What are the potential side effects of fluoroquinolones (FQs)?

Fluoroquinolone Side Effects

Fluoroquinolones cause a wide spectrum of adverse effects, with the most serious being musculoskeletal complications—particularly tendinitis and tendon rupture—which led the FDA to issue a black box warning for all fluoroquinolones in 2008. 1

Musculoskeletal Complications (Most Serious)

Tendon Disorders

• Tendinitis, tendinosis, and tendon rupture are the most clinically significant adverse effects, with the Achilles tendon affected in approximately 90% of cases 1, 2
• Current fluoroquinolone use increases the risk of:
  • Tendon disorders overall (odds ratio 1.7) 2
  • Tendon rupture (odds ratio 1.3) 2
  • Achilles tendon rupture specifically (odds ratio 4.1) 2
• Symptoms can occur as early as 2 hours after the first dose or as late as 6 months after discontinuation (median onset 6 days) 1, 2, 3
• Other tendons can be affected including rotator cuff, patellar tendon, biceps, and hand/foot tendons 1
• Bilateral involvement occurs in more than half of cases 4

High-Risk Populations for Tendon Complications

• Age over 60 years: 4 times higher risk of Achilles tendon rupture compared to general population 2
• Concomitant corticosteroid use: dramatically increases risk (odds ratio 43.2), with 1 in 979 patients experiencing Achilles tendon rupture 2, 4
• Patients with kidney, heart, or lung transplants 3
• History of tendon disorders or rheumatoid arthritis 3
• Athletes and those engaged in strenuous physical activity 4

Other Musculoskeletal Effects

• Arthralgia, impaired fracture healing, and cartilage lesions 1
• Myalgia and rhabdomyolysis 1

Gastrointestinal Effects

• Nausea is the most common adverse effect (0.5-1.8% of patients) and the leading cause of treatment discontinuation (0.6%) 5
• Vomiting and bloating occur in 0.5-1.8% of patients 5
• Clostridium difficile-associated diarrhea (CDAD) can occur and may range from mild diarrhea to fatal colitis 3
• CDAD has been reported up to 2 months after discontinuing antibiotics 3

Central Nervous System Effects

• Dizziness, insomnia, tremulousness, and headache occur in approximately 0.5% of patients 5
• Convulsions and seizures, particularly in patients with CNS disorders or those taking NSAIDs concurrently 3, 6
• Toxic psychoses, increased intracranial pressure (including pseudotumor cerebri) 3
• CNS stimulation leading to tremors, restlessness, anxiety, confusion, hallucinations, paranoia, depression, and rarely suicidal thoughts 3

Peripheral Neuropathy

• Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons 3
• Symptoms include paresthesias, hypoesthesias, dysesthesias, and weakness 3
• May occur soon after initiation and can be irreversible 3
• Requires immediate discontinuation if symptoms develop 3

Cardiovascular Effects

• QT interval prolongation with rare cases of torsade de pointes 3
• Should be avoided in patients with known QT prolongation, uncorrected hypokalemia, or those taking Class IA or III antiarrhythmic agents 3
• Elderly patients are more susceptible to QT interval effects 3

Hepatotoxicity

• Severe hepatotoxicity including acute hepatitis and fatal events reported in postmarketing surveillance 3
• Most cases occur within 14 days of initiation, with majority within 6 days 3
• More common in patients 65 years or older 3
• Symptoms include loss of appetite, nausea, vomiting, fever, weakness, right upper quadrant tenderness, jaundice, and dark urine 3

Dermatologic Reactions

• Rash, pruritus, and photosensitivity occur in 0.2-0.4% of patients 5
• Phototoxicity is significantly more common with 8-halogenated compounds (particularly lomefloxacin) 6
• Severe reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome (rare) 3

Hypersensitivity Reactions

• Can occur even after the first dose 3
• Range from mild rash to severe anaphylaxis with cardiovascular collapse, angioedema, bronchospasm, and respiratory distress 3
• Requires immediate discontinuation at first sign of skin rash or hypersensitivity 3

Myasthenia Gravis Exacerbation

• Fluoroquinolones can cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems 3
• Contraindicated in patients with known myasthenia gravis 3

Other Serious Adverse Effects

• Interstitial nephritis and acute renal insufficiency or failure 3
• Hematologic abnormalities including hemolytic anemia, thrombocytopenia, leukopenia, and agranulocytosis 3
• Hypoglycemia and hyperglycemia, particularly in diabetic patients 3

Critical Clinical Pitfalls

• Do not delay discontinuation if tendon pain, swelling, or inflammation develops—symptoms can progress rapidly to rupture 3
• Avoid prescribing to patients over 60 years with concurrent corticosteroid use unless no alternative exists 2, 4
• Separate administration from antacids, multivitamins with minerals, and sucralfate by at least 2 hours to avoid absorption interference 3
• Monitor for bilateral tendon involvement, not just unilateral symptoms 4
• Consider alternative antibiotic classes in high-risk populations (elderly, athletes, those with history of tendon disorders) 2