emergency department, especially

seizures and agitation

• IV access is often not available for patients with seizures or agitation and alternative routes must be

considered; the drug of choice may change depending on the route of administration

• This handout will focus on the pharmacokinetics of the two most utilized benzodiazepines in the

emergency department, lorazepam and midazolam

Lorazepam

Midazolam

Administration

IV

IM

IV

IM

IN

Dose

Sedation:

• 5-2 mg

Seizure: 4mg

Sedation:

• 5-2mg

Seizure:

• 5 -2mg

(not preferred)

Sedation:

• 5-2mg

Seizure:

• 2mg/kg

(not preferred)

Sedation: 5mg

Seizure:10mg or

• 2mg/kg; max

10mg

Sedation:

• 1mg/kg

Seizure: 0.2mg/kg;

max 10mg

Onset

2-10 min

(longer for

anticonvulsant)

20-30 min

3-5 min

15 min

10 min

Duration

3 – 6 hours for

seizures, up to 8

hours for sedation

Author,

year

Design/ sample

size

Intervention & Comparison

Outcome

Nobay

2004

Prospective,

double-blind,

randomized

N=95

IM midazolam vs. IM haloperidol vs.

IM lorazepam for agitation

Mean time to sedation (min)

Lorazepam: 32.3 (+/-20)

Midazolam: 18.3 (+/-14)

Haloperidol: 28.3 (+/-25)

*lorazepam dropped from study due to

significantly longer time to sedation and

awakening

Silbergleit

2012

Prospective,

double-blind,

randomized,

non-inferiority

N= 893

IM midazolam versus IV lorazepam

for seizure

Seizures absent at time of arrival to ED

IM midazolam: 73.4%

IV lorazepam: 63.4%

Statistically significant for non-inferiority

Faster time to drug administration of IM

midazolam was offset by the faster onset of

IV lorazepam

Haut

2016

Systematic

Review

N=75 studies

• The initial agent used does not have to be the definitive agent for treatment. Utilizing alternative

routes in order to obtain IV access in agitation/convulsing patients is often the safest for both the

patient and staff members. It may also allow therapy to be initiated faster than waiting to obtain

IV access.

• A lack of literature directly comparing all routes of administration for all benzodiazepines should not

limit utilization. Important differences exist in pharmacokinetics of each drug and route of

administration that may be beneficial for specific populations and disease states.

Lorazepam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Accessed 2020, February 24.

http://www.micromedexsolutions.com/

Midazolam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Accessed 2020, February 24.

http://www.micromedexsolutions.com/

Lorazepam. Lexicomp [online database].Hudson, OH. Woltes Kluwer Clinical Drug Information, Inc. Accessed 2020, February 24. http://www.online.lexi.com

Midazolam. Lexicomp [online database].Hudson, OH. Woltes Kluwer Clinical Drug Information, Inc. Accessed 2020, February 24. http://www.online.lexi.com

Nobay, et al. Acad Emerg Med. 2004;11(7):744-49.

Haut, et al. Epilepsy & Behavior. 2016;63:109-17.

Silbergleit, et al. NEJM. 2012;366(7):591-600.

Owusu, et al. Epilepsy & Behavior. 2019;98:161-67.