July 5, 2022 – When Amy Moser had a simple urinary tract infection in her late 20s, her doctor prescribed Cipro, a powerful antibiotic used to treat anthrax and some of the most fearsome bacterial infections.
Nearly 2 weeks after she finished her treatment, her left kneecap dislocated while she was trying on a swimsuit at a retail store. Shortly afterward, she had painful ligament ruptures in her wrists, then her shoulder dislocated, followed by three Achilles tendon tears.
“That’s when I fell apart,” says Moser, a Phoenix health blogger and book author. “From that moment on, for almost the next 2.5 years consistently, I had new tendon tears every few weeks.”
Moser’s doctors had no answer for what was causing her injuries, all of which required surgical fixes. A married mother of three, she was otherwise healthy and fit. So, after her third Achilles tear, she turned to the FDA’s website for answers. There, she found many warnings about side effects of Cipro, Levaquin, and other so-called fluoroquinolones, including risks for tendon and ligament injuries.
“When all the ruptures started to happen, my doctor kept asking me if I’d ever taken Levaquin, and every time I was like, ‘No.’ So I did what all doctors don’t want you to do: I Googled ‘Levaquin,’” she recalls.
Her search led to FDA warnings and articles about the possibility of tendon and ligament ruptures with fluroquinolones.
“That was the first time I’d ever even heard that word ‘fluroquinolones,’ and I found Cipro on that list … and I realized that I’d just been prescribed that before everything started,” she says.
That was 12 years ago. Since then, the FDA has issued more warnings about fluoroquinolone risks. In that time, Moser, now 40, has had more than 30 surgeries to correct tendon ruptures and injuries, including a double-knee replacement this year.
“I am in chronic pain all the time,” she says. “I am chronically injured. I have a lot of tears that I’ve not fixed because they’re very complicated and I don’t know if the rest of my body can handle the strain of recovering from those surgeries.”
Moser’s is hardly an isolated case. Since the 1980s, more than 60,000 patients have reported hundreds of thousands of serious events linked to fluoroquinolones to the FDA, including 6,575 reports of deaths.
The most common side effects were tendon rupture, as well as neurological and psychiatric symptoms. But experts estimate only 1% to 10% of such events are reported to the FDA. That suggests that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, MD, a hematologist at the University of South Carolina’s College of Pharmacy in Columbia.
Yet despite the many patient reports and FDA warnings on dangerous side effects, many doctors continue to wrongly prescribe fluoroquinolones for simple urinary tract infections, sinus infections, and respiratory issues better treated with less risky antibiotics.
“There probably is over-prescription by primary care doctors, for urinary tract infections and respiratory infections, when there could be alternatives that are safer to use,” says Amesh Adalja, MD, an infectious disease specialist and senior scholar with the Johns Hopkins Center for Health Security.
“I would say that’s probably the case in the outpatient setting, not necessarily in the hospital setting or among infectious disease doctors … but I think it’s important to say there are still some judicious uses of fluoroquinolones,” he says. “However, there probably is a lot of injudicious use of fluoroquinolones along with many other antibiotics in the primary care setting.”
FDA Warnings on Fluoroquinolones
Fluoroquinolones are a class of broad-spectrum antibiotics used for decades to treat certain bacterial infections.
FDA-approved fluoroquinolones include ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, delafloxacin (Baxdela), gemifloxacin (Factive) levofloxacin (Levaquin), moxifloxacin (Avelox), and ofloxacin (Floxin). More than 60 generic versions of these brand-name medicines are also on the market, making them among the most prescribed antibiotics in the U.S.
Over the past 2 decades, a wide range of physical and mental health side effects have been tied to fluoroquinolones. As a result of these “adverse event reports” and research published in medical literature, the FDA has required an escalating series of warnings and safety labeling changes for doctors who prescribe these drugs.
- In 2008, the FDA first added a “black box” warning to fluoroquinolones, citing an increased risk of tendinitis and tendon rupture in patients prescribed these meds.
- In 2011, the agency required the warning label to include risks of worsening symptoms for those with myasthenia gravis, a chronic autoimmune disease that causes muscle weakness, vision problems, and speech problems.
- In 2013, regulators required updated labels noting the potential for irreversible peripheral neuropathy (serious nerve damage).
- In 2016, the FDA issued its strongest warning against the use of such antibiotics for simple bacterial infections – such as uncomplicated urinary tract infections (UTIs), acute sinusitis, and acute bronchitis – saying the “association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves and the central nervous system … outweighs the benefits for patients.”
- And in 2018, regulators required safety labeling changes to include warnings about the risks of aortic aneurysm – a life-threatening enlargement of the main vessel that delivers blood to the body – and mental health side effects and serious blood sugar disturbances.
But FDA regulators have stopped short of barring fluoroquinolone use in the treatment of bacterial infections, citing the benefits for certain conditions.
“For some patients, the benefits of fluoroquinolones may continue to outweigh the risks for treatment of serious bacterial infections, such as pneumonia or intra-abdominal infections,” said former FDA Commissioner Scott Gottlieb, MD, “but there are other serious, known risks associated with these strong antibiotics that must be carefully weighed when considering their use.”
In December 2021, a study published in the journal JAMA Network Open found the FDA’s warnings may have helped lower prescribing of the drugs in Medicare patients. But not all doctors have been responsive to those warnings, researchers found.
“An overall decline in change over time and an immediate change in fluoroquinolone prescribing was observed after the 2016 FDA warning,” the authors concluded. “Certain physicians, such as primary care physicians, were more responsive to FDA warnings than others. … Findings of this study suggest that identifying the association of physician and organizational characteristics with fluoroquinolone prescribing practices could help in developing mechanisms for improving de-adoption.”
Some critics say the FDA should do more to spotlight the dangers of fluoroquinolones and require doctors and patients to sign checklist consent forms to show they are aware of the potential side effects of these drugs.
Rachel Brummert, a patient advocate who sits on an FDA consumer advisory board, believes the FDA needs to improve its communication to doctors on fluoroquinolone risks and get tougher with those who continue to inappropriately prescribe the drugs.
“I think there needs to be a system in place, where if something comes down from the FDA about a drug, the physician has to sign off on it, the patient has to sign off on it and mark that they understand that there are these ‘black box’ warnings,” says Brummert, 52, a representative on the FDA’s Medical Devices Advisory Committee.
As an example, she points to Australia’s medical laws requiring doctors and patients to sign a checklist before any fluoroquinolone prescription is approved.
“When a physician prescribes a fluoroquinolone antibiotic, there’s a checklist – does the patient have an infection, is it a simple infection, do they have allergies?” she notes. “And you can’t even get the prescription out – it won’t even print out, it won’t go into the system – unless you check all of the boxes. But we don’t do that here. We don’t have that type of system right now.”
Brummert says such a system might have prevented the harm from taking Levaquin her doctor prescribed for a suspected sinus infection in 2006.
Soon after she began taking the antibiotic, she ruptured her Achilles tendon, requiring surgery. By 2009, she’d had three ruptures, each needing surgical fixes. To date, she’s had more than 30 surgeries to correct tendon ruptures. She’s also had seizures, blood pressure issues, depression, chronic pain, and memory problems she attributes to taking Levaquin.
As it turns out, her doctor misdiagnosed her condition – a misstep that would have been averted with a system like Australia’s, which requires doctors to verify the presence of a bacterial infection through a simple test before prescribing a fluoroquinolone.
“When I got the Levaquin, it was for a suspected sinus infection that it turned out I didn’t even have in the first place,” she notes. “So, I took the Levaquin basically for nothing. But what I would I have asked my doctor had I known is: ‘Why should I take something so strong for so simple an infection?’
“It seems common sense to me now that you don’t prescribe something that can kill anthrax for a simple sinus infection. It’s like an atom bomb killing a mosquito. I agree that there are uses for these drugs, but they are being overprescribed. And so, here I am 16 years later – I’m still rupturing, I’m still having surgery, and I’m still in pain – all for something I didn’t even need medicine for in the first place.”
Should Guidelines Be Stronger?
So, why are so many doctors continuing to prescribe fluoroquinolones for simple infections? Adalja and other experts say several things are at work.
For one thing, Adalja notes, fluoroquinolones are broad-spectrum antibiotics that are effective against dangerous germs, including “gram-negative” bacterial infections, and are “100% bioavailable.” That means they are as effective when given in pill form as they are if put directly into a vein. So they can be used in an outpatient setting or to allow a patient to be discharged from a hospital sooner because they don’t need an IV to receive treatment.
“There are still some uses for these drugs because they are so bioavailable, and I think that drives some of the use, and those are legitimate uses, knowing that there are risks when you do it,” he says. “But no drug is without risks, and you have to weigh risks and benefits – that’s what medicine is about: deciding what the best drug is for a patient.”
But Adalja says the over-prescription of fluoroquinolones is part of the larger trend of antibiotic overuse. That is driving up antibiotic resistance, which in turn is another thing leading doctors to turn to Cipro and other fluoroquinolones after other drugs have proven ineffective.
“You can’t separate this from the fact that 80% of antibiotic prescriptions in the outpatient setting are probably illegitimate or not warranted,” he notes. “And because fluoroquinolones are highly effective drugs against certain pathogens, they are the go-to [drug] for many people who are prescribing antibiotics.”
That’s why patients should be wary whenever a doctor prescribes a fluoroquinolone, or any drug to treat a suspected infection, he says.
“Anytime a patient is getting prescribed an antibiotic by a physician, they should ask: ‘Do I really need this antibiotic?’ That should be the first question they ask,” he advises. “And if they’re getting a fluoroquinolone, they may want to ask: ‘Is this the best antibiotic for me?’”
What You Can Do
Brummert and Moser say they are sharing their stories to raise awareness of the dangers of fluoroquinolones.
Moser has published a book on her experiences, The Magnificent Story of a Lame Author, and provides a wealth of consumer resources on her blog: Mountains and Mustard Seeds.
“As much as I hate what has happened to me, it has put me in a place where I am glad that I can inform other patients,” she says.
Brummert supplements her advocacy work as an FDA adviser with useful materials she provides on her website: Drugwatch.com.
“Pain into purpose – that’s what I call it,” she says. “I can’t change what happened to me, but I can warn others.”
The upshot for patients?
- Check out the FDA’s Drug Safety Communication on Fluoroquinolones online to learn more about the risks and benefits of these powerful antibiotics.
- If you believe you’ve been harmed by fluoroquinolones, visit the FDA’s MedWatch website to report your experiences.
Brummert also advises patients to ask 12 critical questions of any doctor who wants to prescribe a fluoroquinolone, including the following listed on her website:
- For what condition is this medication prescribed, and is there another drug specific to my condition?
- What are the risks associated with this medication, and do the benefits outweigh them?
- Will this medication interact with my other drugs and/or other health conditions?
- What are the “black box” warnings for this medication, and where can I report adverse events?
“I would also do my own research,” she says. “I wouldn’t just take a prescription from a physician and just say, ‘OK, doctor knows best.’”
Moser agrees that you have to be your own patient advocate and not simply take a doctor’s advice on any medical issue without having a deeper conversation.
“I’ve had arguments with doctors who legitimately did not believe me when I told them what happened to me,” she says. “And I actually told them, ‘Go get your Physicians’ Desk Reference [for prescription drugs]’ and they opened the book in front of me and read the warnings. Obviously, they had not been keeping up with the added warnings. So, I do think that doctors do need to be better informed.
“So, yes, it’s the FDA’s responsibility, but it is also the doctors’ responsibility to make sure that they’re watching out for the side effects and they’re reporting them when their patients come up with them and making those connections.”
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