Health Alert - CIPRO
TIMELY INFORMATION FROM Ellie Rudolph
PFPC: Health Alert - CIPRO This also appears in the Fluoride section
the webpage http://www.penweb.org/fluoride/index.html
October 21, 2001
Two months ago we reported on the withdrawal of Bayer's BAYCOL
(Cerivastatin), a fluorinated drug (statin class) which had caused deaths
and serious adverse health effects worldwide (1,2,3).
BAYCOL had been found to cause muscle destruction/wasting - a condition
known as rhabdomyolysis - and displayed compounded toxicity when used
other drugs. It had been linked to at least 31 deaths.
We also showed how the adverse reactions documented with BAYCOL were
largely identical to those of numerous other fluorinated drugs - all
which had been withdrawn from the market in recent years (3).
ANTHRAX AND CIPRO
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 this drug. Pharmacies are reporting record
sales, and on-line prescription services and Internet sites are found
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 mis-informed by irresponsible media
reports, are taking CIPRO, and worse yet - are giving it to their
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, ofloxacin, etc..
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 in treatment for inhalational anthrax
under its "accelerated approval" regulations (5). It had
the unusual step of urging Bayer - the sole manufacturer for all
except India - to file for such approval, supposedly in order to protect
the public from future terrorist attacks. The US Department of Defense
already ordered reserves of CIPRO during the 1991 Gulf War (6).
As mentioned in the info on BAYCOL, temafloxacin and grepafloxacin are
two other fluoroquinolones now withdrawn from the market because they
caused severe liver and renal damage - and deaths, just like fluorinated
drugs from other, different classifications (3).
The same information also exists for CIPRO.
Fatal liver failure associated with ciprofloxacin was reported in the
Lancet in 1994 (7, 8 - 150 more related refs).
Ciprofloxacin has been implicated in several cases of acute renal
failure and is the most established fluoroquinolone to cause such renal
dysfunction (4, 9, 10, 11 - 96 related refs).
The most common side-effects reported due to CIPRO (2-16%) are
gastrointestinal in nature and equal those reported when children
accidentally ingest "too much" fluoride from their toothpaste
- such as
nausea, diarrhea, vomiting, and abdominal pain. Why?
Ciprofloxacin administration 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% of the
children; on day 7 the 24-hour urinary fluoride excretion was higher
88.9% 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
Also in 1996 the Sri Lanka Drug Evaluation Sub-Committee decided that
product information of fluoroquinolone antibiotics should include a
warning stating: "The onset of tendon pain calls for immediate
fluoroquinolone antibiotics." (18)
Achilles tendon rupture was shown to occur even after withdrawal of the
drug. Pathologically there was ultrastructure alteration in tendinocytes.
Just as in other cases of fluoride poisoning, studies in animals show
magnesium deficiency aggravate the induced tendinopathy (14,19).
Just as with BAYCOL, drug interactions with ciprofloxacin have resulted
in fatal outcomes due to potentiation of another drug's effects such
theophylline (4,20), methadone (21), or 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
greatest inhibitory capacity (4).
P450 IA2 prevents the metabolism/inactivation of methylxanthines,
thereby causing increased serum concentrations of drugs like theophylline
and caffeine, which in turn causes excess CNS and cardiac stimulation.
mentioned above, CIPRO also elevates serum fluoride levels.
The liver has been identified as a target organ of fluoroquinolone
toxicity in animal studies (23). Already in the 1930s the same was shown
by Bayer's scientists such as Litzka or Knoll's Kraft who found that
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). Kraft 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- was involved - he even filed patents on behalf of Knoll's using
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 by influencing the physiology of respiration in
neonates. Mice lacking this cytochrome died shortly after birth and
of severe respiratory distress (28). Respiratory distress is a
side-effect of ciprofloxacin also in adults (9). CIPRO also transfers
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, particlularly CIPRO
has been reported (30, 31, 32). This increase has led to the occurrence
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 long term care institutions. The
organism typically infects patients whose normal intestinal flora has
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
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. C. difficile associated diarrhea represents a
economic burden to the healthcare system, conservatively estimated at
billion per year in excess hospital costs in the U.S. alone (33).
The emergence of this "antibiotic resistance" is a result
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 no longer can be used to treat gonorrhea,
because the disease has become resistant to the drug (34).
While the FDA in August 2000 approved CIPRO as the first-line
treatment against anthrax, a few months later (October 2000) it asked
remove BAYTRIL - its equivalent for animals.
The FDA proposed banning the fluoroquinolones, which chicken and turkey
farmers have given to birds in their water since 1995 to help shield
animals from infection. The agency acted after linking the drugs to a
in Campylobacter bacteria immune to the medications. Nearly 18 percent
one common strain that infects humans are now immune to the very same
drugs which were considered the last line of defense against the
Campylobacter is the leading bacterial cause of food poisoning in the
United States. Typically contracted through raw or undercooked meat,
germs afflict more than 2 million people and kill some 500 each year
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
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...
The AMA has advised its members to prescribe CIPRO very cautiously,
saying the worldwide problem of antibiotic resistance poses future dangers
worse than the anthrax attacks of today (Orlando Sentinel, October 20,
Photosensitization can result when light interacts with chemical
agents in the skin and eyes. This process can produce undesirable
consequences, such as phototoxicity (i.e. exaggerated
sunburn), photoallergy, or photocarcinogenicity. People receiving CIPRO
any other fluoroquinolone are warned on the product inserts not to expose
themselves to direct sunlight. Rashs develop on the areas exposed.
Upon UVA-irradiation the "fluorine" of numerous fluoroquinolones
as lomefloxacin and fleroxacin, are "lost" as fluoride
"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 biochemistry and may effect photoreceptors
[Lewis A - "Fundamental studies in the molecular basis of laser
retinal damage" Annual report (Final) March 1 1979 - March 15,
DTIC records (unclassified) AD#177817 (1985)]
MEDLINE has many articles on fluoride and photoreceptor activation (G
OTHER CIPRO SIDE EFFECTS (29):
Abnormal dread or fear, achiness, bleeding in the stomach and/or
intestines, blood clots in the lungs, blurred vision, change in color
perception, chills, confusion, constipation, convulsions, coughing up
blood, decreased vision, depression, difficulty in swallowing, dizziness,
double vision, drowsiness, eye pain, fainting, fever, flushing, gas,
flare up, hallucinations, hearing loss, heart attack, hiccups, high blood
pressure, hives, inability to fall or stay asleep, inability to urinate,
indigestion, intestinal inflammation, involuntary eye movement, irregular
heartbeat, irritability, itching, joint or back pain, joint stiffness,
kidney failure, labored breathing, lack of muscle coordination, lack
loss of appetite, large volumes of urine, light-headedness, loss of sense
of identity, loss of sense of smell, mouth sores, neck pain, nightmares,
nosebleed, pounding heartbeat, ringing in the ears, seizures, sensitivity
to light, severe allergic reaction, skin peeling, redness, sluggishness,
speech difficulties, swelling of the face, neck, lips, eyes, or hands,
swelling of the throat, tender, red bumps on skin, tingling sensation,
tremors, unpleasant taste, unusual darkening of the skin, vaginal
inflammation, vague feeling of
illness, weakness, yellowed eyes and skin.
CIPRO causes fluoride poisoning. Will any practioner know how to deal
this, considering that the ADA has shielded all from proper knowledge
Andreas Schuld, Wendy Small, Trent Harris
Parents of Fluoride Poisoned Children (PFPC)
Vancouver, BC, Canada
1) "Poison Control: Fluorides, the deadly toxin within"
2) 7AM - News: "Cures That Kill?"
3) Dr. Mercola - "Baycol - Another Fluoride Drug Bites the Dust"
News, August 18, 2001)
4) Clinical Toxicology Review - "What Are Fluoroquinolones?"
Massachusetts Poison Control System, Vol. 20, No. 3 (1997)
5) FDA TALK PAPER " APPROVAL OF CIPRO® FOR USE AFTER EXPOSURE
INHALATIONAL ANTHRAX" Food and Drug Administration, U.S. Department
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
ciprofloxacin" Lancet 242:738-739 (1994)
8) 150+ Related References : CIPRO - Liver
9) Hootkins R, Fenves AZ, Stephens MK - "Acute renal failure
oral ciprofloxacin therapy: a presentation of three cases and a review
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
12) Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK - "Safety
ciprofloxacin therapy in children: magnetic resonance images, body fluid
levels of fluoride and linear growth" Acta Paediatr 84(5):555-60
13) Australian Adverse Drug Reactions Bulletin - Vol. 16, No. 2 (May
14) Ramanujam TR - "Fluoroquinolones - A Review" (2001)
15) Petition to Require a Warning on All Fluoroquinolone Antibiotics
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
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
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
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
quinolone antibacterial agent
irloxacin in beagle dogs" Arzneimittelforschung 50(5):485-94
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
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
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,
5, 1950 (Knoll AG)
(Kraft patent on the same organic fluoride compounds used previously
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
German Patent No. 971375, granted Aug. 28, 1951 (Knoll AG)
(patent describing the use of ethanol-amino-hydrofluorides in
28) Pineau T, Fernandez-Salguero P, Lee SS, McPhail T, Ward JM, Gonzalez
- "Neonatal lethality associated with respiratory distress in
cytochrome P450 1A2" Proc Natl Acad Sci U S A 92(11):5134-8
29) Cipro Monograph
30) Coronado VG, Edwards JR, Culver DH, Gaynes RP - "Ciprofloxacin
resistance among nosocomial Pseudomonas aeruginosa and Staphylococcus
aureus in the United States. National Nosocomial
Infections Surveillance (NNIS) System" Infect Control Hosp Epidemiol
31) Smith KE, Besser JM, Hedberg CW, Leano FT, Bender JB, Wicklund JH,
Moore KA, Osterholm MT - "Quinolone-resistant Campylobacter
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,
33) Kurtz CI, Fitzpatrick R - "Anionic polymers as toxin binders
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 HealthScout Reporter, Dec. 1,
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
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