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Scottish Palliative Care Guidelines print pdf

Midazolam


Introduction

Description : Short acting benzodiazepine

Preparations

Buccolam®
Licensed formulation

Midazolam Hydrochloride
5mg in 1ml

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

 

Epistatus®
Unlicensed formulation

Midazolam Maleate
10mg in 1ml

5ml bottle (4 x 1ml doses with 1ml overage) + 4 x 1ml oral syringes
Also available as pre-filled oral syringes of 2.5mg, 5mg, 7.5mg and 10mg.

Note:  Buccolam® is not licensed for use in adults.  Please check your local formulary for preferred product.

Indications

  • Status epilepticus, as an alternative to subcutaneous midazolam or rectal diazepam
  • Prolonged (longer than 5 or 10mins) convulsive epileptic seizures
  • Sedative/anxiolytic in terminal haemorrhage

Cautions

Use with caution in:

  • Elderly patients
  • Chronic renal failure
  • Impaired hepatic function
  • Impaired cardiac function

Contraindications:

  • 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

 Buccal midazolam pharmacokinetic data

Bioavailability

75%

Onset of action

15mins

Time to peak conc

30minutes

Plasma half life

2-5hours

Duration of action

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

  •  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, diazepam gains in potency, relative to midazolam,  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 in about 5% patients.

Dose and Administration

  • 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 <50kg
  • Using the oral syringe provided administer over a period of 2-3 seconds, about half of the prescribed dose to each buccal cavity (between the gums of the lower jaw and the cheek).  If the patient is very difficult to control, then administer the whole dose, over a period of 4-5 seconds, to one buccal cavity.
  • As a last resort, can be administered intra-nasally if the patient foams at the mouth.

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) Sample prescription
  • 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)
  • 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
  • Epistatus® can be ordered by all community pharmacies directly from Special Products Ltd.  Tel: 01932 690325  Fax: 01932 341091

Patient and carer advice points

  • Buccolam®  - Remove oral syringe cap before use to avoid risk of choking
  • Epistatus®- 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®- 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

Further information

  • 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.
  • Midazolam injection can be administered via the buccal route. The volume , however, is often impractical.

 

References