Understanding benzodiazepine differences

Benzodiazepines vary significantly, making it challenging to pinpoint exact equivalents. Differences include potency, duration of action, individual response and licensed indications, all of which must be considered when deciding equivalent benzodiazepines and doses.

Potency

Potency varies widely, which is important when switching from one benzodiazepine to another, as equivalent doses can vary greatly.

Short acting benzodiazepines are more potent compared to long acting benzodiazepines. They carry a higher risk of withdrawal symptoms, such as insomnia, anxiety, loss of appetite and tremor.

Duration of action

The duration of action influences the frequency of dosing and the potential for withdrawal symptoms.

Short acting

Short acting benzodiazepines, such as alprazolam, loprazolam, lorazepam, lormetazepam, oxazepam and temazepam, have a short half-life.

They are rapidly eliminated from the body, causing fluctuations in drug concentrations with peaks and troughs between doses.

Long acting

Long acting benzodiazepines such as chlordiazepoxide, clobazam, clonazepam, diazepam, flurazepam and nitrazepam have a long half-life.

When taken daily, they can accumulate to high concentrations in the body, particularly in fatty tissues. These benzodiazepines are less likely to cause withdrawal symptoms.

Individual response

The response to benzodiazepines varies among individuals, especially in elderly people and those with liver or kidney impairment. This variability must be carefully considered when prescribing benzodiazepines.

Liver impairment

Extra precautions are necessary for people with liver impairment. Diazepam and other long acting benzodiazepines can accumulate to toxic levels. Switching to diazepam may not be suitable for people with liver impairment. An alternative benzodiazepine without active metabolites, such as oxazepam, may be preferred.

Always refer to the individual benzodiazepine’s Summary of Product Characteristics (SmPC) for dosing guidance in people with liver impairment.

Kidney impairment

Lower doses may be needed in people with renal impairment as cerebral sensitivity to benzodiazepines is increased.

Always refer to the individual benzodiazepine’s SmPC for dosing guidance in people with kidney impairment.

Licensed indications

Benzodiazepines have different UK licensed indications. When switching from one benzodiazepine to another it is important to consider the condition being treated.

Licensed indications for each benzodiazepine are stated within this articles approximate equivalence to oral diazepam section and in the individual benzodiazepine’s SmPC.

Considerations before switching

Wide variation in the potency, half-life, individual response and licensing means equivalence is not exact and should be interpreted using your clinical and pharmaceutical knowledge.

Breastfeeding

Refer to our guidance on Using benzodiazepines during breastfeeding to help choose an appropriate benzodiazepine for breastfeeding mothers.

Approximate equivalence to oral diazepam

Diazepam 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 can be given in divided doses.

Approximate equivalence is useful when switching a benzodiazepine to diazepam, or when switching one benzodiazepine to another, using diazepam as an intermediate step. Doses should be tapered according to individual response.

Alprazolam

Alprazolam 250 micrograms is approximately equivalent to diazepam 5mg.

Licensed indication

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.

Licensed indication

Chlordiazepoxide is used short-term for 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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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.

Licensed indication

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).

Further information

Primary care healthcare professionals in England can seek further guidance through our Medicines Advice service. We can provide assistance with switching non-UK licensed benzodiazepine preparations, how to carry out a switch, or if the clinical scenario is complex.

Useful resources

The Ashton Manual provides information on how benzodiazepines work, withdrawal symptoms and how to withdraw.

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