Benzodiazepine Guide

Clinical Disclaimer: Unlike opioid equipotent dosing, benzodiazepine equivalence is much less evidence-based. Most estimates are based on expert opinion, uncited tables, and clinical practice. Clinical judgment is paramount.

The list of benzodiazepines can be divided into 3 groups based on the duration of action and the speed of the onset of action. This calculator primarily uses duration to categorize medications.

1 Convert Current Drug → Alprazolam Units

If you are taking any medication other than Alprazolam, the calculator first standardizes the dose to Alprazolam Equivalent Units.

Alprazolam Units = Current Dose Current Drug Factor

Example: If taking Diazepam (Factor 15), divide your dose by 15.
Note: If you are already taking Alprazolam, your Factor is 1.

2 Convert Units → Target Drug

Multiply the standardized Alprazolam Units by the factor of the drug you want to switch to.

Target Dose = Alprazolam Units × Target Drug Factor

Example: To switch to Lorazepam (Factor 2), multiply the result from Step 1 by 2.

Clinical Warnings & Limitations

⚠️ Large Dosing Ranges

Due to discrepancies in the literature, many benzodiazepine conversions may have a potential conversion range that is extremely variable (e.g., by a factor of 10x or greater). These wide ranges highlight the lack of firm, evidence-based literature.

⚠️ Patient-Specific Factors

No equipotent conversion considers hepatic function, renal function, age, inter-patient metabolic variability, or drug interactions. Benzodiazepine metabolism can differ significantly; therefore, alterations in drug disposition will alter the relative potencies and durations.

⚠️ Varying Durations of Action

Due to differences in half-life, active metabolites, and drug accumulation, benzodiazepine conversions should account for single-dose versus multiple-dose situations. Currently, no conversion estimates capture this difference accurately.

⚠️ Lack of FDA Oversight

Unlike opioid conversions, the FDA does not require manufacturers to describe equivalent dose or potency of benzodiazepines within the package insert.

Impact of Dosage Forms

Most published conversions are based on oral administration. Parenteral formulations may not use the same conversion ratio. Large variances in oral bioavailability highlight significant inter-patient variability:

Drug Bioavailability
Midazolam40% (range 35-75%)
Lorazepam>90%
Diazepam>90% (range 53-97%)
Phenobarbital>90%

Equivalence & Mode of Action Table

We compare each benzodiazepine to Alprazolam (Factor 1).

Drug Factor (vs Alprazolam) Onset Duration
Alprazolam (Xanax)130 min6-20 h
Lorazepam (Ativan)230-60 min10-20 h
Bromazepam (Lexotan)630m - 4h10-20 h
Midazolam IV (Versed)41-3 min2-4 h
Midazolam PO1010-20 min20m - 3h
Chlordiazepoxide501.5 h5-30 h
Clonazepam (Rivotril)11 h18-39 h
Clorazepate (Tranxene)201 h36-200 h
Diazepam (Valium)1530 min20-50 h
Flurazepam (Dalmane)301 h12-100 h
Oxazepam (Serax)303 h3-21 h
Quazepam (Doral)4020-45 min25-100 h
Temazepam (Restoril)3030-60 min10-20 h
Triazolam (Halcion)0.530 min1.6-5.5 h

Example Calculation

Switching from Diazepam 30mg to Lorazepam:
1. Divide current dose by current factor: 30mg / 15 = 2 (Alprazolam Units)
2. Multiply by target factor: 2 × 2 = 4mg Lorazepam

References

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  2. Quan D. Chapter 177. Benzodiazepines. In: Tintinalli JE, Stapczynski JS, Cline DM, Ma OJ, Cydulka RK, Meckler GD, eds. Tintinalli's Emergency Medicine: A Comprehensive Study Guide. 7th ed. New York: McGraw-Hill; 2011.
  3. Ng K, Dahri K, Chow I, Legal M. Evaluation of an alcohol withdrawal protocol and a preprinted order set at a tertiary care hospital. Can J Hosp Pharm. 2011 Nov;64(6):436-45.
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  7. Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. London: Department of Health; 2017.
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  9. Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984 Jul;61(1):27-35.
  10. Pentikäinen PJ, Välisalmi L, Himberg JJ, Crevoisier C. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. J Clin Pharmacol. 1989 Mar;29(3):272-7.
  11. Lorazepam [package insert]. Corona (CA): Watson Laboratories; 2010.
  12. Dhillon S, Oxley J, Richens A. Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients. Br J Clin Pharmacol. 1982 Mar;13(3):427-32.
  13. Ochs HR, Otten H, Greenblatt DJ, Dengler HJ. Diazepam absorption: effects of age, sex, and Billroth gastrectomy. Dig Dis Sci. 1982 Mar;27(3):225-30.
  14. Divoll M, Greenblatt DJ, Ochs HR, Shader RI. Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex. Anesth Analg. 1983 Jan;62(1):1-8.
  15. Nelson E, Powell JR, Conrad K, et al. Phenobarbital pharmacokinetics and bioavailability in adults. J Clin Pharmacol. 1982 Feb-Mar;22(2-3):141-8.
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