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Pharmacology of benzodiazepines used to treat anxiety symptoms/disorders

Pharmacology of benzodiazepines used to treat anxiety symptoms/disorders
Drug Adult oral total daily dose (mg)* Comparative potency (mg) Onset after oral dose (hours) Metabolism Elimination half-life (hours)Δ
Alprazolam 0.5 to 6 0.5 1 CYP3A4 to minimally active metabolites.

11 to 15

16 (older adults)

20 (hepatic impairment)

22 (obesity)
Alprazolam extended release 0.5 to 6 once daily 0.5 1
Bromazepam§ 6 to 30 7.5 1 CYP1A2. No active metabolite. 8 to 20
Chlordiazepoxide§ 5 to 100 10 1 CYP3A4 to active metabolites.

30 to 100

Prolonged in older adults and hepatic impairment
Clonazepam 0.5 to 4 0.25 to 0.5 0.5 to 1 CYP3A4. No active metabolite. 18 to 50
Clorazepate 15 to 60 7.5 0.5 to 1 CYP3A4 to active metabolite. 36 to 200
Diazepam 4 to 40 5 0.25 to 0.5 CYP2C19 and 3A4 to active metabolites.

50 to 100

Prolonged in older adults and renal or hepatic impairment
Lorazepam immediate release

0.5 to 6

0.5 to 4 (hypnotic)
1 0.5 to 1 Non-CYP glucuronidation in liver. No active metabolite. 10 to 14
Lorazepam extended release 1 to 6 mg¥ 1 0.5 to 1 Non-CYP glucuronidation in liver. No active metabolite. 13 to 27
Oxazepam

30 to 120

15 to 30 (hypnotic)
15 to 30 1 to 2 Non-CYP glucuronidation in liver. No active metabolite. 5 to 15
Prazepam§ 15 to 60 15 2 to 3 CYP3A4 to active metabolites.

30 to 200

Prolonged in older adults
Data on drug metabolism and activity of metabolite(s) are for assessment of potential for CYP drug interactions and risk of accumulation. Risk of accumulation is greater, and dose reduction necessary, for older or debilitated adults and for patients with renal or hepatic insufficiency.
* Range of usual total daily dose for treatment of adults with anxiety or panic disorder typically given in divided doses two to four times daily.
¶ Important: Data shown are approximate equal potencies relative to lorazepam 1 mg orally and are NOT recommendations for initiation of therapy or for conversion between agents.
Δ Half-life of parent drug and pharmacologically active metabolite, if any.
◊ Not available in the United States.
§ Use only when other preferred agents are unavailable or not tolerated.
¥ To be used only when converting from immediate release lorazepam. Total daily dose is equal to the current total daily dose of immediate release lorazepam. Dose is given once daily in the morning after discontinuing immediate dose lorazepam tablets the night before.
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