Dated: 21 October 2021

Until recently, people with Addison’s have only received fludrocortisone medication from the brand Aspen when picking up their repeat prescription. This was because Aspen were the only company with a marketing licence for fludrocortisone in UK and Ireland. People with Addison’s have now been receiving fludrocortisone in new boxes and from new brands, such as Mylan, Accord and Tillomed. 

Here we explain more about why there are now new brands of fludrocortisone available on the market and the impact of tablet splitting and scoring lines on the new brand Mylan.

What is Fludrocortisone and why do we need it? 

Fludrocortisone tablets are taken to replace the adrenal hormone aldosterone, which the adrenal gland should normally make. Aldosterone is an important hormone as it acts on your kidneys to tell them to keep salt in your body. Endocrinologists call this hormone a mineralocorticoid. Lack of aldosterone leads to your kidneys constantly ‘leaking’ sodium, which may cause symptoms of low blood pressure such as light-headedness, feeling constantly washed-out, or weak, cramps and spasms in the legs, lower back and abdominal pain. In addition to symptoms, some people may also start to crave salty and sour foods.

To maintain the balance of salts in the bodies of people with Addison’s disease, replacement with fludrocortisone is extremely important. While you probably won’t notice the immediate effect of missing a single day’s dose of fludrocortisone, as your body contains large reserves of salt, most people begin to feel worse once this is used up after missing 2 or 3 days of fludrocortisone treatment.

This is in sharp contrast to your hydrocortisone treatment, where if you miss a dose, you will notice the effects very quickly. You should always remain diligent in taking your fludrocortisone as prescribed by your Endocrinologist and Endocrine team and discuss with them if you are struggling with adhering to the regimen.

	Watch our 3-part video series with CoMICs on YouTube to learn more about: What is Addison’s disease. How to diagnose and treat Addison’s disease. What is adrenal crisis and how to manage it.
	"What is Addison's Disease?"  "Why Salt?" - learn more about fludrocortisone and aldosterone.

New Brands

Now more brands are able to have a marketing licence for fludrocortisone in UK and Ireland, people with Addison’s have been receiving fludrocortisone in unfamiliar boxes and from new brands. From the patient's point of view, when you are on tablets to keep you alive and you are given a new brand on your prescription, it can be concerning. As patients we have to trust this new product not yet knowing much about it at the time of accepting the prescription. Here we aim to explain more about the different brands to give you more information on the fludrocortisone that has become part of your daily routine.  

Background - CMA Case 50455: Fludrocortisone Investigation

Members will remember from our updates in previous ADSHG magazine articles, that the UK Government’s monopolies watchdog, the Competition and Markets Authority (CMA) found the pharmaceutical companies Amilco and Tiofarma had agreed with Aspen an anti-competitive agreement. They agreed to stay out of the fludrocortisone market so that Aspen could maintain its position as the sole supplier in the UK. As a result, the price of fludrocortisone supplied to the NHS increased disgracefully by up to 1,800%. You can find out more about the investigation by the Competition and Markets Authority into the supply of fludrocortisone on the CMA case page or in previous ADSHG magazines.

New brands of Fludrocortisone

Now this CMA case has been concluded, the brand Aspen are no longer the sole supplier of fludrocortisone, which is why people are receiving new brands of fludrocortisone from their pharmacies. The fact that there are now more suppliers of fludrocortisone is positive for the NHS, patients and taxpayers, as it helps prevent price inflation through competition and avoiding drug shortages if there is an issue with one of the manufacturers.

So what are the new brands? Firstly, there are two types of fludrocortisone:

1. ‘Cold Storage Fludrocortisone’ which needs be kept in the fridge, and
2. ‘Ambient Storage Fludrocortisone’ which doesn’t need to be kept in the fridge, meaning the tablet is stable at room temperature until its given expiry date, so can be kept in a cupboard, on the shelf in its box or in a bag.

Many people prefer not to have the fridge variety of fludrocortisone, due to convenience and personal preference. 

Aspen have ceased producing ambient storage fludrocortisone and started producing cold storage fludrocortisone. At the same time a brand called Mylan is producing ambient storage fludrocortisone.

• Mylan state: “We can confirm the product transfer (change of ownership) from Aspen and that we are now selling in Mylan livery. The product is identical to what was being sold by Aspen.”

You may also receive ambient storage fludrocortisone medicine from pharmaceutical companies Accord Healthcare and Tillomed Laboratories. 

 

Tablet splitting – scored lines

As we have all seen many times, tablets that are made to be split have a groove or a scoring line in the centre or form a cross, dividing the pill into equal parts. This is either to facilitate swallowing the tablet making it smaller, or to split the dose; as some people are required to split their fludrocortisone to facilitate their prescribed dose.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) have very strict rules that pharmaceutical companies must adhere to, in order to protect us from poor quality medications reaching the market and patients. One of these rules, is that pharmaceutical companies need to prove to the MHRA, that the tablets they produce of any medication, are the correct dose they state they are. However, making medicines is a bit like baking a cake and it’s nearly impossible to make the exact same cake twice. To account for this unavoidable negligible variation there is a limit set by the MHRA for what level of variation is acceptable, stating any given tablet may only be a maximum of 5% more or less than the stated dose. This means we can rely on the tablets we receive from our pharmacies to be the correct amount of ‘active ingredient’ we require.

Rigorous testing is done to ensure the active ingredient is spread equally within the tablet, so when you split the tablet in half you are indeed getting 50% of the stated dose of that tablet.

 

Mylan break line – Patient Information Leaflet (PIL)

In the case of Mylan fludrocortisone, they have stated that the break line is only present to facilitate making the pill smaller to swallow, not to facilitate dividing the pill into equal parts. However, this is not stated in the Patient Information Leaflet (PIL). Therefore it cannot be guaranteed that each half of the tablet contains exactly half of the stated dose. 

This was a situation we at the ADSHG immediately needed to investigate and resolve with Mylan - it needed to be clear in the Patient Information Leaflet (PIL) what the break line signified. Through working with Mylan and then the MHRA Product Information Quality unit for Medicines, Mylan’s Patient Information Leaflets are now being amended to include this vital detail regarding the break lines. We would like to thank MHRA for working with us at the ADSHG to ensure that the Mylan PIL content is updated. We will keep members updated as we hear more about these vital changes.

Dose Variation with Fludrocortisone - will I become unwell?

In the meantime, if you have received Mylan fludrocortisone and regularly break the pill to facilitate your prescribed dose, our Addison’s Clinical Advisory Panel have confirmed that is very unlikely that a small day-to-day variation from splitting a Mylan fludrocortisone tablet will make you unwell.

People with Addison’s often don’t feel an immediate difference if they miss one fludrocortisone tablet as it has the advantage in that it is longer-acting in the body. In the case of the very small fludrocortisone tablets, it is difficult to imagine how manufacturers can make a big tablet dust mix to press into 50,000 0.1mg tablets, each with the same amount in it, and for one half of one tablet to differ much from the other half. It must be very well mixed before it is shaped, in order to achieve the 5% tolerance which they are legally required to meet and prove to the MHRA.

The point to remember is by getting half the tablet one day, you will get the other half the next day.

As each full tablet must be within 5% of 0.1mg in it, if one half contains 0.03mg, then its partner half must contain 0.07mg. Due to the longer acting action of how fludrocortisone works in the body, this kind of dose variation (if it is present) shouldn’t be a problem.  

However if you do feel unwell, please remember to check the ingredients and excipients of the new tablets in case you have any allergies. You should then discuss your symptoms with your GP and Endocrinologist as they know your individual medical circumstances.

If required you can then report your symptoms using the Yellow Card system. Your GP or Endocrinologist can assist you in submitting a Yellow Card report yourself as a patient, relative or carer, to help highlight what investigations they have taken to rule out any other health issues impacting your new symptoms.

Summary

From the patient's point of view, when you are on tablets to keep you alive and you are given a new brand on your prescription, it can be concerning. As patients we have to trust this new product not yet knowing much about it at the time of accepting the prescription.

We hope this article helps provides some explanation around fludrocortisone, how it works in your body and background to the new brands prescribed. At the ADSHG we advocate knowledge is power, so if you have any concerns, worries or questions, please join on the conversation on our online forum.

Visit Online Forum

Further Information

• For drug shapes, excipients and manufacturing sites, see here. 
• You can find out more about drug price trends on the OpenPrescribing website here.

 

Information correct at the time of publication and reviewed by Addison's Clinical Advisory Panel. Dated: 21 October 2021.

Matthew Heppel is the Advanced Clinical Diabetes and Endocrinology Pharmacist at Hull University Teaching Hospitals NHS Trust, a member of the UK Clinical Pharmacy Association Diabetes and Endocrine Committee and a Clinical Associate Lecturer at the University of Lincoln School of Pharmacy. Matthew joined the Addison's Clinical Advisory Panel in 2021 and is passionate about not just patient safety but ensuring medication is optimal for the patients he serves.

Lisa Shepherd is an Endocrinology Advanced Nurse Practitioner and NIHR Clinical Doctoral Research Fellow at University Hospitals Birmingham NHS Foundation Trust. Lisa is an ADSHG Medical Trustee, as well an active member of the Society for Endocrinology (SfE) Nurse Committee since 2007, including Chair, and an executive board member of the Federation of International Nurses in Endocrinology (F.I.N.E.). She is passionate about improving the care of patients with Addison’s disease, working with patients their relatives and healthcare professionals to achieve this. You can read about her research project VIStAA Study here.

 

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