In May, the FDA warned that fluoroquinolone antibiotics, because of common and sometimes permanent side effects, should only be used as a last resort. The agency followed up in July with language for new label warnings and a Medication Guide to be given to every patient.
Fluoroquinolones have been widely used until recently for urinary tract infections, bronchitis, sinusitis and other infections and include Levaquin (levofloxacin), Avelox (moxifloxacin), Cipro (ciprofloxacin), Floxin (ofloxacin), Factive (gemifloxacin mesylate) and Noroxin (norfloxacin). But for years, public health experts and patients have highlighted orthopedic, gastrointestinal, neurological, visual and renal injuries from taking the drug for only five days.
Fluoroquinolone antibiotics have been among the biggest-selling drug classes. Demand for Bayer's Cipro was so strong after the 9/11 attacks when anthrax-containing letters were sent to media outlets and lawmakers, killing five and infecting 17, daily prescriptions soared to 14,000 a day. Bayer planned to open another plant.
But by 2008, Cipro was under the same cloud as other drugs in its class thanks to an FDA announcement that cautioned fluoroquinolones posed an increased risk of tendinitis and tendon rupture. The FDA warning, which told drug makers to make label changes, said the agency had conducted a new data analysis of tendinitis and tendon ruptures and identified a three times greater risk for patients using fluoroquinolones.
"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."
The watchdog group Public Citizen called for warnings about the tendinitis and tendon rupture side effects with the drug class as early as 1999 and sued the FDA in 2006 to have warnings added. At the time, ten years ago, Public Citizen cited 262 cases of tendon ruptures, 258 cases of tendonitis and 274 other cases of other tendon problems. A more recent count in a medical journal revealed there have been 2,495 reports of tendon rupture linked to fluoroquinolones from their respective approvals date through 2012. There were 1,555 for Levaquin (levofloxacin) and 606 for Cipro (ciprofloxacin) said the research.
Tendinitis and tendon ruptures, it turned out, were the tip of the Levaquin and fluoroquinolone iceberg. In 2013, the FDA admitted under pressure from public health officials and patients groups that the "serious side effect of peripheral neuropathy" (nerve damage) can "occur soon after these drugs are taken and may be permanent." By then, hundreds of lawsuits had charged that warnings falsely claimed that the side effects were "rare" and that symptoms go away on discontinuation. In fact they are often permanent charge patients and patient groups who are raising awareness, coining the term "Fluoroquinolone Toxicity Syndrome."
And there was more to the Levaquin and fluoroquinolone iceberg. Fluoroquinolone use is a "major risk factor for development of community and hospital acquired C. difficile infection," reports the Duke Antimicrobial Stewardship Outreach Network (Dason), the dreaded and tenacious intestinal microbe. The drugs are also linked to mental effects like confusion and hallucinations says Dason, and a medical journal reports psychosis. The Journal of the American Medical Association reported that of 4,384 patients diagnosed with retinal detachment, 445 (10 percent) were exposed to a fluoroquinolone in the year before diagnosis.
Other possible fluoroquinolone side effects include liver injury--which caused Trovan (trovafloxacin), a different fluoroquinolone to be withdrawn--and heart problems--which caused the fluoroquinolone Raxar (grepafloxacin) to be withdrawn after heart-related deaths. Omniflox, another fluoroquinolone, was withdrawn from the market after more than 100 patients experienced allergic events, hemolytic anemia and worse. Patients also experienced kidney dysfunction on Omniflox and half needed dialysis. Others suffered liver dysfunction.
After a decade-long battle with Bayer whose fluoroquinolone Baytril (enrofloxacin) was routinely used in poultry, the government managed to ban the antibiotic's use in poultry water. As with all antibiotics used in livestock, the FDA worried about the development of fluoroquinolone-resistant bacteria sometimes called "superbugs" and the ability to treat human infections.
But fluoroquinolones are still clearly in use on U.S. farms. The USDA's National Residue Program for Meat, Poultry, and Egg Products which tests for six fluoroquinolones found enrofloxacin (Baytril) and ciprofloxacin (Cipro) residues in meat in 2014, 2013 and 2012--the most recent reports available-- and danofloxacin residues in meat in two of the three years.
This summer's FDA fluoroquinolone warnings should have come years earlier--and drug use on the nation's farms is poorly controlled and dangerous.