Fluoroquinolone Antibiotics and Tendonitis

[catbirdseat]

Glad to hear you are recovering. Vancomycin has some serious side-effects too, like potential hearing loss. My wife lost some hearing after taking it. Be sure to get your hearing checked.

 

Last night I watched About Schmidt starring Jack Nicholson. Kathy Bates was in the movie. She showed up in one of my nightmares. Believe me, you DON'T want to have Kathy Bates in your dreams.

[chucK]

Drug companies do carry out large, expensive studies before a medication is approved for use.

 

[...]

 

And while the lawyer web site may not be lying outright, they are definitely giving a slanted view of the data.

 

[...]

 

And while the drug companies comprise the most profitable industry in America, they are heavily regulated by the government.

 

This news story about drug companies hiding results from studies that show their drugs are dangerous, reminded me of this thread.

 

"In a memo from GlaxoSmithKline, leaked last month and published in a Canadian medical journal, the company said negative trial results could not be released because it would damage the profile of the drug."

 

[chucK]

And while the drug companies comprise the most profitable industry in America, they are heavily regulated by the government.

 

Recent dirt on Vioxx and the FDS's lax enforcement of drug companies knowingly selling dangerous drugs.

link1

link2

 

""I would argue that the FDA ... is incapable of protecting America against another Vioxx," he said, because of the FDA's close relationship to the drug companies it regulates."

[catbirdseat]

I wondered when someone would bring this up but I wouldn't have guessed where. What we are seeing right now is a direct effect of the Bush Administration. The Republicans made it known to the FDA that not enough new drugs were being approved and that the FDA was overly concerned with safety.

 

Vioxx was the first of the COX-2 inhibitors to be submitted for approval. The safety problems have been known for a long time. My understanding was that since COX-2 inhibitors have fewer gastric side effects than older NSAIDs, they were considered a step forward in safety. Since sales of the drug have been very good, the company has been against taking it off the market even as the evidence built over time. The company no doubt has other safer molecules in their pipeline to replace it, but didn't want to spend the 100+million dollars to get it on approved.

[chucK]

"The Republicans made it known to the FDA that not enough new drugs were being approved and that the FDA was overly concerned with safety."

 

Do you have any information to support this claim?

[Norman_Clyde]

Hey ChucK, I finally figured out what a tendon is.

[chucK]

Ha ha....errr....yeah (we need an uncomfortably tugging at collar gremlin).

 

You've probably progressed past that treating patients like bugs phase too? You even seem like a doctor that knows what "evidence based" means. We need more doctors like you.

[Norman_Clyde]

I've met doctors such as you describe, so I know what you're talking about and I don't take your observations personally. I'm still embarrassed over my remark to you at a Pub Club once about not being able to "get rid of" patients in a busy ER. I didn't mean it that way, honest!

 

Regarding tendons, these days I even get to see finger tendons right out in the open, and sometimes even stitch them back together. Cool to watch, bad if it's your own hand. But these are usually bagel slicing accidents not involving climbers. I give them plain old Keflex for infection prevention.

[chelle]

 

Interesting thread. Something to note is that a lot of drugs interact with herbal supplements and some foods (and a lot of over the counter stuff). I noticed that several herbs were listed in the interactions lists above. If you take herbal supplements (some common culprits: St. John's Wort, ginko, kava, garlic) or regularly take antacids, make sure your doctor and pharmacist know everything you take.

 

Also, you may want to avoid drinking grapefruit juice if you are taking drugs that have any effect on the liver or are on something that dehyrdates you.

Edited November 24, 2004 by chelle

[catbirdseat]

Also, you may want to avoid drinking grapefruit juice if you are taking drugs that have any effect on the liver or are on something that dehyrdates you.

Grapefruit contains Naringenin which inhibits one of many Cytochrome C isozymes. The result of which is that certain drugs may be metabolized more slowly than normal. This could lead to higher blood concentrations and potential toxicities.

[Thinker]

CBS said: Grapefruit contains Naringenin which inhibits one of many Cytochrome C isozymes. The result of which is that certain drugs may be metabolized more slowly than normal. This could lead to higher blood concentrations and potential toxicities.

 

Is that why they always served citrus drinks at all the Rave parties I went to?

[mneagle]

I came across a recent study that reminded me of this thread. It's a large study that looks at the risk of tendon rupture associated with fluoroquinolones. It's a retrospective analysis of a database but still has some good information. The bottom line is that the overall risk of Achilles tendon rupture looks to be about 3 times higher with a fluoroquinolone but that the overall incidence is still very small. The risk of tendon rupture with a fluoroquinolone was 0.018% (1 / 5,555) and the risk without was 0.006% (1 / 16,666).

 

Although not looked at in this study, other recent research has shown that around 1/3 to 1/2 of the patients with a tendon rupture were also on corticosteroids, like prednisone.

 

Eur J Clin Pharmacol. 2007 May;63(5):499-503. Epub 2007 Mar 3. Links

Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study.Sode J, Obel N, Hallas J, Lassen A.

Department of Infectious Medicine, Odense University Hospital, 5000, Odense C, Denmark, Annmarie.lassen@ouh.fyns-amt.dk.

 

OBJECTIVE: Several case-control studies have reported that the use of fluoroquinolone increases the risk of rupture of the Achilles tendon. Our aim was to estimate this risk by means of a population-based cohort approach. SETTING: Data on Achilles tendon ruptures and fluoroquinolone use were retrieved from three population-based databases that include information on residents of Funen County (population: 470,000) in primary and secondary care during the period 1991-1999. A study cohort of all 28,262 first-time users of fluoroquinolone and all incident cases of Achilles tendon ruptures were identified. MAIN OUTCOME MEASURES: The incidence rate of Achilles tendon ruptures among users and non-users of fluoroquinolones and the standardised incidence rate ratio associating fluoroquinolon use with Achilles tendon rupture were the main outcome measures. RESULTS: Between 1991 and 2002 the incidence of Achilles tendon rupture increased from 22.1 to 32.6/100,000 person-years. Between 1991 and 1999 the incidence of fluoroquinolone users was 722/100,000 person-years, with no apparent trend over time. Within 90 days of their first use of fluoroquinolone, five individuals had a rupture of the Achilles tendon; the expected number was 1.6, yielding an age- and sex-standardised incidence ratio of 3.1 [(95% confidence interval (95%CI): 1.0-7.3). The 90-day cumulative incidence of Achilles tendon ruptures among fluoroquinolone users was 17.7/100,000 (95%CI: 5.7-41.3), which is an increase of 12.0/100,000 (95%CI: 0.0-35.6) compared to the background population. CONCLUSION: Fluoroquinolone use triples the risk of Achilles tendon rupture, but the incidence among users is low.

 

[i_like_sun]

That is nuts. Good research man.

[chucK]

Achilles tendon rupture is being used here because it is a dramatic and disabling injury. It's likely to result in substantial treatment and thus it's pretty sure to be included in someone's medical record. Also if someone's records don't show it, then it's pretty sure that it hasn't happened to that person. This makes it a good outcome for a study.

 

Obviously it depends on the suspected mechanism for the increased risk*, but if it's some sort of systemic change induced in tendon tissue I'd think it would quite likely also increase chances of tendon injuries other than achilles rupture.

 

What do you suppose a climber's risk of tendon injury is? I'd bet it's a thousand of times higher than 1/16,666, probably more like 5% or greater. Triple that and you got a substantial increase in injury risk.

 

* I checked out the article. It states, "The mechanisms behind the fluoroquinolone effect is unknown, but it is probably due to direct toxicity and degenerative changes on collagen fibres [2, 8, 9]. Fluoroquinolones possess chelating properties that are likely involved in tendon toxicity as animals fed a magnesium-deficient diet are at increased risk of fluoroquinolone-induced tendon disorders [13, 14].". Thus if there really is an effect it probably is systemic and acts on all tendons, including the bicep and finger pulley tendons that are most at risk for climbers.

Edited May 25, 2007 by chucK

[JayB]

"The Republicans made it known to the FDA that not enough new drugs were being approved and that the FDA was overly concerned with safety."

 

Do you have any information to support this claim?

 

Seems to me that there were some patient groups lobbying for faster approval as well, but this was restricted - as far as I can remember - to drugs that might be useful against cancer, aids, and other life-threatening diseases.

 

What I've read in the Wall Street Journal, and some of the medical journals that my wife gets is that there's been a fundamental change in the way that drug trials are funded. From what I can remember, it sounded as though drug companies were complaining that the approval process was too slow, and the FDA indicated that funding constraints were making it impossible to move any more quickly, so a compromise emerged in which companies would foot the bill for the costs of the approval process in exchange for faster turn around times.

 

The potential conflict of interest seems fairly obvious here, so one would hope that they implemented some countermeasures to keep the drug company/FDA relationship from devolving into a customer/vendor dynamic, but maybe not...

 

IMO there should be a multiple scales of risk that apply to different classes of drugs and different patient pools. If the drug is for arthritis, for example, and the side effect is an increased risk of cancer after 10-15 years, then it would make sense to allow the drug to enter the market so long as it was restricted to patients over a certain age who understood and accepted the risks associated with taking the drug. Maybe something like this is already in effect...

[catbirdseat]

But Jay that proposal is just too logical.

[JayB]

I seem to remember reading about something like this with Enbrel. From what I can recall they found, after FDA approval, that the drug increased the risk for certain types of cancer after some period of time - but I haven't heard of any mega-lawsuits, implications of corruption, etc arising from this revelation. Maybe the data was too incomplete, but from what I can recall, they basically just added this information to the prescription guidelines and left it up to the doctors and patients to make the choice. Seems like it was a no brainer for old-folks with rheumatoid arthritis figured they'd rather accept the risks than live out the rest of their lives half-crippled with debilitating pain. For the few young folks with the disease, I can see this being more of an issue.

 

Anyway, seems like theres a precedent here even with drugs that are used by younger populations, such as birth control pills. Increases the risks of some cancers, decreases others, and the choice is left up to the patient.

 

Of course, this all presupposes that the risks, when identified, are disclosed promptly.

[i_like_sun]

Does anybody know what kind of biochemistry is involved with the mechanism of action? I'm trying to figure it out....

 

Obviously the connective tissue is altered, so I'm guessing that there could be interference with respiration somehow. Perhaps calcium binding...........???????? Or maybe even interference with Ascorbic Acid - thus jacking up enzyme action and collagen maintenance.

 

Layton????

[iluka]

One issue to be aware of when using the fluoroquinolones on a trip to altitude... According to the drug information for Ciprofloxacin and other members of this class of medicines, dexamethasone may increase the risk of tendon injury. You cannot find any case reports of this happening in the medical literature but it is listed as a potential interaction in the product information for the medicine. Unclear exactly what the risk is but if one were using dexamethasone for altitude illness prevention, it might be wise to avoid Cipro if one developed traveler's diarrhea and use another antibiotic.

[catbirdseat]

Does anybody know what kind of biochemistry is involved with the mechanism of action? I'm trying to figure it out....

 

Obviously the connective tissue is altered, so I'm guessing that there could be interference with respiration somehow. Perhaps calcium binding...........???????? Or maybe even interference with Ascorbic Acid - thus jacking up enzyme action and collagen maintenance.

 

Layton????

It is thought to involve induction of metalloproteinases. Basically, the structural proteins in the tendons are broken down chemically, thus weakening them.

[layton]

Whew! What a thread. Yeah, what he said. I assume folks know about corticosteriods and tissue weakening too. Hard call sometimes.

[i_like_sun]

OK, that makes a lot of sense now. So it somehow stimulates enzymes into catabolism. Thats a major bummer.......

 

 

 

Its great to have chemists around when your NUURD nerve gets squished!