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Fluoroquinolones and tendon ruptures / reported last week at the 41st annual meeting of the Infectious Diseases Society of America.

Study Confirms Increased Risk of Achilles Tendon Rupture With Fluoroquinolone Use

By Peggy Peck

Oct. 15, 2003 (San Diego) — Fluoroquinolone use is associated with increased risk of Achilles tendon rupture, and that increase is "true across the board for exposure to any fluoroquinolone," according to results of nested case-control study reported last week at the 41st annual meeting of the Infectious Diseases Society of America.

Lead author John Seeger, PharmD, PhD, from Ingenix Epidemiology, a pharmaceutical research company in Auburndale, Massachusetts, said the study "puts a quantitative estimate on the elevation in risk of Achilles tendon rupture after exposure to fluoroquinolone antibiotics.... We were able to quantify the association and found that the elevation in risk was on the order of 20% to 30%. This was true across the board for exposure to any fluoroquinolone."

This increased risk is somewhat greater than that reported in other studies. For example, a report by van der Linden and colleagues in the June 1, 2002, issue of the BMJ indicated that fluoroquinolone use was associated with an overall excise risk of 3.2 cases per 1,000 patient-years. Moreover, other studies suggest the risk increases with age, while Dr. Seeger reported that his data suggest the opposite: the relative risk for fluoroquinolone exposure was 1.05 in those older than 60 years (95% confidence interval [CI], 0.47 - 2.33) and was 1.26 in patients younger than 60 years (95% CI, 0.89 - 1.77).

Animal studies demonstrated that "the fluoroquinolone antibiotics weaken tendons," Dr. Seeger said. Case reports show that this increased risk also occurs in humans and that the increased risk was greatest among the elderly.

Dr. Seeger and colleagues used the Ingenix Research Database — a health insurance claims database — to identify 947 cases of Achilles tendon rupture. A random sample of controls matched for time at risk were also selected from the database. Fluoroquinolone exposure specific incidence rates (IR) and rate ratios (RR) were estimated using logistic regression with covariates for age, sex, obesity, fluoroquinolone use, other antibiotic use, corticosteroid use, infection, arthritis, diabetes, and trauma.

Exposure to a fluoroquinolone was associated with an apparent increased risk (RR = 1.27; 95% CI, 0.94 - 1.73) of Achilles tendon rupture. Moreover, the increase was observed in each fluoroquinolone used. A case-control study published in the Aug. 11, 2003, issue of the Archives of Internal Medicine suggested that the increased risk of Achilles tendon rupture associated with fluoroquinolones was greatest during the first month of treatment, but Dr. Seeger said his study suggests the risk is constant over the entire course of treatment.

Moreover, the risk associated with fluoroquinolones was about the same as the increased risk associated with azithromycin and combined nonfluoroquinolone antibiotics.

"Just looking at this study, fluoroquinolones alone don't appear to be an independent risk factor for Achilles tendon rupture," Kelly Randell, DPharm, a research fellow at the University of Illinois, Chicago, College of Pharmacy, told Medscape. Dr. Randell was not involved in the study.

"However, they do seem to increase the risk," she said. "Most patients who develop Achilles tendon rupture on a fluoroquinolone appear to have other risk factors that probably contribute to the [rupture]."

IDSA 41st Annual Meeting: Poster 195. Presented Oct. 10, 2003.

Reviewed by Gary D. Vogin, MD

Comment 1: Failing to get access to the article which reported this study, I am at a loss to find out what the mechanism might be for this class of antibiotics to predispose to Achilles tendon rupture. I have used these antibiotics quite extensively while in practice and cannot recall having seen any complications like this. Not having read the original studies, I feel puzzled (as must a lot of your readers) on this unusual side-effect. I contacted a number of my friends, including one ID specialist, on this and none of them cannot recall either coming across this rare problem.

Comment by R.G. Lacsamana — 10/16/2003 @ 8:46 am

Comment 2: Cipro, at least, also has another disturbing (and more common) side-effect, mental status changes, including, rarely, full-blown delirium. Most common in the elderly, but can happen in young people too. Even mild cases can be quite disturbing to the patient, and frustrating for the doc, leading to admission and work-up for primary neuologic disease. P.O. Cipro is frequently given for UTI, but in my neck of the woods, coverage of the usual UTI bugs is no better than TMP/SMZ’s, and Cipro’s hella expensive as well. I only use it when other antibiotics are contraindicated.

Comment by Slithy Tove — 10/17/2003 @ 12:54 am

Comment 3; For anecdotal reports, one can browse or search the Yahoo quinolone group. I’m impressed by the sheer size of the group: > 600 members, > 16000 messages, as well as by the number and variety of problems people blame on their antibiotics.

Comment by Douglas Ridgway — 10/17/2003 @ 3:14 pm

Comment 4: Obviously I’m the only person on this list who’s read Stephen Fried’s book Bitter Pills. His wife suffered permanent disability as a result of one dose of Floxin, a quinalone antibiotic. Since he is an investigative reporter, he spent many years looking into the issue of drug safety. I guarantee you’ll never think of quinalones as innocuous drugs after reading this book. As Douglas mentioned, there is a whole community of people damaged by this class of drug sharing information with each other.

Comment by Bernie Simon — 10/17/2003 @ 8:30 pm