Tag Archives: EMA

EMA Final Decision re Fluoroquinolones

The European Medicines Agency (EMA) released their final decision regarding fluoroquinolones. You can read the EMA verdict in “Quinolone- and fluoroquinolone-containing medicinal products” and “Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics” (both from the EMA web site). Additional information can be found on the UK Government web site in the article, “Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects.” Changes to European fluoroquinolone labels can be viewed HERE.

From the EMA:

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.

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.

Please excuse me for not knowing exactly how European drug regulation works (and please correct me if I am wrong), but it looks like the EMA makes recommendations, then the various European governments pass down instructions to their citizens.

The UK government web site gave the following recommendations to healthcare providers:

Advice for healthcare professionals:

  • systemic (by mouth, injection, or inhalation) fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses
  • advise patients to stop treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice – sheet for patients

do not prescribe fluoroquinolones:

  • for non-severe or self-limiting infections, or non-bacterial conditions

  • for some mild to moderate infections (such as in acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease; please refer to revised indications in the Summary of Product Characteristics) unless other antibiotics that are commonly recommended for these infections are considered inappropriate (see below)

  • ciprofloxacin or levofloxacin should no longer be prescribed for uncomplicated cystitis unless other antibiotics that are commonly recommended are considered inappropriate (see below)avoid use in patients who have previously had serious adverse reactions with a quinolone or fluoroquinolone antibiotic

  • prescribe with special caution for people older than 60 years and for those with renal impairment or solid-organ transplants because they are at a higher risk of tendon injury avoid use of a corticosteroid with a fluoroquinolone since co-administration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture

  • report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website or via the Yellow Card app (download it from the Apple App Store, or Google Play Store)

I hate that they put “very rarely” into these warnings, seeing as adverse reactions to fluoroquinolones are woefully under-studied and the assertion that these effects are “rare” is based on assumption rather than fact. BUT, these prescriber guidelines, along with the EMA guidelines, are steps in the right direction, and hopefully they will cut unnecessary fluoroquinolone prescriptions significantly.

Here are a few notes about the proposed changes to the European Fluoroquinolone Warning Labels:

  1. It is recommended that fluoroquinolone use be restricted for uncomplicated cystitis, Acute exacerbation of chronic bronchitis and of chronic obstructive pulmonary disease, Acute bacterial rhinosinusitis, and Otitis media acute.
  2. The warning labels are still leaving a lot of discretion to doctors/prescribers, and state, “In [indication] [name of product] should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections.” even though other parts of the warning label note that FQs should not be used for that particular indication. I worry that this may lead to some confusion among doctors/prescribers.
  3. The new warning label notes that people who have experienced adverse reactions to fluoroquinolones in the past should not take fluoroquinolones. “The use of [INN] should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with [INN] should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment.”
  4. The possibility of prolonged, serious, and disabling side effects of fluoroquinolones are noted. “Prolonged, disabling and potentially irreversible serious adverse drug reactions
    Very rare cases of prolonged (continuing months or years), disabling and potentially
    irreversible serious adverse drug reactions affecting different, sometimes multiple, body
    systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients
    receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk
    factors. [INN] should be discontinued immediately at the first signs or symptoms of any
    serious adverse reaction and patients should be advised to contact their prescriber for
    advice.”
  5. I’m slightly shocked that the risk of tendon problems is just-now being added to European warning labels, but it is one of the changes noted. “Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided. At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with [INN] should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.”
  6. Warnings about peripheral neuropathy are also added. “Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients under treatment with [INN] should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially irreversible condition.”
  7. Permanently disabling effects are noted again, “*Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors.”
  8. Disappointingly, the “Package leaflet: Information for the patient” is full of the words “very rarely” when referring to all the potential effects of fluoroquinolones. Again, the exact rate of adverse reactions to fluoroquinolones is unknown (and may be unknowable because of delayed adverse reactions), and I think that it’s a dis-service to patients to downplay the possibility of these serious and severe effects of fluoroquinolones.

THANK YOU, THANK YOU, THANK YOU to all the European advocates that pushed for these changes in fluoroquinolone warnings and prescribing. You have made an enormous difference, and hopefully rates of fluoroquinolone prescriptions will decrease significantly because of your advocacy.

*****

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.

*****

Letter to the EMA

Following is a letter that I (Lisa Bloomquist) wrote to the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). The CHMP will be reviewing fluoroquinolones starting on November 12, 2018, and they will make recommendations for use, marketing, and restriction of fluoroquinolones. Please consider sending a similar letter to them before 11/12/18. Contact information for all CHMP members can be found HERE

Dear CHMP Reviewers,

Thank you for thoughtfully reviewing fluoroquinolones and for considering the following information.

Fluoroquinolone antibiotics are causally associated with tendon ruptures, serious psychiatric disturbances, blood-sugar irregularities, peripheral neuropathy, autonomic nervous system dysfunction, disabling multi-symptom chronic illness, and many other symptoms that are both listed on the US FDA warning labels and noted in the many patient reports that can be found in published case-reports, testimonials provided by victims, and anecdotes. The devastating and disabling effects of fluoroquinolone antibiotics were brought to the attention of the EMA during the PRAC hearing on the 13th of June 2018.  It is my hope that you have listened to the patient testimonials presented to the PRAC, and that you are familiar with the severity of fluoroquinolone toxicity symptoms. In this letter, I will present some mechanisms through which fluoroquinolones lead to the symptoms noted above. I hope that you take these mechanisms into consideration when reviewing fluoroquinolones and making a judgement about their marketing and availability.

Fluoroquinolone Damage Mechanism 1 – Topoisomerase Interruption

The US FDA warning label for ciprofloxacin notes that, “The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.”

Fluoroquinolones are topoisomerase interrupters, and thus, as intended, they disrupt the process of bacterial DNA and RNA replication.

Though it is claimed that fluoroquinolones disrupt bacterial DNA not human nuclear DNA, this argument does not take into consideration the importance of bacterial DNA in human health, the fact that mitochondrial DNA is similar in structure to bacterial DNA, or the potential for promiscuous binding of fluoroquinolones to human nuclear DNA.

Fluoroquinolone Damage Mechanism 2 – Depletion of Mitochondrial DNA

Several studies have noted that fluoroquinolone antibiotics deplete mitochondrial DNA. In “Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2” (1) it is noted that:

“Loss of Top2β or its inhibition by ciprofloxacin results in accumulation of positively supercoiled mtDNA, followed by cessation of mitochondrial transcription and replication initiation, causing depletion of mtDNA copy number. These mitochondrial effects block both cell proliferation and differentiation, possibly explaining some of the side effects associated with fluoroquinolone antibiotics.”

Similar findings were published in 1996 in the article, “Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells” (2).

Fluoroquinolone Damage Mechanism 3 – Increase in ROS and depletion of antioxidants

The study, “Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients” (3) notes that fluoroquinolones decrease superoxide dismutates (SODs) and glutathione, and increase lipid peroxide levels.

Fluoroquinolone Damage Mechanism 4 – Neurotransmitter disruption and GABA inhibition

Fluoroquinolones are known to inhibit the activity of the neurotransmitter GABA, and to disrupt other neurotransmitter activities. The article, “Ciprofloxacin-induced neurotoxicity: evaluation of possible underlying mechanisms” (4) notes the following in its abstract:

Ciprofloxacin (CPX) is a fluoroquinolone antibiotic used for treating respiratory, urinary tract, gastrointestinal and abdominal infections. There are only a limited number of studies related to neurological adverse effects of this drug in therapeutic doses. Therefore, in the present study, we aimed to investigate the influence of CPX, when administered at pharmacological doses, on behavioral parameters of rats and the probable underlying mechanisms. CPX was administered in single oral daily doses of 20 and 50 mg/kg for 14 days in rats. CPX-induced depression and anxiety were evaluated by modified forced swimming test and elevated plus maze test, respectively. Also, spontaneous locomotor activity and motor coordination were assessed by activity cage and Rota-rod apparatus. Effects of CPX administration on brain serotonin, dopamine, γ-amino-butyric acid (GABA), glutamate, adrenaline and noradrenaline levels were determined by high performance liquid chromatography (HPLC) analysis. Contribution of oxidative stress to the changes induced by CPX administration was evaluated by measuring brain catalase, superoxide dismutase, glutathione (GSH) and malondialdehyde (MDA) levels. Our results indicated that depression-like and anxiety-like behaviors were observed only in the 50 mg/kg CPX-administered group with simultaneous decreases in the brain serotonin and GABA levels. In addition, in the brain homogenates of CPX-administered groups, increased MDA as well as decreased GSH and catalase activity with respect to their controls, indicated enhanced oxidative stress and weakened antioxidant defense system. In conclusion, repeated pharmacological doses of CPX were found to induce neurological toxicity. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of ciprofloxacin-induced neurotoxicity.

Several studies, including “Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials” (5) have noted that fluoroquinolone toxicity symptoms mimic those of benzodiazepine withdrawal.

Fluoroquinolone Damage Mechanism 5 – Depletion of Magnesium and Iron

The article, “Integrins on joint cartilage chondrocytes and alterations by ofloxacin or magnesium deficiency in immature rats” (6) notes that, “Recently, we showed that magnesium deficiency induces lesions in knee joint cartilage from 5-week-old rats that are very similar to ofloxacin-induced cartilage defects. We concluded that quinolone-induced arthropathy is probably due to chelation of magnesium and thus a deficit in functionally available magnesium in joint cartilage (Stahlmann et al. 1995).”

The article, “Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells” (7) notes that, “Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent.”

Both cellular magnesium and iron are necessary for multiple enzymatic reactions, and they are necessary for health. Fluoroquinolones deplete both magnesium and iron, and may deplete other crucial minerals too.

Fluoroquinolone Damage Mechanism 6 – Microbiome Destruction

The importance of the gut microbiome has recently been uncovered. As a powerful class of antibiotics, fluoroquinolones disrupt the balance of gut microbiota in many ways. The consequences of gut microbiome disruption are now being uncovered. A disrupted gut microbiome has been linked to various diseases from Parkinson’s to Autism.

Fluoroquinolone Damage Mechanism 7 – Fluorine

Fluoroquinolones are fluorinated drugs, and it is known that fluorine displaces iodine, an element that is essential in the synthesis of thyroid hormones. Excess fluorine is linked to skeletal fluorosis (8), lowered IQ (9), and other health maladies. A significant amount of information about the harm that fluoride does can be found on the Fluoride Action Network web site, www.fluoridealert.org.

Additionally, it is recommended that the question of whether fluoroquinolones are metabolized into fluoroacetate be explored further.

Fluoroquinolone Damage Mechanism 8 – Thyroid Hormone Disruption

A significant amount of information about the connections between fluoroquinolones and thyroid hormone disruption can be found on the web site www.fluoroquinolonethyroid.com, and a summary of the connections can be found onhttp://www.hormonesmatter.com/fluoroquinolone-antibiotics-thyroid-problems-connection/.

Thyroid hormone disruption can lead to multi-symptom chronic illness, and most people suffering from fluoroquinolone toxicity would classify their illness as both multi-symptom and chronic. The connections between fluoroquinolone antibiotics and thyroid hormone disruption should be explored further.

Fluoroquinolone Damage Mechanism 9 – Epigenetic Changes

The article, “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology” (10) notes that:

“Interestingly, extensive changes in gene expression were found in articular cartilage of rats receiving the quinolone antibacterial agent ofloxacin, suggesting a potential epigenetic mechanism for the arthropathy caused by these agents. It has also been documented that the incidence of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolones is increased compared to controls, suggesting the possibility of persistent gene expression changes in the liver and heart.”

Additionally, the published letter, “Hereditary Neuropathy Unmasked by Levofloxacin” (11) notes that a course of levofloxacin triggered Charcot-Marie-Tooth disease in a patient. Charcot-Marie-Tooth disease is thought to be a purely genetic disease, but the possibility exists that fluoroquinolone antibiotics are unmasking the disease.

Fluoroquinolone Damage Mechanism 10 – Increased MMP Expression

The article, “Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells” (12) notes that, “Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells.” This increase in MMP expression may have deleterious effects on all collagen and connective tissues.

Other potential damage mechanisms for fluoroquinolones include triggering mast cell activation, post-hepatic syndrome and liver damage, oxalate overload, extreme sensitivity to quinolones in the environment, calcium and/or potassium channel shifts, and many other possibilities. (http://fluoroquinolonethyroid.com/book_page/additional-mechanisms-to-consider/)

Exactly why some people experience devastating adverse reactions to fluoroquinolones is unknown. However, it is known and well-documented that fluoroquinolones cause a myriad of serious and severe adverse effects. I ask you to please thoughtfully consider each of the above mechanisms for fluoroquinolone damage when evaluating fluoroquinolones.

Thank you for your thought and consideration.

Sincerely,

Lisa Bloomquist

www.floxiehope.com

Durango, Colorado

USA

 

References:

  1. Anu Hangas, Koit Aasumets, Nina J Kekäläinen, Mika Paloheinä, Jaakko L Pohjoismäki, Joachim M Gerhold, Steffi Goffart; Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2, Nucleic Acids Research, Volume 46, Issue 18, 12 October 2018, Pages 9625–9636, https://doi.org/10.1093/nar/gky793
  2. Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells. J W Lawrence, D C Claire, V Weissig and T C Rowe. Molecular Pharmacology November 1, 1996, 50 (5) 1178-1188.
  3. Oxidative Stress Induced by Fluoroquinolones on Treatment for Complicated Urinary Tract Infections in Indian Patients. V Talla and PR Veerareddy. J Young Pharm. 2011 Oct-Dec; 3(4): 304–309. doi:  [10.4103/0975-1483.90242: 10.4103/0975-1483.90242]
  4. Sinem Ilgin, Ozgur Devrim Can, Ozlem Atli, Umut Irfan Ucel, Erol Sener & Ilkay Guven (2015) Ciprofloxacin-induced neurotoxicity: evaluation of possible underlying mechanisms, Toxicology Mechanisms and Methods, 25:5, 374-381, DOI: 10.3109/15376516.2015.1026008
  5. Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials. Br J Gen Pract. 2008;58(550):365-6.
  6. Integrins on joint cartilage chondrocytes and alterations by ofloxacin or magnesium deficiency in immature rats. Förster, C., Kociok, K., Shakibaei, M. et al. Arch Toxicol (1996) 70: 261. https://doi.org/10.1007/s002040050272
  7. Badal S, Her YF, Maher LJ. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells. J Biol Chem. 2015;290(36):22287-97.
  8. Skeletal fluorosis in relation to drinking water in rural areas of West Azerbaijan, Iran Ali Akbar Mohammadi, Mahmood Yousefi, Mehdi Yaseri, Mohsen Jalilzadeh & Amir Hossein Mahvi Scientific Reports volume 7, Article number: 17300 (2017)
  9. Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age in Mexico. Morteza Bashash et al. Published:19 September 2017CID: 097017https://doi.org/10.1289/EHP655
  10. Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology. Antonei B. Csoka and Moshe Szyf. Medical Hypotheses Volume 73, Issue 5, November 2009, Pages 770-780.https://doi.org/10.1016/j.mehy.2008.10.039
  11. Panas, M., Karadima, G., Kalfakis, N., & Vassilopoulos, D. (2011). Hereditary Neuropathy Unmasked by Levofloxacin. Annals of Pharmacotherapy, 45(10), 1312–1313. https://doi.org/10.1345/aph.1P786
  12. Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells. Anthony N. Corps et al. Arthritis and Rheumatology. Volume46, Issue11. November 2002 Pages 3034-3040. https://doi.org/10.1002/art.10617

 

EMA Decision on Fluoroquinolones – Next Steps

The EMA (European Medicines Agency) review of fluoroquinolones is ongoing, and your input is requested/needed.

On June 13, 2018, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) heard testimony from Europeans who suffered from fluoroquinolone toxicity, and on May 10, 2018, the PRAC issued their recommendations. (You can read and view the patient/victim testimonials HERE, HERE, and HERE, and you can read the PRAC’s recommendations HERE.) The next step is for the Committee for Medicinal Products for Human Use (CHMP) to consider the recommendations of the the PRAC on the safety of medicines on the market and recommend changes to the EMA. The CHMP will recommend changes in the marketing of fluoroquinolones, or may even recommend suspension or withdrawal of fluoroquinolones from the market. You can read more about the role of the CHMP HERE.

I would like to encourage everyone who has been hurt by fluoroquinolones to contact the CHMP so that they can take your testimonials and information into consideration when making their decisions and recommendations. Contact information for the CHMP members can be found HERE. I recommend that you send an email with a brief version of your personal story, along with information and references from the articles about fluoroquinolone toxicity that can be found in the “research” section of the Links & Resources page on this site or elsewhere on the internet to both the CHMP Chair (Harald Enzmann) and the Vice-Chair (Bruno Sepodes) I plan to send a letter that contains a combination of the information in the post, “What is Fluoroquinolone Toxicity” and the information that is found in the ebook, Hacking Fluoroquinolones (I’ll post my letter once I write it). You are welcome to use anything I (Lisa Bloomquist) have written on this site, or in my guest-posts on other sites, in your letters to the CHMP.

The CHMP meeting starts on November 12, 2018, and it is recommended that you send your emails to the Chair and Vice-chair of the CHMP as soon as possible.

Miriam Knight, a fluoroquinolone toxicity victim advocate, co-founder of Quinolone Toxicity Support UK, and an administrator for Fluoroquinolone Toxicity Victims in Europe, has written the following letter, and you are welcome to use it as a template. 

Dear Chair, Vice-chair and other members of the Committee for Medicinal Products for Human Use,

We in Europe wish to express our strong concerns regarding the recent recommendations made by the PRAC following their lengthy review into the side effects of Quinolones and Fluoroquinolones. We understand that the recommendations have now been passed to the CHMP for your opinion. We are very disappointed in the findings so far.

Representatives of this group and also individual members from across the EU were invited to speak at PRAC’s Public Hearing in June. From the EMA website we understand that “Contributions at public hearings inform the committee’s decision-making”. Even after taking part in the teleconference last week we are unable to find any evidence in the recommendations that our written and spoken interventions have in any way been used to inform the PRAC’s decision making.

Our main concern is that the evidence which we and others have provided regarding the damage Fluoroquinolones cause to human mitochondrial DNA (MtDNA) has been totally ignored. This evidence has been in the public domain since 1993 (1,2,3), yet is not mentioned in any of the license applications, SmPCs or PILs. Both the summary of the Public Hearing and the recommendations from the review fail to mention it, despite the overwhelming evidence. We despair that the Agency charged with safeguarding Public Health cannot see the huge danger in licensing products that physically damage humans. We hope that the CHMP and the Pharmacogenomic Working Party will at least understand the implications of this mechanism of action and will take the time to study ALL of the available evidence.

The Medical Profession seem to have a problem understanding how and why the Fluoroquinolone class of antibiotics have such wide ranging effects on some patients, indeed most are unable or do not believe patients when they are told of these side effects even with written and recorded evidence (4). It is clearly within the remit of the Pharmacogenomics Working Party to provide advice to the CHMP on general and product-specific matters relating to pharmacogenomics, although perhaps this aspect of the review was beyond the scope of the PRAC.

Not only do Fluoroquinolones have an effect on MtDNA but they also disrupt the metabolic processes of both our mitochondria (e.g. the TCA cycle) and also our cells (5,6). Again, the evidence for this has been glossed over by the PRAC’s recommendations, despite the many testimonies at the Public Hearing attempting to convey the sheer agonising horror inflicted by these drugs.

We understand from the teleconference that the recommendations passed over to the CHMP are more detailed than the brief version that was published prior to the teleconference. We sincerely hope this is so as all we have seen so far is a tenuous nod towards implementing changes with a view to protecting the public. The biggest risk to human health from the Fluoroquinolones is the damage and destruction caused to every cell (6) – which can potentially lead to multisystem problems including organ failure and cancers (4), and which surely outweigh the benefits. The mitochondrial damage also has implications on second generations – something which has yet to be studied. We notice that the PRAC dropped their original proposal to encourage further studies and research to be undertaken with no explanation. We find this decision, along with all of PRAC’s expressed concerns, to be disingenuous, at the least, at most we find it dangerous to future victims as well as present victims.

We cannot urge strongly enough that you fully and properly review all the evidence showing the catastrophic effect Fluoroquinolones can have both physically and mentally (4). A full understanding of why some people are affected immediately while others can tolerate several courses needs to be taught throughout the medical profession. It is simply not good enough to say these effects are “very rare” when it is well known that many people, after experiencing nothing from a first course go on to be affected by a second or third course. Others seem to tolerate repeated courses before just one more tablet sets off a serious reaction. The variety of personal thresholds is believed to depend on the individual’s mitochondrial condition, including either congenital deficiencies or acquired insults.The reality is that if someone takes enough Fluoroquinolones, they will eventually be affected: this cannot be defined as “very rare”. The true figure is unknown and until extensive research is undertaken it will remain unknown.

It is also not good enough to say these effects are “very rare” when it is well known that neither doctors nor patients associate an ADR that occurs weeks or months after cessation of the Fluoroquinolone with that particular drug – yet this is precisely what happens. There are possibly thousands of people who have been affected yet never know; their symptoms often labelled as Fibromyalgia or CFS/ME (which, ironically, have no known cause) or even MS.  Many times we have heard of e.g. eye specialists saying they have prescribed Fluoroquinolones hundreds of times yet no one has reported any problems: why would a patient with sudden muscle or tendon problems go back to their eye specialist? More patients have been seriously affected by Fluoroquinolones than anyone can imagine.

All Medical Professionals, member state Health Agencies and ALL committees working within the EMA have to fully understand the human catastrophe caused by this unique class of drugs (not exactly antibiotics as they have also been used as chemotherapy agents). Until the naïve ‘one size fits all’ approach to medicine is overturned – and this is obviously where the Pharmacogenomics Working Party is essential – innocent patients will continue to be harmed by the innocent doctors who are trying to do no harm.

References*:

1). Acridones and quinolones as inhibitors of ubiquinone functions in the mitochondrial respiratory chain. July 1993 Walter Oettmeier et al
https://pdfs.semanticscholar. org/a9fd/ 33039c3d987093746db40fbd8d7782 f3b078.pdf
2). Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells. Nov 1996 Lawrence JW et al.
https://www.ncbi.nlm.nih.gov/ pubmed/8913349
3). Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2 August 2018 Hangas et al
https://academic.oup.com/nar/ article/46/18/9625/5088042? fbclid= IwAR0Xu4wIXprB3wF6nBP2EZxWinNm mVvUvjIQ8GPHPaLS81KsxE_ ucJZ99K8
4). Fluoroquinolone-induced serious, persistent, multisymptom adverse effects.
Oct 2015. Golomb B. et al
http://casereports.bmj.com/ content/2015/bcr-2015-209821. full
“…with progression that continued following discontinuation evolving to a severe, disabling multisymptom profile variably involving tendinopathy,muscle weakness, peripheral neuropathy, autonomic dysfunction, sleep disorder, cognitive dysfunction and psychiatric disturbance..”
5). Exploiting bacterial DNA gyrase as a drug target: current state and perspectives
Nov 2011 Frédéric Collin et al.
https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3189412/
6).Treatment of the Fluoroquinolone Associated Disability – the pathobiochemical implications
Nov 2017. Michalak K. et al .
https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC5632915/

* These few references have been chosen as the most relevant to this letter.  The PRAC tell us they studied over 400 papers before reaching their decision but have not yet told us which 400.  As all scientists know, it is possible to reach any conclusion you like depending on which papers you quote. There are many more than 400 papers available which show the harm that can be caused by Fluoroquinolones.  Perhaps the best way to judge the danger is to work with the actual sufferers (we are either sufferers or carers ourselves) – as Dr Golomb (4) has done.

Thank you, Miriam, for all your advocacy work with the EMA (including the PRAC and CHMP)! And thank you to all who reach out to the CHMP – your advocacy work is appreciated too!

The PRAC recommendations were disappointing for many fluoroquinolone victims and advocates. Hopefully the CHMP recommendations will be stronger and more protective of patients.

EMA Recommends Restriction of Fluoroquinolones in Europe

The EMA (European Medicines Agency) just released a statement regarding fluoroquinolone use. It can be found through THIS LINK. The press release states:

Fluoroquinolone and quinolone antibiotics: PRAC recommends restrictions on use

Press release 05/10/2018

New restrictions follow review of disabling and potentially long-lasting side effects

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended restricting the use of fluoroquinolone and quinolone antibiotics (used by mouth, injection or inhalation) following a review of disabling and potentially long-lasting side effects reported with these medicines. 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.

Very rarely, patients treated with fluoroquinolone or quinolone antibiotics have suffered long-lasting and disabling side effects, mainly involving muscles, tendons and bones and the nervous system.

Following its evaluation of these side effects, the PRAC has recommended that some medicines, including all those that contain a quinolone antibiotic, should be removed from the market. This is because they are authorised only for infections that should no longer be treated with this class of antibiotics.

The PRAC recommended that the remaining fluoroquinolone antibiotics should:

  • not be used
    • to treat infections that might get better without treatment or are not severe (such as throat infections);
    • for preventing traveller’s diarrhoea or recurring lower urinary tract infections (urine infections that do not extend beyond the bladder);
    • to treat patients who have previously had serious side effects with a fluoroquinolone or quinolone antibiotic;
    • to treat mild or moderately severe infections unless other antibacterial medicines commonly recommended for these infections cannot be used;
  • be used with caution especially for the elderly, patients with kidney problems, patients who have had an organ transplantation or those who are being treated with a systemic corticosteroid. These patients are at higher risk of tendon injury caused by fluoroquinolone and quinolone antibiotics.

The PRAC also recommended that healthcare professionals should advise patients to stop treatment with a fluoroquinolone antibiotic at the first sign of a side effect involving muscles, tendons or bones (such as inflamed or torn tendon, muscle pain or weakness, and joint pain or swelling) or the nervous system (such as feeling pins and needles, tiredness, depression, confusion, suicidal thoughts, sleep disorders, vision and hearing problems, and altered taste and smell).

Prescribing information of individual fluoroquinolone antibiotics will be updated to reflect the restricted use.

The PRAC recommendations will now be sent to EMA’s Committee for Medicinal Products for Human Use(CHMP), which will adopt the Agency’s final opinion.

This outcome from the PRAC of the EMA is due to the advocacy work of many European victims of fluoroquinolones, and especially the brave people who testified before the EMA on June 13, 2018. Here is a video that shows the hearing, and all the moving testimonials:

There is so much more work that needs to be done for those who have been floxed. We need remedies for fluoroquinolone toxicity, and more needs to be done to prevent people from being victimized by these drugs.

Still, the acknowledgement from the EMA, and the recommendations that they have given, are greatly appreciated, and I hope that they will prevent many unnecessary fluoroquinolone prescriptions.

 

 

EMA Hearing on Fluoroquinolone Toxicity Part 2

In the first post about the EMA hearings (EMA Hearing on Fluoroquinolone Toxicity Part 1) I summarized the testimonials provided by Elizabeth Carmouche, Manex Bettan Arguinzoniz, Richard Cooknell, Markus Hamedinger, and Miriam Knight (who also spoke on behalf of Raymond Miller and Geoffrey Robinson). In Part 2, and all subsequent posts about the EMA hearings, rather than summarizing my take on the testimony given, I will quote people directly from the written submissions that they provided to the EMA. Please note that not everything said in the hearing is included in the written submissions, and significant valuable information and insight can be gleaned from listening to the hearing. You can view the entire hearing through the following video:

Speaker 6. Julie Le Normand, France

1. What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?

2. What is your view of the risks associated with quinolone and fluoroquinolone use?

3. In your opinion, what further measures could be taken to optimise the safe use of quinolones and fluoroquinolones?

My name is Julie Le Normand, I’m 37, I’m a French citizen and I am not representing any organization.

Back in November 2017, I had a terrible experience with levofloxacin (TAVANIC 500 mg, to be exact, twice a day for 10 days). That was the first time I ever took fluoroquinolones in my life, and it will certainly be the last.

Quinolones and fluoroquinolones (hereinafter referred to as Q & FQ) are far too broadly prescribed for cases where much less intense medicine would more than suffice for an efficient treatment. Having spoken with numerous people from across the world suffering from their adverse effects, I have learned that Q & FQ have been prescribed for everything from non-complicated urinary tract infections and sinusitis all the way to… anthrax exposure and the plague. I, for example, was prescribed a course of Levofloxacin by my general practitioner for a case of bronchitis/sinusitis at the end of November 2017. I would like the committee to know that I was never warned about the possible severe, longlasting side-effects of this medication by the doctor, nor by any other medical staff. It only took me two days on Levofloxacin after which I had no choice but to stop the medication because of the sudden onset of its adverse effects.

The manufacturers’ notice of the risks associated with Q & FQ is listed merely as “rare.” My experience—and those numerous others who have suffered from them—can attest to the fact that the risks of use of Q & FQ are anything but rare, contrary to what all of us have been led to believe. Please allow me to kindly state to the Committee that I took merely 4 pills in total of levofloxacin over two days, 7 months ago. For some, the adverse effects affecting the musculoskeletal and/or nervous system occur weeks or even months afterwards, which makes it even more difficult to connect the delayed symptoms with a course of antibiotics taken several weeks/months before. For me, the onset was as immediate as it was intense. I started to feel an extreme weakness in my legs. It was so bad that I could neither stand up on my feet nor walk anymore. I cannot do justice to you in describing just how uncomfortable the sensations inside my legs were. It felt as if bugs were crawling on them. Both my ankles and my Achilles heels started to hurt and swell. I could hardly breathe. My blood pressure rose dramatically, and I was overcome with a feeling of confusion and agitation. The experience was so bad that afterwards, I was completely bedridden for more than 3 weeks and on sick leave from work for 6 weeks. I felt depressed. And 7 months out, I still feel weak emotionally. My face has aged suddenly though I’m 37. I did not used to be this way. I used to be a very healthy person. I loved hiking, skiing. I am still a mother to 2 children both under the age of 5. But now I am limited in my physical and emotional capacities, and this is extremely upsetting and unfair. I will say that there have been some concrete improvements since the episode, but a part of me still wonders whether I will ever be able to fully heal from this “toxicity syndrome.” I have seen several doctors, each of whom have been helpless with the various symptoms I experienced. Long-lasting symptoms simply after a few pills of levofloxacin.

Please allow me to state for the record that I’m convinced Q & FQ should be limited only to life or death situations as their adverse side-effects far exceed what they can otherwise treat! In fact, I fear there is no such thing as a “safe use” of Q & FQ as the side-effects seem to be very common, almost the norm. Please allow me to reiterate that in my view Q & FQ should ONLY be prescribed at the hospital in certain circumstances with very cautious care and a thorough monitoring of any possible side-effects. General practitioners should not be able to prescribe them anymore without identifying the bacteria to treat, and in any event, not as a secondary intention but rather as a last resort treatment.

If I may add a final remark, I believe that the topical Q/FQ (such as eyedrops, ear drops) should also be included in this safety review as they are known to cause adverse reactions as well, that can be as severe as those triggered by the oral or IV antibiotics.

I do hope that the outcome of this Public Hearing will lead to:

1. An acknowledgement of a so called FQ associated toxicity syndrome/disability within Europe. To my view, there is an urging need that the EMA acknowledges the existence of a so called FQ associated toxicity syndrome/disability (FQAD, like the US Food and Drug Administration did a couple of years ago).

2. If not a complete BAN of FQs, at least a STRONG restriction of their use within Europe This would be for sure a historic choice (much stronger that the current “black box warnings” used in USA) and would give Europe the leadership in FQ toxicity awareness.

Thank you for your time and consideration and for the opportunity to present my experience to the Committee.

Speaker 7. Elsa Leitão, Germany

My name is Elsa Leitao. I’m from Portugal and I’m currently living in Germany where I work as a scientist in the field of human epigenetics.

I’m 39 years-old and until three years ago I was fairly healthy. Then I was prescribed Ciprofloxacin to treat a regular urinary infection. I had no further warning from my physician about the special risks associated with this drug. After a few days I developed side effects: joint pain, muscle pain, difficulty in walking, lack of strength and general tiredness. It took me several months until I started feeling better but I never got back to my previous health state. I haven’t been able to run longer distances again due to the fragility I still feel in certain tendons. Even after three years, I have sporadic episodes of severe joint pain that I believe are related to the ingestion of certain types of food that I became unable to tolerate.

I think quinolones and fluoroquinolones should only be used in life threatening conditions such has extremely severe infections. These drugs should be avoided when other treatments are possible. I believe that patients prescribed with these antibiotics are in great risk of becoming sicker than before the treatment. Moreover, the side effects take much longer to subside than the initial illness would take to disappear with other treatment and may even become permanently debilitating.

There are a few measures I think should be taken to optimise the safe use of these drugs: 1) Physicians should be better instructed about the severe long lasting side effects the administration of these drugs might have; these instructions should be clearly passed to medical school teachers, medical students and working physicians, so all links in the chain can simultaneously acquire this knowledge. 2) Physicians should inform the patients about the potential toxicity, so the patients can be alert to the appearance of potentially alarming signs. 3) Packages should contain clear warning labels. 4) The products information should be changed with regard to the use of these drugs to the treatment of non-severe infections.

Although this public hearing is more focused in trying to improve the future use of these drugs, I think the past shouldn’t be forgotten nor the patients whose life was most severely and permanently affected. In this regard, efforts should also be taken in understanding how to treat these patients.

Speaker 8. Jarosław Linka, Poland

1) What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?

Fluoroquinolone (FQs) antibiotics are currently one of the most frequently prescribed drugs in Europe and play a very important role in treatment for bacterial infections, such as pneumonia, sinusitis, bronchitis, urinary tract infections, as well as for prostatitis. However, FQs are extremely toxic, have high potentials for adverse effects (AE) and associated with potentially long-lasting, frequently permanent, serious sides effects. Adverse reactions (ADRs) are often delayed for some weeks or months after cessation of FQs drug therapy, which makes it extremely difficult to make a correct medical diagnosis and apply symptomatic treatment. They belong to the group of broad-spectrum antibiotics, effective for both gram-positive and gram-negative bacteria. FQs employ their antibacterial effect by preventing bacterial DNA from unwinding and duplicating through inhibition of their topoisomerase and gyrase, which differentiate them from other common antibacterial agents. This mechanism places them closer to chemotherapy drugs then other antibiotics, which mostly interfere with specific steps in homeostatic cell wall biosynthesis. As a result of this broad-spectrum and misunderstanding of their safety profile, doctors in Europe consider them as a safe treatment option and prescribe them even as an empirical first line antibiotics therapy. This is leading to an overuse of FQs, and in consequence tens of thousands of people suffer by them each year, yet nearly all those damages remain misdiagnose or undiagnosed. Patients after FQs ADRs frequently are diagnosed as having Lyme disease, multiple sclerosis, neuropathies of every kind, lupus, rheumatoid diseases and most often fibromyalgia. Only a handful of doctors are aware of a devastating effects of FQs. The rest are uninformed and often deny the existence of fluoroquinolone associated disability (FQAD).

2) What is your view of the risks associated with quinolone and fluoroquinolone use?

According to the latest research and available literature, FQs toxicity results from many causes, including the formation of reactive oxygen species, and generation of oxidative stress damage of the mitochondrial DNA, as well as from the chelation of metals and a change in gene expression. These mechanisms explain the reason why FQs are often reported, to cause permanent and serious sides effects to: tendon, muscles, joints, nerves and other organs. Other long-lasting problems involve the cardiovascular system (QT interval prolongation), musculoskeletal system disorders (arthropathy, muscle weakness, joint pain and swelling), chronic fatigue and diabetes mellitus. Moreover, FQs have recently been discovered to induce delayed adverse neuropsychiatric effects including dizziness, sleep disturbance, anxiety, suicidal thoughts, hallucinations, psychosis, depression and recurrent mania. All the side effects should be mentioned on the patient info label, especially including psychiatric and potential delayed mitochondrial toxicity (like mitochondrial DNA depletion and mutations.)

3) In your opinion, what further measures could be taken to optimise the safe use of quinolones and fluoroquinolones?

The overuse of FQs and the growing number of reports on ADRs often leading to the fluoroquinolone associated disability (FQAD) is the main reason to avoid FQs when other safer alternatives are available. FQs should only be used as the last resort, exclusively in a hospital, by a well trained specialist. Unfortunately routine blood and urine tests are generally non-contributory to diagnoses of FQ’s ADR or FQAD, so specific molecular and genetic tests should be provided as quickly as possible. Special studies are necessary to find genetic factors underling susceptibility and the genotypes predisposing to ADRs. Multicenter clinical trials on long-lasting FQAD in large groups of patients are also required. Immediately, the basic guidelines and standard treatment methods for ADR and FQAD should be developed. This can’t be left to desperate patients and only several aware doctors who try to help them, like it was in my case. After one year of visiting numerous clinics in Poland, Germany, China, and USA I have finally found doctors, who were willing to help me and are aware of the FQ toxicity syndrome. Based on published data analysis and subsequent empirical searching, an individualised treatment plan was developed, which significantly reduced or even reversed some of my damage caused by Levofloxacine. Although, after three years my quality of life is better, a lot of environmental factors can induce intermittent episodes of symptoms. I am still suffering from chronic fatigue, Achilles and other tendons tendinopathy, multilevel degenerative disc disease, peripheral and small fibre neuropathy, uncommon food sensitivities, muscle weakness and headaches. A Review of currently available knowledge of possible ways to treat of FQAD, inspired by my case, was published last year in the Oxidative Medicine and Cellular Longevity under the title: “Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochehemical Implications”

I hope that a PRAC meeting will set new restrictions for FQs and new procedures of their use only in hospitals, under long-term supervision and as a last resort treatment. Limited action from EMA such as just copying FDA’s warning from June 26, 2016 will probably keep the current status quo for their use and spreading of their devastating delayed side effects, what we can still observe with the growing number of cases of FQAD from the United States.

https://doi.org/10.1155/2017/8023935

Speaker 9. Andrea Noya, Italy

As someone who’s suffered and is still suffering serious side effects from a fluoroquinolone, prescribed to me more then a year ago, I’d like to share my experience, in the hope that more consciousness would be applied, when using these types of drugs and also in the hope of bringing these side effects to the attention of the many doctors, that still seem to ignore them.

Answering the questions:

1. I think quinolones and fluoroquinolones are powerful and effective drugs that should be only prescribed for serious or life threatening infections.

2. The risks, in my opinion, exceed the benefits. A patient shouldn’t suffer serious or disabling side effects from a drug prescribed to treat or even prevent a common infection.

3. In my opinion, more restricting laws should be applied to this class of drugs and it should be mandatory for doctors to be better informed and trained on the use of quinolones and fluoroquinolones.

(Please note that Andrea Noya goes into significantly more detail about his experience with fluoroquinolone toxicity in his testimony.)

Speaker 10. Joshua Sutton, UK

My name is Joshua Sutton and I am a business student at Sheffield Hallam University.

I would like to begin by saying that there is a place for Fluoroquinolones in modern medicine, and the use of them in a proper manner could be very effective. However, the current use of them is far too frivolous and exceptionally dangerous. These drugs have such strong capabilities of causing major damage, as two days after the treatment of Ciprofloxacin for an unconfirmed and nonurgent infection my neurological health greatly deteriorated. The impact that these drugs have had on my life is beyond belief.

My view on the risks of Fluoroquinolones is that they very often outweigh the benefits, especially for unconfirmed and non-urgent infections. I was prescribed Ciprofloxacin on the 5th June 2017 by my GP. It was the 17th June when I first realised something was wrong, where my vision became very slurry and I felt very disorientated. This was accompanied by a horrible brain fog sensation that has never gone away, extreme light sensitivity and then walls of black snakes down the walls which ended up being the development of eye floaters.

Starting on the next day, the 18th June, I developed a terrible tremor and loss of sensation in my hands and feet where I quickly lost the ability to do even the most basic of tasks; tying my shoe laces, holding a knife and fork or even dressing myself. I would have excruciating deep rooted pains and aches down my glutes and hamstrings down into my feet, and the same down my arms into my hands that would refine me to my bed. The tops of my hands and feet would also be extremely sore, where moving my toes or fingers or clenching a fist would be agony.

I have burning and tingling pains and sensations all over my peripherals and head and face, and my limbs would consistently go numb. I couldn’t hold my phone up to use it as my hands and arms would quickly go numb and I would awake every morning with both my arms hanging by my side completely dead. I would and still get burning sensations down my back and limbs that makes even the weight of a cotton t-shirt against my skin excruciating. In addition to this, I would also find it impossible to empty my bladder and would have to strain to do so even a little bit.

Onto the fatigue and weakness, I would be so weak to the point where I couldn’t turn over a chicken breast in a frying pan or pick my feet up as I was walking so I would simply trip up over my own feet regularly. I would find it impossible to complete daily tasks. I was very reliant on my Mum to look after me and care for me during this period and I have had to make some major lifestyle adjustments in result of all of this. I am still very fatigued to this day and have great difficulty concentrating on anything. My cognitive abilities have been greatly affected by all this.

Alongside this, I have also been seeing a Cognitive Behavioural Psychotherapist to help me handle the anxiety involved with these symptoms.

Moving on, my opinion on further measures to optimise the safety of Fluoroquinolones should be to discontinue the use of them for unconfirmed and non-urgent infections, only allow GP’s to use them as a last resort, perhaps if the patient has allergies or sensitivities to many other alternative antibiotics. Also, the use in hospitals should also be as a last resort, and any prescribing doctor should not only be fully aware of the adverse capabilities of Fluoroquinolones but also discuss any adverse reaction symptoms with the patient so they are well informed because if they begin to have adverse symptoms during their course and continue taking them they are going to be very unwell for a very long time.

Fundamentally, this is all an iatrogenic catastrophe and there needs to be immediate regulation to mitigate these risks involved.

Ciprofloxacin took away my health, my fitness and my sanity, and for that, its unforgivable.

*****

EMA Hearing on Fluoroquinolone Toxicity Part 1

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) held a hearing regarding the risks of permanent and disabling effects of fluoroquinolones (i.e. Fluoroquinolone Toxicity) on Wednesday June 13, 8018. More than 100 patient testimonials were submitted to the PRAC, and several dozen people who suffered from fluoroquinolone toxicity testified before the PRAC in-person.

The patients who testified were asked to answer three questions:

  1. What is your view on the role of quinolones and fluoroquinolones in the treatment of infections?
  2. What is your view of the risks associated with quinolone and fluoroquinolone use?
  3. In your opinion, what further measures could be taken to optimize the safe use of quinolones and fluoroquinolones?

You can watch the hearing, and listen to the patient testimonials, through this video:

All of the patient testimonials were moving, thought-provoking, and insightful. Thank you to all who testified – many of whom traveled hundreds of miles/kilometers to get to the hearing. It is because of the people who testified (including those who testified in writing) that the PRAC now knows how truly devastating fluoroquinolones are. Hopefully they will be moved to action by the testimonials provided.

A transcript of the hearing will be published, and I will link to it when it is available. In the meantime, I will highlight some of the testimonials given during the hearing. I highly recommend that you watch the video, as the words directly from the victims’ mouths are much more powerful than my synopsis.

Elizabeth Carmouche testified that she was given ciprofloxacin as a prophylactic “in case” she got a urinary tract infection or travelers’ diarrhea while on holiday. She only took two of the prescribed pills, and has been suffering from the devastating effects of those pills for more than two years. She went from being an active to a woman with no pain, to suffering from severe joint, muscle, tendon, and bone pain, as well as peripheral neuropathy. She testified that doctors were unable to help her, and many dismissed the connection between ciprofloxacin and her ill health. She asserted that the following measures need to be taken:

  1. There needs to be official recognition of fluoroquinolone toxicity syndrome, and doctors need to be made fully aware of what the syndrome entails.
  2. Bayer, and the other pharma companies that produce fluoroquinolones, need to identify the precise mechanism of damage done by fluoroquinolones, and those companies need to establish a protocol for healing those who have been hurt by fluoroquinolones.
  3. Patients damaged by fluoroquinolones should be treated and guided by medical professionals.
  4. A red-flag system needs to be put in patient records so that those who have experienced an adverse reaction to a fluoroquinolone are never given fluoroquinolones again.

In closing, Elizabeth notes that fluoroquinolones are linked to mitochondrial damage, and that mitochondrial damage is linked to many diseases including Parkinson’s, Alzheimer’s, and other serious and severe diseases.

The next presenter was a pharmacist from Northern Spain named Manex Bettan Arguinzoniz (Bettan). He was just 37 years old when ciprofoxacin destroyed his body, mind, and health. He went from being athletic and able to play with his children, to being unable to do many of the activities that he loves. Despite being a pharmacist, he was unaware of the debilitating, disabling, and devastating effects of ciprofloxacin. He also found that his doctors and other specialists were unaware of the extent of the damage done by fluoroquinolones. His doctor (who is also his father in law) was only convinced of the link between Bettan’s health problems and ciprofloxacin when another doctor who had studied at the Mayo Clinic noted the reality of the link. Bettan suggests that fluoroquinolones be restricted so that they are only used in life-or-death situations in hospitals. He suggests that a stronger, possibly black-box, warning be added so that patients are aware of the dangers of fluoroquinolones.

One of the EMA PRAC members asked Bettan if he got his information about fluoroquinolone toxicity from patient testimonials or scientific papers. He answered that he read many papers about fluorouinolones. There are hundreds of research papers about fluoroquinolones and the damage they do listed on https://floxiehope.com/fluoroquinolones-links-resources/.

The next presenter was Richard Cooknell. Richard was a firefighter before he was poisoned by quinolones. He is still unable to work, and suffers from many ill effects. He asserts that quinolones are used too widely, and that their use should be restricted to life-or-death situations. Richard points out that fluoroquinolones are often inappropriately prescribed for non-bacterial chronic prostatitis. He also points out that there is no information in the warning label about the effects of fluoroquinolones being permanently disabling, or that adverse reactions can be delayed. Richard was able to gain a diagnosis of fluoroquinolone toxicity by a rheumatologist, and he asked that fluoroquinolone toxicity be more officialy recognized and diagnosed by more doctors.

Richard points out that his prostatitis was non-bacterial, as many cases of prostatitis are, and that he never should have been given fluoroquinolones for a non-bacterial ailment. The post, “Cipro is no better than a PLACEBO at treating chronic prostatitis / chronic pelvic pain syndrome” goes over some information about this.

Richard also points out that NSAIDs and steroids have caused set-backs for him and many other victims of fluoroquinolones toxicity.

The next speaker was Markus Hamedinger. Markus suffers from tendon and joint pain, and has received a confirmed diagnosis of fluoroquinolone toxicity. Fluoroquinolone toxicity has severely affected Markus’s life, and he is unable to do many of the activities that he used to enjoy. His symptoms have not improved in the 2+ years that he has been sick.

Markus asserts that fluoroquinolones are used too often, and that they are inappropriately used when other, safer, antibiotics could be used. He notes the delayed adverse reactions to fluoroquinolones are a factor in keeping the effects of fluoroquinolones under-recognized. He says that doctors need to be made aware of exactly which infections need to be treated by fluoroquinolones, and which infections can be treated with other antibiotics. He also states that fluoroquinolone use should be banned in agriculture, to prevent exposure to fluoroquinolones from occurring through meat consumption.

The PRAC Chairwoman asked a question about repeated exposure making the reaction worse, and Markus noted that his reactions got worse and worse with each fluoquinolone exposure.

The next presenter was Miriam Knight. Miriam also presented on behalf of Raymond Miller and Geoffrey Robinson. Miriam is the co-founder of Quinolone Toxicity Support UK, and is also an administrator for Fluoroquinolone Toxicity Victims in Europe.

Miriam asserts that there is no role of quinolones/fluoroquinolones in the treatment of disease. She notes that mitochondrial DNA wasn’t known, studied, or acknowledged when quinolones were developed, and that they are chemotherapeutic agents.

Miriam points out that despite the official death toll from quinolones being low, there are many people who are hurt by these drugs in fatal ways – including aortic aneurysm.

Miriam notes the damage done by quinolones to mitochondrial DNA, and how mitochondrial DNA damage effects individuals differently depending on a variety of factors.

Miriam asserts, “There will never be a safe use of quinolones. They will always cause damage, observed or not.” And she also states that if removing them from the market is impossible, they should at least be severely restricted.

Miriam also asserts that quinolone toxicity should be a diagnosable illness with a diagnosis code. This is incredibly important in getting it acknowledged and quantifying the damage done by quinolones.

Miriam connects the dots between chronic pain, fibromyalgia, ME/CFS and fluoroquinolone toxicity.

*****

There are several dozen other testimonials. In the interest of the attention-spans of those reading this, I am going to split my notes about the hearing into several posts. This is the first of __ (tbd) posts about the hearing.

THANK YOU to all who testified. The testimony provided is wonderful, thoughtful, passionately delivered, and those who provided it represented themselves and the “floxie” community wonderfully!

End note – To those who testified, if I misspelled your name, please let me know. Also, if anyone would like me to publish their testimony directly, please send it over. Thank you!