Last June, in “Historic Summit: Flox and Tox Get Together”, I told you about the European Medicines Agency’s Review and Public Hearing into the side effects of Fluoroquinolones.
It was only the second time in the EMA’s history that they’d decided to hold a Public Hearing (because of the amount of public interest in this review) (1), so it was indeed historic. They later said to their stakeholders that the process of holding Hearings would “ lead to better safety recommendations; in line with real needs of patients and healthcare professionals as identified during hearings”(2). Please remember that quote.
The review finally came to a halt in October when the committee who did all the work (PRAC) handed over their recommendations to another committee (CHMP) to see if they agreed – which they did. The recommendations are now waiting for the European Commission to rubber stamp them and they will then become law.
If I tell you that I am quoted in a Scottish Newspaper as saying “The recommendations don’t really amount to much more than what the warning leaflets say already,” I think you might get an idea of just how far-reaching these new recommendations aren’t (3). I wrote to the PRAC committee with a blow by blow rebuttal of their proposals and finished it with “I find nothing in these recommendations that could not have been produced in February 2017” – that’s when the Review was started.
As a quick reminder of what exactly we’re talking about here, the Fluoroquinolones (FQs) are a unique class of synthetic antibiotics, the most popular of which is Ciprofloxacin (Cipro). Its siblings are Levofloxacin (Levaquin), Moxifloxacin (Avelox) and Ofloxacin (Floxin) and there are many other generic names so always check for the class – Fluoroquinolone. They’re unique because their mechanism of action targets bacterial DNA to prevent bacteria from replicating.
The clever people who developed FQs in the 1960s knew they didn’t affect our cellular DNA and possibly weren’t aware that we also had mitochondrial DNA (MtDNA – discovered in the 1960s). However, certainly by the early 1990s when the first Cipro licence was sought, there was academic evidence that mammalian MtDNA was damaged along with bacterial DNA as they happen to share a couple of enzymes (apparently from when everything was floundering in the Primaeval Soup) (4). I can find no reference to this significant problem in later licence applications (e.g. 2010) nor in the latest versions of the package leaflets (2019 – available on line). We’re human, so MtDNA is very important to us; our mitochondria are generally referred to as the powerhouses of our cells and if their DNA is damaged so are we.
In addition, the FQs also affect the way each of our cells goes about its business. I’m not that good at biochemistry but there are some amazing processes that happen during the metabolism of our cells and it seems that FQs mess up just about every single process (5,6). In other blogs (The Myth of the Magic Bullet and Guerilla Guide.) you can read about the devastating chaos that can happen when someone is floxed. Doctors always shake their heads in disbelief when sufferers of FQ Toxicity (Floxies) present with a huge variety of seemingly unrelated symptoms yet, if they would consider that every organ, every system, every part of the body has been affected they would understand. Not that they would be able to help, of course, as the only cure for this illness caused by their drugs is rest. That’s it. There is no cure.
All this was stated in different ways at the Public Hearing. Some very sick people dragged themselves across Europe to address the Committee and many others wanted to but were not selected. These sufferers desperately wanted to take the opportunity to tell the members of the PRAC how they were previously fit and healthy, apart from maybe a UTI or prostatitis pain. They then took this antibiotic, prescribed by a trusted doctor, and it literally stole their normal lives. They were left with an agonising physical and mental hell: I’m not being a drama queen here, simply telling the truth.
Only thirteen sufferers were selected to speak because of time constraints, along with eight professional speakers including a Bayer representative. Apparently, the PRAC also took into consideration many written testimonials presented by support groups like ours from several European countries and evidence from the manufacturers themselves. We were later told that over 400 academic papers had been studied before the recommendations were made, which interests me, and I have asked for the list of these papers. I’m interested because I have no idea if they have seen any of the papers I used when writing our group’s report. For example, I quoted from the 1996 paper (4) which demonstrated how Fluoroquinolones damage mammalian mitochondria, and also a 2017 paper (5,6), which explains at length how FQs create havoc in all mammalian cells by interfering with the many different metabolic processes and causing oxidative stress. The recommendations seem to make it clear that neither these papers were considered.
Most doctors don’t understand why the symptoms are so varied with muscle and joint pains, gut problems, insomnia and panic attacks, tingling or burning skin, agonising nerve pains, insomnia, hallucinations and anxiety. Most doctors have no idea that sometimes these effects don’t start for weeks or months after the pills have been taken. Most doctors see a Fluoroquinolone as a marvellous cure-all; if in doubt – Cipro will sort it out. I could almost accuse some doctors of being extremely lazy; rather than send a sample off to be cultured isn’t it quicker to just prescribe Cipro as it will kill anything?
One other thing about FQ Toxicity is that the majority of patients will take a course of it and think nothing of it. They may take two or three courses and I’ve even heard of someone taking around fifty courses for a chronic problem. I get to hear about these people as they write for help after finding themselves in pain, with a torn tendon perhaps, or one of the other myriad symptoms. Why some can tolerate so much while others are flattened by just one tablet is not really a mystery when you consider our differences in genetic make-up and research is being carried out at the moment to try to find the ‘key’. We already know that FQs (and certain other drugs that affect mitochondria) should not be given to people with various genetic deficiencies, one big problem being that often people are unaware of a deficiency until they take an FQ! To us, it’s more a case of not IF someone will be affected but WHEN.
I naively hoped that putting all our evidence in front of the PRAC would do the job. I also helpfully pointed out that the original licence applications had not mentioned mitochondria and oxidative stress and nor had subsequent applications. Nothing I have seen or heard from the EMA has made me think that they have in any way acknowledged this information. And yet they must know, the evidence is there, so surely they know that these drugs are causing serious, life threatening problems in what were healthy individuals with only a simple or suspected infection?
No? OK, so we have more work to do. A lot more work. The new recommendations will hopefully restrict most of the FQ prescribing for simple infections. Although this was reduced anyway in the UK thanks to the antimicrobial stewardship scheme, apparently FQs are extremely popular in many other European countries with Greece winning the top prize, so they will see the most benefit. The recommendations also said that the Quinolone-only drugs, which are the early versions from before a fluorine molecule was added to make them really potent (and which made them Fluoroquinolones), would be withdrawn from the market. This, again, is more of a big deal for other countries as these older drugs were already withdrawn or simply just not used in the UK.
One point we’re really upset about is that the Committee don’t seem to have paid much attention to all the testimonies from men saying they were seriously affected after being given Cipro for suspected prostatitis (7). Cipro and its sibling Ofloxacin are the recommended antibiotics for prostatitis and the present UK guidelines say to prescribe either for 4 to 6 weeks. No mention is made of waiting for culture to check for actual infection, and lower down the page there is a statement that actually says a meta-analysis found that “antibiotics were no more effective than placebo for treating CP/CPPS (Chronic Prostatitis/Chronic Pelvic Pain Syndrome) (8). The recently published recommended changes to the Product summaries for doctors (SmPCs) and the patient leaflets (PILs) have no changes listed for Cipro’s use with prostatitis and only a simplified list for Ofloxacin – with no mention of suspected prostatitis. To all the men who have had their lives ruined by these drugs I can only say I’m sorry, we’ll try harder…
If you want to look at these recommended changes you can find them on the EMA link below (1), just above the blue banner that says ‘key facts’ (it’s a pdf with ‘article 31’ in the title). One thing I will admit they are trying to make clear is the warnings on the patient leaflets. Apparently the EMA expect that a patient should read these warnings and then discuss with their doctor about the suitability of this antibiotic for their condition. Between them they are supposed to make a risk/benefit assessment before deciding whether to use a FQ. My experience of a UK doctor’s ten-minute appointment is that a discussion will rarely happen although this expectation cleverly shifts any ensuing blame directly onto the patient who has been adequately warned (they should have read the leaflet!). Perhaps in the make-believe world of the European Commission this all makes sense. Whether it will actually meet the “real needs of patients and healthcare professionals as identified during hearings” remains to be seen: I, and many others, very much doubt it.
1). EMA Public Hearing page; scroll down for agenda and list of speakers/ text of written interventions and the summary report (available in several languages). Scroll further for the video of the Public Hearing (4 hours!).
Editorial Note: Post by Miriam Knight
4). https://www.ncbi.nlm.nih.gov/pubmed/8913349 (but abstract only available)
5). Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications