Head of Medicines Management Head Office, 99 Waverley Road St Albans, Hertfordshire AL3 5TL
4 May 2012
To All Health Care Professionals HPFT/HCC Learning Disabilities Services in Hertfordshire
Dear Colleagues
Re: BUCCAL MIDAZOLAM
You will be aware that there have been recent alerts about the availability of different buccal midazolam products which may have caused some confusion. These products are available in different strengths and this could pose a risk to service users if you are unaware of this. It is important where possible to continue using the same brand to avoid switching the brand of product.
Service users accessing HPFT services are prescribed the buccal midazolam product Epistatus which is available either in a bottle or in syringes. These should always be prescribed by brand name. Epistatus is not licensed in adults or in children but has been used as a “special” for several years in learning disability services across the UK and in HPFT. All the training and shared care arrangements within learning disability services relate to the Epistatus brand. There has been added confusion recently with several MHRA alerts about certain batches and volumes of Epistatus being changed (see links below to MHRA).
A new buccal midazolam product called Buccolam ® has been launched and is licensed by the MHRA for children but not for adults. This product is available in a different strength of midazolam per ml to Epistatus. Buccolam brand has sometimes been prescribed by GPs and this may cause confusion to users and carers.
Clearly there is a desire to use this product within paediatrics as it is licensed by the MHRA for children.
Because of this confusion and several incidents where the two products have been interchanged and transferred without informing the users and carers a group of
Page 1 of 5 healthcare professionals from several organisations in Hertfordshire met to agree the best course of action. The background and the current recommendation are outlined.
Background
An MHRA Drug Safety Update issued in October 2011 introduced the new licensed buccal midazolam (Buccolam) and provided a warning about the care that is needed when transferring from unlicensed formulations e.g Epistatus. http://www.mhra.gov.uk/home/groups/dsu/documents/publication/con131944.pdf
Since then there have been three further MHRA Drug Alerts about modifications which have been made to the unlicensed Epistatus product in terms of the luer tip, the markings on the plunger and the positioning of the plunger stop; together causing a potential for overdose if not recognised. http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON143794 http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON146522 http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON149813
Following the MHRA alerts some guidance was issued from the National Patient Safety Agency http://www.nrls.npsa.nhs.uk/resources/type/signals/?entryid45=132975
NICE Clinical Guideline – Epilepsy CG137 Prolonged or repeated seizures and convulsive status epilepticus http://guidance.nice.org.uk/CG137/NICEGuidance/pdf/English
• Only prescribe buccal midazolam or rectal diazepam for use in the community for children, young people and adults who have had a previous episode of prolonged or serial convulsive seizures. [new 2012]
• Administer buccal midazolam as first-line treatment in children, young people and adults with prolonged or repeated seizures in the community. Administer rectal diazepam if preferred or if buccal midazolam is not available. If intravenous access is already established and resuscitation facilities are available, administer intravenous lorazepam. [new 2012]
Buccal Midazolam Products available:
Epistatus 10mg in 1ml (1mg midazolam base in 0.1ml)
Presentations - there are two presentations:
1. A multi-dose pack of Epistatus is supplied as 5ml of liquid in a 30ml amber bottle. The bottle is over-sized to enable the care person to grip it securely while removing the child resistant closure. A 1ml overage is supplied to ensure that 4x1ml doses can be removed quickly and completely. Each 0.1ml of buccal midazolam liquid contains 1mg of midazolam base.
Page 2 of 5 The pack contains a carton with instructions for use on the side panel, an information leaflet, an amber glass bottle with tamper evident child resistant closure and 4x 1ml purple oral dosing applicators calibrated with 0.1ml markings.
2. Pre-filled syringes (PFS packs) Each pack contains 2 x 1ml purple oral dosing applicators. Each oral dosing applicator is prefilled with one of the following doses – 2.5mg, 5mg, 7.5mg, 10mg. There are two oral dose applicaors in each child resistant pack.
Storage: 15 -250C Shelf life: 2 years multi-dose pack. 1 year pre-filled syringes.
• Epistatus is an unlicensed special which has been used for several years in both paediatrics and in adults for service users with Learning Disabilities • Each service user in learning disability services has an individual management plan with training provided to the staff and carers from specialist services. • The MHRA has received a submission for licensing for adult and paediatric use from Special Products Ltd. • The midazolam salt in Epistatus is midazolam maleate. However, the clinical trial papers relate to the hydrochloride salt on the basis of buccal administration of midazolam hydrochloride injection. Information from Special Products Limited is that they are hopeful about obtaining a licence for adults and children but they do not have a date. The MHRA has asked them for evidence based on the midazolam maleate product. • It is very important to prescribe as brand Epistatus pre-filled syringe or bottle to ensure continuity of the same strength.
Epistatus Pack Size
Midazolam maleate (Epistatus) 5ml 10mg in 1ml * Midazolam maleate 2 syringes 2.5mg in 0.25ml Midazolam maleate 2 syringes 5mg in 0.5ml Midazolam maleate 2 syringes 7.5mg in 0.75ml Midazolam maleate 2 syringes 10mg in 1 ml
Page 3 of 5 Buccolam ® 10mg in 2ml (1mg midazolam base in 0.2ml)
Presentations
Pre-filled syringes containing 2.5mg, 5mg, 7.5mg and 10 mg midazolam
Licensed Dose and administration
Age range Dose Label colour 3 to 6 months in a hospital 2.5mg in 0.5ml yellow setting (monitoring and resuscitation available) >6 months to <1year 2.5mg in 0.5ml Yellow 1 year to <5 years 5mg in 1ml Blue 5 years to <10 years 7.5mg in 1.5ml Purple 10 years to <18 years 10mg in 2ml Orange
• Buccolam is licensed in Paediatrics. No adult licence has been applied for. • Volume administered would be larger than Epistatus as the strength of the solution is half that of Epistatus
Comparative Cost
Buccal Midazolam Products Drug Tariff (March 12) Per dose Buccolam 10mg/2ml PFS (4) £91.50 £22.80 Buccolam 7.5mg/1.5ml PFS (4) £89.00 £22.30 Buccolam 5mg/1ml PFS (4) £85.50 £21.38 Buccolam 2.5mg/0.5ml PFS (4) £82.00 £20.50
Epistatus 10mg/ml (5ml) £90.68 £22.67
Factors to consider
• Errors have occurred in Hertfordshire with substitutions made by GPs and Community Pharmacists between Epistatus and Buccolam (and other brands) without professionals and carers being made aware of the difference in strength. There are other specials supplied across Hertfordshire which may add to the confusion ( Epi-Calm, UL Medicines, Suptamid)
• MHRA recommend that if a branded product is available, then this should be used rather than an unlicensed product even if it is used for an “off-label” indication; unless there is a good clinical reason for prescribing the unlicensed product. Note: Buccolam is only licensed for Paediatrics. Buccolam is not licensed for adults. Most service users in Learning Disability services are adults. Epistatus is unlicensed for both.
• The Buccolam dose is twice the volume per mg dose to be placed in the mouth. Concern was raised about aspiration or this larger volume being spat out or
Page 4 of 5 swallowed (where it would be ineffective). The manufacturers clearly state that half the dose should be placed in one side of the mouth and half in the other.
• HPFT/HCC Learning Disability teams have been advising use of Epistatus for several years and has developed shared care protocols and training (for bottles) for healthcare professionals and carers. This affects a large number of service users with learning disabilities and a switch to a different product would have significant resource implications and a sudden switch would be unsafe in the short term.
• Tertiary Referral Centres and surrounding organisations are in the process of making a decision e.g. East Anglia Epilepsy Network, Great Ormond Street In many cases switching to the licensed product Buccolam with others remaining with Epistatus. Different products will cause confusion across organisations so it is important to be aware of the different products.
• Buccolam Information leaflets for carers and product packaging states very boldly that the use is only up to 18 years. Carers will be very concerned about the suitability for adults with learning isability. The product packaging for Epistatus is directed at all ages.
• HPFT/HCC clinicians and service users are familiar with the product.
Recommendation:
HPFT has recommended that we continue to prescribe the Epistatus by brand name either in a bottle or in a syringe. The decision will be reviewed in 6 months time.
Buccolam is being prescribed by paediatricians in acute trusts and Hertfordshire Community Trust and also by some tertiary referral hospitals. Therefore it is important that we remain alert to the possibility that brands may be inadvertently exchanged.
Reason for recommendation despite the MHRA guidance to use a licensed product when available:
It was considered that the packaging and information leaflets for Buccolam will cause concern for our users and carers as it emphasises that this is only licensed for children.
Training and individual care packages for Epistatus are in place for a large number of service users in Learning Disability Services in HPFT. Systems are well established for training and carer information.
Dr Kamalika Mukherji, Consultant Psychiatrist, Learning Disability Services HPFT Alan Lim, Specialist Epilepsy Nurse, Learning Disability Services HPFT Janet Howell, Head of Medicines Management HPFT May 2012
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