What are the secondary effects of quinolones (fluoroquinolones)?

Secondary Effects of Quinolones

Quinolones can cause serious adverse effects including tendinopathy, peripheral neuropathy, CNS disorders, QT prolongation, photosensitivity, and musculoskeletal events, and should be used only when there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria.

Common Adverse Effects

• Gastrointestinal effects: Nausea, dyspepsia, vomiting, and diarrhea are among the most frequently reported adverse reactions during fluoroquinolone therapy 1, 2
• Central nervous system effects: Dizziness, insomnia, nervousness, somnolence, and anxiety may occur, with symptoms potentially appearing after the first dose 3, 4
• Skin reactions: Rash and photosensitivity reactions, especially with exposure to UV light or sunlight 4, 5

Serious Adverse Effects

Musculoskeletal Effects

• Tendinopathy: Tendinitis and tendon ruptures (particularly Achilles tendon) can occur within hours of starting treatment or months after completion 6
  • Risk factors include age >60 years, concomitant corticosteroid use, kidney/heart/lung transplants, renal failure, and previous tendon disorders 6, 1
• Arthropathy: Reported in pediatric patients at rates of 9.3% compared to 6.0% in control patients 7

Neurological Effects

• Peripheral neuropathy: Sensory or sensorimotor axonal polyneuropathy resulting in paresthesias, hypoesthesias, dysesthesias, and weakness 6, 8
  • Symptoms may be irreversible and require immediate discontinuation of the medication 8
• Seizures and increased intracranial pressure: Including pseudotumor cerebri 8
• Psychiatric effects: Anxiety, confusion, hallucinations, paranoia, depression, and rarely suicidal thoughts or acts 4, 8

Cardiovascular Effects

• QT interval prolongation: Can lead to rare but potentially fatal torsade de pointes 7, 8
  • Higher risk with sparfloxacin and grepafloxacin compared to other fluoroquinolones 9
  • Should be avoided in patients with known QT prolongation, uncorrected hypokalemia/hypomagnesemia, and those taking Class IA or III antiarrhythmic agents 8, 1

Other Serious Effects

• Hypersensitivity reactions: Can range from mild skin reactions to severe manifestations including anaphylaxis 8
• Clostridium difficile-associated diarrhea: Can range from mild diarrhea to fatal colitis 8
• Hepatotoxicity: Severe hepatotoxicity including acute hepatitis and fatal events have been reported 8
• Glucose homeostasis disorders: Hypoglycemia or hyperglycemia can occur, particularly in diabetic patients taking oral hypoglycemic agents 4, 10

Risk Factors for Adverse Effects

• Age: Elderly patients are at higher risk for tendinopathy, CNS effects, and QT prolongation 1
• Renal impairment: Requires dose adjustment for renally excreted quinolones (e.g., ofloxacin, levofloxacin) 1
• Concomitant medications:
  • Corticosteroids increase risk of tendinopathy 1
  • Class IA or III antiarrhythmic agents increase risk of QT prolongation 8
  • NSAIDs may increase seizure risk 5
• Pre-existing conditions:
  • CNS disorders that predispose to seizures 8
  • Myasthenia gravis (can be exacerbated) 6
  • History of tendon disorders 7

Pediatric Considerations

• Fluoroquinolones cause arthrotoxicity in juvenile animals 3
• Limited approved indications in pediatric patients: complicated urinary tract infections, pyelonephritis, and post-exposure treatment for inhalation anthrax 3
• Should be restricted to situations where there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria 3

Risk Mitigation Strategies

• Avoid use in patients with risk factors for tendon complications when possible 7
• Monitor ECG in patients with liver cirrhosis 6
• Avoid extensive exposure to UV light during therapy 4
• Discontinue immediately if signs of peripheral neuropathy, tendinopathy, or hypersensitivity occur 6, 8
• Consider alternative antibiotics in high-risk patients 7

Bacterial Resistance Concerns

• Increased use of fluoroquinolones has led to increased bacterial resistance 3
• Resistance mechanisms include mutations in target enzymes, efflux pumps, and plasmid-encoded resistance proteins 3
• Fluoroquinolones should be used judiciously to prevent further resistance development 3