East & South East England Specialist Pharmacy Services
East of England, London, South Central & South East Coast
East Anglia Medicines Information Service
Medicine Review
Medicine / Trade name / Midodrine (unlicensed*)Manufacturer / unlicensed
Indication / Postural hypotension
Document status / Reviewed at Suffolk CCGs D&TC 12thNovember 2013 and CPG 9th December 2013
Date of last revision / 1/11/2013
Traffic light decision
/ Green – Hospital initiated, GP prescribedPrescribers rating / Not assessed
Source of review / The embedded new medicines evidence summary from NICE contains information on – mechanism of action, class of medicines, indication, dose, treatment alternatives, likely place in therapy, evidence for use, side effects, comparative costs of other medicines and estimated use.
NNTs not calculated.
According to costs in the NHS Prescription Cost Analysis for England 2011 the 2 types of 2.5mgmidodrine tablets listed cost £1.48 or £2.01 each, and the 2 types of 5mg midodrine tablets cost£1.04 or £1.55 each. For a dose of 10mg midodrine taken 3 times a day, this would costbetween £6.24 and £24.12 a day depending on which tablets are taken.
*Midodrine does not have marketing authorisation in the UK for the treatment of postural hypotension or for any other indication, therefore it is an unlicensed medicine in the UK. Midodrine is licensed in the USA, and in several EU countries, such as Germany, France, Ireland, Italy and Spain.
Future alternatives / Nil known
Potential number of patients per 100,000 population / The NHS Prescription Cost Analysis for England 2011 reported that 16,500 prescription items ofmidodrine were dispensed in the community in 2011. The net ingredient cost of theseprescriptions was £2,011,800. However, the prescription cost analysis does not include
information on the indications for which the drugs were prescribed.
Decisions sought from other bodies / Cambridgeshire and Peterborough CCG– Not on formulary, however available on a named patient basis via shared care with Papworth Hospital only ‘Midodrine for idiopathic orthostatic hypertension or neurocardiogenic syncope’
Norfolk TAG – not considered
SMC – not considered
AWMSG - not considered
Decision review date / 2 years following decision or unless superseded by NICE guidance or substantial and significant new evidence becomes available.
Comments
Julie Brache Consultant Elderly Services IHT
I do use it for patients with falls/syncope and significant orthostatic hypotension. The evidence base for treating OH is rather limited so I’ll describe how I use it. OH is very common in the frail elderly so caution has to be used not to treat a drop in BP alone, only to use it for symptomatic drop associated with a history of falls or syncope that are suggestive of a BP mediated cause. My practise is to use it 3rd line. 1st is self management advice and medication review (this is enough for a significant proportion of my patients, especially the younger ones), 2nd line is fludrocortisone.
I have been prescribing it and monitoring and changing doses in clinic, once a month until established then asking the GP to take over the prescription, I’m not currently prescribing it for anyone. I probably start less than 12 patients a year.
Sharmistha Nadi Consultant Elderly Services IHT
I would agree completely with Julie.
Duncan McNab Cardiologist IHT
I would agree with the comments below. My experience with fludrocortisone is that it is rarely a great success with neurocardiogenic syncope (although I do start with it as my first agent) and that in the small numbers of patients who do require midodrine, it can be a life-changer. I have always followed these patients up, to screen for hypertension, especially at night, whilst supine, but if there were rigorous protocols in primary care to ensure this was done, it could be continued in Primary Care.
Gerry Rayman Consultant Physician Diabetes and Endocrinology IHT
I do not have the time to sift through the document that you have sent. Basically, I have a single patient whose life is dependent on midodrine in whom I have to issue a repeat prescription every three months. This has been the case for this individual for more than 5 years. It is a pain for both me and the patient to keep corresponding re the prescription. All I want out of this is for the GP to now be able toissue the prescription. In the next few year I may have 2 or 3 more such prescription. The place in therapy this therapy in diabetic postural hypotension has been accepted by diabetologists for many years.
Andrew Owen Cardiologist IHT
I would like to be able to use this occasionally, but at present it is difficult because GP’s cant/won’t continue with the prescription. They should.
Craig ParkinsonConsultant Physician Diabetes and Endocrinology IHT
I think we should bear in mind the difficulties we sometimes face with patients who have postural orthostatic hypotension or neurocardiogenic syncope. I can think of some patients who attend hospital on a very regular basis as a consequence and others where there quality of life and ability to work has been dramatically impaired by these conditions.
In this context we should make available all options for treatment. There are in fact very few, and whilst I agree that fludrocortisone should be used first line the introduction of midodrine is quite commonly required by patients with these conditions in my experience. I believe the numbers will be higher than those suggested so far. I have picked up approximately 4 new patients this year and I know of other existing patients, and if we are all, individually seeing a handful of patients there is cumulatively a reasonable patient cohort (although not clearly defined and not likely to represent huge numbers). I am also concerned that we, as yet, have no input from the COE teams and I certainly know that Dr Lockington see’s many patients with this problem. How much use of midodrine takes place in that group of patients however is not clear to me.
I would suggest that a shared care document is developed, with the initiation being undertaken by a consultant specialist, and after 3-6/12 of dose stabilisation the ongoing prescription should be picked up by the GP. It is not a high cost drug, but these patients can be a significant challenge and as such we must have this option available.
Damian Morris Consultant Physician Diabetes and Endocrinology IHT
I agree with Paul & Duncan. Will be small numbers.
Duncan Fowler Consultant Physician Diabetes and Endocrinology IHT
I agree with Paul Venables. I use it very occasionally on patients with orthostatic hypotension resistant to other therapies. It is small numbers (I can think of just a couple of patients) and should be consultant initiated and stabilised with then transfer of prescribing to GP with their agreement (possibly under some shared care policy if they wish).
Paul Venables Consultant Cardiologist IHT
I think this has a place for shared care. I use the drug selectively for both Orthostatic Hypotension and Neurocardiogenic Syncope. I would strongly advise we include the latter as Cambridge have done. This invariably involves me prescribing the drug until I’ve seen them tolerating it well as a follow-up, then the GP could prescribe.
I did bring this up in the last round of e-mails, was it considered?
Review prepared by Sarah Cavanagh, East Anglia Medicines Information Service
May be freely copied by NHS agencies Not to be used for promotional purposes
Grids used to assist the NHS Suffolk PCT Drug & Therapeutics Committee in reaching a decision about new medications
For many years scientists have recognised two types of research:
Primary: original studies, based on observation or experimentation on subjects.
Secondary: reviews of published research, drawing together the findings of two or more primary studies.
In biomedical science there is general agreement over a hierarchy: the higher up a methodology is ranked, the more robust and closer to objective truth it is assumed to be. The orthodox hierarchy looks something like this-
Rank: / Methodology / Description1 / Systematic reviews and meta-analyses / Systematic review: review of a body of data that uses explicit methods to locate primary studies, and explicit criteria to assess their quality.
Meta-analysis: A statistical analysis that combines or integrates the results of several independent clinical trials considered by the analyst to be "combinable" usually to the level of re-analysing the original data, also sometimes called: pooling, quantitative synthesis.
Both are sometimes called "overviews."
2 / Randomised controlled trials
(finer distinctions may be drawn within this group based on statistical parameters like the confidence intervals) / Individuals are randomly allocated to a control group and a group who receive a specific intervention. Otherwise the two groups are identical for any significant variables. They are followed up for specific end points.
3 / Cohort studies / Groups of people are selected on the basis of their exposure to a particular agent and followed up for specific outcomes.
4 / Case-control studies / "Cases" with the condition are matched with "controls" without, and a retrospective analysis used to look for differences between the two groups.
5 / Cross sectional surveys / Survey or interview of a sample of the population of interest at one point in time
6 / Case reports. / A report based on a single patient or subject; sometimes collected together into a short series
7 / Expert opinion / A consensus of experience from the good and the great.
8 / Anecdotal / Something a bloke told you after a meeting or in the bar.
Adapted from Systematic reviews, What are they and why are they useful? ScHARR 2008
To Decide if a Medication Is To Be Used In Suffolk
Criterion to be measured / Tends to poor5 / 4 / Medium
3 / 2 / Tends to good
1
Quality of evidence in the papers reviewed / Low / Medium / High
Magnitude of effect inferred from trials reviewed / Low / Medium / High
Are trial end-points surrogate markers or clinical outcomes?
Clinical usefulness of trial end-points / Low / Medium / High
Known Side Effect Profile / High / Medium / Low
Known Interactions / High / Medium / Low
Concern re Possible Side Effects Not Yet Uncovered / High / Medium / Low
Balance of Benefit To Harm (side effects toxicity interactions etc) / Poor / Medium / Good
NNT / High / Medium / Low
Comparison Of Effectiveness With Other Medicines In Use For The Same Condition / Poor / Medium / Good
Severity of Condition to be Treated / Severe / Medium / Trivial
Novel drug or member of existing class
Uptake (estimated proportion of people with this condition likely to be prescribed the medication under consideration – maximum and minimum uptake)
Is the drug to be used in Suffolk?
Prescriber’s Rating Definitions
- Bravo! -The drug is a major therapeutic advance in an area where previously no treatment was available.
- A real advance - The product is an important therapeutic innovation but has certain limitations.
- Offers an advantage - The product has some value but does not fundamentally change present therapeutic practice.
- Possibly Helpful - The product has minimal additional value, and should not change prescribing habits except in rare circumstances.
- Judgement reserved - The Committee postpones its judgement until better data and a more thorough evaluation of the drug are available.
- Nothing New - The product may be a new substance but is superfluous because it does not add to the clinical possibilities offered by previous products available. In most cases these are “me-too” products.
- Not acceptable - Product without evident benefit over others but with potential or real disadvantages.
(With acknowledgement to Prescrire)
To Decide Where A Medication Is To Be Used In Suffolk
Criterion / Red4 / Amber
3 / Green
2 / Blue
1
Skills of the prescriber / Experience Of The Condition / Specific / Specific / Specific / General
Diagnosis / Specific / Specific / Specific / General
Monitoring Progress Of Treatment / Difficult / Specific / General / General
Therapy / Patient Selection / Difficult / Specific / Specific / Easy
Initiation Of Treatment / Difficult / Difficult / Easy / Easy
Dose Titration / Difficult / Specific / Easy / Easy
Monitoring Of Side Effects / Complex / Easy / Easy / Easy
Method Of Administration / Complex / Normal / Normal / Normal
Discontinuation Of Treatment / Complex / Complex / Easy / Easy
References
Jonsen A. Bentham in a box: Technology assessment and health care allocation. Law Med. Health Care. 1986;14:172-174
Suffolk Drug & Therapeutics Committee Responsibility for prescribing, Hospital Trust or GP
Review prepared by Sarah Cavanagh, East Anglia Medicines Information Service
May be freely copied by NHS agencies Not to be used for promotional purposes