FDA’s updated fluoroquinolone warnings: What urologists should know

Dr. Cox is director of the Office of Antimicrobial Products in the Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.

Fluoroquinolones have risks and benefits that should be carefully considered before prescribing to patients for uncomplicated bacterial infections, including urinary tract infections. Prescribers should know that the FDA has updated its warnings to say that fluoroquinolones should not be prescribed to patients who have other treatment options for acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated urinary tract infections. That is the latest thinking from the U.S. Food and Drug Administration about a class of drugs that have been in use for decades.

Recently, the FDA approved safety labeling changes for fluoroquinolones, including an updated Boxed Warning and Warnings and Precautions, to enhance warnings about their association with disabling and potentially permanent side effects that can occur together. Adverse reactions to fluoroquinolone can range from severe acute events to effects on multiple body systems that can be long-lasting and potentially irreversible.

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A new FDA safety review found that side effects involving the tendons, muscles, joints, nerves, and central nervous system can occur together in the same patient. Side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially become permanent. Because the risk of these serious side effects generally outweighs the benefits for patients who have other treatment options, the FDA has determined that fluoroquinolones should be reserved for use in patients who have no alternative treatment options.

For serious bacterial infections, such as complicated intra-abdominal infections, bacterial pneumonia, plague, or prophylaxis of anthrax, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain as a therapeutic option.

FDA-approved and currently available fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets (Cipro XR), moxifloxacin (Avelox), ofloxacin (Floxin), and gemifloxacin (Factive).

Serious adverse events

Following are some examples of adverse events related to fluoroquinolones. If a patient develops symptoms of any of these conditions while these antibiotics, they should be stopped immediately and the patient should be switched to an alternative antibacterial drug-unless the benefit of the continued fluoroquinolone treatment outweighs the risk.

Tendinopathy and tendon rupture. In patients of all ages, fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture, most frequently involving the Achilles tendon. The risk for tendinitis and tendon increases in patients over 60 years of age, patients taking corticosteroid drugs, and patients with kidney, heart, or lung transplants. Prescribers should also be aware of other factors that may increase the risk of fluoroquinolone-associated tendon rupture, such as strenuous physical activity.

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Peripheral neuropathy. Peripheral neuropathy can occur in the arms or legs any time after a fluoroquinolone is taken by mouth or injection and can last for months to years after the drug is stopped or it can be permanent.

Central nervous system effects. While side effects involving the central nervous system tend to be infrequent, seizures, increased intracranial pressure, headaches, dizziness, confusion, and psychosis have been reported in association with fluoroquinolones. Other psychiatric side effects that can occur include nervousness, agitation, insomnia, anxiety, nightmares, paranoia, and depression/suicidal thoughts. Prescribers should be aware of the seriousness of these side effects and that they can occur in patients who do not have a past history of neuro-psychiatric problems.

Disabling and potentially irreversible serious adverse reactions. Disabling and potentially irreversible serious adverse reactions from different body systems can occur together in the same patient. These adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). Patients of any age or without pre-existing risk factors have experienced these adverse reactions.

Product labeling

Additional safety information contained in the product labeling includes:

• exacerbation of muscle weakness in patients with myasthenia gravis

• hypersensitivity reactions including anaphylaxis

• prolongation of the QT interval

• disturbances in blood glucose

• association with C. difficile diarrhea

• photosensitivity and phototoxicity.

Informing prescribers

Prescribers may not be aware of the potential serious side effects related to fluoroquinolones. When considering antibacterial drug treatment options, prescribers should balance the benefits of systemic fluoroquinolone therapy with the risks of adverse reactions. The FDA encourages prescribers and pharmacists to counsel patients to read the Medication Guide provided with each fluoroquinolone prescription.

The FDA is continuing to investigate safety issues with fluoroquinolones and is asking health care providers to report adverse reactions to MedWatch, the online FDA adverse event reporting system.

Links for more information can be found here:

http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm500325.htm

http://www.fda.gov/Drugs/DrugSafety/ucm511530.htm

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513183.htm

http://www.fda.gov/safety/medwatch/howtoreport/ucm085568.htm