The True Story of Cipro
Recently, the pharmaceutical company Bayer was forced to recall its fluorinated cholesterol-lowering drug Baycol (Cerivastatin) as it had caused deaths and serious adverse health effects worldwide.1, 2, 3 Baycol had been found to cause muscle destruction and wasting–a condition known as rhabdomyolysis–and displayed compounded toxicity when used with other drugs. It had been linked to at least 31 deaths.
The adverse reactions documented with Baycol were largely identical to those of numerous other fluorinated drugs–all of which had been withdrawn from the market in recent years. 3
As a result of the current anthrax scare, another fluorinated drug called Cipro has received extensive media coverage and the name has become familiar to millions almost overnight. As soon as the first cases of anthrax resulting from suspicious mail became known, there were wide reports of a hectic run on this drug.
Mass hysteria seems present as governments, pharmacies and individuals everywhere are stockpiling Cipro. Pharmacies are reporting record sales, and on-line prescription services and Internet sites are selling the drug at more than $7.00 per pill.
People everywhere–hyped into believing their flu-like symptoms are caused by anthrax exposure and misinformed by irresponsible media reports–are taking Cipro. Worse yet, they are giving it to their children.
What is Cipro?
Cipro is ciprofloxacin, a fluorinated quinolone, belonging to a class of fluorinated antibiotics which also include enoxacin, fleroxacin, temafloxacin, grepafloxacin, norfloxacin, sparfloxacin, tosufloxacin, lomefloxacin and ofloxacin.
Ciprofloxacin has been in use since 1987 for a variety of other indications and is the most widely used fluoroquinolone in humans and animals worldwide.4
In 2000, the FDA approved its use as a treatment for inhalational anthrax under its "accelerated approval" regulations.5 The FDA had actually taken the unusual step of urging Bayer– the sole manufacturer for all countries except India–to file for such approval, supposedly in order to protect the public from future terrorist attacks. The US Department of Defense had already ordered reserves of Cipro during the 1991 Gulf War.6
Temafloxacin and grepafloxacin are two other fluoroquinolones now withdrawn from the market because they had caused severe liver and renal damage–and deaths, just like fluorinated drugs from other, different classifications, such as Baycol.3 The same information also exists for Cipro.
Fatal liver failure associated with ciprofloxacin was reported in the Lancet in 1994.7,8
Ciprofloxacin has been implicated in several cases of acute renal failure and is the fluoroquinolone most established to cause such renal dysfunction.4,9,10,11
The most common side-effects due to Cipro, reported in 2-16 percent of cases, are gastrointestinal in nature and equal those reported when children accidentally ingest "too much" fluoride from their toothpaste. These symptoms include nausea, diarrhea, vomiting and abdominal pain. Why?
Ciprofloxacin administration always results in elevated serum fluoride levels.12 In a series of tests evaluating the safety of ciprofloxacin in children, serum fluoride levels increased after 12 hours in 79 percent of the children; on day 7 the 24-hour urinary fluoride excretion was higher in 88.9 percent of children observed.12
Just as in the case of Baycol and other fluorinated drugs, Cipro can cause musculo-skeletal disorders such as rhabdomyolysis. Since the introduction of fluoroquinolones on the market in 1987, more than 200 cases of rhabdomyolysis, tendinitis, tendon rupture, etc. have been reported in the literature.4,13,14,15
In October 1994 the Japan Pharmaceutical Affairs Bureau was first to amend the product information for fluoroquinolones to state that rhabdomyolysis may occur.16
In 1996, the FDA also issued directives to manufacturers to include warning statements on all fluoroquinoline product inserts to alert patients and caregivers to the potential for tendinitis and tendon rupture.17 In the same year, the Sri Lanka Drug Evaluation Sub-Committee decided that the product information sheet on fluoroquinolone antibiotics should include the following warning: "The onset of tendon pain calls for immediate withdrawal of fluoroquinolone antibiotics."18
Achilles tendon rupture was shown to occur even after withdrawal of the drug with examination showing pathological ultrastructure alteration in tendinocytes. Just as in other cases of fluoride poisoning, studies in animals show that magnesium deficiency aggravates the induced tendinopathy.14,19
Fatal Drug Interactions
Just as with Baycol, drug interactions with ciprofloxacin have resulted in fatal outcomes due to potentiation of another drug’s effects including theophylline,4,20 methadone21 and warfarin.22
Just like Baycol and other fluorinated drugs, ciprofloxacin is a potent inhibitor of the thyroid hormone-regulated P 450 enzyme system in the liver. Of all fluoroquinolones, ciprofloxacin and enoxacin have shown the greatest inhibitory capacity.4
P450 IA2 prevents the metabolism and inactivation of methylxanthines, thereby causing increased serum concentrations of drugs like theophylline (found in tea) and caffeine (found in coffee and soft drinks), which in turn causes excess central nervous system and cardiac stimulation. As mentioned above, Cipro also elevates serum fluoride levels.
The liver has been identified as a target organ of fluoroquinolone toxicity in animal studies.23 As early as the 1930s, scientists at Bayer and Knoll had discovered that all organic fluoride compounds tested (including those used for fluoroquinolone production) interfered with thyroid hormone activity in liver and muscle tissue. Meanwhile, they also showed "anti-bacterial" activity. This led to the development of many fluorinated medications, including the numerous compounds then used very successfully in the treatment of hyperthyroidism.24,25 A Dr. Kraft of the Knoll corporation invented many fluorinated "medications." When it was discovered that some of these organic compounds had the same detrimental effects on teeth and bone as inorganic fluoride (although much less actual F ion was involved) he even filed patents on behalf of Knoll for use of these compounds in dental preparations.26,27
Pregnant women should never take ciprofloxacin. Cipro transfers through the placenta. It inhibits P450 1A2 which has been shown to be critical for neonatal survival as it influences the physiology of respiration in neonates. Mice lacking this cytochrome died shortly after birth and showed symptoms of severe respiratory distress.28 Respiratory distress is also a side-effect of ciprofloxacin in adults.9 Cipro also transfers through breastmilk.
Resistance to Bacteria
Taking Ciprofloxacin can spur germs to mutate so that future bacterial infections become untreatable. During the last decades a dramatic increase in bacterial strains multiresistant to antibiotics, particularly Cipro, has been reported.30,31,32 This increase has led to the occurrence of incurable bacterial infections with a fatal outcome, and a particularly serious problem in connection with hospital-acquired infections.
For example, Clostridium difficile has become one of the most common acquired organisms in hospitals and longterm care institutions. The organism typically infects patients whose normal intestinal flora has been disturbed by the administration of a broad-spectrum antibiotic such as Cipro. The diarrhea and inflammatory colitis associated with infection represent a serious medical and surgical complication leading to increased morbidity and mortality, and prolonging hospital stays by an average of nearly three weeks. This is especially true for the elderly and for patients with serious underlying diseases who are the most likely to develop the infection. Diarrhea associated with C. difficile represents a major economic burden to the healthcare system, conservatively estimated at $3-6 billion per year in excess hospital costs in the US alone.33
The emergence of "antibiotic resistance" is a result of the overwhelming use of antibiotics in human and veterinary medicine. High rates of fluoroquinolone resistance have been reported in many countries.30 For example, in Asia Cipro can no longer be used to treat gonorrhea, because the disease has become resistant to the drug.34
While the FDA approved Cipro as the first-line treatment against anthrax in August, 2000, a few months later, in October, 2000, it asked Bayer to remove Baytril–its equivalent for animals.
The FDA has also proposed banning the fluoroquinolones, which chicken and turkey farmers have given to birds in their water since 1995 to help shield the animals from infection. The agency acted after linking the drugs to a large increase in Campylobacter bacteria immune to the medications. Nearly 18 percent of one common strain that infects humans is now immune to the very same drugs which were considered the last line of defense against the infection.
Campylobacter is the leading bacterial cause of food poisoning in the United States. Typically contracted through raw or undercooked meat, the germs afflict more than 2 million people and kill some 500 each year in the US, according to the CDC.
While Abbot voluntarily withdrew its version of the antibiotic (SaraFlox), Bayer decided to challenge the FDA. The company had the option to comply with the proposed ban or seek a hearing to determine whether such a move was justified. Bayer refused to comply with the ban, a move that kicked off a lengthy process that could take years.35 Meanwhile Bayer gets to poison the world, and make huge profits from it.
According to one report, the American Medical Association has advised its members to prescribe Cipro very cautiously, citing the fact that the worldwide problem of antibiotic resistance poses future dangers worse than the anthrax attacks of today.34
Photosensitization can result when light interacts with chemical agents in the skin and eyes. This process can produce undesirable clinical consequences, such as phototoxicity(exaggerated sunburn), photoallergy, or photo-carcinogenicity. People receiving Cipro or any other fluoroquinolone are warned on the product inserts not to expose themselves to direct sunlight. Rashes develop on the areas exposed.
Upon UVA-irradiation, the "fluorine" of numerous fluoroquinolones such as lomefloxacin and fleroxacin, are "lost" as fluoride.36
According to a US government report, "We have discovered that anions can activate visual photoreceptors in the dark. One anionic activator is the commonly used dental agent fluoride. The data on in vitro preparations indicate that these anions modulate photoreceptor bio-chemistry and may affect photoreceptor sen-sitivity. . . "38
Medline has many articles on fluoride and G-protein-coupled photoreceptor activation.35
In summary, Cipro causes fluoride poisoning. But will any practitioner know how to deal with this, considering that the American Dental Association has shielded all practitioners from proper knowledge of fluoride toxicity?
Other Cipro Side Effects29
|Abnormal dread or fear||Joint or back pain|
|Bleeding in the stomach||Kidney failure|
|Bleeding in the intestines||Labored breathing|
|Blood clots in the lungs||Lack of muscle coordination|
|Blurred vision||Lack or loss of appetite|
|Change in color perception||Large volumes of urine|
|Confusion||Loss of sense of identity|
|Constipation||Loss of sense of smell|
|Coughing up blood||Neck pain|
|Difficulty in swallowing||Pounding heartbeat|
|Dizziness||Ringing in the ears|
|Drowsiness||Sensitivity to light|
|Eye pain||Severe allergic reaction|
|Gout flare up||Swelling of the face, neck, lips, eyes, or hands|
|Hallucinations||Swelling of the throat|
|Hearing loss||Tender, red bumps on skin|
|Heart attack||Tingling sensation|
|High blood pressure||Unpleasant taste|
|Hives||Unusual darkening of the skin|
|Inability to fall or stay asleep||Vaginal inflammation|
|Inability to urinate||Vague feeling of illness|
|Intestinal inflammation||Yellowed eyes and skin|
|Involuntary eye movement|
About the Author
Andreas Schuld, Wendy Small and Trent Harris are founding members of Parents of Fluoride Poisoned Children (PFPC), located in Vancouver, BC, Canada. Visit their website at bruha.com/fluoride.
1. "Poison Control: Fluorides, the deadly toxin within" http://www.prn.usm.my/bulletin/nst/2001/nst34.html
2. 7AM – News: "Cures That Kill?" http://www.7amnews.com/2001/features/081801.shtml
3. Dr. Mercola – "Baycol – Another Fluoride Drug Bites the Dust" (PFPC News, August 18, 2001) http://www.mercola.com/2001/aug/18/fluoride_drugs.htm
4. Clinical Toxicology Review – "What Are Fluoroquinolones?" CTR, Massachusetts Poison Control System, Vol. 20, No. 3 (1997)
5. FDA Talk Paper "Approval of Cipro® for Use AFter Exposure to Inhalation Anthrax," Food and Drug Administration, U.S. Department of Health and Human Services, Public Health Service, 5600 Fishers Lane, Rockville, MD 20857 (2000)
6. CNN – Reuter’s, July 27, 2000
7. Fuchs S, Simon Z, Brezis M – "Fatal hepatic failure associated with ciprofloxacin" Lancet 242:738-739 (1994)
8. 150+ Related References : CIPRO – Liver http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=4&db=m&term=cipro&liver
9. Hootkins R, Fenves AZ, Stephens MK – "Acute renal failure secondary to oral ciprofloxacin therapy: a presentation of three cases and a review of the literature" Clin Nephrol 32(2):75-8 (1989)
10. Reece RJ, Nicholls AJ – "Ciprofloxacin-induced acute interstitial nephritis" Nephrol Dial Transplant 11(2):393 (1996)
11. 90+ Related References : CIPRO – Renal failure http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=4&db=m&term=cipro&renal&failure
12. Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK – "Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth" Acta Paediatr 84(5):555-60 (1995)
13. Australian Adverse Drug Reactions Bulletin – Vol. 16, No. 2 (May 1997)
14. Ramanujam TR – "Fluoroquinolones – A Review" (2001) http://www.mcsindia.org/doctors/Epharma/january.asp
15. Petition to Require a Warning on All Fluoroquinolone Antibiotics (HRG Publication #1399) http://www.citizen.org/publications/release.cfm?ID=6595
16. Information on Adverse Reactions to Drugs No.128, October 1994
17. FDA Medical Bulletin – Vol. 26, No.3 (October 1996)
18. 27th Meeting of the Drug Evaluation Sub-Committee, Ministry of Health, Colombo (November 1996)
19. Shakibaei M, de Souza P, van Sickle D, Stahlmann R – "Biochemical changes in Achilles tendon from juvenile dogs after treatment with ciprofloxacin or feeding a magnesium-deficient diet" Arch Toxicol 75(6):369-74 (2001)
20. Clinical Toxicology Review, Vol. 20, No. 3 (1997)
21. Herrlin K, Segerdahl M, Gustafsson LL, Kalso E – "Methadone, ciprofloxacin, and adverse drug reactions" Lancet 356(9247):2069-70 (2000)
22. Ellis RJ, Mayo MS, Bodensteiner DM – "Ciprofloxacin-warfarin coagulopathy: a case series" Am J Hematol 63(1):28-31 (2000)
23. Guzman A, Garcia C, Demestre I – "Subchronic toxicity of the new quinolone antibacterial agent irloxacin in beagle dogs" Arzneimittelforschung 50(5):485-94 (2000)
24. Kraft K – "Über die Synthese einiger aromatischer Fluorverbindungen" Knoll Research, Chem Ber. 84(2):150-156 (1951) (describes manufacturing processes of numerous organic fluorides, after it was shown that all organic fluoride compounds displayed stronger anti-thyroid activity than the mere "fluoride ion.")
25. Kraft K, Dengel F – "Über die Synthese einiger aromatischer Fluorverbindungen, II. Mitteilung" Chem Ber 85(6):577-582 (1952) (more reports on organic fluoride investigations. . . "in regards to their characteristics in lowering BMR as well as anti-bacterial activity")
26. Zutavern EP, Kraft K – "Verfahren zur Herstellung von organischen Salzen der Fluorwasserstoffsäure" German Patent No. 855118, granted Dec. 5, 1950 (Knoll AG) (Kraft patent on the same organic fluoride compounds used previously in the treatment of hyperthyroidism, now patented as anti-caries agents!)
27. Eichler O, Kraft K – "Verfahren zur Herstellung einer alkalischen, seifenfreien, reagibles Fluor neben Calciumcarbonat enthaltenden Zahnpasta" German Patent No. 971375, granted Aug. 28, 1951 (Knoll AG) (patent describing the use of ethanol-amino-hydrofluorides in toothpaste…)
28. Pineau T, Fernandez-Salguero P, Lee SS, McPhail T, Ward JM, Gonzalez FJ – "Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2" Proc Natl Acad Sci U S A 92(11):5134-8 (1995)
29. Cipro Monograph http://www.healthsquare.com/pdrfg/pd/monos/cipro.htm
30. Coronado VG, Edwards JR, Culver DH, Gaynes RP – "Ciprofloxacin resistance among nosocomial Pseudomonas aeruginosa and Staphylococcus aureus in the United States. National NosocomialInfections Surveillance (NNIS) System" Infect Control Hosp Epidemiol 16(2):71-5 (1995)
31. Smith KE, Besser JM, Hedberg CW, Leano FT, Bender JB, Wicklund JH, Johnson BP, Moore KA, Osterholm MT – "Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998" N Engl J Med 340(20):1525-32(1999)
32. CDC Special Report: "Emerging Mechanisms of Fluoroquinolone Resistance" David C. Hooper Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
33. Kurtz CI, Fitzpatrick R – "Anionic polymers as toxin binders and antibacterial agents" US Patent 6,290,946, GelTex Pharmaceuticals, Inc. (2000)
34. Orlando Sentinel, October 20, 2001
35. Bayer Balks at Banning Poultry Antibiotic – FDA, citing resistance, seeks removal" By Adam Marcus, Health Scout Reporter, Dec. 1, 2000
36. Chignell CF – "Mechanisms of chemically induced photosensitivity" CRISP Data Base, National Institutes Of Health, CRISP/99/ES50046-20 (1998).
37. Photoreceptor/fluoride – 50+ References http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=4&db=m&term=photoreceptor&fluoride
38. Lewis A – "Fundamental studies in the molecular basis of laser induced retinal damage" Annual Report (Final) March 1 1979 – March 15, 1985 US DTIC records (unclassified) AD#177817 (1985).