Andrew Herxheimer’s Golden Rules of Using Medicines

Today is the final day of the MHRA‘s contribution to a Europe wide social media campaign from the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) programme to improve the reporting of adverse drug reactions (ADRs) to schemes like the Yellow Card Scheme. Perhaps ironic, given this is occurring in the week we hear EMEA will be moving to Amsterdam.

It reminded me that I should share Andrew Herxheimer‘s golden rules on using medicines. Andrew was a sad loss to the drug safety community in 2016. I was lucky enough to have met Andrew at several drug safety conferences over the years, and worked on the odd committee with him. The first conference I ever presented at (European Society of Pharmacovigilance Verona, 2000), I cautiously presented some work on coding of ADRs. The first comment from the audience? Andrew with “Yes, very interesting, but what are are you going to do about it.” His emphasis. That was the first time I met him.

Reporting adverse drug reactions was in his Golden Rules of prescribing, which Jeff Aronson skillfully paraphrased in the BMJ.

Andrew Herxheimer’s Golden Rules on using medicines.

  1. Think what you could do instead of using a medicine.
  2. Unless you have a special reason, avoid new medicines. Stick to those about which a lot is known from many sources and which have been used for over 10 years; bad news about a drug often takes years to emerge.
  3. Before deciding to use a medicine be clear whether it is to relieve a symptom, to cure a disease, to remedy some deficiency, or to prevent something. It doesn’t make any sense at all to prevent something in the future if it’s going to cause you some problem now.
  4. Ask a doctor or pharmacist you trust, someone who understands it a bit better than you do, how well the medicine works, what problems people have had with it, and what happened.
  5. If you have to take medicines, get to know as much as you can about those that help you.
  6. Everybody is different and you must learn how your own body reacts to medicines.
  7. Keep a diary of your experiences with a medicine: why you took it, how much for how long, what happened and when, how well it worked, and anything you didn’t like.
  8. If something bad happens that you suspect may have been caused by a medicine, report it on a yellow card; ask a doctor, pharmacist, or nurse to help you do that or to do it for you.
  9. When you have a problem about an adverse reaction or something difficult to discuss with your doctor, take someone with you to the consultation, because four ears are better than two; there are too many things to think about and an independent opinion is well worth having.

 

Pharmacists and work-related stress

The recent tragic case of Alison Stamps is another example of the wider issue of workplace morale and stress in the Pharmacy profession, which is a safety issue both for pharmacists and their patients. It was one of my disappointments, as a member of the Royal Pharmaceutical Society’s English National Board, to see a failure of all pharmacy organisations to effectively grapple with this issue in a meaningful way. Meetings were held, platitudes were spoken, but no substantial action was taken. Sometimes concerns about target culture were dismissed as pharmacists who did not wish to engage with changing professional roles, rather than as substantial concerns about the way metrics could be mis-used by poor management structures.

It is pleasing to see that concern has reached Parliament about this issue. We must do better.

Transcript here. Video below.

Image from My Diliff – Own work, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=1634181

How to damage your liver… naturally

An interesting case of a naturopath attempting to dissolve gallstones:

A 38-year-old non-alcoholic, non-diabetic man with gallstone disease was prescribed three tablespoons of Epsom salt (magnesium sulfate crystals) with lukewarm water for 15 days for ‘stone dissolution’ by a naturopathy practitioner. He developed loss of appetite and darkening of urine from the 12th day on treatment and jaundice from the second day after treatment completion.

The patient was found to have liver necrosis on biopsy. The case report is strongly suggestive that the liver disease was due to the over-use of the Epsom salts, with few risk factors for liver disease or negative tests for viral infections. The patient did have some evidence suggestive of pre-existing steatohepatitis, which was thought to have made the patient more susceptible to this adverse effect.

Removal of the Epsom salts led to recovery of the patients after around 6 weeks. Be careful where you seek advice.

Philips CA, et al. Severe liver injury due to Epsom salt naturopathBMJ Case Reports 2017; doi:10.1136/bcr-2017-221718

Picture from deadmanjones under a Creative Commons licence.

Drug safety lessons from deaths

In the Arms of Morpheus

The role of the coroner has evolved from its early tax-gathering history, when it was a method of collecting revenue from suicides for the government and investigating the English habit of murdering their Norman invaders, to a modern role of investigating sudden, violent and unnatural deaths for the benefit of all of society. We thought improving drug safety might be one of those benefits.

The coroner system exists in some form across the world. Since medication errors are a worldwide problem, information from deaths suspected to be due to medication reported by coroners would be a potentially useful source of pharmacovigilance data. A colleague and I, and one of our first MPharm graduates from the University of Birmingham, decided to investigate the utility of UK coroner reports concerning medication errors.

We found their reports reflected some current and longstanding drug safety concerns, with opiates and anti-coagulants figuring in nearly half of coroners’ reports we looked at. The reports contain valuable and rich pharmacovigilance data, however some of the wider lessons from individual cases may be lost.

You can read the paper at Drug Safety here.

Post Image: In the Arms of Morpheus, Sir William Ernest Reynolds-Stephens, 1894.

Information sources for adverse drug reactions

Earlier this year, I attended the PRIMM conference, where some work I have been involved with was presented (led by Prof Janet Krska’s team at The Medway School of Pharmacy). Patients were surveyed about their information sources for adverse drug reactions.

Some of the outcomes are in line with prior research, such as a significant proportion of patients finding patient information leaflets less than easy to understand. General Practitioners were the top source of information on adverse drug reactions (69%). Pharmacists were less well used than General Practitioners(28%), and were beaten by the internet (37%). This is despite only 14% of respondents trusting the internet.

So despite being viewed as easy to access (76%) and trustworthy (73%), Pharmacists are not being appropriately used to address information deficits about adverse drug reactions. This is a pity. As the healthcare professional with arguably the greatest knowledge of medicines, Pharmacists should be a key source of drug safety for patients, and be able to interpret the drug safety data in the context of the patient’s particular circumstances. Certainly, they are in an accessible position to reduce the workload of General Practitioners in this area.

O’Donovan B, Rodgers RM, Cox AR and Krska J. Patients’ use of information sources regarding side effects Pharmacoepidemiology and Drug Safety, 2017; 26:15-16 (Prescribing And Research In Medicine Management (Uk & Ireland) Annual Conference 2017, University Of Coventry London Campus, January 28th 2017: “Deprescribing – Is Less More?”)

Brexit and Pharmacovigilance

EMA

One of the areas that the UK has led on in the EU, and worldwide, is the science of pharmacovigilance and regulatory science. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is a world class organisation in drug regulation, and has been a leader on drug safety since the thalidomide disaster in the 1960s. Since 1995, the European Medicines Agency (EMA) has regulated drug approvals centrally and has sought to harmonise drug safety and pharmacovigilance systems across the EU and across the pharmaceutical industry. EMA is a the EU equivalent of the US’s FDA. It plays a crucial role in the provision of safe medicines, and in the delivery of new medicines across the EU’s single market.

By creating a harmonised system of regulation it allows the pharmaceutical industry to market products across Europe more easily, and yet at the same time increases the safety of medicines by pooling drug safety resources, including spontaneous reports of adverse effects. Prior to this companies had to negotiate a complex system of individual member state regulatory systems.

EMA is in large part built on a MHRA model, with a knowledge base of UK experts in drug regulation and pharmacovigilance. Even the EU legislation has the clear imprint of British expertise. The UK’s black triangle is now Europe wide. EMA is based in London, employing 600 staff (mainly British). There is concern about its future if we leave the EU.

In the event of a Brexit, which could also cast uncertainty over the future of the bank authority, Europe’s equivalent of the U.S. Food and Drug Administration may have to find a new home, in a jolt to the current drug approval system.

This could slow the approvals of medicines across Europe during this transition process, including in Britain if it has to re-engineer its system.

Losing Britain could also punch a big hole in the EMA’s scientific capability, since British experts are the biggest single contributors to its drug assessment system.

EMA would most likely re-locate to another EU state, and there would be a loss of UK staff from the agency. Drug regulation in the EU and UK would be disrupted. The pharmaceutical industry damaged for a short period. In the medium to long term, it is likely the a corresponding increase in MHRA staff (presumably obtained from EMA staff unwilling to relocate) could take over work that previously EMA carried out. In the short term, a difficult transition phase would occur. Indeed, as noted in the Reuters article above one could argue that EU drug regulation would be more damaged than the UK’s: UK experts led on 27 new drug approvals, compared to 15 by German experts in 2014 – the next highest group. Even if one accepted that the MHRA would adjust relatively quickly compared to EMA, the damage to harmonisation, and pooled resources for drug safety, would be a net loss for the UK.

UK pharmaceutical companies may also end up having to apply for UK licencing and EU licencing, unless the UK was willing to accept drug licencing from an EU body they are no longer part of (which is as unlikely as them accepting FDA approvals, and hardly the ‘sovereignty’ the Leave group are voting for).

Drug regulation and pharmacovigilance may not be the deciding factor for anyone in the EU vote, but it highlights the complexities of the relationships we have in the EU. A Leave vote should come with a drug safety warning in this area at least.