Equivalent Benzodiazepine Calculator

Calculates equipotent benzodiazepine doses

ClinCalc.com » Neurology » Benzodiazepine Equivalence Calculator

Benzodiazepine Regimen From: Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Flurazepam (Dalmane) Lorazepam (Ativan) Midazolam (Versed) - IV Midazolam (Versed) - PO Oxazepam (Serax) Phenobarbital (Luminal) Quazepam (Doral) Secobarbital (Seconal) Temazepam (Restoril) Triazolam (Halcion) mg To: Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Flurazepam (Dalmane) Lorazepam (Ativan) Midazolam (Versed) - IV Midazolam (Versed) - PO Oxazepam (Serax) Phenobarbital (Luminal) Quazepam (Doral) Secobarbital (Seconal) Temazepam (Restoril) Triazolam (Halcion)

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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.1,2,3,4,5,6 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.

- 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.

- 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:

Drug Bioavailability Midazolam 40% (range 35-75%) 7,8 Lorazepam >90% 9 Diazepam >90% (range 53-97%) 10,11,12 Phenobarbital >90% 13

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.14 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