What is the incidence of adverse effects with fluoroquinolones?

From the Guidelines

Fluoroquinolones are associated with a significant incidence of adverse effects, including musculoskeletal events, with rates ranging from 6.0% to 9.3% in pediatric patients 1.

Adverse Effects

• The most common adverse effects include musculoskeletal events, such as arthralgia and arthritis, which have been reported in 9.3% of patients receiving ciprofloxacin compared to 6.0% in control patients 1.
• Neurologic adverse events, such as dizziness, nervousness, and insomnia, have also been reported, with rates ranging from 0.1% to 3% 1.
• A rare but serious complication associated with fluoroquinolones is tendon rupture, which is estimated to occur at a rate of 15 to 20 per 100,000 treated patients in the adult population 1.

Risk Factors

• The risk of adverse events is dose- and duration-dependent, with higher risks observed at doses above 500mg per day and treatment durations exceeding 14 days.
• Advanced age, antecedent steroid therapy, and underlying diseases, such as hypercholesterolemia, gout, rheumatoid arthritis, end-stage renal disease/dialysis, and renal transplantation, have been identified as risk factors for tendon rupture 1.

Patient Population

• The incidence of adverse effects may vary depending on the patient population, with pediatric patients appearing to have a lower risk of musculoskeletal events compared to adult patients 1.
• However, the risk of tendon rupture in pediatric patients is not well established, and further studies are needed to determine the incidence of this adverse event in this population 1.

From the FDA Drug Label

Adverse Events In clinical trials, 1534 children (6 months to 16 years of age) were treated with oral and intravenous levofloxacin Children 6 months to 5 years of age received levofloxacin 10 mg/kg twice a day and children greater than 5 years of age received 10 mg/kg once a day (maximum 500 mg per day) for approximately 10 days A subset of children in the clinical trials (1340 levofloxacin-treated and 893 non-fluoroquinolone-treated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocol-defined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) during 60 days and 1 year following the first dose of the study drug Children treated with levofloxacin had a significantly higher incidence of musculoskeletal disorders when compared to the non-fluoroquinolone-treated children as illustrated in Table 9. Vomiting and diarrhea were the most frequently reported adverse events, occurring in similar frequency in the levofloxacin-treated and non-fluoroquinolone-treated children In phase 3 clinical trials, 1,945 levofloxacin-treated patients (26%) were ≥ 65 years of age. Severe, and sometimes fatal, cases of hepatotoxicity have been reported postmarketing in association with levofloxacin. Elderly patients may be more susceptible to drug-associated effects on the QT interval.

The incidence of adverse effects with fluoroquinolones, specifically levofloxacin, includes:

• Musculoskeletal disorders: significantly higher incidence in children treated with levofloxacin compared to non-fluoroquinolone-treated children
• Vomiting and diarrhea: most frequently reported adverse events, occurring in similar frequency in levofloxacin-treated and non-fluoroquinolone-treated children
• Hepatotoxicity: severe and sometimes fatal cases reported postmarketing in association with levofloxacin, more common in patients 65 years of age or older
• QT interval prolongation: elderly patients may be more susceptible to drug-associated effects on the QT interval 2
• Tendon disorders: higher risk in older patients, usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants 2

From the Research

Incidence of Adverse Effects with Fluoroquinolones

• The incidence of adverse effects with fluoroquinolones, particularly tendinopathy, has been a concern due to its potential for long-term sequelae, including chronic pain and mobility restrictions 3, 4, 5, 6.
• A study found that 34 (18.5%) participants developed tendinopathy out of 184 TB patients who received fluoroquinolones, with risk factors including younger age, female sex, and prolonged usage of levofloxacin 4.
• Another study reported that the expected risk of Achilles tendinopathy or rupture was 0.17% for levofloxacin, 0.17% for ciprofloxacin, 1.40% for ofloxacin, and 0.31% for other molecules, with ofloxacin showing a significantly higher rate of complications 6.
• Fluoroquinolones have also been associated with other adverse effects, including phototoxicity, seizures, gastrointestinal effects, nephrotoxicity, and hypersensitivity reactions 5, 7.

Risk Factors for Adverse Effects

• Patient-specific risk factors for fluoroquinolone-associated tendinopathy include older age, receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation 3.
• Other risk factors include younger age, female sex, and prolonged usage of levofloxacin 4.
• Chronic renal diseases, concomitant use of corticosteroids, and age over 60 years have also been recognized as risk factors for fluoroquinolone-induced tendon disorders 5.

Management of Adverse Effects

• Conservative treatment, reducing the dose or discontinuation of fluoroquinolones, has been shown to successfully improve symptoms of tendinopathy 4.
• It is essential to consider the specific adverse effect profiles of fluoroquinolones when choosing them for treatment of bacterial infections, particularly in elderly patients or those with certain comorbidities 5.