The perils of prescribing fluoroquinolones

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Applied Evidence

The perils of prescribing fluoroquinolones

J Fam Pract. 2013 April;62(4):191-197

By

Heather Holmstrom, MD

Joel J. Heidelbaugh, MD, FAAFP, FACG

These broad-spectrum antibiotics—notable for combatting pathogens resistant to other drugs—have a small but noteworthy potential for adverse effects. This review and patient handout highlight signs and symptoms to watch for.

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References

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PRACTICE RECOMMENDATIONS

• Evaluate liver function before initiating fluoroquinolone (FQ) therapy, and avoid prescribing these antibiotics for patients at increased risk for hepatotoxicity. C

• Avoid prescribing FQs for patients with a history of prolonged QT syndrome. C

• Closely monitor older patients being treated with FQs, particularly if they have atherosclerosis or epilepsy. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

PATIENT HANDOUT
Taking a fluoroquinolone antibiotic?

CASE Sara Z, a 62-year-old patient with a history of chronic urinary tract infections, presents with a 3-day history of dysuria and urinary frequency. Her last 2 urine cultures found Escherichia coli resistant to trimethoprim-sulfamethoxazole, amoxicillin, and cephalosporins. So her family physician ordered a urine culture and prescribed a 7-day course of ciprofloxacin empirically.

Five days later, Ms. Z returned, suffering from nonbloody diarrhea and bilateral Achilles tendon pain.

If you were treating Ms. Z, what would your next step be?

Widely used to treat urinary tract, skin, and pulmonary infections and to fight infections resistant to other antibiotics, fluoroquinolones (FQ) are generally regarded as safe in both inpatient and outpatient settings. Yet these broad-spectrum antibiotics are associated with both common and rare adverse effects, as well as a number of drug-drug interactions.

FAST TRACK

Adverse effects of fluoroquinolones result in ED visits at an estimated rate of 9.2 per 10,000 prescriptions.

The Centers for Disease Control and Prevention estimates that adverse events from FQs leading to emergency department (ED) visits occur at a rate of 9.2 for every 10,000 prescriptions. That’s higher than the ED rates for cephalosporins (6.1 per 10,000) and macrolides (5.1 per 10,000), but far lower than for penicillins (13 per 10,000), clindamycin (18.5 per 10,000), sulfonamides (18.9 per 10,000), and vancomycin (24.1 per 10,000).¹

In fact, adverse events associated with FQs range from mild and self-limiting to rare and severe. This review discusses both. Relatively common adverse effects and drug-drug interactions are discussed in the text, while the TABLE² includes a broader range of potential adverse effects. You’ll also find a handout for patients taking FQs on page 195 that clearly describes signs and symptoms that need to be reported right away.

TABLE
Fluoroquinolones: Adverse effects to guard against*²

Cardiovascular Hypotension Torsades de pointes	Immunologic Anaphylactoid reaction Hypersensitivity reaction
Dermatologic Eruption (angioedema, pruritus, rash, urticaria)	Musculoskeletal Arthralgias Myalgias Polyarthritis Tendinopathies
Drug-drug interactions Antacids (calcium carbonate, histamine-2 receptor antagonists) Antiarrhythmics Digoxin Ferrous sulfate Phenytoin Sucralfate Theophylline Warfarin^†	Neurologic Confusion Dizziness Drowsiness Hallucinations Headaches Seizures
Endocrine/Metabolic Glycosuria Hyper- and hypoglycemia	Ocular Diplopia Halos/hazy vision Photophobia Visual hallucinations
Gastrointestinal Diarrhea Hepatotoxicity Nausea/Vomiting	Psychiatric Psychoses Suicidal ideation
Hematologic Anemia Leukopenia Thrombocytopenia	Respiratory Dyspnea
*This is not a complete list of potential adverse effects associated with fluoroquinolones. ^†Fluoroquinolones may potentiate warfarin.

A black box warning of tendinopathies

FQs exhibit an affinity for connective tissue, with higher concentrations found in bone and cartilage than in serum. While FQs are therefore well suited for treating orthopedic-related infections,³ they also increase the risk of tendinopathies.

In the last 2 decades, numerous case reports linking tendinitis and FQs have been published.^4-6 In 2008, the US Food and Drug Administration (FDA) issued a black box warning of tendinitis and tendon rupture. Patients on FQ therapy should be advised to stop taking the antibiotic at the first sign of pain, swelling, or inflammation in a tendon, the FDA advises.⁷

How common is this adverse effect? A case-control study of 22,194 patients with a diagnosis of nontraumatic tendiopathy determined that FQ use resulted in a 1.3-fold risk of tendon rupture and more than a 4-fold risk of rupture of the Achilles tendon. One Achilles tendon rupture would occur for every 5958 patients treated with FQs, the researchers estimated.⁸

The precise mechanism by which FQs lead to tendinopathies is not completely understood. Studies suggest that the antibiotics cause a decrease in the synthesis of type I collagen, elastin, fibronectin, and beta (1)-integrin, and time- and concentration-dependent increases of cellular apoptosis.⁹ In vitro studies have shown inhibition of both cell proliferation and fibroblast metabolism when tissue is exposed to FQs, which may impede tissue healing.¹⁰

Which patients are at higher risk? The risk of FQ-associated tendinopathies is greatest in patients older than 60 years; in kidney, heart, and lung transplant recipients; and in patients taking an FQ with concomitant corticosteroid therapy. Decreased renal clearance of the medication may play a role in the increased risk.¹¹

FAST TRACK

Older age and concomitant corticosteroid therapy are associated with a higher risk for fluoroquinolone-associated tendinopathy.

GI problems are common, especially in kids and older patients

Gastrointestinal (GI) disturbances are common in patients taking FQs, and typically occur more frequently in children and older adults, and in those taking higher doses. Reactions attributable to ciprofloxacin, for example, include nausea (affecting 1.4%-4% of adults and 2.7% of children taking the drug), vomiting (1%-2% of adults and 4.8% of children), diarrhea (<1%-2% of adults and 4.8% of children), and abdominal pain or discomfort (<1%-1.7% of adults and 3.3% of children).¹²