Fluoroquinolone antibiotics have been used to treat a wide range of infections caused by bacteria. Because of recent safety information, use of fluoroquinolones should be restricted to infections which do not respond to other medications and should be limited in sensitive populations including children and the elderly.
The U.S. Food and Drug Administration has issued a new safety warning regarding the use of fluoroquinolones or “floxins” and an increase in the risk of a serious side effect. The new alert states that with the use of quinolone antibiotics, the risk of aortic aneurysm may double. Prior warnings have also been issued for tendon rupture and against use in children and adults when another option is available.
Manufacturers of fluoroquinolones have already faced thousands of lawsuits for tendon rupture, aortic dissection and other injuries but may be facing more lawsuits for due to the warning aortic aneurysm.
Fluoroquinolone medications approved in the U.S. include:
- Levaquin (levofloxacin)
- Cipro (ciprofloxacin)
- Avelox (moxifloxacin)
- Factive (gemifloxacin)
- Floxin (ofloxacin)
- Noroxin (norfloxacin)
What Are Fluoroquinolones?
The fluoroquinolones, sometimes called “quinolones” or “floxins” were discovered accidentally and were some of the first antibiotics available to treat gram (-) infections. Though researchers have created thousands of analogs, many were found to be too toxic to use. Some fluoroquinolones were introduced to the market but had to be withdrawn and only a few are currently available for use.
Because of possible harmful effects on the heart, tendons, and nerves, the FDA has said quinolones should not be the first choice for treatment of common illnesses.
Some of the uses of fluoroquinolones have included:
- Urinary tract infection
- Skin and soft tissue infection
- Sexually transmitted infection
- Bone and joint infection
- Infectious diarrhea
- Hospital-acquired infections
Fluoroquinolone Side Effects
Like all medications, fluoroquinolones may cause side effects, most of which are mild to moderate but others may be more severe.
Common side effects may include:
- Nausea and vomiting
Side effects which may be more serious include:
- Allergic symptoms of rash, itching, facial swelling or difficulty breathing
- Watery diarrhea
- Tingling or unusual pain
- Changes in skin, urine or stool color
- Fast or pounding heartbeat
- Severe headache, dizziness or fainting
- Severe nervousness or anxiety
- Hallucinations, confusion, or unusual behavior
- Sudden pain or popping
- Swelling or fluid collection
Any of these symptoms may be serious and should be reported immediately.
Aortic Dissection and Aortic Aneurysm
The U.S. Food and Drug Administration issued a December 2018 warning stating that fluoroquinolones have been associated with an increased risk of fatal cardiac complications including aortic aneurysm and aortic dissection. The agency states that the risk of aortic aneurysm may increase by two times, beginning immediately after the medications are started and continuing for up to 60 days after the medications are discontinued.
As part of the way they work, fluoroquinolones act as “chelators” which may affect the formation of collagen and interfere with cells that make and repair cartilage. This may lead to weakened cartilage in the body.
The aorta is the largest blood vessel in the circulatory system and carries oxygenated blood from the heart to the body tissues. It is a rigid vessel which is formed and supported by a collagen structure. When collagen is weakened by fluoroquinolone use, the aorta wall may thin and bulge or tear.
Aortic aneurysm occurs when a bulge or balloon develops in the wall of the aorta and may rupture. Aortic dissection occurs when a tear develops in the inner lining which then splits away from the middle layer. In either case, aortic rupture and cause a massive hemorrhage or blood loss, quickly resulting in death.
Certain risk factors will increase the chance of aortic aneurysm including:
- history of blocked blood vessels
- high blood pressure
- genetic conditions which affect collagen formation including Marfans syndrome and others
This follows after two studies, published in 2015 in BMJ (British Medical Journal) and JAMA (Journal of the American Medical Association) indicate that the drugs may damage cartilage in the aorta, the same way they cause tendons to rupture. The aorta is the large vessel which brings blood to the heart to be pumped to the body. It gets its structure from the same type of collagen that makes up cartilage in the Achilles and other tendons and may be weakened in the same way.
Aortic aneurysm occurs when the aorta wall begins to thin and bulge and if ruptured, massive bleeding will occur. Aortic dissection occurs when the inner layer of the aorta develops a tear. Blood may enter and separate, or “dissect”, the inner and middle layer and may burst the vessel in the same manner. In either case, a ruptured aorta may quickly result in death.
Fluoroquinolone Tendon Rupture
Fluoroquinolone use has also been linked to an increased risk of tendon rupture due to disruption of cartilage formation and repair. Tendons which connect bone to muscle are constructed of cartilage and may be negatively affected by fluoroquinolone use, resulting in tendinopathy or tendon rupture.
Studies indicated that fluoroquinolones are toxic to collagen I, which makes up most of the cartilage in large tendons. The drugs weaken collagen through “chelation”, by encouraging minerals such as calcium, magnesium or aluminum to stick to the cells. They may also interfere with cartilage repair by inhibiting enzymes or killing some of the cells needed to make new cartilage, known as chondrocytes.
Tendinopathy or tendon rupture risk may increase within days or even hours of taking a fluoroquinolone antibiotic and may be 3 or 4 times higher than normal. The risk is also higher in those over 60, organ transplant patients, or those taking anti-inflammatory steroids like prednisone. Fluoroquinolones should not be used in children unless medically necessary.
Fluoroquinolone FDA Warnings
The FDA has issued a number of warnings about the dangers of fluoroquinolones.
In 2008, the U.S. Food and Drug Administration issued a” black box warning” regarding the dangers of fluoroquinolones and tendon rupture. The FDA began requiring that manufacturers print information about the risk of tendon damage in a “black box” at the top of prescribing information for all fluoroquinolones. A black box statement is the most severe warning that can be given about a prescription medication. Manufacturers were also required to create a patient information guide about the risks.
In 2015, an FDA advisory committee was called to evaluate the usage of fluoroquinolones in routine treatment of simple infections. The committee reviewed reports of tendon rupture, nerve damage, and cardiac events associated with fluoroquinolone use and determined that medications should not be used as a first choice for uncomplicated urinary tract infections, sinusitis and bronchitis.
In June 2016, prescribing information for all fluoroquinolones was changed to state that the medications should not be used if other treatments were available and to discontinue use if serious side effects occurred. Information about nerve damage or neuropathy was also added to the patient medication guide.
Between 2017 and 2020 opted to discontinue manufacturing brand-name fluoroquinolones though unexpired medications or generics may still be available.
Fluoroquinolone Lawsuit Information
In past years, many fluoroquinolone lawsuits for tendon injuries and other serious side effects were settled, though some fluoroquinolone neuropathy cases may still be pending in federal courts.
The most recent safety warning brought a number of new lawsuits and indicates that additional lawsuits may be expected for aortic aneurysm. Current fluoroquinolone lawsuits for aortic aneurysm and aortic dissection have been limited largely to people who took the medication within 60 days prior to the event. No additional settlements have been disclosed.
Notwithstanding claims relating to this product, the drug/medical device remains approved by the U.S. FDA.