Fluoroquinolone Antibiotics Safety Warnings
The U.S. Food and Drug Administration (FDA) has issued multiple warnings regarding fluoroquinolone safety. The most recent safety alert, issued in December of 2018, warns of the increased risk for aortic aneurysm when taking fluoroquinolones. The risk for aortic aneurysm may be doubled, particularly in certain groups of patients. Aortic aneurysm is a medical condition in which a ballooning of the largest vessel in the body, the aorta, can rupture, quickly resulting in hemorrhage and death.
Other FDA warnings have included:
- 2008 – a black box warning issued regarding an increased risk of tendon rupture.
- 2015 – prescribing information was changed to indicate that fluoroquinolones should not be used in certain, simple or uncomplicated infections including urinary tract, sinus and bronchial infections but should be reserved for more serious conditions
- 2016 – a warning recommending that fluoroquinolone use be restricted in children, to be used only in infections that did not respond to other medications or when other medications could not be used
- 2016 – the warning also included additional information about an increased risk of nerve damage
- 2018 – warning issued about mental status changes and adverse effects on blood sugar levels
Fluoroquinolone antibiotics, also called “floxins” have been used to treat a wide variety of bacterial infections. Though they were once more widely used, current recommendations restrict their use to infections which do not respond to other medications and limit use in certain populations such as children and the elderly.
Fluoroquinolone medications available in the U.S. include:
- Cipro (ciprofloxacin)
- Levaquin (levofloxacin)
- Avelox (moxifloxacin)
- Factive (gemifloxacin)
- Noroxin (norfloxacin)
- Floxin (ofloxacin)
Other fluoroquinolone medications have been discontinued and withdrawn from the market after serious side effects and concerns over toxicity.
Uses of fluoroquinolones have included:
- Urinary tract infection
- Skin and soft tissue infection
- Sexually transmitted infection
- Bone and joint infection
- Hospital-acquired infections
- Infectious diarrhea
Fluoroquinolone Side Effects
Fluoroquinolones work by interrupting or inhibiting DNA synthesis in bacteria. They also may cause certain side effect, most of which are mild to moderate.
Common side effects may include:
- Nausea and vomiting
More severe or serious side effects may include:
- Symptoms of allergy (rash, itching, facial swelling or difficulty breathing)
- Watery diarrhea
- Changes in skin, urine or stool color
- Fast, irregular or pounding heartbeat
- Sudden or severe headache, dizziness or fainting
- Severe nervousness or anxiety
- Hallucinations, confusion, or other unusual behaviors
- Tingling or unusual pain
- Sudden pain or popping sensation
- Swelling of abdomen or extremities
Severe or serious side effect symptoms should be reported immediately.
Fluoroquinolone Antibiotics Aortic Aneurysm and Aortic Dissection
In December of 2018, the FDA issued a warning stating that fluoroquinolone antibiotics have been associated with increased risk of cardiac side effects which may be fatal. The chance of aortic aneurysm or aortic dissection may be doubled, beginning when medications are first taken and continuing for up to 60 days after fluoroquinolones are discontinued.
The aorta is the large, rigid blood vessel that carries blood from the heart to the body. Aortic aneurysm occurs when the rigid structure of the aorta wall begins to thin and bulge. If this aneurysm or bulge ruptures, massive bleeding or hemorrhage 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.
Studies show that fluoroquinolones are toxic to collagen I, a substance which makes up most of the support tissue and gives structure to large blood vessels such as the aorta and cartilage in large tendons of the body. Fluoroquinolones may weaken collage by encouraging minerals such as calcium to stick to the cells, in a process known as chelation. They may also interfere with cartilage repair by blocking enzymes or by eliminating cells known as chondrocytes which are needed to make new cartilage.
Certain groups of patients are at increased chance of aortic aneurysm including those who:
- Are elderly
- Have a history of blocked blood vessels
- Have high blood pressure
- Have a genetic condition which affects collagen formation including Marfans syndrome and others
Fluoroquinolone Antibiotics Tendon Rupture
Because of the effects on cartilage formation and repair, fluoroquinolone antibiotics may increase the risk for tendon rupture. Tendon rupture or tendinopathy risk may be 3 to 4 times higher in those who take fluoroquinolones than in patients who are not taking the medications. The increased risk begins right after the medication is started and continues for up to 60 days after discontinuation.
In 2008, the FDA issued a black box warning, the most serious warning issued by the agency, regarding fluoroquinolone use and tendon rupture. The warning also recommended that fluoroquinolone use should be restricted in those over age 60, organ transplant patients and those taking anti-inflammatory medications and stated that use in children should be limited to medical necessity.
Fluoroquinolone Antibiotics Lawsuits and Settlements
Manufacturers of fluoroquinolone antibiotic medications have faced a number of lawsuits filed by people who had taken the medications and experienced serious side effects. Certain medications including ofloxacin and others have been discontinued in Europe and other countries outside of the U.S. Inside of the U.S., medications including Levaquin are no longer manufactured but may still be available in pharmacies. A number of lawsuits may have been settled against manufacturers of fluoroquinolone antibiotics, but none are ongoing.
Levaquin Prescribing Information, RxList (12/2018)