Lorazepam v Midazolam

[gigeordie]

Dear All,

I was wondering if any hospital pharmacists have come across using an unlicensed lorazepam suspension for status epilepticus? I work in a hospital manufacturing unit and we have had several requests for lorazepam 4mg/ml suspension recently which they are administering buccally.
This was kickstarted by an alleged 'one off, emergency' request from the clincal team for a buccal lorazepam solution due to the tablets being unavailable and the patient not tolerating midazolam. Unfortunately this has now opened the flood gates for more requests.

We have pointed out that there is now a licensed Midazolam Buccal preparation as we are not too keen on continuing to supply the lorazepam suspension as it is not strictly a buccal formualtion. For some reason the clinical team don't seem keen on the licensed Midazolam or the S/L Lorazepam tabs either.

Whilst we acknowledge that the Lorazepam suspension is unlicensed and therefore up to the prescriber how it is administered we can't seem to get an answer as to why they won't use a licensed product which should surely be the preferable option.

[Nik]

What about using midazolam injection orally ? I've not come across the use of lorazepam suspension for buccal use where I work as people use Buccolam. I just wonder about how quickly the lorazepam will be absorbed and for what reason the clinicians prefer it over midazolam. I don't know whether you've read Pfizer's letter in this weeks BMJ responding to a letter from Cambridge Hospitals regarding the shortage of IV lorazepam. "Currently we expect to be back in stock of IV lorazepam in second quarter of 2013" !

http://www.bmj.com/content/343/bmj.d5962.full.pdf

[johnep]

Not heard of use of Lorazepam in epilepsy before, what are the advantages over diazepam or midazolam?. Appreciate half lives may be a factor.
johnep

[Nik]

IV lorazepam is 1st line for use in convulsive status epilepticus. Diazepam is very lipophilic and has a large volume of distribution. Although it rapidly redistributes into the brain, it then quickly redistributes into fat tissues, causing CNS levels to drop. Of course you can give a second dose of 10mg according to BNF, but this is then likely to lead to accumulation. Lorazepam is less lipid soluble so will take a little longer to reach effective concentrations in the brain - however as it doesn't redistribute into fat, it has a longer duration of action. IV midazolam not appropriate as it has an extremely short duration of action. High strength midazolam not generally kept on acute medical wards as NPSA report from 2008 highlighted risk of overdose.

[johnep]

Thanks Nik, very clear answer. Knew the Benzodiazepines were lipid loving but did not know they had greatly differing physical properties in regard oil/water systems.
Good piece of CPD.
johnep

[Nik]

No problem - incidentally midazolam has good lipophilic and hydrophilic properties, allowing it to both enter the brain easily, and cross the buccal mucosa rapidly.

[gigeordie]

Thank you for your help Nik. We are urging them to use Buccolam as they are somewhat wooly in the reasoning for giving Lorazepam

[Nik]

No worries - I would've though using 0.5-1ml of a 10mg/ml midazolam solution would be easier than fiddling about with lorazepam !

[gigeordie]

Finally we have some information from the clinical team. The Lorazepam suspension given buccally is specialist end of line treatment. It is used when neither buccal Midazolam or rectal Paraldehyde are effective and the patient continues in status.

Unfortunately we still don't know why they can't use Lorazepam SL tabs!

It's back to the drawing for us as we try and reformulate a liquid formulation more in line with other buccal preparations. The clinical team have decided that if it stops fitting then bioavailability is adequate in their eyes. The joys of unlicensed manufacturing.......

[Nik]

If it's specialist end of line treatment, then the excuse that the clinical team "don't seem that keen on using licensed midazolam or S/L tabs" doesn't really hold up ! Also wouldn't adding another benzo just be delaying the inevitable, ie phenytoin or phenobarb or even ITU for refractory status ?