Fluoroquinolones Linked to Life-Threatening Blood Vessel Complications

A study published in a recent issue of JAMA Internal Medicine revealed two potentially fatal complications of a commonly used class of antibiotics.[1] It was the first human study investigating whether the antibiotics, known as fluoroquinolones, could damage the body’s largest blood vessel, the aorta.

The study was important because fluoroquinolones are very widely (and often unnecessarily) used and because the two complications identified in the study can be life-threatening.

Fluoroquinolones

Fluoroquinolones are effective in treating a variety of serious bacterial infections, such as pneumonia[2] and kidney infections,[3],[4] especially in patients with serious cases or at higher risk of complications from certain infections. (See table, for a list of all currently approved oral fluoroquinolones.)

However, the drugs are widely overused for infections for which they are not first-choice drugs. For example, they are almost certainly being overused for lung and urinary tract infections.[5]

Fluoroquinolones can damage collagen, the building block of many of the body’s tissues, such as tendons.[6] In 2006, in response to hundreds of reports of tendon rupture and tendinitis occurring in patients on fluoroquinolones, Public Citizen successfully petitioned the Food and Drug Administration (FDA) for a prominent black-box warning on all fluoroquinolone labels about the risk of such adverse events.[7],[8]

The authors of the JAMA Internal Medicine study sought to investigate whether the antibiotics could damage the wall of the aorta, which is also made up of collagen, and thus lead to a ballooning of (aortic aneurysm) or tear in (aortic dissection) the aorta’s wall.[9]

Aortic aneurysm and dissection

An aortic aneurysm can occur in either the chest or the abdomen.[10] It is more common in older men, and leading risk factors include smoking, chewing tobacco, cardiovascular disease and family history.[11]

Aortic aneurysms can exist for many years without causing symptoms. However, there is always a risk of an aneurysm rupturing — especially once it reaches a certain size — which is a medical emergency and almost always fatal unless promptly treated.

Aortic dissection involves a tear within the inner layers of the aorta, allowing blood to leak into the wall of the blood vessel. This condition often develops suddenly[12] and is considered a life-threatening medical emergency.[13] A common symptom is severe chest pain that can spread to the back, shoulder, neck, arms or legs.[14] Without treatment, the dissection can result in a rupture of the aorta and, even in the absence of a rupture, quickly can lead to dizziness, sweating, rapid heart rate, nausea or vomiting, pale skin, and other signs of dangerously low blood pressure.[15] A dissection can result from an aortic aneurysm[16] but also can happen in the absence of an aneurysm.

The study

The JAMA Internal Medicine study obtained information on nearly 150,000 patients in Taiwan’s National Health Insurance Research Database.[17] The study compared fluoroquinolone use between patients who had experienced aortic aneurysm or dissection and those who had not. Overall, patients with an aortic aneurysm or dissection were approximately twice as likely to have received a fluoroquinolone prescription in the previous 60 days as patients, matched for age and other characteristics, who had not experienced either condition. Patients over 70 and women were more likely to have an aortic aneurysm or dissection within a year of using fluoroquinolones. Finally, the study found that longer fluoroquinolone use (more than two weeks) was linked to a higher risk of either complication.

Oral Fluoroquinolones Currently Approved In the U.S.*[19]

*As of Jan. 15, 2016. Combination medicines not included in this table.
** Do Not Use
*** Limited Use

What You Can Do

You should take fluoroquinolones only for bacterial infections for which the medicines are approved by the FDA. You should review these conditions with your doctor.

If your doctor decides to treat you with a fluoroquinolone, you should first discuss whether the drug is the first choice for the infection you have, and also discuss the drug’s serious risks. In addition to the risks of tendon injury and, possibly, aortic aneurysm and dissection, side effects include seizures, tremors, disabling nerve disorders, potentially fatal abnormal heart rhythms and skin damage.[18]

Always take the complete prescribed course of any antibiotic, and never stop any medication without talking with your doctor.

References

[1] Lee CC, Lee MT, Chen YS, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-47.

[2] Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/CAP%20in%20Adults.pdf. Accessed January 15, 2016.

[3] Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-120.

[4] DailyMed. Levaquin (levofloxacin) label. July 2014. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aa2bfa2-0b24-49ba-806e-07afdbb984ec. Accessed February 11, 2016.

[5] Public Citizen. Testimony Before the FDA’s Antimicrobial Drugs and Drug Safety and Risk Management Advisory Committees Regarding Fluoroquinolone Antibiotics. November 5, 2015. http://www.citizen.org/documents/2282.pdf. Accessed January 15, 2016.

[6] Lee CC, Lee MT, Chen YS, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-1847.

[7] Ibid.

[8] Public Citizen. Public Citizen v. Food and Drug Administration (FDA) (Fluoroquinolone). http://www.citizen.org/litigation/forms/cases/getlinkforcase.cfm?cID=444. Accessed January 14, 2016.

[9] Lee CC, Lee MT, Chen YS, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-1847.

[10] National Library of Medicine. MedlinePlus. Aortic aneurysm. https://www.nlm.nih.gov/medlineplus/aorticaneurysm.html. Accessed January 14, 2016.

[11] Mayo Clinic. Abdominal aortic aneurysm. Risk factors. http://www.mayoclinic.org/diseases-conditions/abdominal-aortic-aneurysm/basics/risk-factors/con-20023784. Accessed January 15, 2016.

[12] National Library of Medicine. MedlinePlus. Aortic dissection. https://www.nlm.nih.gov/medlineplus/ency/article/000181.htm. Accessed January 13, 2016.

[13] Coady MA, Rizzo JA, Goldstein LJ, Elefteriades JA. Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections. Cardiol Clin. 1999;17(4):615-635; vii.

[14] National Library of Medicine. MedlinePlus. Aortic dissection. https://www.nlm.nih.gov/medlineplus/ency/article/000181.htm. Accessed January 13, 2016.

[15] Ibid.

[16] Centers for Disease Control and Prevention. Aortic Aneurysm Fact Sheet. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_aortic_aneurysm.htm. Accessed January 14, 2016.

[17] Lee CC, Lee MT, Chen YS, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-1847.

[18] Food and Drug Administration. FDA Briefing Document. Joint meeting of the Antimicrobial Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. November 5, 2015. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM467383.pdf. Accessed January 15, 2016.

[19] Complete list of fluoroquinolones obtained from two sources, on January 15, 2016: 1) a word-search of the Drugs@FDA website for “oxacin” (https://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm); and 2) the Merck Manual, Professional Version. Fluoroquinolones (http://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/fluoroquinolones).