FDA: Antibiotics raise tendon rupture risk

WEDNESDAY July 9, 2008 (foodconsumer.org) -- The U.S. Food and Drug Administration (FDA) issued a letter to the manufacturers of certain antibiotics to request that a Boxed Warning in the product labeling be printed to highlight the increased risk of tendinitis and tendon rupture among patients taking these medications.

The affected antibiotics include Bayer AG's Cipro and Avelox, Oscient Pharmaceuticals Corp's Factive, Depomed Inc's Proquin XR, Johnson & Johnson's Levaquin and Floxin and Merck & Co Inc.'s Noroxin. The generic form of Cipro, ciprofloxacin and the generic form of Floxin, ofloxaci are also affected. These drugs belong to a class known as fluoroquinolones.

The request was based on the agency’s new authority under the Food and Drug Administration Amendments Act of 2007 and the FDA action was triggered by its findings that these drugs have some serious safety issues that patients and doctors need to know.

The FDA conducted a new analysis of the literature and postmarketing data on adverse reports and confirmed that use of fluoroquinolones is associated with an increased risk of tendon rupture. Additionally, despite the current warning of tendon rupture in the product labeling, large numbers of tendon related adverse events continue to be reported to the agency.

The risk of developing fluoroquinolone-linked tendinitis and tendon rupture is particularly high in people older than 60 and in those who are taking corticosteroid drugs and in kidney, heart, and lung transplant patients, the FDA says in its public statement.

According to Reuters, Dr. Renata Albrecht, a top health official at the FDA, said that the estimated risk of tendon rupture is about three times higher among patients who used the concerned antibiotics. The general population has a rate of tendon rupture of 1 in 100,000.

Most cases of tendon rupture occurred in the Archilles tendon, with some to shoulders, biceps, hands, and elsewhere. Rupture may be avoided if patients act early enough. But some patients can’t recover.

The FDA also sent a notice to health care professionals today to alert them to the increased risk of tendinitis and tendon rupture in patients who are taking these antibiotics and to highlight new concerns about the risk.

"Patients experiencing pain, swelling, inflammation of a tendon or tendon rupture should be advised to stop taking their fluoroquinolone medication and to contact their health care professional promptly about changing their antimicrobial therapy," the FDA advised in its statement.

"Patients should also avoid exercise and using the affected area at the first sign of tendon pain, swelling, or inflammation."

These drugs are approved for treatment or prevention of certain bacterial infections. They can't be used to treat or prevent viral infections such as colds or flu.

"Fluoroquinolones are effective in treating certain bacterial infections, but health care professionals and patients need to be aware of the increased risk associated with the use of these drugs of developing tendinitis and tendon rupture, particularly for certain patient populations," said Edward Cox, M.D., director, Office of Antimicrobial Products, Center for Drug Evaluation and Research. 

"The FDA believes it is important to highlight and strengthen information regarding possible side effects of fluoroquinolones because it may affect decisions about the relative risks and benefits associated with these products."

The FDA requires a systemic or uniform updated warning language to be used in the product labeling. However, the warning is valid only for systemic use of fluoroquinolones, pills, tablets, capsules, and injectable formulations, but not for topical applications.

The manufacturers have 30 days to respond or submit the safety labeling changes including the Boxed Warning and the Medication Guide.

Because of the magnitude of the side effects of these medications, the FDA also requests that the patient medication guide be updated to reflect the increased risk of tendinitis and tendon rupture.

Most patients can tolerate the antibiotics of concern, but some will develop other serious adverse reactions including convulsions, hallucinations, depression, abnormalities in heart rhythm, or severe diarrhea, the FDA says.

The severe adverse effects of these antibiotics have been known for quite a long time. In 2006, Public Citizen sued the FDA to have the boxed warnings carried on the product labeling because of the reporting of 262 cases of tendon ruptures, 258 cases of tendinitis and 274 cases of other tendon problems through the end of 2005.

Sidney Wolfe, health head of Public Citizen's Health Research Group, told Reuters that roughly 100 more cases were reported after that time.

The consumer group actually was calling for tendon warnings early in 1996 and sued the FDA to force companies to notify physicians about the risk.

By Sue Mueller, and edited by Heather Kelley.
Jul 9, 2008 - 1:34:59 PM