Links and Resources

Writing to your GP

We have produced the letter below to show your doctor that your symptoms are not just in your head. It's deliberately short and gives just a few references so he/she should manage to read it during an appointment. The letter text is in bold, dark blue.  Just copy and paste it into a document, add a date – and add your name if you want to, then print.

__________________________________________________________________________________

Understanding the Fluoroquinolones: A Unique Class of Antibiotics

 

Dear Doctor,

 

EMA Review into side effects

The fluoroquinolone (FQ) antibiotics, especially ciprofloxacin and levofloxacin, were the subject of an EMA review recently which included a Public Hearing – only the second ever in the EMA's history [1]. The FQs come with a huge list of warnings about possible side effects which are said to be very rare and that the benefits far outweigh the risks. It has become clear that this is not the case and this letter was written by us, Quinolone Toxicity Support UK, after we were invited to speak at the Public Hearing.  We want to help doctors understand better the complex signs of adverse drug reactions (ADRs) from FQs.  We are also working closely with the MHRA, who have asked for our input and our advice on how to raise awareness amongst patients and clinicians.

 

Delayed adverse reactions and illnesses without a cause

The new EMA regulations make it clear that if a patient taking an FQ reports side effects, the drug should be stopped immediately. What has also been made very clear is that these ADRs might not actually start until several weeks or even months after cessation of the drug – and they can be equally as serious and long lasting as any that start immediately [2]. These late-onset problems are common, especially all-over pain or CNS disturbances and we appreciate the difficulty in diagnosing them. We have for example several members who were told a number of years ago that they have fibromyalgia, ME or a psychiatric problem. They have only recently discovered from their records that they were given one or more courses of an FQ sometime prior to that diagnosis. This is not to say FQs are the only cause of fibromyalgia etc., but we now know from experience that it is one such cause. We hope that research will soon be undertaken to look at how many patients with, say, fibromyalgia or perhaps derealisation, were given an FQ in the year or so before their diagnosis.

 

How many cases?

The MHRA Yellow Card figures [3] are updated monthly with the numbers of ADR reports linked to the individual FQs.  The MHRA know that the system is underused and that only 10%-15% of any ADRs are ever reported so an extrapolated estimate from the latest FQ figures is that possibly 85,000 patients have severe problems and there may have been 1500 deaths. This does not include those who were affected, but neither their GPs nor their specialists had any idea that their very real pain resulted from an FQ antibiotic. At the Hearing we were asked about the numbers of sufferers and we had to say that, whilst we are not sure, the number is probably a gross underestimate. There must be many people who simply do not realise that the painful symptoms they suffer could be due to an FQ.

Understanding

We hope that the new EMA ruling and extra information about ADRs from FQs, along with the Antimicrobial Stewardship scheme, will reduce FQ use to a minimum. We are aware, however, that many specialists who prescribe an FQ will never actually know if the patient has an ADR, because the patient will go to their GP and not back to the specialist if they have tendon or gut problems. Please could you look back at what your patient has been prescribed, as any side effect can be serious, long term or even permanent (e.g. peripheral neuropathy).  We know there is no known cure yet and do appreciate that your time is limited as a GP due to other pressures, but belief and understanding will help enormously. You already know that, for the patient, the therapeutic effects of being listened to and heard cannot be overestimated.

 

Tolerance thresholds

It is really important for all GPs to be aware that a few patients can react immediately after taking just one tablet, whilst many others can successfully take one or more courses of an FQ before they reach their tolerance threshold. Please do not assume a patient will not react to an FQ because they did not react to a previous course and please be aware that someone who has shown only a mild reaction in the past will most likely have very severe reactions next time. Studies show that the effects are cumulative over one or more courses [4] and that reactions rarely present as a single symptom. They can appear in any combination, or as a cluster of seemingly random and unconnected symptoms, up to perhaps 12 months after cessation of the drug [2].

 

More information

There are many academic papers regarding both the short-term and long-term dangers of FQs and we have given the URLs of some examples below. The latest published in 2018 [5] discusses how FQs damage mitochondrial DNA (although this was known in 1996) and one from 2017 [6] describes the biochemical disruptions to every cell process. We hope you find these useful.

 

Quinolone Toxicity Support UK was founded in 2015 to help and provide information to both sufferers and medical professionals in the UK. We appreciate you reading this letter and ask that you share the information with your medical colleagues.

 

Thank you,

 

Miriam Knight

Debbie Carol

Co-founders

Quinolone Toxicity Support UK

quintoxuk@btinternet.com

www.quintoxsupport.co.uk

 

February 2019

 

 

References

1. https://www.ema.europa.eu/en/medicines/human/referrals/quinolone- fluoroquinolone-containing-medicinal-products

Full overview, recommendations (pdf), transcript and video of Public Hearing

2. http://casereports.bmj.com/content/2015/bcr-2015-209821.long

Fluoroquinolone-induced serious, persistent, multisymptom adverse effects.

Beatrice Golomb 2015, or at...

   http://www.myquinstory.info/wp-content/uploads/2015/10/FQ-induced-serious-persistent-multisx-adverse-effects-BMJ-Case-Reports.pdf

Golomb et al.

 

3. https://yellowcard.mhra.gov.uk/iDAP/

 

4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895369/

Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria. Dean P. Jones et al. April 2010 (Threshold Effects in Mitochondrial Toxicity).

 

5. https://academic.oup.com/nar/article/46/18/9625/5088042

Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2. Hangas et al Oct 2018

 

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632915/

Treatment of the Fluoroquinolone Associated Disability - The Pathobiochemical Implications. Michalak et al. 2017

__________________________________________________________________________________

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Yellow Cards

 

It's very important that you report your Adverse Reactions to MHRA (Medicines and Healthcare Products Regulatory Agency) via the Yellow Card Scheme.  Your doctor or pharmacist should also be advised and they may possibly send in a Yellow Card as well.

https://yellowcard.mhra.gov.uk

Go to this link and follow the easy instructions.  It helps if you have the packaging with you as they ask for the batch number and dates the drugs were taken.  If you feel you can't do this yourself, ask someone to do it for you.  MHRA actively encourage patients to register any potential side effects from any drug and to update frequently if the effects continue. They also want doctors to send in reports even if they only suspect that a drug may be causing a problem, although most doctors don't seem to be aware of this.

You can also email MHRA directly for information about  fluoroquinolones such as updates to the Patient Information Leaflets (PILs), statistics of how many people have been affected etc.  We believe it's important to keep reminding them about how dangerous these drugs are, so the more emails they receive the more notice they'll have to take.

info@mhra.gsi.gov.uk

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

EMA Review

The European Medicines Agency (EMA) announced in February 2017 that they were starting a review of the “persistence of side effects known to occur with quinolone and fluoroquinolone antibiotics”. As part of the review, the EMA held a Public Hearing in June 2018 where patients/carers and health professionals from all over Europe came together to give evidence to the Committee (PRAC) undertaking the review.  The review finally closed in October 2018 and the recommendations were published in November. These recommendations have now been adopted as law (please see the bottom of this section).

A representative gave evidence on behalf of this group and several of our members also spoke as individuals, telling their own painful stories. We were happily surprised that many of the medical professional speakers also stated how serious – and dangerous – the side effects can be. The transcript of the statements and the video of the hearing (all five hours of it) can be seen by clicking the links below – individual statements can be seen by clicking on 'show more' and then the speaker's name.

https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products

We have also submitted a full report about fluoroquinolone toxicity to the review Committee along with several updates as new information becomes available. Many members have written independently to the Committee with their own experiences and we encourage new sufferers to also submit their stories – we firmly believe they can't know how bad it is if no one tells them.

European Commission final, legal decision on the EMA Review

 

https://www.ema.europa.eu/en/documents/referral/quinolone-fluoroquinolone-article-31-referral-disabling-potentially-permanent-side-effects-lead_en.pdf

The above PDF document from the EMA is the final text that was approved and made legally binding by the European Commission on 11 March 2019.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

MHRA and FDA

These links are to past MHRA Drug Safety Updates (DSUs) followed by the US Food and Drug Administration (FDA) alerts to show just how far behind we are with regard to warnings about fluoroquinolones.

MHRA

https://www.gov.uk/drug-safety-update/levofloxacin-some-indications-restricted  (from Sept 2012)

https://www.gov.uk/drug-safety-update/moxifloxacin-increased-risk-of-life-threatening-liver-reactions-and-other-serious-risks       (from Jan 2011)

https://www.gov.uk/drug-safety-update/norfloxacin-restricted-use-in-urinary-infections   (from Dec 2008)

http://webarchive.nationalarchives.gov.uk/20090511015115/http://mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON023077&RevisionSelectionMethod=LatestReleased   (from 2008 re moxifloxacin - page 8)

The MHRA issued this DSU in November 2018 about the increased risk of aortic aneurysm:

https://www.gov.uk/drug-safety-update/systemic-and-inhaled-fluoroquinolones-small-increased-risk-of-aortic-aneurysm-and-dissection-advice-for-prescribing-in-high-risk-patients

* * * NEW, issued on 21 March 2019 * * *

MHRA Drug Safety Alert (DSU)

https://www.gov.uk/drug-safety-update/fluoroquinolone-antibiotics-new-restrictions-and-precautions-for-use-due-to-very-rare-reports-of-disabling-and-potentially-long-lasting-or-irreversible-side-effects

MHRA Central Alert

https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=102852

FDA

The FDA issued two new warnings about the risks of fluoroquinolone adverse reactions in 2018, the first was concerning  low blood sugar levels and mental health side effects [07/10/2018]

FDA Fluoroquinolones and Diabetes - Drug Safety Communication.pdf

while the second was about increased risk of ruptures or tears in the aorta blood vessel in certain patients [12-20-2018]

https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm

Prior to these announcements the FDA issued major restrictions and recommendations in July 2016

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513183.htm

or the full pdf can be read here – but it's 69 pages long.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020634s067,020635s073,021721s034lbl.pdf)

The main points here are taken from the summary in the press announcement:

“It’s important that both health care providers and patients are aware of both the risks and benefits of fluoroquinolones and make an informed decision about their use.”

“...fluoroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system. These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent.”

“Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated urinary tract infections, the FDA has determined that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options. For some serious bacterial infections, including anthrax, plague and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option.”

During the 2016 US Presidential Race between Hillary Clinton and Donald Trump it was revealed that Mrs Clinton had been prescribed a 10 day course of Levaquin (levofloxacin) for mild pneumonia.  (http://www.usatoday.com).  This is one of the illnesses the FDA had just announced  it shouldn't be used for.

http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm

This update from the FDA was issued on the 12th May 2016 as a pre-cursor to the July announcement, and says much the same. It comprehensively covers ALL fluoroquinolone antibiotics and states:

“The U.S. Food and Drug Administration is advising that the serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with sinusitis, bronchitis, and uncomplicated urinary tract infections who have other treatment options.  For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options."

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM365078.pdf

This one from August 2013 required ALL fluoroquinolone packaging (except eye and ear drops) to carry warnings of the “serious side effect of of peripheral neuropathy” which may become permanent.

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126085.htm

The FDA issued this alert in July 2008 advising manufacturers of fluoroquinolones to add a boxed warning (known as a Black Box) to highlight the dangers of the increased risk of developing tendinitis and tendon rupture with taking these drugs.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

The BMJ

 

The British Medical Journal is one of the world's oldest yet highest-ranking medical journals so we were delighted when they published two papers about fluoroquinolones in September 2015.

FQ-induced serious, persistent, multisx, adverse effects - BMJ case reports.PDF

This demonstrates that fluoroquinolones cause persistent multisymptom adverse effects.

https://bmjopen.bmj.com/content/5/11/e010077.full

This concludes that fluoroquinolones are associated with subsequent tendon ruptures and may also contribute to aortic aneurysms.

https://www.bmj.com/content/324/7349/1306

This third paper was published in 2002 and demonstrates a link between fluoroquinolones and tendinitis, especially in those over 60.  An increased risk was seen if corticosteroids were taken at the same time.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Other Journals

https://www.nature.com/articles/d41586-018-03267-5

Published in Nature Magazine 2018.

http://natajournals.org/doi/pdf/10.4085/1062-6050-49.2.09

This is a useful paper published in the Journal of Athletic Training in June 2014, which outlines the dangers of applying normal sports injury techniques to fluoroquinolone damaged tendons.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175508/pdf/bcp0072-0381.pdf    The British Journal of Clinical Pharmocology published this article in 2011, describing the neurotoxic effects of the different groups of antibiotics.  Scroll down 4 pages to see Table 2, and fluoroquinolones are discussed at the bottom of that page.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Daily Mail Articles

The Daily Mail has featured fluoroquinolones quite a few times over the years with the first article that involved QTSUK being published in May 2016, after we contacted them.

https://www.dailymail.co.uk/health/article-6642189/The-antibiotics-cure-infection-leave-pain.html  -  28 January 2019

https://www.dailymail.co.uk/health/article-6324427/Common-antibiotic-doctors-say-organ-failure.html?    Published in the Mail on Sunday, October 2018

http://www.dailymail.co.uk/health/article-5983853/Why-doctors-doling-antibiotics-left-thousands-crippling-pain.html  published in the Daily Mail July 2018

http://www.dailymail.co.uk/health/article-3593515/Antibiotics-got-rid-chest-infection-Jane-says-destroyed-health.html  2016

http://www.dailymail.co.uk/health/article-3451468/Common-antibiotics-trigger-DELIRIUM-Drugs-cause-confusion-hallucinations-agitation-weeks-study-warns.html   2016

http://www.dailymail.co.uk/health/article-2097415/Taking-antibiotics-ruptured-tendon-The-hidden-dangers-everyday-drugs-assume-harmless.html    2012

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Other Articles

https://www.heraldscotland.com/news/16997241.the-crippling-side-effects-of-routinely-prescribed-antibiotics/?

Published in The Herald (Scotland), October 2018

http://www.iflscience.com/health-and-medicine/just-one-antibiotic-treatment-can-alter-your-gut-microbiome-months/

Published in November 2015, this paper shows how antibiotics disrupt your gut – for up to 12 months in the case of ciprofloxacin. For the less colourful but full academic paper go to

http://mbio.asm.org/content/6/6/e01693-15.full

https://www.washingtonpost.com/national/health-science/it-pays-to-read-the-warnings-when-you-open-up-a-prescription/2015/08/03/a29e11b4-d70e-11e4-b3f2-607bd612aeac_story.html

Another Washington Post story, and very informative.

http://www.theguardian.com/commentisfree/2012/jul/10/growing-menace-adverse-drug-reactions

The journalist himself had a brief episode of being floxed - 2012.

http://www.theecologist.org/News/news_analysis/897407/popular_antibiotic_ciprofloxacin_linked_to_uk_deaths.html

Published in 2011 – nothing's changed.

http://www.ph.ucla.edu/epi/bioter/newciprosameeffects.html

Published as 'New Cipro, Same Side Effects' in the Washington Post December 2002, this article discusses the introduction of Cipro XL, the one a day tablet.  It also usefully mentions the 2000 postal workers from North East Washington who were put on a 60 day course of Cipro after 2 colleagues died from anthrax exposure the previous year.

https://chriscwharris.wordpress.com

One of our members is bravely writing a blog about his life, his symptoms and his ups and downs.  You may like to read it to see what happens, to sympathise, or to just say you never knew.

https://floxiehope.com/

There are links to over 200 academic papers and media articles on the Floxie Hope website plus many articles written by Lisa Bloomquist herself.