Dr. Jay Cohen on quinolone risks/CNS damage

[Guest guest]

Cohen is an MD. I found it interesting that the Lyme experts at the

last Virginia Lyme conf. “Hope to Heal Lyme” did not mention

quinolones for Lyme. This used to be their big gun antibiotic. – a Carnes

http://www.medicationsense.com/articles/may_aug_05/warning_antibiotics_05220

5.html

In autumn 2004, the FDA mandated new warnings in the labeling of quinolones

about nerve injuries associated with quinolones. The new warning reads:

" Peripheral Neuropathy: Rare cases of sensory or

sensorimotor axonal

polyneuropathy affecting small and/or large axons resulting in paresthesias,

hypoesthesias, dysesthesias and weakness have been reported in patients

receiving quinolones, including [name of specific quinolone]. [The drug]

should be discontinued if the patient experiences symptoms of neuropathy

including pain, burning, tingling, numbness, and/or weakness or other

alterations of sensation including light touch, pain, temperature, position

sense, and vibratory sensation in order to prevent the development of an

irreversible condition. "

This is an important, overdue warning. Moreover, it

specifically tells

doctors to discontinue treatment if any of these symptoms occur. You can

find this warning regarding Cipro on page 823 of the 2005 Physicians' Desk

Reference (PDR). However, you will not find this warning in the write-ups

of Levaquin, Floxin, or Tequin in the 2005 PDR (I did not check the other

quinolones). You can find the warnings elsewhere. For example, some

are

listed at the FDA website:

www.fda.gov/medwatch/SAFETY/2004/sep04_quickview.htm. You can also find

this warning in the package inserts for each of these drugs.

In addition, quinolone write-ups in the 2005 PDR contain

" Warnings "

sections that list " Central Nervous System Disorders. " The

Cipro write-up

lists dizziness, confusion, tremors, hallucinations, depression, and an

increased risk for people predisposed to seizures. The Levaquin write-up

(page 2503) lists tremors, restlessness, anxiety, lightheadedness,

confusion, hallucinations, paranoia, depression, nightmares, insomnia, may

increase risk for people predisposed to seizures, and rarely, suicidal

thoughts or acts. Tequin (page 1079) and Floxin write-ups (page 2497)

contain similar lists. All quinolone write-ups also contain lists of

symptoms involving the central and peripheral nervous system under the

section for " Adverse Reactions. " Lists of reactions involving

other systems

such as cardiovascular or musculoskeletal can also be found in this section.

Quinolone write-ups also contain specific warnings about

tendon

ruptures, stating that some have required surgical repair or resulted in

prolonged disability. Tendon ruptures can occur during or after quinolone

therapy. Treatment with steroids may increase the risk of tendon rupture

with quinolones.

Also worth noting, the write-ups for some quinolones state

that these

drugs have been associated with changes in people's electrocardiograms.

Called " prolongation of the QT interval, " this adverse effect may be

associated with abnormal cardiac rhythms. Some of these arrhythmias can

be

serious, such as the " torsade de pointes " listed with Levaquin.

This

reaction alone should make doctors pause before prescribing Levaquin or

quinolones that cause QT interval prolongation. Other drugs (e.g.,

Seldane,

Hismanal, Propulsid) were withdrawn because they cause QT interval

prolongation.

The Potential Impact of the New Warnings

Overall, it should be helpful that quinolone package inserts

now include

warnings about peripheral neuropathies (injuries to the nerves outside the

brain or spinal cord). 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 PDR, or for

doctors who consult the PDR after patients complain about side effects.

Either way, the hope is that these warnings will lead to quicker recognition

of these side effects and prompt discontinuation of the quinolone. The

quicker the drugs are stopped, the better. My belief is that once you

develop a problem, even if it is minor, with a quinolone, you should not

take any quinolone again. It is believed that toxicities with quinolones

are cumulative, so reexposure is risky.

Hopefully, the new warnings will also make doctors pause

before

prescribing quinolones for common infections of the bladder, prostate, or

sinuses. The seriousness of potential reactions -- tendon ruptures,

nerves

injuries, joint pains, cardiac effects -- warrant a very cautious attitude

about prescribing quinolones. There is some evidence that by their

chemical

major, quinolones may be toxic to human tissue. At the same time,

quinolones can be very important antibiotics when used properly, and most

people given quinolones do not develop serious side effects.

Nevertheless,

quinolones are overused for minor conditions when other, safer antibiotics

would suffice. My stance is that quinolones should be reserved for

serious

infections for which other antibiotics have been ineffective or for

organisms that are only sensitive to quinolones. Even then, quinolones

should be used carefully with close monitoring for side effects.

At the very least, people being placed on quinolones should

be warned

about possible side effects: joint, muscle, or tendon pain or rupture, nerve

pain (burning, electrical sensations, tingling), muscle weakness, thinking

or memory problems, heart palpitations, rapid heart rate, gastric problems,

skin rash, or psychological symptoms. People have a right to informed

consent, which means that they should be advised of the possible benefits

and risks of any treatment. Because quinolone reactions sometimes occur

quickly, patients need to be informed so that they can alert their doctors.

Unless there is a medically urgent reason to the contrary, quinolone

treatment should be stopped immediately.

Treatment Possibilities

This is the information I have posted previously with some

new wrinkles.

However, please realize that these are simply suggestions. There are no

known specific antidotes to quickly reverse a quinolone reaction. By

necessity, people have tried many different treatment methods, and results

are spotty. I do not know if any of the suggestions below are highly

effective, but having experienced a severe, years-long disability myself in

the mid-1990s (not a quinolone reaction) and now having improved

considerably, I encourage people to keep asking questions and trying things.

Many people sustaining quinolone reactions turn to their

regular doctors

and specialists. Some doctors try to be helpful, but many are uninformed

about quinolone reactions or uninterested. Some doctors just cannot

conceive that quinolones could cause such serious, long-term reactions.

Doctors are taught that drug companies and the FDA conduct intensive

research to ensure the safety of new drugs. This is untrue.

According to

an article in JAMA: " Discovery of new dangers of drugs after marketing is

common. Overall, 51% of approved drugs have serious adverse effects not

detected prior to approval2. " Many doctors are not aware of this.

In any event, doctors may suggest a variety of

medications. For nerve

or neuropathic pain (tingling, burning or electrical sensations), drugs such

as Neurontin (gabapentin) or anti-seizure drugs may be recommended.

Tricyclic antidepressants are known to help some neuropathies. The

best-known tricyclic is amitriptyline (Elavil), which is sedating, so it

might also be helpful for people also experiencing insomnia. For others,

it

will be too sedating. Nortriptyline is as effective as amitriptyline for

neuropathies, and nortriptyline generally causes less sedation or other side

effects. Desipramine is similar to nortriptyline and may actually

increase

energy in people who are fatigued. In others, desipramine can cause

anxiety. Avoid tricyclics in people with cardiac conditions or symptoms.

Muscle spasms, twitching, tremors, and seizures may be

helped with

long-acting anti-anxiety benzodiazepines such as clonazepam (Klonopin) or

diazepam (Valium). Some doctors may recommend Xanax, which is a poor

muscle

relaxant but effective for reducing anxiety. Xanax is fine for PRN

(intermittent) use. Xanax works fast and is not usually sedating, but

when

taken three or four times every day, it can quickly cause dependency with

severe withdrawal reactions. The long-acting benzodiazepines can also

cause

dependency, but in my experience, less frequently than Xanax does. With

any

of these drugs, the lowest dosage that works should be used.

SSRI antidepressants (Zoloft, Paxil, Prozac, Effexor, etc.)

may be

helpful for depression. Because some people's nervous systems are very

sensitive to these drugs, they should be started at very low doses and

increased very gradually, if necessary. By " lower doses, " I

mean doses that

are lower than the lowest doses recommended by manufacturers. For

example,

although the usual starting dosage of Prozac is 20 mg/day, 5 mg/day has been

effective in clinical studies and works for many people.

Anti-inflammatory drugs are controversial: some people have

written to

me that they have been helped with anti-inflammatory drugs, especially for

muscle/joint/tendon pain, but others have written that these drugs have

worsened their conditions. Corticosteroids (cortisone, etc.) are very

controversial. Doctors sometimes prescribe steroids in the hope of

reducing

the reactions, but many people have written that steroids actually made

their reactions worse. Steroids can increase the risk of tendon ruptures

with quinolones.

There may be other medications used for quinolone reactions

that I have

not listed here. This list is not intended to be comprehensive. It

merely

reflects my knowledge, which is limited. For more complete, updated

information, please ask your doctor or pharmacist. Also, check the

websites

listed at the bottom of this article.

Alternative Possibilities

Magnesium in doses of 400-1000 mg/day may be useful for

reducing

neuropathic pain or muscle spasms in some people. Feedback from quinolone

sufferers about magnesium has been mixed. The U.S. recommended daily amount

of magnesium is 320 mg for women and 400 mg for men. Use of higher

dosages

should always be done with the supervision of a healthcare practitioner.

Seniors, people with kidney disorders, and those taking medications for

cardiovascular or neurological disorders should have medical supervision

even for RDA doses of magnesium. Interestingly, Dr. Flockhart also

recommends magnesium for quinolone reactions. Dr. Flockhart recommends

low

doses of milk of magnesia (1 or 2 teaspoons twice-daily), to be taken for

several months. His theory is that because of the affinity of minerals for

quinolone antibiotics, magnesium might help leech some remaining

fluoroquinolone molecules from the tissues.

I am not a fan of milk of magnesia, which is a

laxative. If the goal is

to absorb magnesium in order to get it into the tissues, chelated magnesium

(e.g., magnesium aspartate, magnesium glycinate) or a magnesium solution

(e.g., magnesium chloride) are absorbed better than milk of magnesium or

cheap magnesium supplements. It has also been suggested that magnesium

could be used with calcium and other minerals. The fact is, no one knows.

There's little solid science, so it is trial and error. (For more

information on magnesium, please go to the other magnesium sections of this

website.)

B-vitamins have been reported to reduce tingling.

Pyrodoxine (vitamin

B6) and pantethine (a derivative of pantothenic acid) have been reported to

improve some types of nerve pain. One person wrote to me that high doses

of

lecithin had helped with memory problems. This is not farfetched.

Lecithin

contains several substances essential for normal nerve functioning. One

of

these is phosphatidylcholine.

For anxiety or agitation, or to increase GABA in the nervous

system,

many alternative doctors recommend taking GABA, which is an amino acid.

GABA has some similar qualities to Valium and Xanax, and it may be helpful

for anxiety, nervousness, or insomnia. Too much GABA can cause sedation.

Inositol is also used for treating anxiety.

There are several alternative methods for reducing

inflammation.

Omega-3 fatty acids (fish or flax oils) increase the anti-inflammatory

prostaglandins (PGE3) in cell membranes. GLA, found in primrose or borage

seed oil, increases PGE1, which is also anti-inflammatory. Studies have

shown that high doses of omega-3 fatty acids and of GLA reduce the pain of

arthritis. This method takes time, several months, because it requires a

rebalancing of the prostaglandins in the membranes of trillions of cells,

but the ultimate reduction in inflammation is better, in my experience, than

with prescription anti-inflammatory drugs. Omega-3 fatty acids and GLA

are

just two of many alternative methods for reducing inflammation.

If you are interested in alternative supplement and diet

possibilities,

I would suggest consulting with a knowledgeable alternative practitioner.

Many doctors have adopted alternative methods because they became

dissatisfied with the drug-oriented mindset of mainstream medicine. In my

experience, alternative doctors are much more receptive to patients'

concerns about medication side effects. Good alternative practitioners

are

also far more knowledgeable about the biochemical systems of the body.

They

have tests to measure people's levels of fatty acids, amino acid,

antioxidants, minerals (including toxic minerals), and many other factors

that may explain why some people are more vulnerable to certain diseases or

reactions. Good alternative doctors are knowledgeable about magnesium and

other minerals, GABA, omega-3 fatty acids, and many other human-compatible

therapies. For example, alternative practitioners use alpha lipoic acid

for

treating neuropathies. Alpha lipoic acid has long been used in Europe, and

there is a considerable medical literature on this substance. Few

mainstream doctors are aware of alpha lipoic acid, magnesium, or the other

natural remedies I have discussed above. I cannot say that alternative

doctors have the answer to quinolone reactions. I can only say that it is

another option worth considering.

If you run out of options with your mainstream doctors and

would like to

consult with an alternative practitioner, ask your friends whom they have

seen and recommend. Half of the population has consulted with an

alternative practitioner at one time or another. You can also find

practitioners via the websites of the American College

for the Advancement

of Medicine (www.ACAM.org) or the American Holistic Medical Association

(www.AHMA.org). One caveat: many alternative practitioners do not accept

insurance and many of their tests are not covered by health insurance plans.

Another caveat: different alternative practitioners use different methods;

ask questions, ask for written information; many offices will send brochures

or other information about practitioners' methods.

In Summary

Fluoroquinolone-linked reactions are nasty. These

reactions vary from

minor to extremely serious. Some are disabling. Recovery varies

from

individual to individual, with some reactions resolving quickly and others

lasting years. As far as I know, none of the companies that manufacture

quinolones has attempted to study how to help people sustaining severe

quinolone reactions. The manufacturers seem content to list tendon

ruptures

or neuropathies when the FDA finally demands it, while ignoring the

thousands of people who are suffering. To me, this is

unconscionable. Then

again, if you have looked at my website, you know that for many years I have

been concerned about the failure of the drug industry to adequately ensure

drug safety.

If you have not already done so, please submit a Medwatch

report to the

FDA about your quinolone reactions. The FDA moves slowly, but with enough

reports and pressure from patients (and some doctors, hopefully), the FDA

will examine a problem. Filing a Medwatch report is easy to do at:

www.fda.gov/medwatch/report/consumer/consumer.htm

<http://www.fda.gov/medwatch/report/consumer/consumer.h>

.. Or call

800-FDA-1088).

I regret that I cannot provide you with more specific,

proven treatment

options for these terrible reactions. I hope that some of the suggestions

above are helpful or at least provide ideas that stimulate other

possibilities. Whether you have a mild, moderate, or severe reaction to a

quinolone, I hope that your condition resolves soon.

Sincerely,

Jay S. Cohen, M.D.