Equivalent Benzodiazepine Calculator
Calculates equipotent benzodiazepine doses
ClinCalc.com » Neurology » Benzodiazepine Equivalence Calculator
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About This Calculator
This conversion tool estimates a reasonable equipotent dose between two benzodiazepines. Unlike opioid equipotent dosing, benzodiazepine equivalence is much less evidence-based and poorly described in the literature. In fact, most benzodiazepine equivalence estimates are based on expert opinion, uncited tables in published documents, and clinical practice.
All benzodiazepine conversions used in this calculator are based on published equipotent dose estimates.1,2,3,4,5 The bulk of these publications come from an alcohol withdrawal setting using oral dosage forms. The following guiding principles govern the calculator's logic:
- When equivalence discrepancies exist in the literature, a reasonable dose range is provided to emphasize the lack of confidence in the conversions
- Unless otherwise stated, all conversions are based on oral dosage formulations
Large Dosing Ranges
Due to discrepancies in the literature, many benzodiazepine conversions may have a potential conversion range that is extremely variable (eg, by a factor of 10x or greater). These wide ranges of confidence highlight the lack of firm, evidence-based literature supporting specific conversion ratios.
Issues with Benzodiazepine Conversions
In addition to an overall lack of evidence to support specific conversions, there are a number of other limitations that should be recognized:
- 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.
- Patient-specific factors - No equipotent conversion considers hepatic function, renal function, age, inter-patient metabolic variability, or drug interactions. Benzodiazepine metabolism and excretion can differ significantly; therefore, alterations in drug disposition will alter the relative potencies and durations of each benzodiazepine.
- 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.
Given the numerous issues with benzodiazepine equivalence, the importance of reasonable clinical judgment, clinical experience, appropriate patient monitoring, and dose titration are of even greater significance.
Impact of Dosage Forms
Most benzodiazepines included in this calculator are only available as oral dosage forms. Midazolam, lorazepam, diazepam, and phenobarbital are available in both parenteral and oral formulations.
Because published benzodiazepine dose conversions are based on oral administration, parenteral formulations may not use the same conversion ratio. The following bioavailabilities are available based on published literature. Note how the large variances in oral bioavailability highlight the significant inter-patient variability:
||40% (range 35-75%) 6,7
||>90% (range 53-97%) 9,10,11
This calculator only accounts for differences in bioavailability with midazolam. Other dosage forms, with a bioavailability of >90%, are assumed to have complete bioavailability for calculation purposes.
Conversion of IV Midazolam
Unlike nearly all other benzodiazepine conversions, the conversion between intravenous midazolam and lorazepam has been well studied in mechanically ventilated patients.13 A commonly cited double-blind trial suggests a conversion of 1 mg IV lorazepam to 2 mg of IV midazolam, which is further supported using a midazolam oral bioavailability of 40% due to a significant first-pass effect. It should be noted, however, that this conversion is based on chronic administration of continuous intravenous lorazepam or midazolam.
Phenobarbital and Secobarbital
Although phenobarbital and secobarbital are not benzodiazepines, they are commonly grouped with this drug class and cited within benzodiazepine conversion charts due to their use in alcohol withdrawal. While barbiturates do share similar pharmacology to benzodiazepines, they have a more concerning safety profile with a higher incidence of respiratory depression.
References and Additional Reading
- Miller NS, Gold MS. Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence. Am Fam Physician. 1998 Jul;58(1):139-46. PMID 9672434.
- 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.
- 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. PMID 22479099.
- Sostmann HJ, Sostmann H, Crevoisier C, Bircher J. Dose equivalence of midazolam and triazolam. A psychometric study based on flicker sensitivity, reaction time and digit symbol substitution test. Eur J Clin Pharmacol. 1989;36(2):181-7. PMID 2721543.
- Lieberman JA, Tasman A. Handbook of Psychiatric Drugs. John Wiley & Sons Incorporated; 2006.
- Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984 Jul;61(1):27-35. PMID 6742481.
- 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. PMID 2723115.
- Lorazepam [package insert]. Corona (CA): Watson Laboratories; 2010. DailyMed Monograph.
- 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. PMID 7059446.
- 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. PMID 7075421.
- 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. PMID 6849499.
- 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. PMID 7068937.
- Barr J, Zomorodi K, Bertaccini EJ, et al. A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology. 2001 Aug;95(2):286-98. PMID 11506097.