Levaquin, Cipro, Avelox Risks Pose A Concern In Face of Modest Benefits: FDA Reviewers

Federal drug regulatory officials indicate that the potential side effects of Levaquin, Cipro, Avelox and other fluoroquinolone antibiotics may outweigh the benefits provided by the medications in many cases, as patients often receive the drugs for infections that would typically resolve themselves. 

In advance of a joint meeting of the agency’s Antimicrobial Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on Thursday, FDA reviewers released briefing documents that suggest many users may be unnecessarily exposed to a risk of long-term peripheral neuropathy, tendon damage and other problems linked to use of the antibiotics.

The two FDA advisory committees are set to discuss the potential fluoroquinolones risks, and make recommendations to the agency about what regulator actions may be necessary to protect consumers.

The review and the hearing come amid growing concerns over the peripheral neuropathy risks with Levaquin, Avelox and Cipro, potentially leaving users with long-term, debilitating nerve damage

While the advisory committees’ recommendations are not binding on the FDA, the agency often factors those recommendations heavily in any regulatory decisions about whether to strengthen label warnings, remove medications from the market or limit use of the drugs.

One of the briefing documents provided to the committee members is a review by FDA staffers (PDF) that looked at the benefits and risks of Levaquin and similar fluoroquinolones drugs when used to treat acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis in patients with Chronic Obstructive Pulmonary Disease (ABECB-COPD), and uncomplicated urinary tract infections (UTIs). All of these are common reasons the popular antibiotics are prescribed.

Reviewers found that in many cases, the drugs appear to have few benefits, if any.

“An evaluation of placebo-controlled trials in ABS or mild ABECB-COPD show that a large proportion of patients randomized to receive placebo recovered and thus these illnesses appear to be self-limited for many patients,” the reviewers noted. “Indeed some of these trials showed no differences in outcome measures when comparing the antibacterial drug to placebo.”

The briefing documents do note that there appears to be benefits for patients hospitalized for moderate or severe ABECB-COPD and in the treatment of uncomplicated UTIs. However, they also cautioned doctors to consider the drugs’ risks as well.

“When considering the potentially modest treatment benefits of antibacterial drugs for these three indications, the risks of the fluoroquinolone antibacterial drugs should be taken into consideration,” the reviewers warned. “Over the life-cycle of these drugs, several adverse reactions have been reported, and most of them were not evident in the -re-approval safety databases.”

The reviewers warned doctors to be concerned about the risks of permanent peripheral neuropathy, tendon ruptures and cardiac arrhythmias, saying that those that resulted in long-term injuries or permanent disability are of “a particular concern.”

In its own briefing materials (PDF) provided to the committees, Bayer, the manufacturer of Avelox and Cipro, warned that the infections its drugs were used to treat were not “trivial” and, if left untreated by antibiotics, could result in meningitis, brain abscess and other serious complications. The company noted that the rate of serious side effects raised by reviewers were either rare or very rare.

Antibiotic Nerve Damage Risks

Levaquin, Avelox and Cipro are among the most widely prescribed antibiotics in the United States, generating billions in annual sales.

In 2013, the FDA issued a drug safety communication to announce that it was requiring the manufacturers of Levaquin and other fluoroquinolones to change their warning labels about the risk of peripheral neuropathy problems, providing warnings for the first time that symptoms of nerve damage may continue for months or even years after an individual stops taking the drug.

Prior warnings suggested that peripheral neuropathy was a rare risk for users of Levaquin, Avelox and Cipro, and indicated that the problems often resolve once the medications are no longer used. However, many users have been left with a long term and permanent Levaquin neuropathy injury, leading the FDA to require warnings about the permanent nature of the nerve damage in many cases.

In 2014, a study published in the medical journal Neurology added further support for these warnings, indicating that side effects of Levaquin and other fluoroquinolones may double the risk of peripheral neuropathy.

A growing number of Levaquin lawsuits, Avelox lawsuits and Cipro lawsuits are now being pursued on behalf of users diagnosed with permanent nerve damage, alleging that the antibiotic manufacturers failed to adequately warn consumers and the medical community about the potential long-term risks of peripheral neuropathy.

In August, the U.S. Judicial Panel on Multidistrict Litigation (JPML) centralized all of the fluoroquinolone litigation pending throughout the federal court system before U.S. District Judge John R. Tunheim in the U.S. District Court for the District of Minnesota. Given the similar questions of fact and law, the cases have been consolidated for pretrial proceedings to reduce the risk of duplicative discovery into common issues, avoid conflicting pretrial orders from different courts and to serve the convenience of the parties, witnesses and the courts.