Fluoroquinolones such as Cipro, Levaquin & Avelox are intended to kill or stop the growth of bacteria. This family of antibiotics was first discovered in the 1960s, but it wasn’t until the late 1980s that Cipro and other modern fluoroquinolones first hit the market. At the time, doctors primarily prescribed them to treat urinary tract infections. Since then, they have become the go-to antibiotic for many infections.
These drugs are potent and are approved for the treatment or prevention of serious bacterial infections including anthrax, plague and bacterial pneumonia.
Other approved uses include the treatment of:
- Skin and skin structure infections
- Bone and joint infections
- Complicated intra-abdominal infections
- Infectious diarrhea
- Typhoid fever (enteric fever)
- Uncomplicated cervical and urethral gonorrhea
- Chronic bacterial prostatitis
- Lower respiratory tract infections
- Urinary tract infections
- Acute uncomplicated cystitis
- Acute bacterial sinusitis
- Acute pyelonephritis
- Acute bacterial exacerbation of chronic bronchitis
- Acute bacterial sinusitis.
A U.S. Food and Drug Administration (FDA) safety review found fluoroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system. These side effects can occur hours to weeks after exposure to the drugs and may potentially be permanent, according to the agency. For that reason, the FDA has announced that patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated urinary tract infections should only use fluoroquinolones when no alternative treatment options exist.
As with other antibacterial drugs, fluoroquinolones do not treat viral infections such as colds, flu or bronchitis in people who are otherwise healthy. They should be used “only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria,” according to the drug’s label. This is to reduce the development of drug-resistant bacteria and to maintain the effectiveness of fluoroquinolones and other antibacterial drugs.
Types of Fluoroquinolones
Six fluoroquinolones are currently available in the U.S. They can be administered in pills, injections and topical creams. Generally, fluoroquinolones are broken down into two categories: the older group (ciprofloxacin, norfloxacin, ofloxacin) and the newer group (gemifloxacin, levofloxacin, and moxifloxacin).
The most popular drugs in the class are:
- Cipro and Cipro XR (ciprofloxacin)
- Avelox (moxifloxacin)
- Levaquin (levofloxacin)
Other fluoroquinolones exist such as Floxin (ofloxacin) and Factive (gemifloxacin) but are not as widely used. Maxaquin (lomefloxacin), Raxar (grepafloxacin hydrochloride) and Zagam (sparfloxacin) are no longer available in the U.S. Noroxin (norfloxacin) was discontinued by its manufacturer, Merck.
Cipro, Cipro XR, Proquin XR (ciprofloxacin) Uses & Dosages
Cipro is the most widely used of all the fluoroquinolones, making up about 66 percent of all prescriptions each year. Some 21 million Americans take this drug annually. It was originally approved in 1987 and is a second-generation fluoroquinolone. Doctors often prescribe it to treat mild-to-moderate respiratory and urinary tract infections, but it also treats other conditions, including gonorrhea, infectious diarrhea and anthrax.
Cipro comes in the following formulas and doses:
Oral Tablets: 100 mg, 250 mg, 500 mg and 750 mg
Extended-release tablets: 500 mg and 1,000 mg (available only as generic)
Intravenous: 200 mg to 400 mg
Levaquin (levofloxacin) Uses & Dosages
Levaquin is the second-most-popular drug in the class, accounting for more than 28 percent of all prescriptions. It is a third-generation fluoroquinolone, originally approved in 1996. In 2010, it was the best-selling antibiotic in the U.S. Like Cipro, it treats respiratory and urinary tract infections. It also treats other conditions, including plague, anthrax, bronchitis and pneumonia.
Levaquin comes in the following formulas and doses:
Oral Tablets: 250 mg, 500 mg and 750 mg
Intravenous: 500 mg
Avelox (moxifloxacin) Uses & Dosages
The third-most-popular fluoroquinolone in the U.S. is Avelox, a fourth-generation medication. The number of Avelox prescriptions dropped 78 percent from 2.7 million prescriptions in 2010 to 609,000 prescriptions in 2014. The FDA approved the drug in 1999 to treat multi drug-resistant types of Streptococcus pneumoniae – bacteria that cause pneumonia, ear infections and meningitis, among other conditions. It also treats skin infections, cellulitis and intra-abdominal infections.
Avelox comes in the following formulas and doses:
Oral Tablets: 400 mg
Intravenous: 400 mg
Factive and Floxin account for about .0005 percent of the total number of prescriptions for the class. Noroxin, Maxaquin, Raxar and Zagam are no longer on the market in the U.S.
- Factive — available in 320mg tablets and treats chronic bronchitis and pneumonia.
- Floxin — available in 200, 300 and 400mg tablets. This drug is more toxic than others in its class and often causes adverse events in patients.
- Noroxin — discontinued in 2014 for unclear reason. It was available in 400mg tablets to treat sexually transmitted diseases and urinary tract infections.
- Maxaquin — no longer available in the U.S. Though, it may still be used in generic versions.
- Raxar — withdrawn from the market in 1999 because it was shown to cause adverse cardiac events.
- Zagam — withdrawn from the market in 2001 because of phototoxicity and cardiac events.
Fluoroquinolone Contraindications and Interactions
Fluoroquinolones may not work as well if taken with certain foods, drugs or supplements, including antacids, multivitamins, iron, calcium, milk, cheese and nuts. Studies also have explored a link between tendon disease and concurrent use of steroids and fluoroquinolones. One report showed that half of patients with fluoroquinolone-induced tendon rupture had been taking steroids at the same time. In 2008, the FDA released a public warning about this risk.
A 2013 study published by the Canadian Medical Association Journal found that the risk of acute kidney injury grows almost five times more likely if a patient uses fluoroquinolones alongside the common heart drugs renin-angiotensin-system blockers. Pregnant women, children and adults older than 60 are at increased risk of bad reactions from fluoroquinolones. Some studies found the drugs were toxic to a developing fetus. Because these drugs may affect muscles, doctors do not recommend their use in children. The risk of adverse events is also greater for people with liver disease or those taking non-steroidal anti-inflammatory drugs (NSAIDs) like Advil or aspirin.
Drug interactions in fluoroquinolone labels include:
- Metal cations
- Antidiabetic agents
- Non-steroidal anti-inflammatory drugs
- Phenytoin Methotrexate
Black Box Warnings
When the FDA determines that an approved drug carries significant risks, the agency requires that drug manufacturers add a black box warning to the product. This allows both doctors and users to become aware of the risks associated with using the medication. A black box warning is a serious step — just one away from removing a medication from the shelves.
Studies show people who have taken fluoroquinolones to treat infections may be at risk for developing life-altering side effects such as tendon problems, deadly heart conditions and permanent nerve damage. The FDA has added and enhanced black box warning information to fluoroquinolone labels since 2008 as new risks have come to light.
The FDA concluded that fluoroquinolones are associated with tendinitis and tendon rupture. The agency notified drug makers that they needed to add a warning to all fluoroquinolone medication information, outlining the increased risk of developing these conditions.
The FDA added to the black box warning the risk of worsening symptoms of myasthenia gravis, a long-term neuromuscular disease that leads to varying degrees of muscle weakness.
The FDA added a warning to fluoroquinolone labels for a form of permanent nerve damage called peripheral neuropathy.
Following a 2015 FDA advisory committee meeting where experts discussed the dangers of fluoroquinolones, the FDA added another warning. In May 2016, the agency had advised doctors to avoid using fluoroquinolones in patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated urinary tract infections that can be cured with other medications. In July, the FDA mandated this labeling addition.
Side Effects of Cipro, Levaquin and Avelox
Over the years, the FDA has received reports of life-changing adverse events in patients who have taken fluoroquinolone antibiotics. The most severe side effects of fluoroquinolones are considered rare. Some can be fatal. Common side effects of fluoroquinolones include headaches, lightheadedness, nausea, diarrhea, dizziness and trouble sleeping.
Serious side effects involving the tendons, muscles, joints, nerves, the central nervous system and other body systems include:
- Inflammation of the tendons
- Tendon rupture
- Tingling or pricking sensation
- Numbness in arms or legs
- Muscle pain
- Joint pain or swelling
- Suicidal thoughts
Other side effects include abnormally rapid or irregular heartbeat, ringing or buzzing in the ears, vision problems, skin rash, sensitivity of skin to sunlight, fatigue and worsening of myasthenia gravis.
Life-Threatening Heart Problems & Fluoroquinolones
The lining of the aorta is made up of collagen. Scientists suspect that fluoroquinolones break down collagen in the body. Two 2015 studies published in JAMA and BMJ medical journals reveal a connection between fluoroquinolones and collagen damage that may lead to aortic aneurysms.
An aortic aneurysm is a bulge in the aorta, which is the artery responsible for carrying blood from the heart through the chest and torso.
Aortic aneurysms can act in two ways:
- Tears can form in the aorta, allowing blood to leak in between the layers of tissue in the vessel wall, separating them. This is called aortic dissection.
- The aneurysm can also rupture, which is when it bursts completely, causing bleeding inside the body.
According to the JAMA study, fluoroquinolones were associated with a two-fold increase in risk of dissection and aneurysm within 60 days of using the drug. Authors said, “clinicians should continue to be vigilant for the appearance of aortic aneurysm and dissection in high-risk patients treated with fluoroquinolones.”
The BMJ study found nearly a three-fold increase in the risk of aneurysm. Authors of this study followed about 1.7 million patients and found one third of them received a prescription for a fluoroquinolone. “Reducing unnecessary fluoroquinolone treatments or prolonged treatment courses might have possibly prevented more than 200 aortic aneurysms in this population,” study authors said.
Aortic aneurysms were the primary cause of 9,863 deaths in 2014, and dissections and ruptures are the cause of most deaths from aortic aneurysms, according to the Centers for Disease Control and Prevention.
Aortic Aneurysm Rupture
Aortic aneurysms weaken the aortic wall and are more likely to burst. They can occur in the abdomen (abdominal aortic aneurysm) or in the chest (thoracic aortic aneurysm).These weak spots are extremely dangerous, and once they burst, a patient has a 50 percent chance of survival. Aneurysms often have no symptoms. These bulges may be found while testing for other conditions on a CT scan or ultrasound of the heart. When the thoracic aneurysm ruptures, people have difficulty breathing, severe chest pain or severe back pain or may lose consciousness. A ruptured aneurysm is an emergency situation and must be treated immediately. Doctors may prescribe surgery or an aortic stent.
Dissection interrupts the blood flow to other organs by blocking other blood vessels that feed them. This can lead to stroke, paralysis, kidney failure and other problems. All dissections can lead to death, and it is extremely important to catch them early. Doctors typically use CT scans to diagnose them. Treatment may or may not require surgery to replace the dissected portion of the aorta.
Symptoms of aortic dissection include:
- Chest pain
- Paralysis of an arm or leg
- Appearance of having a stroke or heart attack
- Loss of pulse in affected arm or leg
- Flu-like symptoms
- Back pain
- Loss of consciousness
- Difficulty speaking
- Loss of vision
- Dizziness or confusion
Fluoroquinolone Antibiotics & Tendon Problems
The medical community has long been aware of an association between fluoroquinolones and tendon problems. In 2008, the FDA released a safety alert, warning the public of this potential risk. The agency cautioned patients taking fluoroquinolones who notice signs of tendon pain, swelling or inflammation to contact their doctor right away, stop taking the drug, and avoid exercise and movement of the affected area.
The agency required makers of Cipro, Levaquin, Avelox and other fluoroquinolones to add a black box warning for tendon rupture to medication labels. It also asked pharmaceutical companies to develop a medication guide. The FDA’s Adverse Events Reporting System confirmed that tendon ruptures in patients taking fluoroquinolones continue to increase.
Reports of ruptures and tears of tendons exist for the following body parts:
- Achilles tendon (most prevalent)
- Rotator cuff (shoulder)
Peripheral Neuropathy & Fluoroquinolone Use
In 2013, the FDA announced it was strengthening warnings in the labels for fluoroquinolones to better describe the disabling side effect peripheral neuropathy. Previous warnings about this serious nerve damage were not strong enough or clear enough, the FDA said. In particular, it said older labels failed to explain fully that neuropathy damage can happen immediately after taking the drugs and can be permanent. The FDA told doctors and consumers to discontinue the medication immediately if symptoms of nerve damage surface.
An FDA review of its Adverse Event Reporting System showed a continued association between the drugs and the crippling nerve disorder, which occurs in the arms and legs. In fact, the onset of peripheral neuropathy after starting fluoroquinolone therapy was rapid, often within a few days. In some patients, the symptoms had lasted for more than a year, even after users had stopped taking the drugs. Several patients were continued on fluoroquinolones despite their showing signs of the disorder. The FDA ultimately concluded peripheral neuropathy can occur at any time during treatment with fluoroquinolones and can last for months to years after the drug is stopped or be permanent.
A study published in 2014 by the peer-reviewed journal Neurology further supported the FDA’s findings. The study showed long-time users of fluoroquinolones had twice the risk of developing peripheral neuropathy, while new users had a slightly greater risk. Researchers said “clinicians should weigh the benefits against the risk of adverse events when prescribing these drugs to their patients.” Researchers studied more than 30,000 men in the U.S. from 2001 to 2011.
Fluoroquinolones can cause nerve damage that lasts for months to years after the drug is stopped.
Peripheral neuropathy affects about 20 million Americans, according to the National Institutes of Health (NIH). It occurs when the peripheral nervous system is damaged by injury, illness or exposure to certain drugs, like fluoroquinolones. Patients using fluoroquinolones who develop any symptoms of peripheral neuropathy should tell their doctors right away. Symptoms of peripheral neuropathy include pain, burning, tingling, numbness or weakness. Some people may notice a change in sensation to light touch, pain or temperature, or the sense of body position. Doctors can perform a number of tests to determine the extent of nerve damage, and the type of neuropathy is classified according to the nerves that are damaged.
Severe Symptoms of Peripheral Neuropathy
Damage to the nerves interferes with the messages coming from the brain to the rest of the body. These confused messages can wreak havoc on the types of sensations someone feels. For example, a person may feel severe pain in response to sensations that should not cause pain, like feeling pain from bed sheets, or numbness in fingers and toes. The nerves in the hands and feet are the first to be affected. Depending on the person, symptoms may present in a few days, weeks or years. Some forms are chronic and worsen over time. Neuropathy is typically not fatal, but it can cause a lifetime of suffering.
Some severe symptoms include:
- Burning pain at night
- Muscle wasting
- Organ or gland dysfunction
- Sweating/ lack of sweating
- Digestive issues
- Poor sexual function
- Poor bowel control
Peripheral Neuropathy Treatment
There are over 100 different kinds of neuropathy. Each type has its own symptoms, prognosis and treatment. After doctors diagnose a specific type of nerve damage, they discuss treatment options. In the beginning, they will address the cause, whether hormones, vitamin deficiencies or exposure to toxic medications. Sometimes, removing issues that caused the damage allows nerves to regenerate. Adopting a healthy diet and exercise can also help manage symptoms.
In many cases, doctors may have to prescribe strong drugs including pain killers and antidepressants that have their own laundry list of side effects. Opioid pain killers can also leave some people addicted. Surgery to kill problematic nerves and stop pain is only considered after all other courses of action are exhausted and only work when a single nerve is affected.
Other Problems Associated with Fluoroquinolone Antibiotics
Due to the expanding number and severity of fluoroquinolone-related problems, medical professionals can now diagnose Fluoroquinolone-Assisted Disability (FQAD) in patients. Individuals with FQAD are defined as U.S. patients who were reported to be previously healthy and have suffered debilitating side effects from fluoroquinolone use. The diagnosis of FQAD was established in order to organize the diverse list of problems that can result from using these drugs. FQAD sufferers are patients who have been given fluoroquinolones when their conditions could have been cured with a far less powerful medication.
In 2013, the FDA released a Safety Communication warning about over-prescribing fluoroquinolones and said current warnings were not clear enough. Specifically, the agency said “the potential rapid onset and risk of permanence were not adequately described,” and the “permanent damage among patients exposed to these medications cannot be calculated.” Then in 2016, the FDA announced that fluoroquinolones were too risky for use in minor infections such as uncomplicated urinary tract infections. However, many doctors have not updated their prescribing practices accordingly, and some researchers say fluoroquinolones are still over-prescribed for minor issues like earaches and sinusitis.
Doctors Speak on Fluoroquinolones
Infectious disease physician Dr. Lindsey R. Baden told Consumer Reports that doctors tend to overprescribe fluoroquinolones because the drugs are effective against many bacteria.
Dr. Mahyar Etminan, an epidemiologist at the University of British Columbia, told The New York Times that overusing these drugs is like “trying to kill a fly with an automatic weapon.”
Dr. Jay S. Cohen, an author and professor of psychiatry who discussed preventing medication side effects, spent years detailing the dangers of fluoroquinolones, which he called the “worst medication disaster in U.S. history.”
In a 2013 study, American and Canadian researchers teamed up to explore the risk of kidney disease in users of fluoroquinolone antibiotics. They found the risk of acute kidney injury is doubled in people who have used fluoroquinolones, especially ciprofloxacin and moxifloxacin. This condition requires hospitalization and often involves expensive renal care and multiple follow-up visits.
These drugs have also been linked to fluoroquinolone toxicity. This uncommon condition occurs in people who have adverse reactions to even small amounts of fluoride, a primary building block of fluoroquinolones. Toxicity is often detected when patients visit their doctors and complain about musculoskeletal symptoms such as hip pain that worsens with movement. There is no medically recognized syndrome associated with fluoroquinolone toxicity.