Green – For medicines routinely initiated and used by generalists


Description: Short acting benzodiazepine

note: syringe pump and syringe driver are both relevant terms


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Midazolam Injection


5mg in 1ml

Ampoules of 10mg in 2ml for IV, IM, rectal use


subcutaneous administration

Midazolam injection can be administered via the buccal, sublingual or intranasal
route. The volume, however, is often impractical. Midazolam may sting if
administered intra-nasally.


Licensed formulation in paediatrics


5mg in 1ml

Pre-filled oral syringes of 2.5mg. 5mg, 7.5mg and 10mg



Licensed formulation in paediatrics

Unlicensed formulation


10mg in 1ml

10mg/ml prefilled syringe. Also available as pre-filled oral syringes of 2.5mg, 5mg, 7.5mg. (licensed formulation for 18 years or under)


Unlicensed formulations:

5ml bottle (4 x 1ml doses with 1ml overage) + 4 x 1ml oral syringes.

  • Note:  There are a number of different strengths of midazolam injection available (1mg/ml, 2mg/ml, 5mg/ml). In palliative care the most concentrated form of the injection is prescribed to maximise dosing options for single site subcutaneous injection where the volume limit is approximately 2ml i.e. 10mg in 2ml.
  • Buccolam and Epistatus are not licensed for use in adults.  Please check your local formulary for preferred product.
  • Buccolam is half the strength of Epistatus – be aware of difference in strength when prescribing.



Clinical indications and off label use

  • Status epilepticus, as an alternative to rectal diazepam
  • Prolonged (longer than 5 or 10mins) convulsive epileptic seizures
  • Sedation prior to procedures
  • Confusion and restlessness
  • Sedative/anxiolytic in terminal haemorrhage or agitation at the end of life
  • Spasticity or skeletal muscle spasm
  • Persistent hiccups
  • Anxiety/panic e.g. in severe breathlessness at end of life – seek specialist advice
  • Alcohol withdrawal at end of life



Use with caution in:

  • Elderly patients
  • Chronic renal failure
  • Impaired hepatic function
  • Impaired cardiac function
  • In obese patients, the half life can be increased due to increased volume of distribution



  • Known hypersensitivity
  • Marked neuromuscular respiratory weakness including unstable myasthenia gravis
  • Severe respiratory depression
  • Acute pulmonary insufficiency
  • These are not absolute contraindications if the patient is in the last days of life. Careful titration is however necessary


Important drug interactions

  • Midazolam is a major substrate of CYP3A4.
  • Please refer to current edition of BNF for significant drug interactions.  
  • Fatalities have occurred after concurrent administration with higher than approved doses of olanzapine.


Midazolam pharmacokinetic data

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46 to 68%

Onset of action





2 mins

Time to peak concentration

30 minutes

30 minutes

30 minutes

30 minutes

14 mins

Plasma half life

2 to 5hours





Duration of action

less than 4hours with a 5mg dose*
(*individual variation)






Switching between benzodiazepines

Changing benzodiazepines - seek specialist advice if uncertain

  • These doses/ratios are approximate (≈) and not exact equivalent doses and should be used as a guide.
  • Dose conversions should be conservative and doses are usually rounded down (Note – check available strengths).
  • Adjust doses in accordance with patient’s condition; reduce less if severe pain.
  • Monitor closely; extra care if frail, elderly patient; renal or hepatic impairment.


Approximate equivalent anxiolytic-sedative doses (PCF6)


Dose Oral

Dose SC





250micrograms to 500micrograms

250micrograms to 500micrograms









2mg to 3mg








  • As an antiepileptic agent - in single doses midazolam is considered to be twice as potent as diazepam.
  • As a sedative, in single doses, midazolam is considered to be three times more potent than diazepam.
  • With multiple doses midazolam gains in potency because of a prolonged plasma half-life.


Side effects

  • As for other benzodiazepines
  • Drowsiness and sedation (may persist for several hours after administration)
  • Respiratory depression occurs in about 5% patients.


Dose and administration

Seizures (refer to seizures guideline)

  • Generally administered sublingually or bucally: 10mg initially; repeated after 10 minutes if no effect and the patient is breathing normally. If no effect apparent 5 minutes after the second dose, seek medical help.


Note: Consider a reduced dose (5mg) in elderly patients and patients under 50kg.

  • Using the oral syringe provided administer over a period of 2 to 3 seconds, about half of the prescribed dose to each buccal cavity (between the gums of the lower jaw and the cheek). If administration to the patient is very difficult to control, then administer the whole dose, over a period of 4 to 5 seconds, to one buccal cavity.
  • As a last resort, can be administered intra-nasally if the patient foams at the mouth.


Dying patients unable to take oral medication

  • Anti-epileptic drugs have a long half-life, however ongoing management should be considered:
    • Midazolam 5mg subcutaneously (SC). Buccal midazolam is another option and can be acceptable for patients.
    • Midazolam 20mg to 30mg via continuous subcutaneous infusion (CSCI) over 24 hours can be used as maintenance therapy.


Sedative/anxiolytic in terminal haemorrhage (refer to bleeding guideline)

Midazolam 5mg to 10mg buccal/SC/IM/IV


Spasticity or skeletal muscle spasm (seek specialist advice)

If muscle spasms fail to respond to oral muscle relaxants such as baclofen, tizanadine, dantrolene or diazepam: Midazolam: 2mg to 5mg SC or 10mg in 24 hours by CSCI.


Persistent hiccups (refer to hiccups guideline)

Where hiccups fail to respond to other measures such as prokinetics seek specialist advice.


Anxiety/panic, for example, in severe breathlessness at end of life

2mg to 5mg SC/SL/buccal. CSCI 5 to 10mg over 24 hours. Seek specialist advice


Agitation or delirium

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Intermittent anxiety or distress

Midazolam SC 2mg to 5mg, hourly, as required. If 3 or more doses are administered in 4 hours, seek advice. If 6 doses are required in 24 hours, seek medical review/advice.

Persistent anxiety or distress

First step:

Midazolam SC

10mg to 20mg over 24 hours in a syringe pump + midazolam SC 5mg hourly, as required.

Second step:

Titrate midazolam with advice, SC 10mg to 60mg over 24 hours in a syringe pump + QTlevomepromazine SC 10mg to 25mg, 6 to 12 hourly as required. Use lower doses if not used previously and in frail elderly.

Stop any QThaloperidol.


Alcohol withdrawal at end of life

Seek specialist advice


Practice points

  • Midazolam is a Schedule 3 CD (Controlled Drug), therefore all prescriptions must satisfy CD prescription requirements to be valid and include details of the dose, form, strength, directions for use and total quantity (in both words and figures. Please refer to sample prescription.
  • The injection preparation prescribed for adults and held by the palliative care community networks is 10mg in 2ml.
  • Patients on regular benzodiazepines who have developed a tolerance to their effects may require a higher dose.
  • An overdose can be treated with Flumazenil (short-acting benzodiazepine antagonist). Flumazenil should be available in in-patient settings where midazolam is used (NPSA alert).
  • Epistatus is an unlicensed medication and as such has no marketing authorisation in the UK.
  • Epistatus can be prescribed by the patient’s GP for the indications listed in liaison with local palliative care specialists.
  • Patients should receive an initial supply on discharge to allow adequate time for the community pharmacist to order. The lead time for Epistatus is approximately 4 working days although may be longer in remote and rural areas.
  • Midazolam injection can be administered via the buccal route. The volume, however, is often impractical.

Patient and carer advice points

  • Buccolam ­– remove oral syringe cap before use to avoid risk of choking.
  • Epistatus (5ml bottle) – the bottle cap must be replaced immediately to prevent evaporation. If the liquid is allowed to evaporate some of the midazolam will precipitate, exhibited as cloudiness or as white particles in the liquid. The pack must be discarded if the solution is not clear.
  • Do not store in a fridge.
  • Epistatus (5ml bottle) – the dose markings are on the syringe plunger not the syringe barrel.
  • Do not place the syringe between the patient’s teeth as they might bite the syringe
  • If using the injectable solution sublingually or buccally, ensure needle is removed from syringe tip prior to administration.