PFPC: Health Alert - CIPRO
October 21, 2001
Dear All,
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 with
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 of
which had been withdrawn from the market in recent years (3).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 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, 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 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).
ADVERSE EFFECTS:
As mentioned in the info on BAYCOL, 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two other fluoroquinolones now withdrawn from the market because they had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 (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).
FLUORIDE
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 in
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.
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).
Also in 1996 the Sri Lanka Drug Evaluation Sub-Committee decided that the
product information of fluoroquinolone antibiotics should include a warning
stating: "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. Pathologically there was ultrastructure alteration in tendinocytes.
Just as in other cases of fluoride poisoning, studies in animals show that
magnesium deficiency aggravate the induced tendinopathy (14,19).
DRUG INTERACTIONS/DEATH:
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 the
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. 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). Already in the 1930s the same was shown by
Bayer's scientists such as Litzka or Knoll's Kraft who found 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). 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 showed symptoms
of severe respiratory distress (28). Respiratory distress is a side-effect
of ciprofloxacin also 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, particlularly 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 long term 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. C. difficile associated diarrhea represents a major
economic burden to the healthcare system, conservatively estimated at $3-6
billion per year in excess hospital costs in the U.S. alone (33).
The emergence of this "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 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 Bayer to 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 the
animals from infection. The agency acted after linking the drugs to a jump
in Campylobacter bacteria immune to the medications. Nearly 18 percent of
one common strain that infects humans are 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...
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,
2001).
PHOTOSENSITIVITY
Photosensitization can result when light interacts with chemical agents
in the skin and eyes. This process can produce undesirable clinical
consequences, such as phototoxicity (i.e. exaggerated
sunburn), photoallergy, or photocarcinogenicity. People receiving CIPRO or
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 such
as lomefloxacin and fleroxacin, are "lost" as fluoride (36).
"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 sensitivity..."
[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)]
MEDLINE has many articles on fluoride and photoreceptor activation (G
protein-coupled) (35).
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, gout
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 or
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 with
this, considering that the ADA has shielded all from proper knowledge of
fluoride toxicity?
Andreas Schuld, Wendy Small, Trent Harris
Parents of Fluoride Poisoned Children (PFPC)
Vancouver, BC, Canada
pfpc@istar.ca
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
INHALATIONAL 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 Nosocomial
Infections 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 HealthScout 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