Feb. 7, 2019 -- In 2006, Rachel Brummert developed a sinus infection, and her doctor prescribed Levaquin, one of a class of powerful antibiotics called fluoroquinolones. Shortly after she began taking the drug, she went on an errand. While crossing a parking lot, her Achilles tendon ruptured. Her foot went limp. The agony felt unbearable.
“I felt the tendon snap and then ball up,” she recalls. “It was more painful than kidney stones.”
By 2009, she’d had three ruptures. Each required surgery. Her orthopedic surgeon couldn’t understand why this was happening to Brummert, who was otherwise healthy. They began to review her medical history, and he stopped her when she mentioned the Levaquin. The previous year, the FDA had warned that tendon ruptures were a potential consequence of taking this class of drug.
To date, Brummert, who lives in Charlotte, NC, has had 25 tendon ruptures. That’s not all. She also has memory problems, trouble balancing, seizures, and sudden drops in blood pressure. All are rare but known side effects of fluoroquinolones.
“They are completely unpredictable,” Brummert, 48, says of her ongoing symptoms.
FDA adds warnings
In the past year, more concerns about the drugs’ side effects have led the FDA to issue new warnings about their use. In December, the federal agency announced that, in rare cases, the drugs have caused tears or ruptures in the heart, called aortic dissections, which can be fatal. Five months earlier, in July, the FDA updated the safety label of fluoroquinolones to include stronger warnings about mental health side effects like trouble paying attention, disorientation, and memory loss.
The same update also raised concerns about severe drops in blood sugar levels that could lead to a coma, especially in the elderly and in people with diabetes. Previous FDA warnings included the risk of harm to tendons, muscles, joints, nerves, and the central nervous system, all of which can occur in the same person and may be permanent, as happened to Brummert, who testified before the FDA panel that led to the 2016 warning.
“They are over-prescribed because they are so potent and so easy to use,” says Antonio Crespo, MD, an infectious disease specialist at Orlando Health. “It’s very important that prescribers understand the risks.”
Over-prescribed with limited uses
Fluoroquinolones have been in use for decades. In addition to Levaquin (levofloxacin), those prescribed today include Cipro (ciprofloxacin) and Avelox (moxifloxacin). In a study published last year, researchers reported that fluoroquinolones are the third most commonly prescribed antibiotic for adults. More than 1 in 20 of those prescriptions, however, were for conditions that did not require antibiotics, while nearly 20% were prescribed to treat infections for which they should not be used as the first treatment.
Crespo says fluoroquinolones effectively treat a variety of infections, including complicated urinary tract infections and bacterial infections of the prostate, stomach, and bacterial forms of pneumonia and other respiratory infections. Because they can be prescribed in pill form, he says, they can be given to patients with serious infections that might otherwise require a hospital stay for intravenous antibiotic treatment. The strength of the drugs, he says, may lead prescribers to rely on them more than they should.
It’s also important that the drugs be used in the right circumstances. In 2016, the FDA advised that fluoroquinolones not be used to treat sinus infections, bronchitis, and uncomplicated urinary tract infections, except in patients that have no other treatment options. For example, they may be given to people who are allergic to penicillin or have certain serious bacterial infections.
“For more uncomplicated infections, the risk is higher than the benefit,” says Andrea Pallotta, PharmD, a pharmacy clinical specialist in infectious disease at the Cleveland Clinic.
Weakness, aches follow use
David Melvin, 57, has been living with the aftermath of fluoroquinolones for more than a decade. A retired state police officer who lives in rural Illinois, Melvin took a high dose of Levaquin in 2007 for a suspected infection in his right testicle.
At the time, he was in excellent health, he says. He biked 7 to 10 miles a day and bench-pressed as much as 300 pounds. But not long after he finished his course of drugs, he started to feel weakness throughout his body and his endurance dropped significantly. After 9 months of vague and subtle symptoms, the muscles in his legs began to ache severely, and he sought treatment.
He saw two neurologists, a rheumatologist, and then specialists at the University of Chicago before he learned that he had suffered nerve damage, though his doctors could not find a cause.
But his own research had led him to strongly suspect fluoroquinolones. He started a blog about his experiences in 2009.
“At first it was an outlet for my frustration,” says Melvin, whose symptoms eventually led him to an early retirement. “I was unprepared for the amount of people contacting me daily.”
Research from personal experience
Among those contacts were a handful of researchers interested in the effects of fluoroquinolones, some of whom had had their own experiences with the drugs. Together, they began to pursue a link between fluoroquinolones and the family of side effects that they seemed to trigger.
“One of our struggles has been to get the acknowledgement that this happens,” Melvin says.
In 2015, the FDA reviewed reports of previously healthy people who had disabling side effects after taking fluoroquinolones for garden-variety sinus infections, urinary tract infections, and bronchitis. Out of 1,122 such cases, the agency found 178 people, or 16%, who had had at least two different types of side effects, including heart and central nervous system problems, that lasted at least a month and as long as 9 years. The FDA dubbed this condition fluoroquinolone-associated disability, or FQAD.
However, the report’s authors acknowledge that the system for reporting side effects does not catch all cases, so the number of people with devastating side effects is likely much higher. One estimate suggests that no more than 10% of all serious side effects get reported.
Overall, the number of people who reported serious side effects from the 1980s through 2015 exceeds 60,000, and that number includes more than 6,500 deaths, according to a recent study.
In its December warning, the FDA said certain conditions made people taking fluoroquinolones twice as likely to have an aortic dissection, or rupture. The agency advised against prescribing such antibiotics to the elderly as well as to people with high blood pressure, peripheral artery disease, or genetic conditions like Marfan syndrome and Ehlers-Danlos syndrome.
But the list of people who should not take them is longer than that, Crespo says. People on kidney dialysis as well as those with diabetes should avoid fluoroquinolones. Fluoroquinolones also should not be taken by people currently on steroids or medications that treat arrhythmia. And because some fluoroquinolones also have been linked to liver damage, people with liver problems should not take them.
Cause of danger unclear
Why these drugs cause such harm remains a mystery, but some scientists believe fluoroquinolones may damage parts of cells called mitochondria, which create the energy that cells need. Another unknown: Why do these side effects only occur in a small number of otherwise healthy people? It’s possible that some people have genes that make them prone to harm from fluoroquinolones or that fluoroquinolones directly affect and alter certain genes. But that theory has not been adequately tested.
Melvin would like to see a requirement that patients sign informed consent forms detailing the risks before they begin taking fluoroquinolones, and he hopes that prescribers start to reserve them for life-and-death infections.
“They can kill hard-to-reach infections, but the collateral damage they cause is unacceptable,” Melvin says.
Pharmacist Heather Free, PharmD, says that serious side effects from fluoroquinolones are rare. For example, she points out that 1% to 3% of patients report mental health difficulties like disorientation and memory loss or central nervous system side effects such as tingling or prickling sensations that could indicate nerve damage. These can occur after just one dose, she says.
“However rare, it’s always something you should keep in the back of your mind that it is possible,” says Free, a pharmacist consultant and spokesperson for the American Pharmacists Association. She specializes in infectious disease.
Still have a role
Free does not want people to be afraid to take fluoroquinolones if they truly need them, but she understands the very real concerns that patients might have. She advises people to talk to both their prescriber and pharmacist. Make sure they know your health history and any medication you currently take. And ask them to explain why they think this type of drug is right for you, Free says.
“Know the game plan and why it was selected,” Free says. “Don’t be scared, but do be knowledgeable.”
While fluoroquinolones do require caution, Pallotta says, keep in mind that they may be necessary. “Discuss the risks and benefits with your physician. Some patients have life-threatening infections where, if we don’t give certain antibiotics, they could have very devastating outcomes.”
Crespo agrees. “They have a role to play and can be a very good choice.” Still, he says patients should not hesitate to ask their doctor about other options.
“You don’t want to use these drugs if you don’t have to, if there are alternatives,” he says.
For Brummert, the anger she felt at the doctor who prescribed Levaquin for her has transformed into what she considers a silver lining: Her passion for advocacy and awareness.
“It’s possible my doctor just didn’t know, that doctors just don’t get the message,” Brummert says. “These FDA warnings come out but they are not reaching the doctors. I want to help change that.”