Don't Take That Pill! The Ignored Risks of Fluoroquinolones

[Guest guest]

Thought this one was interesting and updated...

 

http://www.counterpunch.org/cox01122008.html

 

January 12 / 13, 2008

 

By Stan Cox

 

The case studies are scattered around in the medical journals: a

62-year-old woman with acute psychosis; a 73-year-old man with " severe

delirious psychotic features " ; a woman of 47 suffering from insomnia

and barely able to stand or walk; a 62-year-old woman who ruptures her

Achilles tendon; a man, 75, struck with repeated seizures; a

64-year-old diabetic woman with life-threatening hypoglycemia.

 

All of those people had suffered the side effects of a specific class

of antibiotics known as fluoroquinolones. Because they target bacteria

and not our own tissues, antibiotics are often not scrutinized for

side effects by the Federal Drug Administration (FDA) or manufacturers

as carefully as are, say, psychiatric drugs. But in the bodies of

people, cats, rats, and mice, fluoroquinolones not only kill bacteria

but also appear to attach to certain brain and nerve receptors, kill

tendon cells, and cause other kinds of havoc.

 

Clinical trials conducted over three decades in the process of gaining

FDA approval for fluoroquinolones -- which encompass many drugs, among

the most familiar of which are ciprofloxacin (Cipro) and levofloxacin

(Levaquin) [1] -- showed that psychiatric and central-nervous-system

problems occurred in more than 10 percent of patients.[2] Such trials,

as well as " adverse drug reaction " (ADR) reports that began to be

filed by US doctors and patients once the drugs were being marketed,

indicated serious reactions in about 1 to 2 percent of cases in which

the drugs are administered.

 

A study of ADRs in Italy, published in 2005, found that among more

than 50 types of drugs, fluoroquinolones accounted for 11 percent of

all adverse events and were involved in the largest number of serious

problems, edging out antidepressants.[3]

 

When, near the end of one of those ask-your-doctor commercials, a

fast-talking disembodied voice reads off a drug's side effects,

usually over a scene involving fields of waving grass and a puppy dog,

it tends to sound like a lot of nasty stuff that's going to happen to

someone else. But in reading and writing about the pharmaceutical

industry for the past couple of years, I started wondering about what

life is like for the real people who do experience those side effects.

Then last fall, when my own father was assaulted with terrible

symptoms apparently caused by a widely prescribed fluoroquinolone, I

didn't have to wonder any longer.

 

 

" A remarkable safety record "

 

If even only one person in 100 suffers a grave side effect of such a

popular class of drug, that can mean millions of people affected. At

their worst, fluoroquinolones can ruin or, potentially, end lives. On

the Internet, people who have been " floxed " as they call it (because

the generic names of many such drugs contain the letters " flox " ) come

together in forums and discussion groups to swap graphic accounts of

searing pain, psychosis, blistering skin, kidney and liver damage,

muscle-wasting, tendon rupture, hallucinations, insomnia, suicidal

thoughts, and panic attacks. Award-winning journalist Stephen Fried

was moved to write a book, Bitter Pills: Inside the Hazardous World of

Legal Drugs (1999) after his wife Diane suffered long-term damage

after taking a single pill of a fluoroquinolone called Floxin.

 

Dr. Jay Cohen, a medical researcher and associate professor at the

University of California, San Diego, published a paper on peripheral

neuropathy caused by fluoroquinolones on 2001. Since then, he says, " I

have received several hundred emails, most of which relate terrible,

often catastrophic reactions to Levaquin, and some to Cipro. These

reactions are slow to pass, leaving some people disabled for months or

years. It is an awful problem. "

 

Clinical trials and case studies published by doctors in leading

medical journals also make it clear that such problems exist, but in

the journals, it's common to see conclusions like this, from a 2002

paper: " Levofloxacin [Levaquin] has been used in more than 200 million

prescriptions, with a remarkable safety record. " [4]

 

In their practices, doctors often appear to be attributing

fluoroquinolone damage to other causes. Says Cohen, " Unfortunately,

many doctors do not know that fluoroquinolones can cause such severe,

long-lasting reactions. When a reaction occurs, some doctors deny that

it could have been caused by the drug. Doctors order a battery of

tests to seek other causes, but the tests usually show nothing. "

 

 

The spoils of war

 

People who find themselves under assault by bacteria (including the 2

million who get infected each year in hospitals) desperately need

antibiotics. And, better late than never, there is a growing awareness

that the use of antibiotics must be planned much more rigorously, to

curtail the development of resistant bacteria. But the popularity of

some of the drugs has as much to do with historical accident as with

safety and efficacy.

 

The huge commercial success of the fluoroquinolones can be traced to

1990 and Operation Desert Shield, when the US military was concerned

that Iraqi forces with whom they were soon to do battle were planning

to use anthrax as a bacterial weapon. The armed forces ordered 30

million doses of the fluoroquinolone ciprofloxacin -- Cipro -- to be

administered to troops as a preventative measure. That drug was chosen

mainly because it was new, and the Iraqis would not have been expected

to have selected an anthrax strain resistant to it.[5]

 

Although no anthrax attack is known to have been launched in Kuwait or

Iraq (and Desert Storm veterans have blamed the side effects of the

antibiotic for some of the symptoms of Gulf War Syndrome), Cipro got

the reputation as a kind of superdrug, and sales rose through the 90s.

The actual anthrax attacks of October 2001 triggered a wave of

panic-buying and pill-swallowing, and Cipro's manufacturer Bayer

responded by producing 200 million additional doses within two months.

 

A shocked David Flockhart, chief of clinical pharmacology at the

Indiana University School of Medicine, told the Los Angeles Times,

" Cipro is basically a big gun whose benefits outweigh its risks in

certain circumstances, but the bigger gun you use, the more damage you

can expect as collateral. " [6] Of more than 3000 postal employees who

took Cipro following the anthrax attacks, 26 percent had problems with

their digestive system, and 14 percent reported neurological problems.[7]

 

Cipro and its newer fluoroquinolone cousins have since become the most

frequently prescribed class of antibiotics in the US, accounting for

one prescriptions out of four. By 2003, more than a half-billion

prescriptions had been written for Cipro and Levaquin alone.[8] Under

contracts then in effect, the Defense Department and Veterans

Administration together were dispensing about 9 million doses of

fluoroquinolones per year.[9]

 

The quinolone family of antibiotics grew out of research on

anti-malarial drugs, which also carry a heavy load of side effects.

One member of that family, a malaria medication called mefloquine

(Larium), has become notorious for causing problems that include,

according to FDA, " psychiatric symptoms ranging from anxiety,

paranoia, and depression to hallucinations and psychotic behavior. On

occasions, these symptoms have been reported to continue long after

mefloquine has been stopped. "

 

In what passes for innovation in the pharmaceutical industry,

companies continue to modify the chemical structure of

fluoroquinolones in search of similar, effective antibiotics that be

patented. One recent study warned that members of the newest

generation of such drugs, judging from their chemical structures, are

even more likely to cause adverse side-effects than are now-popular

ones like Cipro and Levaquin.[10] Because the truly informative

testing of drugs occurs not during the FDA approval process but

through their use by millions of patients, a lot of people are certain

to experience damage from these drugs first-hand.

 

 

One victim's story

 

At 77, my father was a specimen of good health who ate a solid

vegetarian diet and would regularly bike 20 or more miles in a day. So

it came as a terrible blow when, in October, he had to go in for

emergency cardiac artery bypass and valve-replacement surgery.

Complications of the surgery kept him hospitalized longer than

expected -- with two more trips to the operating room -- weak,

exhausted, and down to only 125 pounds from his former 155.

 

A full month after being admitted, he finally seemed to begin

recovering. But at that point, he plunged once again into a terribly

weakened state, sleeping little or not at all, his arms and legs

almost constantly in motion, unable to walk without falling backward.

That went on for almost two weeks, until he made a quick turnaround,

regained his ability to walk, and was discharged.

 

When he had been out of the hospital for five days, feeling wiped out

but not ill in any way, a physician's assistant decided that he needed

an antibiotic prescription in case he might have pneumonia. The drug

was Levaquin. He took the first dose that night, and by the following

evening, he was going downhill fast. He spent almost all of the next

day in bed, too weak to walk or even sit up, spending most of the time

with his eyes closed or in a blank stare, making bizarre sounds and

gestures.

 

Unable to get any answers from his doctors, my mother and I, in

desperation, stopped giving him the Levaquin. (As a geneticist, I was

as aware as anyone of the rule that says never to stop an antibiotic

in mid-course, but we were indeed desperate.) Within 36 hours, he had

begun improving remarkably but remains very weak six weeks later. His

doctor has since concluded that he never had pneumonia.

 

When I went back and looked at my father's 33-page hospital file of

doctors' notes, along with the 146-page (!) daily file of medications

he'd been given, I saw that his earlier abrupt deterioration, a month

into the hospital stay, had coincided with the start of a course of a

fluoroquinolone called moxifloxacin (Avelox), also given for suspected

(but nonexistent) pneumonia. The just-as-abrupt improvement that led

to his discharge occurred a day and a half after his last dose of

moxifloxacin.

 

 

Who's minding the (drug)store?

 

The label for Levaquin includes information that is typical for

fluoroquinolones: " Convulsions and toxic psychoses have been reported

in patients receiving quinolones, including levofloxacin. Quinolones

may also cause ... tremors, restlessness, anxiety, lightheadedness,

dizziness, confusion and hallucinations, paranoia, depression,

nightmares, insomnia and, rarely, suicidal thoughts or acts. These

reactions may occur following the first dose. "

 

In, 2004 the FDA issued a new warning on fluoroquinolones, stating

that treatment should be stopped if patients felt strange neurological

symptoms like " pain, burning, tingling, numbness, and/or weakness ...

in order to prevent the development of an irreversible condition. " In

2005-06, the Illinois Attorney general and the group Public Citizen

petitioned the FDA to add a so-called " black box " warning to packages,

this one regarding the danger of tendon rupture, a well-documented

effect of the drugs. So far, no action has been taken.

 

Jay Cohen responded to FDA's addition of the 2004 statement by asking,

" The question is, will doctors notice these warnings? Doctors do not

reread package inserts or the PDR every time they prescribe the same

drug. Moreover, the package inserts of quinolones are very long, and

the information can easily be overlooked. Perhaps the greatest

usefulness of the new warnings may be for patients who develop side

effects with quinolones and who consult the Physician's Desk Reference

[PDR], or for doctors who consult the PDR after patients complain

about side effects. " [11]

 

In that sense, the warning does its job, but too late for the patient:

Once my father was in big trouble, I indeed looked up the fine-print

warnings. Among several of his doctors with whom I discussed his

experience with fluoroquinolones afterward, none had known that the

drugs can have serious effects on the central nervous system -- yet

none was surprised that they do.

 

One of the nurses told us that the cardiac-surgery patients she sees

are " generally sent home with about 20 prescriptions. " Without some of

the drugs he received during surgery and his six-week hospital stay,

my father would not have survived. But as he struggled to regain his

health, he twice had his recovery reversed (and, it seems, nearly

ended altogether) by the side effects of drugs prescribed for an

illness that he never actually had.

 

Tragically, his overmedication is not unusual. Studies of outpatients

have consistently shown that more than half the drugs they were taking

were unnecessary. By one estimate, 20 million unnecessary antibiotic

prescriptions are written in the US every year and as many as 100,000

Americans die annually from reactions to prescription drugs of all

kinds.[12] With a toll like that, the costs of overmedication can't

fully be measured in dollars. (And one study found that only 6 percent

of adverse reactions are accurately reported.)

 

A survey of patients admitted to two hospitals' emergency departments

found that for half of those patients who were taking multiple drugs

at the time, it was the pharmaceuticals themselves that had landed

them in the emergency room. Another survey of patient charts found

that three-fourths of the time, the documents did not accurately list

all the drugs being taken.[13]

 

The risks of drugs in general are known to be much higher in elderly

patients. As what one letter to the Journal of Clinical Oncology

called " the leading drug consumers " , our older friends and relatives

have far too many opportunities for drugs to interact with an existing

medical condition or another drug. At any given time, says one study,

78 percent of people over 65 years of age are on medications -- and

half of that group are regularly taking five or more drugs.[14]

 

Elderly patients not only take more drugs; they also have more health

problems that can magnify the side effects and often mislead patients

and doctors about what ails them. In the words of one researcher, " It

is easy to ascribe decline in functional status to worsening disease

or old age and not thoroughly investigate the contribution of

inappropriate drug therapy. " [15] That's what happened to my father;

until the drug effects became too obvious to ignore, we all assumed he

was still suffering aftershocks of surgery.

 

Another study put its finger on the bigger problem, noting that

despite having learned in medical school about systematic approaches

to prescribing, " physicians learn how to prescribe in 'real-world'

settings ... and they are influenced by their peers, pharmaceutical

company marketing, healthcare systems, and patient demands and

expectations. " [16]

 

Hazardous interactions among medications continue to be a big issue in

medicine. Through hard experience, medical administrators have come up

with a list of the ten most dangerous drug interactions, and two of

those involve fluoroquinolones. But as for actually preventing such

problems, there is always more talk than action. Were a proposed drug

to be safety-tested not only on its own, but in combinations with

other drugs, its sponsoring company would have to shell out many times

as much money and spend a lot more development time.

 

That won't happen. Drug executives are already threatening to stop

developing antibiotics altogether, because in the companies' eyes,

they don't justify the cost of research and testing. That's because

they are usually prescribed only for a matter of days at a time, not

for many years like the more profitable lifestyle drugs and treatments

for chronic diseases.[17]

 

Having in their inventories a class of antibiotics that's so popular

among physicians and on which so many chemical variations-on-a-theme

are possible, companies are not acknowledging the toll being taken by

fluoroquinolones on vulnerable patients. Jay Cohen says, " As far as I

can tell, the manufacturers have not lifted a finger to try to help

these people, nor have they undertaken research to try to explain

these reactions and to develop measures to help patients avoid them. "

 

He adds that drugs like Levaquin, Cipro, or Avelox " should not be used

as first line antibiotics. Other, safer drugs should be tried first.

The need for antibiotic therapy with fluoroquinolones should be gauged

carefully, and unnecessary use should be avoided. "

 

Unfortunately, most people don't learn about the risks of

fluoroquinolones or other drugs until, like me, they encounter them

first hand and look around for information. Then they find sites like

Cohen's www.medicationsense.com or the most comprehensive

fluoroquinolones victims' site, www.fqresearch.org. That site is

urging that the drugs never be used " unless there is a direct threat

to the patient's life or limb. "

 

Stan Cox is a plant breeder and writer in Salina, Kansas. His book

Sick Planet: Corporate Food and Medicine will be published by Pluto

Press in April. They can be reached at: t.stan.

 

NOTES

 

1. See the long list of fluoroquinolones at

http://www.fqresearch.org/alphabetical_listings.htm

 

2. For example, see www.fda.gov/cder/foi/nda/96/020634-1.pdf

 

3. Galatti et al., Neuropsychiatric reactions to drugs: an analysis of

spontaneous reports from general practitioners in Italy.

Pharmacological Research 3: 211 (2005)

 

4. Rubinstein and Camm, Carditoxicity of fluroquinolones. Journal of

Antimicrobial Chemotherapy 49: 593 (2002)

 

5. Enserink, Researchers question obsession with Cipro. Science 294:

759 (2001)

 

6. Krucoff, Drug of choice has a downside. Los Angeles Times, 29 Oct. 2001

 

7. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5047a2.htm

 

8. Rubinstein and Camm (2002) and Houston Chronicle, 1 Nov. 2001

 

9. http://www.fbodaily.com/

 

10. Mandell and Tillotson, Safety of fluoroquinolones: An update.

Canadian Journal of Infectious Diseases 13: 54 (2002)

 

11. http://www.medicationsense.com/

 

12. See references in http://www.lef.org/magazine/

 

13. Both studies referenced by Delafuente, Understanding and

preventing drug interactions in elderly patients. Clinical Reviews in

Oncology/Hematology 48: 133 (2003)

 

14. Jörgensen et al, Prescription drug use, diagnoses, and healthcare

utilization among the elderly. Annals of Pharmacotherapy 35: 1004 (2001)

 

15. Deafuente (2003)

 

16. Hanlon et al., Suboptimal prescribing in older inpatients and

outpatients. Journal of the American Geriatrics Society 49: 200­209 (2001)

 

17. Projan, Why is big Pharma getting out of antibacterial drug

discovery? Current Opinion in Microbiology 6: 427 (2003)

 

*****

Best,

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