How benzodiazepines differ

There are differences between benzodiazepines which make it difficult to suggest exact equivalents:

Potency

There are major differences in potency which is important when switching from one benzodiazepine to another.

Pharmacokinetics

Benzodiazepines can vary significantly in their speed of metabolism and elimination.

When benzodiazepines that have a long half-life, such as diazepam, are taken every day they can accumulate to high concentrations in the body (mainly in fatty tissues).

Benzodiazepines such as alprazolam and lorazepam have relatively short half-lives. They are eliminated fairly rapidly and cause concentrations in the body to fluctuate with peaks and troughs between each dose.

Sedation

Benzodiazepines vary in the amount of sedation that they cause.

Licensed indications

There are differences in the licensed indications of benzodiazepines. When switching from one benzodiazepine to another it is important to consider what condition the benzodiazepine is being used for.

Approximate equivalence to oral diazepam

Inter-patient variability, different half-lives and differing levels of sedation mean that equivalence is not exact and should be interpreted using clinical and pharmaceutical knowledge. Doses should be titrated against patient response.

Diazepam has a wide range of licensed uses. It is used short-term for severe anxiety, muscle spasm, alcohol withdrawal, epilepsy, cerebral palsy and as a pre-medication. Despite its long half-life, the daily dose is usually given in divided doses.

Alprazolam

Alprazolam 250 micrograms is approximately equivalent to diazepam 5mg. Alprazolam is used short-term for severe anxiety. The daily dose is usually given in 2 or 3 divided doses.

Chlordiazepoxide

Chlordiazepoxide 12.5mg is approximately equivalent to diazepam 5mg. Chlordiazepoxide is used short-term for severe anxiety, muscle spasm and alcohol withdrawal. The daily dose is usually given in 3 or 4 divided doses.

Clobazam

Clobazam 10mg is approximately equivalent to diazepam 5mg. Clobazam is used short-term for severe anxiety and as adjunctive therapy in psychosis, schizophrenia and epilepsy. The daily dose can be given in divided doses or as a single dose at night. Doses higher than 30mg should be given in divided doses.

Clonazepam

Clonazepam 250 micrograms is approximately equivalent to diazepam 5mg. Clonazepam is used for the treatment of epilepsy. The dose may be given as a single daily dose at night or in 3 or 4 divided doses.

Flurazepam

Flurazepam 7.5mg to 15mg, is approximately equivalent to diazepam 5mg. Flurazepam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Loprazolam

Loprazolam 500 micrograms to 1mg, is approximately equivalent to diazepam 5mg. Loprazolam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Lorazepam

Lorazepam 500 micrograms is approximately equivalent to diazepam 5mg. Lorazepam is used short-term for severe anxiety, associated insomnia, and as a pre-medication. The dose is taken in divided doses (for anxiety) or at night (for insomnia). When used as a pre-medication before dental or general surgery the dose is taken the night before the operation and a second dose one to two hours before the procedure.

Lormetazepam

Lormetazepam 500 micrograms to 1mg, is approximately equivalent to diazepam 5mg. Lormetazepam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Nitrazepam

Nitrazepam 5mg is approximately equivalent to diazepam 5mg. Nitrazepam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Oxazepam

Oxazepam 10mg is approximately equivalent to diazepam 5mg. Oxazepam is used short-term for severe anxiety and associated insomnia. The dose is taken in three or four divided doses (for anxiety) or at bedtime (for insomnia).

Temazepam

Temazepam 10mg is approximately equivalent to diazepam 5mg. Temazepam is used short-term for the treatment of insomnia, and as pre-medication before minor surgical and investigative procedures. The dose is taken at bedtime (for insomnia), or half to one hour before the procedure (as pre-medication).

Hepatic and renal impairment

Concomitant renal or hepatic impairment should be taken into consideration when prescribing benzodiazepines. Extra precautions apply in patients with hepatic dysfunction as diazepam and other longer-acting benzodiazepines may accumulate to toxic levels. For example, switching to diazepam may not be appropriate in this group of patients.

In patients with renal impairment, cerebral sensitivity to benzodiazepines is increased, so lower doses may be needed.

Refer to the individual benzodiazepine’s Summary of Product Characterstics (SPC) for dosing guidance when administering to patients with renal or hepatic impairment.

Further reading

• Ashton CH. Benzodiazepine equivalence table (2007).
• Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. Update 2017  London: Department of Health.
• Full prescribing information for the benzodiazepines can be accessed: www.medicines.org.uk.

 

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