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Benzodiazepine Dosage Converter Based on Potencies



Benzodiazepine Dose Conversions. Comparative dosages for alprazolam, diazepam, lorazepam, oxazepam, temazepam, clonazepam, chlordiazepoxide.

Mechanism of Action - Benzodiazepines


Mechanism of action: Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.

Hepatic disease: Depending on the agent, dosage reductions of 50% are required in mild to moderate impairment  and most agents should be avoided in severe/acute liver disease.  Refer to the specific package insert in all cases.

Converting From:

 
(Total daily oral dose in mg)

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Background info - dosing information

Alprazolam (Xanax ®)

 Dosing (Adults)Anxiety: Immediate release: Effective doses are 0.5-4 mg/day in divided doses; the manufacturer recommends starting at 0.25-0.5 mg 3 times/day; titrate dose upward; maximum: 4 mg/day.    Anxiety associated with depression: Immediate release: Average dose required: 2.5-3 mg/day in divided doses.    Panic disorder: Immediate release: Initial: 0.5 mg 3 times/day; dose may be increased every 3-4 days in increments leq 1 mg/day; many patients obtain relief at 2 mg/day, as much as 10 mg/day may be required.
Pharmacokinetics:  Short-acting.  Peak level:  1-2 hours.  Average half-life (variable): 12 hours (9-20 hours).  
Maximum dose: 4 - 10 mg depending on indication.


Bromazepam

Dosing (Adults):  Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded. The usual dose is 3 mg twice or three times daily. In severe conditions up to 6 -12 mg twice or three times daily.  Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom free. The overall duration of treatment generally should not be more than 8 -12 weeks, including a tapering off process.   In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patient's status.
Pharmacokinetics:  Short-acting.  Peak level:  1-4 hours.  Average half-life (variable): 20 hours (8-30 hours).
Maximum dose: 30 - 60 mg


Chlordiazepoxide (Librium ®):

 Dosing (Adults)Anxiety:  Oral: 15-100 mg divided 3-4 times/day.
I.M., I.V.: Initial: 50-100 mg followed by 25-50 mg 3-4 times/day as needed.   Preoperative anxiety: I.M.: 50-100 mg prior to surgery.  Ethanol withdrawal symptoms: Oral, I.V.: 50-100 mg to start, dose may be repeated in 2-4 hours as necessary to a maximum of 300 mg/24 hours.  Note: Up to 300 mg may be given I.M. or I.V. during a 6-hour period, but not more than this in any 24-hour period.
Pharmacokinetics:  Long-acting.  Peak level:  1-4 hours.  Average half-life (variable): 100 hours
Maximum dose: ~300 mg



Clonazepam (Klonopin ®):

 Dosing (Adults):   Seizure disorders:  Initial daily dose not to exceed 1.5 mg given in 3 divided doses; may increase by 0.5-1 mg every third day until seizures are controlled or adverse effects seen (maximum: 20 mg/day).  Usual maintenance dose: 0.05-0.2 mg/kg; do not exceed 20 mg/day. 
Panic disorder
: 0.25 mg twice daily; increase in increments of 0.125-0.25 mg twice daily every 3 days; target dose: 1 mg/day (maximum: 4 mg/day)
Pharmacokinetics:  Long-acting.  Peak level:  1-4 hours.  Average half-life (variable): 34 hours (18-50 hours).
Maximum dose: 20 mg




Clorazepate (Tranxene ®):

 Dosing (Adults)Anxiety: Regular release tablets (Tranxene® T-Tab®): 7.5-15 mg 2-4 times/day .
Sustained release (Tranxene®-SD): 11.25 or 22.5 mg once daily at bedtime.  Ethanol withdrawal: Initial: 30 mg, then 15 mg 2-4 times/day on first day; maximum daily dose: 90 mg; gradually decrease dose over subsequent days.
Pharmacokinetics:  Long-acting.  Peak level:  0.5 -2 hours.  Average half-life (variable): 100 hours
Maximum dose: 90 mg


Diazepam (Valium ®):

 Dosing (Adults)Anxiety/sedation/skeletal muscle relaxant: Oral: 2-10 mg 2-4 times/day
I.M., I.V.: 2-10 mg, may repeat in 3-4 hours if needed.  Sedation in the ICU patient: I.V.: 0.03 to 0.1 mg/kg every 30 minutes to 6 hours.  Status epilepticus: I.V.: 5-10 mg every 10-20 minutes, up to 30 mg in an 8-hour period; may repeat in 2-4 hours if necessary. Rapid tranquilization of agitated patient (administer every 30-60 minutes): Oral: 5-10 mg; average total dose for tranquilization: 20-60 mg.
Pharmacokinetics:  Long-acting.  Peak level (oral):  1-2 hours.  Average half-life (variable): 100 hours
Maximum dose: ~40 mg


Flurazepam (Dalmane ®):

 Dosing (Adults)Short-term treatment of insomnia: 15-30 mg at bedtime   Elderly: Insomnia: Oral: 15 mg at bedtime; avoid use if possible.
Pharmacokinetics:  Long-acting.  Peak level:  0.5 - 1 hour.  Average half-life (variable): 100 hours (40-250 hours).
Maximum dose: 60 mg


Lorazepam (Ativan ®):

 Dosing (Adults)Anxiety/sedation: 1-10 mg orally in 2-3 divided doses. Usual dose: 2-6 mg/day in divided doses. Initial dose should not exceed 2 mg in debilitated patients.  Insomnia: 2-4 mg orally at bedtime. Operative amnesia: I.V.: Up to 0.05 mg/kg; maximum: 4 mg/dose.  Status epilepticus: 4 mg IV over 2 to 5 minutes. May repeat in 10-15 minutes.  Usual maximum dose: 8 mg.
Pharmacokinetics:  Short-acting. Onset of action:  Hypnosis: I.M.: 20-30 minutes.  Sedation: I.V.: 5-20 minutes.  Anticonvulsant: I.V.: 5 minutes, oral: 30-60 minutes. Average half-life (variable): 15 hours (8-24 hours).
Maximum dose: 10 mg (oral)


Oxazepam  (Serax ®):

 Dosing (Adults)Anxiety: 10-30 mg 3-4 times/day.  Ethanol withdrawal: 15-30 mg 3-4 times/day. Hypnotic: 15-30 mg
Pharmacokinetics:  Short-acting.  Peak level:  1-4 hours.  Average half-life (variable): 8 hours (3-25 hours).
Maximum dose: 120 mg


Temazepam (Restoril ®):

 Dosing (Adults)Short-term treatment of insomnia 15-30 mg at bedtime.
Pharmacokinetics:  Intermediate-acting.  Peak level:  2-3 hours.  Average half-life (variable): 11 hours (3-25 hours).
Maximum dose: 30 mg


References

Benzodiazepine Equivalence Charts:

  1. Arana and Rosenbaum, Handbook of Psychiatric Drug Therapy, 4th Edition, 2000.
  2. Clinical Handbook of Psychotropic Drugs, 4th revised edition, Bezchlibnyk-Butler et al. editors (Clarke Insitute of Psychiatry, Toronto), Hogrefe & Huber.
  3. Gelenberg AJ, Bassuk EL.  The Practitioner's Guide to Psychoactive Drugs. Springer, 1997 - 536 pages (page 234).
  4. Hughes W. Clinical Pharmacy.  Macmillan Education AU, Dec 15, 2001 - 512 pages (page 167).
  5. Ruiz P,  Strain EC. Lowinson and Ruiz's Substance Abuse: A Comprehensive Textbook.  Lippincott Williams & Wilkins, Apr 15, 2011 - 1074 pages (chapter 35: pages 503-504).
  6. Substance Use Disorders: A Practical Guide By Stuart Gitlow 2nd edition.
  7. Tyrer PJ, Silk KR.  Cambridge Textbook of Effective Treatments in Psychiatry. Cambridge University Press, Jan 24, 2008 - 920 pgs (pg 301).
Benzodiazepine equivalent dosage converter