Tag Archives: Fluoroquinolone toxicity

The A to Z of Fluoroquinolone Toxicity Syndrome

The following was written by Kim Jansen. You can read Kim’s story of fluoroquinolone toxicity HERE

If you are interested in writing a guest-post for floxiehope.com, please let me know. Here is a post with more information about writing for floxiehope.

Here is a version of this post that is easier to read and print. It’s a great overview of fluoroquinolone toxicity to give to your loved-ones. The A to Z of Fluoroquinolone Toxicity Syndrome

The A to Z of Fluoroquinolone Toxicity Syndrome

A. Antibiotic. Fluoroquinolones are a family of broad-spectrum antibiotics that are commonly used to treat a variety of illnesses such as respiratory and urinary tract infections. Types of fluoroquinolones (along with their brand-names in brackets), include: ciprofloxacin (Cipro); levofloxacin (Levaquin); moxifloxacin (Avelox); gatifloxacin (Tequin); ofloxacin (Ocuflox/Floxin/Floxacin); norfloxacin (Noroxin). These antibiotics have serious side effects, with the term ‘fluoroquinolone toxicity syndrome’ being used to refer to the condition experienced by those who suffer from these side effects.

B. Bayer. Bayer is a pharmaceutical company that manufactures Cipro and Avelox. Bayer is currently facing a new lawsuit from a complainant, who has been diagnosed with peripheral neuropathy (see ‘Nerve Damage’ entry below) since 2011. She alleges that Bayer knew that Cipro could cause chronic or permanent peripheral neuropathy soon after receiving FDA (U.S) approval in 1987. By 1988, the drug companies possessed at least one published case report that constituted a safety “signal” that fluoroquinolones were associated peripheral nerve damage and that further investigation and study were necessary to protect patients. Since then, numerous other studies have affirmed this connection. This complainant’s Cipro lawsuit joins hundreds of other fluoroquinolone toxicity claims pending against manufacturers of fluoroquinolone antibiotics.

C. Central Nervous System Damage. Fluoroquinolones are able to penetrate the blood brain barrier, thus also able to damage a person’s central nervous system . The FDA in America acknowledged this fact and placed a warning about potential CNS damage on fluoroquinolone medication (see ‘FDA Warnings’ entry below). Some of the side effects of CNS damage include insomnia, restlessness, seizures, convulsions, and psychosis. An extensive collaborative investigation by scientists and member of a social network in 2016 found that 93 of 94 respondents of a survey reported fluoroquinolone-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of fluoroquinolone initiation or days to months of fluoroquinolone discontinuation. They also discovered that mice treated with ciprofloxacin had lower grip strengths, reduced balance, and depressive behaviour compared with the controls.

D. DNA Damage. Fluoroquinolones work by inhibiting the replication of bacterial DNA. Tests have shown that these antibiotics also damage healthy DNA, including mitochondrial DNA. This is one of the likely reasons why the damage caused by fluoroquinolone toxicity affects multiple body systems and is persistent.

E. EMA. Public Hearing. In June 2018, the EMA (European Medicines Agency) held a public hearing to discuss the serious health concerns surrounding side effects of quinolones and fluoroquinolones. On 15 November 2018, EMA finalised a review of serious, disabling and potentially permanent side effects with quinolone and fluoroquinolone antibiotics given by mouth, injection or inhalation. The review incorporated the views of patients, healthcare professionals and academics presented at EMA’s public hearing on fluoroquinolone and quinolone antibiotics in June 2018. Here is an excerpt from the press release of their findings:
EMA’s human medicines committee (CHMP) endorsed the recommendations of EMA’s safety committee (PRAC) and concluded that the marketing authorisation of medicines containing cinoxacin, flumequine, nalidixic acid, and pipemidic acid should be suspended. The CHMP confirmed that the use of the remaining fluoroquinolone antibiotics should be restricted. In addition, the prescribing information for healthcare professionals and information for patients will describe the disabling and potentially permanent side effects and advise patients to stop treatment with a fluoroquinolone antibiotic at the first sign of a side effect involving muscles, tendons or joints and the nervous system.

F. FDA Warnings. The U.S. Food and Drug Administration has issued a series of warnings over the last number of years regarding serious and potentially permanent adverse side effects of fluoroquinolones, including a ‘Black Box’ warning (its strongest warning possible) in 2008, which it has upgraded numerous times since. A summary of the warnings is below:
a. 2008 – increased risk of tendinitis and tendon rupture.
b. 2011 – fluoroquinolones may have neuromuscular blocking activity.
c. 2013 – the potential for irreversible peripheral neuropathy (serious nerve damage).
d. 2016 – disabling and potentially permanent serious side effects that can occur together which may involve the tendons, muscles, joints, nerves, and central nervous system.
e. 2018 (July) – may cause significant decreases in blood sugar, potentially resulting in coma, as well as certain mental health side effects, including disturbances in attention, disorientation, agitation, nervousness, memory impairment, and serious disturbances in mental abilities called delirium.
f. 2018 (December) – the risk of aortic aneurysm and dissection.
Fluoroquinolones are now deemed to be a ‘drug of last resort’ in the U.S for most infections. The clinical guidelines in Australia, whilst not quite as strong, clearly indicate that fluoroquinolones should be reserved for serious bacterial infections for which an alternative treatment is not available. The reality of over-prescription and lack of physician awareness of the side effects of fluoroquinolones indicate a significant disconnect between the official regulatory bodies and current medical practice.

G. Glutathione. Glutathione is an important antioxidant. It is comprised of three amino acids (cysteine, glutamic acid, and glycine) present in most mammalian tissue. Glutathione also acts as a free radical scavenger and a detoxifying agent. A 2011 study found that the fluoroquinolone antibiotic Ciprofloxacin causes a significant decrease in glutathione levels in the body (a 25.5% decrease in levels by the fifth day of treatment.) . The reduction of glutathione in the body caused by fluoroquinolones is likely to be a contributing factor to the oxidative stress (see ‘Oxidative Stress’ entry below) caused by fluoroquinolones. Tests conducted on rats also revealed administering Ciprofloxacin resulted in a significant decrease in glutathione content in the liver.

H. Heart Damage. Due to its collagen-depleting mechanism, fluoroquinolones can cause serious damage to the heart. The U.S FDA released a warning in December 2018, stating that patients should avoid fluoroquinolone antibiotics due to an increased risk of heart-vessel tears. ‘These tears,’ it stated, ‘called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death’.

I. Income loss. One of the all-too frequent associated impacts of fluoroquinolone toxicity is the sufferer’s inability to continue in paid employment. There are many media and online stories where people share the devastating impact this drug has had, not just on their health, but on their family relationships, their livelihood and their ability to be financially independent. One such news story is footnoted here.

J. Johnson & Johnson. Johnson & Johnson’s Janssen Pharmaceuticals unit discontinued production of the fluoroquinolone antibiotic Levaquin in December 2017, amid growing concerns over the serious side effects and complications potentially associated with the use of fluoroquinolone antibiotics. Another likely reason for this discontinuation by Johnson & Johnson is due to its having lost millions of dollars in previous lawsuits over Levaquin, (including settling 845 lawsuits over Levaquin in 2012) . There are still hundreds of individuals waiting to have their cases heard over debilitating injuries caused by Levaquin and other fluoroquinolones, which is another likely reason for Johnson & Johnson’s decision. Johnson & Johnson’s decision to cease manufacturing this drug does not constitute a product recall, with the drug still being available with the J&J brand until 2020 and generic versions of the drug continuing indefinitely at this stage.

K. Kidney Damage. Fluoroquinolone antibiotics can cause kidney damage including renal failure. A 2013 study found a twofold increased risk of acute kidney injury requiring hospital admission with the use of fluoroquinolone antibiotics among adult men.

L. Levaquin. Levaquin is the brand name of a type of fluoroquinolone antibiotic manufactured by Janssen Pharmaceutical (see ‘Johnson & Johnson’ entry above). The drug’s scientific name is levofloxacin. Levaquin has been the subject of hundreds of lawsuits by patients who have suffered debilitating side effects from this drug.

M. Mitochondrial Toxicity. The mitochondria are rod-shaped organelles that are the ‘power generators’ of cells, ‘turning sugars, fats and proteins that we eat, into forms of chemical energy that the body can use to carry on living’. Fluoroquinolones damage mitochondrial DNA, resulting in a range of disabling symptoms in sufferers, including pain, weakness and fatigue.

N. Nerve Damage. Many sufferers of fluoroquinolone toxicity syndrome experience nerve damage, often resulting in peripheral neuropathy. Peripheral neuropathy is a condition in which the nerves in the peripheral nervous system become damaged. Usually the disorder affects the nerves that provide sensation, which causes pain, tingling, and burning symptoms of the nerves affected, frequently, but not limited to, the hands and feet. The U.S. Food and Drug Administration enhanced its warnings of fluoroquinolone side effects in 2013 to include ‘the potential for irreversible peripheral neuropathy’.

O. Oxidative Stress. ‘Oxidative stress occurs when excess oxygen radicals are produced in cells, which could overwhelm the normal antioxidant capacity. [Oxidative stress can lead to damage of] proteins, lipids, and DNA, which could lead to cytotoxicity, genotoxicity, and even carcinogenesis when damaged (mutated) cells can proliferate.’ A scientific study conducted in 2011 demonstrated that fluoroquinolone antibiotics are a significant cause of oxidative stress, with tests revealing this stress was ‘greatest 5 days after exposure to ciprofloxacin and levofloxacin therapy, which indicates the formation of reactive oxygen species as in previous studies with fluoroquinolones. These results [were] further supported by [a] decrease in plasma antioxidant status by 77.6% and 50.5% for ciprofloxacin and levofloxacin respectively’24. They concluded their report with the finding that ‘[t]here was a considerable increase in lipid peroxide levels indicating an enormous oxidative stress’ in patients taking fluoroquinolones and suggested that increase in oxidative stress may be responsible for the pathological mechanism of tendinitis (see ‘Tendon Ruptures’ entry below).

P. Pain. Pain is often (but not always) the first symptom fluoroquinolone toxicity sufferers experience. This can occur after the first dose taken. The pain usually begins in the legs or feet before spreading to other parts of the body. The pain will often be constant and remain for months or years. Pain in joints, hands, feet, tendons and nerves (see ‘Nerve Damage’ entry above) is common, ranging in severity from a dull ache to, extreme, sharp, unbearable pain. Many case studies document patients living with extreme, ongoing pain that cannot be medically managed.

Q. Quinolones. Quinolones are an earlier generation of the current fluoroquinolone family of antibiotics (although quinolones are still in limited use). A fluorine atom was added to the quinolone’s central ring system, thus creating fluoroquinolones, which have proven to be more effective in disrupting bacterial DNA than the quinolone form of the antibiotic.

R. Relapse. Many sufferers of fluoroquinolone toxicity syndrome report (often multiple) relapses of their symptoms, sometimes years after the initial onset of their illness. This is likely due to the multi-system, cellular and oxidative-stress nature of this toxicity. Sometimes a relapse can be caused by a specific trigger, such as the subsequent use of NSAIDs (such as ibuprofen) or steroid medications.

S. Suicide. There have been thousands of reported cases of deaths linked to fluoroquinolone toxicity (over 6500 to the end of 2015 in the U.S alone). This number, however, does not include the large number of people who have taken their own lives after experiencing sudden and extreme mental health side effects from fluoroquinolones. A group of doctors wrote an article for the European Journal of Internal Medicine in which they report on the concerning number of suicides or attempted suicides by patients on fluoroquinolone antibiotics. They cite that in the United States, 40% of reported fluoroquinolone-related suicide events occurred within two weeks of taking fluoroquinolone medication. Many of these patients had no previous mental health issues.

T. Tendon Ruptures/Tendonitis. One of the most common adverse side effects of fluoroquinolones is tendon damage, including tendon ruptures, frequently to the Achilles tendon. This is due to a combination of factors, including fluoroquinolones being responsible for destroying collagen (collagen is a major component of tendons). A study in 2015 investigated the impact of fluoroquinolones on collagen and discovered that fluoroquinolones ‘were associated with almost a tripling of the risk of tendon ruptures—a recognised collagen-associated adverse event induced by these medications.’ Perhaps of even greater concern was their finding that ‘fluoroquinolones were associated with a similar increase in the risk of aortic aneurysms.’

U. Under-reporting. It is almost certain that fluoroquinolone toxicity is under-reported. Drug safety professionals estimate that only 10% of adverse events (across all drugs) are reported to the FDA every year, in part due to physicians having no requirement or incentive to report adverse reactions. It is highly likely that the rate of adverse reaction reporting for fluoroquinolone antibiotics is lower still, for the following reasons:
a. The noticeable symptoms of fluoroquinolone toxicity can take months to manifest, thus making it more likely that the patient does not connect their ‘new’ symptoms with a course of fluoroquinolone antibiotics they took previously.
b. Many medical practitioners are still unaware of, or refuse to acknowledge, the damage that fluoroquinolone antibiotics can cause. This is evidenced in the frequency with which these antibiotics are prescribed for uncomplicated (suspected) infections when safer alternatives are available. As one report states: ‘Despite these seemingly significant numbers and overwhelming reports from patients, physicians continue to prescribe fluoroquinolone antibiotics unsystematically, against US Food and Drug Administration recommendations. Thus, adverse reactions to fluoroquinolones are often not reported by physicians, nor by the patient themselves. Even though significant under-reporting is extremely likely, there are over 200,000 reported cases of adverse reactions to fluoroquinolone antibiotics in the U.S alone, tens of thousands of these being serious and over 6,000 reported deaths. 1,498 cases of adverse reactions to Ciprofloxacin have been submitted to Australia’s Therapeutic Goods Administration (up to 18 January 2019).

V. Vitamins and Minerals. There is no quick cure or treatment for fluoroquinolone toxicity. Healing plans usually focus on rest and a diet/supplement regime which aims to replenish those essential elements that have been depleted or damaged by the drug. One of the most important mineral supplements is magnesium. This is because fluoroquinolones deplete magnesium from the body and also because toxicity from fluoroquinolones is reduced by the supplementation of magnesium (as proven through tests conducted on both humans and rats).

W. Weakness and Fatigue. Alongside pain, muscle weakness and fatigue are often the first symptoms fluoroquinolone toxicity sufferers experience. The weakness is likely a result of the cellular damage caused by the drug, including damage to the mitochondria in the cells (see ‘Mitochondrial Toxicity’ entry above). As a consequence, many sufferers are (mis)diagnosed with CFS/ME (Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis).

X. The X Factor (the unknowns). Scientists and medical professionals are still discovering all the ways in which fluoroquinolones adversely affect the body and mind. Much is still unknown about the long-term impacts of this drug. One of the more frightening discoveries in recent years is the likelihood that fluoroquinolone toxicity sufferers are at a significantly higher risk of developing Parkinson’s Disease and Alzheimer’s due to the long-term oxidative stress caused by this drug and by the damage it causes to the cells’ mitochondria (see ‘Oxidative Stress’ and ‘Mitochondrial Toxicity’ entries above). In 2014, A U.S. medical practitioner, Charles Bennett, who has conducted a great deal of research on fluoroquinolone toxicity, filed a citizen’s petition with the FDA seeking to expand the black box warning to include mitochondrial toxicity as one of its side effects, with the concern that it can lead to Parkinson’s Disease and Alzheimer’s.

Y. Years. People who suffer from fluoroquinolone toxicity often take years to recover, whilst others experience little improvement in their symptoms, even years after first suffering toxicity (as evidenced by some of the speakers at the EMA public hearing in June 2018).

Z. ZZZZ (sleep). The European Medicines Agency’s 2018 public hearing and investigation into fluoroquinolones concluded that sleep problems (including nightmares and insomnia) were among the many long-term side effects of fluoroquinolone toxicity. Sadly, much of the medical profession world-wide seems to have no trouble being asleep to the dangers of fluoroquinolones, with doctors continuing to prescribe this drug in the millions each year for uncomplicated health conditions where safer, as effective antibiotics are available. Patients also continue to report having been prescribed fluoroquinolones without being given any information about the risk of serious, potentially permanent, side effects.

References:

  1. The Marshall Protocol Knowledge Base. “Fluoroquinolone Antibiotics”: https://mpkb.org/home/othertreatments/antibacterials/fluoroquinolones
  2. Arentz Law Group. “Cipro Lawsuit Alleges Bayer Actively Concealed Irreversible Peripheral Neuropathy Risks.” https://arentzlaw.com/defective-drug/cipro-lawsuit-peripheral-neuropathy/
  3. Dr Joseph Mercola. “Antibiotic Alert: The Drug the Doctor Ordered Could Cause Deadly Side Effects.”
    https://articles.mercola.com/sites/articles/archive/2012/10/20/fluoroquinolones-side-effects.aspx
  4. Oncology Practice. “Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network.” https://www.ncbi.nlm.nih.gov/pubmed/26955658
  5. Nucleic Acids Research. “Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase-2.” https://academic.oup.com/nar/article/46/18/9625/5088042
  6. European Medicines Agency. “Quinolone- and fluoroquinolone-containing medicinal products – European Commission Final Decision.” https://www.ema.europa.eu/en/medicines/human/referrals/
    quinolone-fluoroquinolone-containing-medicinal-products
  7. FDA Drug Safety Communication. “FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects.” https://www.fda.gov/drugs/drugsafety/ucm511530.htm
  8. U.S. Food and Drug Administration. “FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections”. https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
  9. U.S National Library of Medicine. “Glutathione.” https://pubchem.ncbi.nlm.nih.gov/compound/glutathione
  10. Journal of Young Pharmacists. “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249743/
  11. Drug and Chemical Toxicology. “Ciprofloxacin‐Induced Glutathione Redox Status Alterations in Rat Tissues.” https://www.tandfonline.com/doi/abs/10.1081/DCT-120037504?journalCode=idct20
  12. Medical Xpress. “Certain antibiotics tied to deadly heart vessel tears: FDA.”
    https://medicalxpress.com/news/2018-12-antibiotics-tied-deadly-heart-vessel.html
  13. Al Jazeera. “Left paralysed from Fluoroquinolone antibiotic toxicity.”
    https://www.aljazeera.com/indepth/features/2017/09/left-paralysed-fluoroquinolone-antibiotic-toxicity-170919135407632.html
  14. RX Injury Help. “Janssen Discontinued Levaquin Production as Concerns Over Fluoroquinolone Side Effects Grow.” https://www.rxinjuryhelp.com/news/2018/07/18/janssen-discontinued-levaquin-production-as-concerns-over-fluoroquinolone-side-effects-grew/
  15. Drug Injury Law: Medical and Legal Information. “Johnson & Johnson settles 845 Levaquin Lawsuits.” https://www.drug-injury.com/drug_injury/2012/11/johnson-johnson-settles-845-levaquin-lawsuits.html
  16. Arentz Law Group. “Levaquin pulled from market to avoid lawsuit.”
    https://arentzlaw.com/defective-drug/jj-stops-levaquin-sales/
  17. Canadian Medical Association Journal. “Risk of acute kidney injury associated with the use of fluoroquinolones.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708027/
  18. Thomas J Henry Law. “Johnson & Johnson Settles Levaquin Lawsuits”. https://thomasjhenrylaw.com/blog/dangerous-drugs-devices/johnson-johnson-settles-levaquin-lawsuits/
  19. Mitochondrial Biology Unit. http://www.mrc-mbu.cam.ac.uk/what-are-mitochondria
  20. Oncology Practice. “Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network.” https://www.mdedge.com/hematology-oncology/article/106661/patient-survivor-care/fluoroquinolone-related-neuropsychiatric
  21. Journal of Investigative Medicines: “Permanent Peripheral Neuropathy: A Case Report on a Rare but Serious Debilitating Side-Effect of Fluoroquinolone Administration.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528905/
  22. Medicine Net. “Peripheral Neuropathy Causes, Symptoms, and Treatment Medications.” https://www.medicinenet.com/peripheral_neuropathy/article.htm#peripheral_neuropathy_definition_and_facts
  23. Science Direct. “Oxidative Stress.” https://www.sciencedirect.com/topics/neuroscience/oxidative-stress
  24. Journal of Young Pharmacists: “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249743/
  25. Journal of Pain & Palliative Care Pharmacotherapy. “Intractable Acute Pain Related to Fluoroquinolone-Induced Peripheral Neuropathy.” https://www.ncbi.nlm.nih.gov/pubmed/28358229
  26. US National Library of Medicine. “Fluoroquinolone-induced serious, persistent, multisymptom adverse effects.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600819/
  27. US National Library of Medicine. “Fluoroquinolones interactions with nonsteroidal anti-inflammatory drugs.” https://www.ncbi.nlm.nih.gov/pubmed/15176310
  28. European Medicines Agency. “EMA public hearing on quinolones and fluoroquinolones.” https://www.ema.europa.eu/en/documents/other/public-hearing-quinolone-fluoroquinolone-written-interventions_en.pdf
  29. Nature. “When antibiotics turn toxic.” https://www.nature.com/articles/d41586-018-03267-5
  30. European Journal of Internal Medicine. “Fluoroquinolone-associated suicide.” https://www.ejinme.com/article/S0953-6205(18)30284-X/fulltext
  31. The Journal of Clinical and Aesthetic Dermatology. “The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921747/
  32. BMJ Journals. “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study.” https://bmjopen.bmj.com/content/5/11/e010077
  33. PSQH: Patient Safety and Quality Healthcare. “A Closer Look at FDA’s Adverse Event Reporting System.” https://www.psqh.com/analysis/a-closer-look-at-fdas-adverse-event-reporting-system/
  34. Oxidative Medicine and Cellular Longevity. “Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632915/
  35. Journal of Investigative Medicine. “Permanent Peripheral Neuropathy: A Case Report on a Rare but Serious Debilitating Side-Effect of Fluoroquinolone Administration.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528905/
  36. Therapeutic Goods Administration (Australia) Database of Adverse Event Notifications – medicines https://apps.tga.gov.au/PROD/DAEN/daen-report.aspx
  37. American Society for Microbiology. “Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1803142/
  38. ME Association UK. “Update: MHRA issues new restrictions and precautions for Fluoroquinolone antibiotics 29 March.” https://www.meassociation.org.uk/2019/03/update-mhra-restrictions-and-precautions-for-fluoroquinolone-antibiotics-28-march-2019/
  39. CBS Chicago. “Safety Advocate: Powerful Antibiotics Being Overprescribed.”
    https://chicago.cbslocal.com/2015/03/11/safety-advocate-powerful-antibiotics-being-overprescribed/
  40. European Medicines Agency. “Public Hearing on quinolone and fluoroquinolone antibiotics” .
    https://www.youtube.com/watch?v=1vao8o5NGUc
  41. European Medicines Agency. “Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics.” https://www.ema.europa.eu/en/news/disabling-potentially-permanent-side-effects-lead-suspension-restrictions-quinolone-fluoroquinolone

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The Term “Flox”

When I tell people about this site they often ask me what the terms flox, floxed, and floxie mean. I am not a lexicographer by any stretch, and these are not official definitions, but here are my answers:

Flox (noun): A shorthand term for the multi-symptom, chronic illnesses brought on by fluoroquinolone antibiotics that are referred to as Fluoroquinolone toxicity or Fluoroquinolone Associated Disability (FQAD).

Flox (verb): To be afflicted with fluoroquinolone toxicity or FQAD. The term “flox” is typically used in the past tense as “floxed,” as in, “I was floxed by cipro in 2011.”

Floxie (noun): A person who suffers from fluoroquinolone toxicity or FQAD.

The term “flox” comes from the names of the fluroquinolone antibiotics. All the fluoroquinolones contain “flox” in their names – ciproFLOXacin, levoFLOXacin, moxiFLOXacin, gatiFLOXacin, oFLOXacin, etc. As communities of victims of these drugs formed, people found it easier to say, “I’ve been floxed” or, “I’m a floxie” than to say, “I am going though a multi-symptom illness brought on by fluoroquinolone antibiotics.” Perhaps the term “FQAD” would have been just as easy to say as “flox,” but “flox” preceded “FQAD” by more than a decade and the term has stuck.

The earliest written record of the term “flox” that I can find is in Stephen Fried’s 1998 bestselling book, “Bitter Pills: Inside the Hazardous World of Legal Drugs.” In it, Fried describes his wife’s severe, primarily psychiatric, adverse reaction to ofloxacin, a fluoroquinolone antibiotic. Fried noted that the community of people who had been hurt by this class of drugs referred to themselves as “floxies” and spoke of their condition as being “floxed.” (EDIT/NOTE – Please see Mr. Fried’s comment below for correct information about the early usage of the term “flox.)

Most journal, and even news, articles don’t use the terms “flox” or “floxie.” They typically refer to the constellation of symptoms that “floxies” deal with as “adverse reactions to fluoroquinolone antibiotics” or they don’t refer to the syndrome as a whole at all, rather, they’ll list the symptoms that their featured victim suffers from, and then note that the victim attributes those symptoms to fluoroquinolone antibiotics. A couple news articles have used the term FQAD, as it was coined by the FDA, and is seen as a bit more official than “flox.”

In online communities new terms are often coined, and they gain traction in those communities. “Flox” is one of those terms. The terms “flox” and “floxie” are primarily used on the internet in support groups for victims of fluoroquinolones. The biggest Facebook group for victims of fluoroquinolones is The Fluoroquinolone Toxicity Group, and their url is https://www.facebook.com/groups/floxies/ (note the “floxies” in the url – it’s easier than https://www.facebook.com/groups/FluoroquinoloneToxicityGroup). Additionally, this site is one of the more popular blogs about fluoroquinolones, and it’s called Floxie Hope. The terms “flox” and “floxie” are used throughout blogs and support groups dedicated to fluoroquinolone toxicity.

People within the “floxie” groups and communities know these terms and what they mean and imply. The people in the “floxie” community know when someone says that they are “severely floxed” that it means that person is suffering from more symptoms than they can count or name and that they are likely bed or house bound as a result of their fluoroquinolone-induced injuries. Of course, everyone’s experience is different, and people are encouraged in these communities to further describe their pain and their experience, but it’s far easier to say, “I’m severely floxed” than it is to list dozens of symptoms then say that those symptoms were caused by fluoroquinolone antibiotics.

Some people really hate the terms “flox” and they particularly hate the term “floxie.” They see the terms as silly and flippant, and they see it as disrespectful to those who are suffering from fluoroquinolone toxicity. Fluoroquinolone toxicity IS a serious and severe illness, and it should be taken seriously by doctors, patients, regulators, and everyone else. It is not a joke, or something to be taken lightly. It is a life-altering, often disabling, syndrome. Fluoroquinolones have maimed and killed people, and fluoroquinolone toxicity should be taken as seriously as other multi-symptom, chronic, mysterious illnesses like M.S., Lupus, Lyme Disease, M.E./CFS, etc.

Neither “flox” nor “floxie” are particularly serious terms, and I empathize, and even agree with, those who see it as minimizing the seriousness and severity of fluoroquinolone toxicity.

But… sometimes terms just stick. Both flox and floxie are terms that have resonated with people in the community, and they have stuck. Many people find it easier to describe their illness as being “floxed” than to describe it any other way. It resonates with people more to say, “floxies unite!” than it does to say, “victims of fluoroquinolone antibiotics come together!” For the purposes that the the terms are used, they work well for expressing what people want and need to say. I don’t think that anyone who uses the terms “flox” or “floxie” mean any disrespect to the illness or the people suffering from it. In fact, most of the people using the terms are either victims of fluoroquinolones or those who love a victim of fluoroquinolones.

I am writing this post on a site called Floxie Hope, so I am, of course, somewhat biased. I like the term “floxie” and it has become part of my brand (if you can say that a blog has a brand). I think that the term sticks in people’s minds and it resonates with them. There is an understanding of what it means–at least within our community. The naming of this site was somewhat accidental–I was trying to figure out how to create a web site and this was supposed to be my place-holder site until I figured out the mechanics of blogging, then I was supposed to think of a more well thought out name for the official site, but then this site got rolling while named Floxie Hope, and 5.5 years later, it’s still going and here we are.

I hear the people who think that “flox” and “floxie” aren’t serious enough terms to connote the severity of fluoroquinolone toxicity. In a lot of ways, I think they’re right. BUT, I don’t think that the term has held this community back. We have made a lot of progress over the last decade. We still have a lot of work to do, but millions of people have become aware of fluoroquinolone toxicity and fluoroquinolone dangers over the last decade, and part of the momentum of this community is our shared language and our shared understanding of terms like “flox.”

The terms “flox” and “floxie” are ingrained in our community, and they are likely here to stay as long as fluoroquinolones are hurting people (I hope for the extinction of the term through the strict limiting of the drugs – but we’re a long way from that and it’s certainly a matter for another post). I think that the terms are doing more good (through ease of communication, bringing people together, and having terms that resonate with many) than harm.

I am hopeful that the terms “flox” and “floxie” will someday be so well understood and accepted that they make it into the dictionary. The only criteria for words making it into the dictionary is that they appear in edited text, so I actually hope that more journalists start using the terms “flox” and “floxie” in their articles. Having the terms “flox” and “floxie” in the dictionary would be wonderfully validating, and it would help to increase awareness of fluoroquinolone toxicity.

When I describe this site, I often try to tell the back-story and give the long explanation of how I was hurt by ciprofloxacin. Sometimes the person who I’m talking to says something like, “Oh, you’ve been floxed – that happened to my sister-in-law.” The word is getting out, and the terms “flox” and “floxie” are spreading. It’s a good thing. Awareness is one of the most important steps toward change, and short, easy-to-remember terms like “flox” and “floxie” help people to become aware of the dangers of fluoroquinolones.

*****

NY Resolution to Heal My Gut

Seven years after I got floxed, and 5.5 years since I wrote my recovery story, I am still doing well. I am working at a job that I enjoy, I am in a good relationship, I can hike, bike, swim, and otherwise move my body, I have my reading comprehension and intellect back, my energy level is decent, and my autonomic nervous system generally operates as it’s supposed to. I feel good, and I’m living a good life. As I’ve said many times before, I hope that my recovery gives you hope for your healing.

With it noted that I’m generally healed, and that I feel good in most areas of my life, I’m going to confess that…

My gut is a mess, and I am worried about it.

I have no idea whether my gut issues are from being floxed or not. GI tract problems weren’t part of my initial floxing–I didn’t have any gut issues until recently. But in the last year(ish), my gut has started to have… issues. Unfortunately, there is no way to describe GI issues without describing bowel movements, so here goes – I haven’t had a normal textured poo in ages. It has been at least a year. TMI? Sorry.

Poorly formed stools are definitely a sign of inflammation and other gut issues, and, despite the fact that I feel generally okay, I’m concerned about my gut health.

I want a gut that doesn’t hurt every day, that forms healthy-textured poos, and that I don’t worry about. I don’t want to be concerned that I’m developing IBS, or crohn’s disease, or that I have c-diff, or anything else. I’m guessing that I don’t have any of those things, and that I just have an inflamed gut, but I don’t want that either. I want a healthy, happy, healed gut that feels good and operates entirely normally. I don’t think that’s too much to ask for. I also think that my gut is my responsibility, and that no one other than me can do anything about MY gut health.

It’s December 28th as I write this, and the beginning of the new year seems as good a time as any to commit to healing my gut. Here are some of the things I plan to do to heal my gut in 2019 (public accountability is good, right?):

Clean up my diet

When I first got floxed I ate only meat and veggies. I was scared of most foods, and I ended up losing weight and feeling worn-down because I wasn’t ingesting enough calories. After I got over the fear of food, I added fruits and other good things to my diet, and ended up eating as outlined in The Floxie Food Guide. But, after a while of feeling better, I stopped restricting my diet entirely. I didn’t eat much processed food because I’ve never liked processed food, but I ate whatever I wanted. Perhaps my GI issues are the result of my “anything goes” diet (or maybe my GI issues stem from something else like mold in my house or fluoride in my city’s water or a parasite – it’s hard to tell). Anyhow, it’s time to restrict my diet again with the hope of calming the inflammation in my intestines.

Step 1: Give up gluten. My husband has been on a bread-baking kick lately, so this will take some willpower, but it has helped so many people, and it seems like a logical first step, so, I’m going to go gluten-free and see if that helps.

Step 2: Give up legumes. I like beans, but they make me feel like crap.

Step 3: Limit dairy. I love dairy too much to say that I’m going to give it up, but I’m going to try to be cognizant of how much I eat and how it makes me feel and limit it.

I want to be able to sustain these changes, so these are the only things I’m going to do at first. If they don’t work, I’ll move on to a more restricted protocol – probably something close to The Wahls Protocol because it has helped so many fellow “floxies.”

I’ve noticed that oatmeal makes me feel better generally, so I’m going to eat more oatmeal. I’ve also noticed that spicy food tends to make me feel worse, so I’m going to limit them even though many spices are supposed to be anti-inflammatory.

Cut the coffee and alcohol

This is a no-brainer, right? No explanation is necessary as to why these need to go in order for me to heal my gut. It’s hard though, so, here’s my public accountability.

Note that the coffee I drink is decaf. I haven’t been able to tolerate caffeinated coffee post-flox.

I really like both coffee and alcohol, and this is going to be tough. I’m only committing to cutting down on them, not to completely giving up either, but I can commit to cutting the coffee by 50% and the alcohol by 80%.

Eat probiotic foods

Sauerkraut and kimchi, here I come. Luckily, I like both.

Meditate, breathing exercises, eat mindfully, and otherwise stimulate the vagus nerve to heal the gut

Our guts are connected to our brains via the vagus nerve, and stimulating and toning the vagus nerve through meditating, breathing exercises, mindfulness, and other activities, can heal both the gut and the brain.

Here is an interesting post about how a guy healed his IBS through stimulating his vagus nerve through gargling: How I Cured My Irritable Bowel Syndrome.

As I was going through the early stages of my fluoroquinolone toxicity journey I was really good about meditating, doing breathing exercises, going to the chiropractor and/or acupuncturist, and doing other things that stimulated my vagus nerve. I think that these things helped me to heal. They were part of my healing journey, and I recommend them to others because they are healing for the body, mind, and spirit, and because they stimulate the vagus nerve and trigger the release of acetylcholine. Like watching my diet, conscientiously doing activities that stimulated my vagus nerve fell to the wayside as I healed. I felt good, so I didn’t need to do breathing exercises to feel better. But, I think that all the vagus nerve healing exercises were helpful for my gut when I was doing them, and that they’ll be helpful for my gut if I do them again.

Shoot, I wrote a book about healing the vagus nerve – I should make the time to practice what I preach.

Step 1: Meditate daily

Step 2: Swim weekly – it forces breathing exercises, and movement is good for the vagus nerve.

Step 3: Eat mindfully

Step 4: Gargle and/or hum daily

 

Those are my resolutions, and I hope that they result in a happier, healthier gut.

I’m open to suggestions for gut healing. Please feel free to comment below to let me know what has helped you to heal your gut. As you may gather from the post above, I am not willing to go on a super-restrictive diet unless/until all else fails, but I am willing to hear suggestions. I’m also open to trying supplements that heal the gut including aloe juice, collagen, bone broth, probiotic supplements, etc. If you have any recommendations based on personal experience with gut-healing supplements, please comment below.

Whenever someone asks in the forums about how to heal from fluoroquinolone toxicity, someone always answers, “heal your gut.” They’re right, of course–but it’s easier said than done. There are people in the “floxie” community who are much more better about having a “clean” diet than I am who still struggle with GI issues and other symptoms of fluoroquinolone toxicity. I’m hopeful that my modified “clean-ish” diet will help my gut to heal, and that the other things mentioned above help too. I want to acknowledge though, that “healing the gut” is not simple and that there isn’t a single answer for how to do it. I’m hopeful that the steps noted above will help me, and that I’ll have a healthier, happier gut in 2019 than I did in 2018.

*****

 

 

 

 

FDA Warns About Increased Risk of Aortic Aneurysm and Dissection with Fluoroquinolone Antibiotics

On December 20, 2018, the US FDA released a review that “found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main artery of the body, called the aorta. These tears, called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death. They can occur with fluoroquinolones for systemic use given by mouth or through an injection.” (source)

This acknowledgement from the FDA came three years after two major studies showed a statistically significant increase in risk of aortic dissection and aneurysm with fluoroquinolone use. The studies, “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” (JAMA Internal Medicine, 2015), and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” (BMJ Open, 2015) both found that fluoroquinolone use is associated with an increased risk of aortic aneurysm and dissection, with “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” concluding that:

“Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.”

Both “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone” and “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study” are major studies, with “analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011” for the former, and 1.7 million older adults in Ontario, Canada, for the later. They are robust studies that show a statistically significant association between fluoroquinolone-use and aortic aneurysm and dissection.

The FDA took too long to warn the public about the dangers of aortic aneurysm and dissection post exposure to fluoroquinolones, but, better late than never. Here is the full text of the FDA announcement that was published on Thursday December 20, 2018:

[12-20-2018] A U.S. Food and Drug Administration (FDA) review found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main artery of the body, called the aorta.  These tears, called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death.  They can occur with fluoroquinolones for systemic use given by mouth or through an injection.

Fluoroquinolones should not be used in patients at increased risk unless there are no other treatment options available.  People at increased risk include those with a history of blockages or aneurysms (abnormal bulges) of the aorta or other blood vessels, high blood pressure, certain genetic disorders that involve blood vessel changes, and the elderly.  We are requiring that a new warning about this risk be added to the prescribing information and patient Medication Guide for all fluoroquinolones.

Fluoroquinolone antibiotics are approved to treat certain bacterial infections and have been used for more than 30 years.  They work by killing or stopping the growth of bacteria that can cause illness.  Without treatment, some infections can spread and lead to serious health problems (see List of Currently Available FDA-Approved Systemic Fluoroquinolones).

Health care professionals should avoid prescribing fluoroquinolone antibiotics to patients who have an aortic aneurysm or are at risk for an aortic aneurysm, such as patients with peripheral atherosclerotic vascular diseases, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients.  Prescribe fluoroquinolones to these patients only when no other treatment options are available.  Advise all patients to seek immediate medical treatment for any symptoms associated with aortic aneurysm.  Stop fluoroquinolone treatment immediately if a patient reports side effects suggestive of aortic aneurysm or dissection.

Patients should seek medical attention immediately by going to an emergency room or calling 911 if you experience sudden, severe, and constant pain in the stomach, chest or back.  Be aware that symptoms of an aortic aneurysm often do not show up until the aneurysm becomes large or bursts, so report any unusual side effects from taking fluoroquinolones to your health care professional immediately.  Before starting an antibiotic prescription, inform your health care professional if you have a history of aneurysms, blockages or hardening of the arteries, high blood pressure, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome.  If you have been prescribed a fluoroquinolone to treat an infection, do not stop the antibiotic without first talking to your health care professional.

We reviewed cases reported to FDA* and four published observational studies1,2,3,4 that showed an increased risk of aortic aneurysm or dissection associated with fluoroquinolone use (see Data Summary).  How some of the studies were designed or carried out, and the ways the data were analyzed could affect the study findings; however, taken together, the results of all four studies provide consistent evidence of an association between fluoroquinolone use and aortic aneurysm or dissection.  The underlying mechanism for this risk cannot be determined from these studies, and the background risk of aortic aneurysm can vary depending on the population.  The background risk has been estimated from nine aortic aneurysm events per 100,000 people per year in the general population to 300 aortic aneurysm events per 100,000 people per year in individuals at highest risk.  Because multiple studies showed higher rates of about twice the risk of aortic aneurysm rupture and dissection in those taking fluoroquinolones, FDA determined the warnings were warranted to alert health care professionals and patients.

We communicated safety information associated with fluoroquinolones in July 2018 (significant decreases in blood sugar and certain mental health side effects), July 2016 (disabling side effects of the tendons, muscles, joints, nerves, and central nervous system), May 2016 (restricting use for certain uncomplicated infections), August 2013 (peripheral neuropathy), and July 2008 (tendinitis and tendon rupture).

To help FDA track safety issues with medicines, we urge patients and health care professionals to report side effects involving fluoroquinolones or other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

More information about the link between fluoroquinolones and aortic aneurysm and dissection can be found in these studies or articles:

  1. JAMA Internal Medicine, “Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone
  2. BMJ Open, “Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study
  3. BMJ, “Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study
  4. Baylor College of Medicine, “Ciprofloxacin increases risk of tears, rupture in mouse aortas

Additionally, here are some news articles about the FDA acknowledgement of the link between fluoroquinolones and aortic aneurysm and dissection:

  1. CNN, “Certain antibiotics may cause aortic aneurysm, FDA warns
  2. NBC News, “FDA warns some antibiotics can cause fatal heart damage: Drugs commonly used to treat upper respiratory infection, urinary tract infections should not be prescribed to patients already at risk
  3. Medscape, “More Fluoroquinolone Safety Concerns
  4. WRIC ABC 8 Richmond, “Commonly prescribed antibiotics can cause potentially deadly ruptures, FDA warns

Are Fluoroquinolones Causing Connective Tissue Disorders that are Leading to ME/CFS?

The symptoms of fluoroquinolone toxicity often mimic those of ME/CFS (Myalgic encephalomyelitis/chronic fatigue syndrome). Many people suffering from fluoroquinolone toxicity experience debilitating fatigue, and some are bed-bound and permanently disabled from this symptom, along with all the others that come along with fluoroquinolone toxicity. Both fluoroquinolone toxicity and ME/CFS are multi-symptom, chronic syndromes that are poorly understood and often disregarded by those in the medical community. Research into the mechanisms behind both fluoroquinolone toxicity and ME/CFS show that mitochondria (the energy centers of our cells) are likely related to both diseases, and so is autonomic nervous system dysfunction, mast cell activation, metabolomics, epigenetics, immune system dysfunction, hormonal imbalances, and other areas of human biology. Both fluoroquinolone toxicity and ME/CFS also have significant overlap with other diseases such as Ehlers-Danlos syndromes (EDS), Postural orthostatic tachycardia syndrome (POTS), and fibromyalgia.

The similarities between fluoroquinolone toxicity and ME/CFS may mean that they have a similar root mechanism…. or they may not. The root cause of fluoroquinolone toxicity is, of course, fluoroquinolones. (The mechanism behind fluoroquinolone toxicity is much more complex and the answer to the question of HOW fluoroquinolones hurt people is still being uncovered.) Most people who have ME/CFS don’t report that their symptoms started with fluoroquinolone exposure (though there is almost certainly some overlap, and there are likely some people who have been diagnosed with ME/CFS whose disease started with a fluoroquinolone prescription). There seem to be a variety of triggers that set off ME/CFS in previously healthy individuals, including, but not limited to, mold exposure and sensitivity, and exposure to a viral infection that the body never fully recovers from.

While it is possible that there are many cases of ME/CFS that were brought on by fluoroquinolones, and thus are “actually” fluoroquinolone toxicity (labels, shmables), it is also possible that both diseases/syndromes have a similar underlying mechanism despite different causes, and it is also possible that though the symptoms and features of both diseases are similar, they are actually different on a mechanistic and/or cellular level.

Though the possibilities for differences between fluoroquinolone toxicity and ME/CFS are potentially significant, the similarities are obvious, and it is likely that research that helps ME/CFS sufferers will help fluoroquinolone toxicity sufferers.

There is a theory about the mechanism behind ME/CFS that has recently come to my attention that could, potentially, tie it more directly to fluoroquinolone toxicity. The theory, in a nutshell, is this:

Some people with ME/CFS have an underlying predisposition for EDS, and thus collagen synthesis is disordered and connective tissues are weakened. The ligaments of the craniocervical junction (where your skull meets your first vertebra) become weak and this leads to craniocervical instability (CCI) and atlantoaxial instability (AAI) (together, CCI/AAI). When people suffer from CCI/AAI their neck ligaments don’t sufficiently hold up their head and their brain stems are compressed into their spines. This causes many symptoms of ME/CFS. (I’m not sure exactly how – ask someone who has done far more research into ME/CFS and/or CCI/AAI than me.)

You can read about how CCI/AAI relates to ME/CFS in these two links:

  1. MEchanical Basis
  2. A new diagnosis to add to the list: I have craniocervical and atlantoaxial instability

How does this relate to fluoroquinlones?

It is well known that fluoroquinolone antibiotics (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, Floxin/ofloxacin, and a few others) damage connective tissues–including musculoskeletal connective tissues like tendons, cartilage, bone, and muscle, as well as other connective tissues such as ocular tissue (including the retina)eardrums, and cardiac/heart tissue. Multiple studies have found that fluoroquinolones are toxic and damaging to connective tissues. Given the wide differences in tissues that fluoroquinolones have been shown to deleteriously affect–from cartilage to cardiac tissue–it is reasonable to assert that they damage all connective tissues throughout the body. (Read any of the articles in the citations listed below for information about how fluoroquinolones damage connective tissues.)

Given that fluoroquinolones damage connective tissues (probably all connective tissues – see links below), it is possible that they weaken the tendons of the neck and thus lead to CCI/AAI. CCI/AAI then leads to multi-symptom chronic illness including all the symptoms of ME/CFS (which are too numerous to count).

This weakening of tendons and subsequent CCI/AAI likely occurs more often in people with underlying connective tissue disorders like EDS. I suspect (though I have no proof of this) that there are many kinds of EDS that have not yet been identified, and that more people have the genes for a variation of EDS than those who can currently be diagnosed with the disease. It’s also possible that a genetic predisposition toward EDS is not necessary for fluoroquinolones to cause extensive connective tissue damage, and that they do so in everyone who is exposed to them (at varying levels, of course). Fluoroquinolones have been shown to damage dog and rat connective tissues, especially tendons, and human connective tissues exposed to fluoroquinolones have also shown extensive damage both in-vitro and through analysis of people exposed to fluoroquinolones. I have a hard time believing that all the rats, puppies, and people whose tissues were sampled all had underlying EDS prior to their tissues being destroyed by fluoroquinolones. However, it’s possible that underlying genetic predispositions, including those for EDS, determine how severely people are affected by fluoroquinolones. More research is, of course, needed.

Are fluoroquinolones causing CCI/AAI? And is CCI/AAI leading to ME/CFS? Given the large number of studies showing that fluoroquinolones destroy connective tissues and interfere with collagen synthesis, it’s quite plausible (even likely) that they cause CCI/AAI. How, and if, CCI/AAI is connected with ME/CFS is another question. But given the experiences of the authors of MEchanical Basis and A new diagnosis to add to the list: I have craniocervical and atlantoaxial instability, it’s a possibility that is certainly worth exploring.

 

Sources for the assertion that fluoroquinolones cause connective tissue destruction and disordered collagen synthesis:

Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population. Hall, Mederic M. et al. PM&R , Volume 3 , Issue 2 , 132 – 142

Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D. Oral Fluoroquinolones and the Risk of Retinal Detachment. JAMA. 2012;307(13):1414-1419. doi:10.1001/jama.2012.383

Tsai WC, Hsu CC, Chen CP, et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res. 2011;29(1):67-73

Lee C, Lee MG, Chen Y, Lee S, Chen Y, Chen S, Chang S. Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-1847. doi:10.1001/jamainternmed.2015.5389

Kaleagasioglu F, Olcay E. Fluoroquinolone-induced tendinopathy: etiology and preventive measures. Tohoku J Exp Med. 2012;226(4):251-258.

Adel Alrwisan, Patrick J. Antonelli, Almut G. Winterstein; Quinolone Ear Drops After Tympanostomy Tubes and the Risk of Eardrum Perforation: A Retrospective Cohort Study. Clin Infect Dis 2017; 64 (8): 1052-1058. doi: 10.1093/cid/cix032

EMA Committee Recommends Restricting Fluoroquinolones

The European Medicines Agency (EMA) put out the press release entitled “Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics” on November 16, 2018. It goes over the recommendations of the EMA’s Committee for Medicinal Products for Human Use (CHMP), and expands on the earlier recommendations of the Pharmacovigilance Risk Assessment Committee (PRAC). Following are some highlights from “Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics.”

“The CHMP confirmed that the use of the remaining fluoroquinolone antibiotics should be restricted. In addition, the prescribing information for healthcare professionals and information for patients will describe the disabling and potentially permanent side effects and advise patients to stop treatment with a fluoroquinolone antibiotic at the first sign of a side effect involving muscles, tendons or joints and the nervous system.”

This is a strong statement from the EMA. It is recommended that the fluoroquinolones that remain on the market in Europe (including, but not limited to, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, and norfloxacin) will be restricted, and patients and healthcare providers alike will be given information about the disabling effects of these drugs. That’s a HUGE step in the right direction!

“Restrictions on the use of fluoroquinolone antibiotics will mean that they should not be used:

  • to treat infections that might get better without treatment or are not severe (such as throat infections);
  • to treat non-bacterial infections, e.g. non-bacterial (chronic) prostatitis;
  • for preventing traveller’s diarrhoea or recurring lower urinary tract infections (urine infections that do not extend beyond the bladder);
  • to treat mild or moderate bacterial infections unless other antibacterial medicines commonly recommended for these infections cannot be used.”

This list is great, and if it, combined with the US FDA’s list of ailments for which fluoroquinolones should not be used, is followed, fluoroquinolone prescriptions will be cut significantly.

I am particularly pleased to see that the EMA is recommending against use of fluoroquinolones for treatment of chronic prostatitis. Too many men have been severely injured by fluoroquinolones given to them for treatment of non-bacterial prostatitis, a condition for which fluoroquinolones are no better than a placebo.

It is also wonderful to see that the EMA is recommending against the prescription fo fluoroquinolones for prevention of traveller’s diarrhea/diarrhoea. No one should ever be prescribed a drug as dangerous and consequential as fluoroquinolones “just in case” they get traveller’s diarrhea.

“Importantly, fluoroquinolones should generally be avoided in patients who have previously had serious side effects with a fluoroquinolone or quinolone antibiotic. They should be used with special caution in the elderly, patients with kidney disease and those who have had an organ transplantation because these patients are at a higher risk of tendon injury. Since the use of a corticosteroid with a fluoroquinolone also increases this risk, combined use of these medicines should be avoided.”

Yes – exactly – fluoroquinolones should be avoided in people who have previously experienced side-effects from fluoroquinolones. More information about that can be found in “The Next Time Will be Worse: Cross-Reactivity of Fluoroquinolones.”

I would say that fluoroquinolones should never be used on patients who are elderly, who have kidney disease, or who have had an organ transplant, but use “with special caution” is a step in the right direction.

“The CHMP opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU countries. National authorities will enforce this decision for the fluoroquinolone and quinolone medicines authorised in their countries and they will also take other appropriate measures to promote the correct use of these antibiotics.”

Stay tuned. I’ll highlight the final decision made by the EMA once it is published.

The EMA press release, “Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics” also contains the following guidance for patients:

Information for patients

  • Fluoroquinolone medicines (which contain ciprofloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin and rufloxacin) can cause long-lasting, disabling and potentially permanent side effects involving tendons, muscles, joints and the nervous system.
  • These serious side effects include inflamed or torn tendon, muscle pain or weakness, and joint pain or swelling, walking difficulty, feeling pins and needles, burning pain, tiredness, depression, problems with memory, sleeping, vision and hearing, and altered taste and smell.
  • Tendon swelling and injury may occur within 2 days of starting treatment with a fluoroquinolone but may even occur several months after stopping treatment.
  • Stop taking a fluoroquinolone medicine and contact your doctor at once in the following cases:
    • at the first sign of tendon injury, such as tendon pain or swelling – rest the painful area;
    • if you get pain, feel pins and needles, tingling, tickling, numbness or burning, or weakness especially in the legs or arms;
    • if you get swelling in the shoulder, arms or legs, have walking difficulty, feel tired or depressed or have problems with your memory or with sleeping or you notice changes with your vision, taste, smell or hearing. You and your doctor will decide if you can continue treatment or if you need to take another type of antibiotic.
  • You may be more prone to joint pain or swelling or tendon damage if you are aged over 60 years, your kidneys do not work well or you have received organ transplantation.
  • Speak with your doctor if you are taking a corticosteroid (medicines such as hydrocortisone and prednisolone) or need to have treatment with a corticosteroid. You may be especially prone to tendon damage if you are taking a corticosteroid and a fluoroquinolone medicine at the same time.
  • You should not take a fluoroquinolone medicine if you have ever had a serious side effect with a fluoroquinolone or a quinolone medicine and you should speak with your doctor immediately.
  • If you have any questions or concerns about your medicines, speak to your doctor or pharmacist.

And it also contains the following guidance for prescribers:

Information for healthcare professionals

  • Fluoroquinolones are associated with prolonged (up to months or years), serious, disabling and potentially irreversible drug reactions affecting several, sometimes multiple, systems, organ classes and senses.
  • The serious side effects include tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impaired hearing, vision, taste and smell.
  • Tendon damage (especially to Achilles tendon but also other tendons) can occur within 48 hours of starting fluoroquinolone treatment but the damage may be delayed several months after stopping treatment.
  • Patients who are older, have renal impairment or have had solid organ transplantation and those being treated with a corticosteroid are at higher risk of tendon damage. Concomitant treatment with a fluoroquinolone and a corticosteroid should be avoided.
  • Fluoroquinolone treatment should be discontinued at the first sign of tendon pain or inflammation and patients should be advised to stop treatment with a fluoroquinolone and speak with the doctor in case of symptoms of neuropathy such as pain, burning, tingling, numbness or weakness so as to prevent development of potentially irreversible condition.
  • Fluoroquinolones should generally not be used in patients who have had serious adverse reactionsassociated with the use of quinolone or fluoroquinolone medicines.
  • Up-to-date summary of product characteristics should be consulted for authorised indications when considering treatment with a fluoroquinolone medicine. This is because the indications for these medicines have been restricted.
  • The benefits and risks of fluoroquinolones will be monitored continuously and a drug utilisation study will evaluate the effectiveness of the new measures to reduce inappropriate use of fluoroquinolones by investigating changes in prescribing behaviour.

Healthcare providers should also be informed that there is no known cure or remedy for fluoroquinolone toxicity, and that the effects of these drugs can be permanent.

This information should also be given to patients.

Overall, I’m pleased with the CHMP recommendations, and I’m hopeful that the final, binding ruling from the EMA is as strongly worded, and even more comprehensive.

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Fluoroquinolone Toxicity Awareness Friday

Today, Friday November 9th 2018, is the first Fluoroquinolone Toxicity Awareness Friday. Please join me, and other fluoroquinolone toxicity awareness advocates, in spreading the news far and wide about the dangers of fluoroquinolones, and the devastation and destruction that fluoroquinolones have brought to too many lives.

Mark A Girard, fellow fluoroquinolone victim and advocate, posted this on his Facebook page(s):

Please join in as we do all sorts of things to raise awareness about FQs. We chose the final Friday before Antibiotic Awareness Week (Nov 12-19) so that people remember what they saw or read or heard when they see something else about antibiotics in the media. This is a genuine grass roots effort to get the help we need and deserve and to prevent others from suffering similar damage. We are hoping people will reach out to the media, to government agencies, to their friends and families and so on. We will be discussing all sorts of things people can do and of course everyone is encouraged to contribute in their own unique ways. Use your skills and your imagination and help us to build an annual tradition that makes a difference in more people’s lives each November. If you want, you can continue with awareness efforts all week long with me, but we are hoping to get something going where we all do something on Friday, whether it is to tell your story on your timeline or to share a favourite article, newscast or meme. It’s a Horton Hears a Who situation so please take some time and add your voice to the shouting and maybe they will finally hear us loud and clear. Thanks!

Please feel free to copy and paste it into your status, or, if you’re Facebook friends with Mark, please share it. Or you can let your friends and family know about Fluoroquinolone Toxicity Awareness Friday by sharing this post.

Some suggested things to share are:

  1. Amy Moser’s VIRAL post, “This Antibiotic Will Ruin You
  2. Popular and influential news story – CBS Los Angeles, “Southland Firefighter Says Popular Antibiotic Poisoned His Body, His Life
  3. Popular and influential news story – WSB TV 2 Atlanta, “Local woman says popular antibiotic killed her husband
  4. In-depth investigative report – PBS Frontline Investigation, “Certain Antibiotics Spur Widening Reports of Severe Side Effects
  5. News story out of Europe – Daily Mail, “Antibiotics got rid of her chest infection – but Jane says they destroyed her health
  6. Story in the well-respected journal, Nature, “When antibiotics turn toxic
  7. New York Times column, “Popular Antibiotics May Carry Serious Side Effects
  8. Popular post on Floxie Hope, “FDA Announces that Permanent Peripheral Neuropathy is to be Added to Warning Labels for Fluoroquinolone Antibiotics
  9. Popular post on Floxie Hope, “New Study Finds that Ciprofloxacin Depletes Mitochondrial DNA
  10. Popular post on Floxie Hope, “Letter from Bayer to Doctors Regarding Cipro and Avelox

There are links to hundreds of other articles and news stories on the “Links & Resources” page of this site.

Please share these, and anything else that brings attention to the devastating effects of fluoroquinolones, on social media, with your friends and family, with influential news organizations, with politicians, etc. Get the news out far and wide – THANK YOU!

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