Impact case study database

Before 2013 the risks of long-term consumption of sodium-containing effervescent, soluble and dispersible medications had not been characterised and manufacturers were not required to highlight the sodium content of prescription or over-the-counter medications. George’s work [R2] therefore highlighted an important but overlooked source of ingested sodium. Subsequently, information campaigns, regulatory action and lobbying ensured proper labelling of sodium-containing formulations to help prescribing professionals and consumers of over-the-counter products make informed decisions when choosing which products to use.

Changes in prescribing as a direct result of George’s work

Analysis of prescribing trends using The Health Improvement Network (THIN) and Prescription Cost Analysis databases indicated that George’s publication [R2] influenced prescribing practices for sodium-containing medications in the UK [E1]. Interrupted time series analysis of THIN data showed that the monthly prescribing rate of sodium-containing formulations was stable between 2009 and 2013; however, following publication of [ R2] the slope reduced significantly by 0.26 per month (95% confidence interval -0.45 to -0.07; p=0.009). The slope for non-sodium standard formulations did not change.

Regulatory and labelling changes

George’s work triggered action on salt in effervescent medications at both UK and EU level; according to the Director of Vigilance and Risk Management of Medicines, MHRA [E2]:

The paper was evaluated and discussed at several of the Agency’s Commission on Human Medicines (CHM) Expert Advisory Groups (EAGs) in 2013/2014…There was agreement that the labelling of sodium in product information at the time of the paper, did not provide meaningful information to guide clinicians, pharmacists or patients and help them choose appropriate medicines in terms of sodium content.

All Expert Groups advised that the high levels of sodium in some medicines, particularly those that dissolve, should be highlighted in the product information of all medicines containing different levels of total sodium.

The UK presented the issue and its expert advice to several European bodies in 2014/2015 including the Pharmacovigilance Risk Assessment Committee (PRAC), the Excipients Drafting Group (ExcpDG), the European Medicines Agency’s Paediatric Committee (EMA’s PDCO) and the Co-ordination Group for Mutual Recognition and Decentralised Procedures (CMDh).

George’s results were also highlighted in a report presented to the UK Parliament in 2015 by the Commission on Human Medicines and the British Pharmacopoeia Commission [E3].

Responding to George’s findings, the EMA commissioned a Europe-wide signal detection programme to assess the impact of sodium-containing medications on cardiovascular health. In 2015 the PRAC published new guidance for sodium labelling and recommended an update to the EMA Excipient Guidelines [E4, E5].

In October 2017 the European Commission updated its Excipient Guideline to require all Marketing Authorisation Holders to submit Variation Documentation within 12 months. The labelling of medicines manufactured, sold or consumed in Europe now features warnings about the effects of sodium loading with prolonged use. For medications exceeding 17 mmol/tablet the Summary of Product Characteristics and Patient Information Leaflet must both state how much sodium they contain.

Impacts on professionals – doctors, prescribers, pharmacists and dispensers

George’s work and the consequent change in labelling regulations have triggered changes in prescribing advice which have been promulgated internationally via websites aimed at prescribing professionals (e.g. [ **E6]**) and influenced recent updates to NICE Guidance; for example, the August 2020 update to NICE guidance on “Analgesia - mild-to-moderate pain” [E7] contains a scenario on paracetamol which advises:

Avoid effervescent preparations of paracetamol where possible, particularly in people with hypertension, heart failure, and renal failure — if oral paracetamol is required in a person with swallowing difficulty, use paracetamol suspension in place of effervescent preparations (which contains up to 6 g salt in a 4 g per 24 hours dose).

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Impacts on consumers/patients

Educating clinicians about the risks of consuming high-salt containing medications helps to protect patients receiving them by prescription; however, many over-the-counter effervescent medications also contain high salt concentrations. Package labelling and inserts must now provide consumers of over-the-counter products with the information they need in order to make an informed decision about their use (e.g. **[E9]**).

Influence on the wider debate on dietary sodium intake

In 2014 George was invited to join Consensus Action on Salt and Health (CASH, now called Action on Salt **[E10]**). This group of 25 internationally recognised scientific experts has persuaded the Department of Health (England) to mandate a further 10% reduction in salt thresholds from its 2012 targets with the aim of saving 6000 lives each year.

The Director of Vigilance and Risk Management of Medicines at the MHRA confirms that George’s study “raised an important potential public health issue” [E2]. European Medicines Labelling Legislation changed as a result, thus reducing the prescribing of potentially harmful high-sodium medications, ensuring the provision of better information to consumers of over-the-counter medications and contributing to efforts to reduce dietary sodium intake worldwide.