What are the potential side effects of fluoroquinolones (e.g. ciprofloxacin, levofloxacin) in adults, particularly those over 60 years old with a history of tendon disorders or neurological disorders?

Side Effects of Fluoroquinolones

Fluoroquinolones carry FDA black box warnings for tendinitis and tendon rupture, with particularly high risk in adults over 60 years old, those on corticosteroids, and patients with prior tendon disorders—these patients should receive alternative antibiotics whenever clinically feasible. 1

Musculoskeletal Complications (Most Serious)

Tendon Disorders

• Tendinitis, tendinosis, and tendon rupture are the most clinically significant adverse effects, affecting tendons, cartilage, bone, and muscle 2
• The Achilles tendon is involved in 90% of cases, though rotator cuff, patellar, biceps, hand, and foot tendons can also be affected 3, 1
• Risk increases 4.1-fold for Achilles tendon rupture compared to non-users, with absolute risk of 12 additional cases per 100,000 persons within 90 days of treatment 4, 3
• Bilateral involvement occurs in more than half of cases, requiring examination of both sides 4, 3
• Symptoms typically appear within 1 week (median 6 days) but can occur as early as 2 hours after first dose or as late as 6 months after discontinuation 4, 1

High-Risk Populations for Tendon Injury

• Age over 60 years: 4-fold increased risk, with 1 rupture per 1,638 treated patients 3, 1
• Concomitant corticosteroid use: dramatically escalates risk to odds ratio of 43.2 for Achilles tendon rupture 4, 3
• History of tendon disorders (including rheumatoid arthritis) 2, 1
• Kidney, heart, or lung transplant recipients 1
• Strenuous physical activity or athletes: 50% of fluoroquinolone-associated tendon disorders occur during sports participation 4
• Renal failure 1

Other Musculoskeletal Effects

• Arthralgia, impaired fracture healing, and cartilage lesions 2
• Myalgia and rhabdomyolysis 2

Neurological Complications

Central Nervous System Effects

• Dizziness, insomnia, tremor, headache occur in approximately 0.5% of patients 5, 6
• Seizures and convulsions, particularly in patients with epilepsy or CNS disorders 2, 1
• Confusion, weakness, depression may be mistakenly attributed to old age in elderly patients and remain unreported 6
• Restlessness, nervous excitation, hallucinations, and phonism in moderate to severe cases 7
• Increased intracranial pressure with persistent headache and blurred vision 1

Peripheral Neuropathy

• Peripheral neuropathy with pain, burning, tingling, numbness, and weakness may occur soon after initiation and can be irreversible 1, 8
• Small fiber neuropathy is a recognized complication 8
• Discontinue immediately if symptoms of peripheral neuropathy develop 1

Risk Factors for CNS Toxicity

• Elderly patients over 60 years 7
• Intravenous administration 7
• Past history of neurological diseases (epilepsy, pronounced arteriosclerosis) 6, 7
• Drug combinations, especially with theophylline (particularly enoxacin) 9

Exacerbation of Myasthenia Gravis

• Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness 1
• Deaths and requirement for ventilatory support have been reported 1
• Avoid levofloxacin entirely in patients with known myasthenia gravis 1

Cardiovascular Complications

• QT interval prolongation leading to potentially fatal arrhythmias, more common with moxifloxacin 2, 6
• Contraindicated in patients with: congenital or acquired QT prolongation, clinically relevant bradycardia, heart failure with reduced ejection fraction, history of symptomatic arrhythmias, uncorrected hypokalaemia or hypomagnesaemia 2, 6
• Avoid concurrent use with Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic agents 2, 1
• Aortic dissection and aneurysm rupture 8

Gastrointestinal Effects

• Nausea is the most frequent adverse effect (0.5-1.8% of patients) and leading cause of treatment discontinuation (0.6%) 5
• Vomiting, bloating, dyspepsia, and diarrhea 5, 6, 9
• Clostridioides difficile infection 8

Hepatic Toxicity

• Transient increases in liver function tests are common 2
• Acute hepatitis (rare but potentially fatal) 2
• Severe hepatotoxicity with fatal events reported, particularly with moxifloxacin in patients with Child-Pugh C cirrhosis 2
• Discontinue immediately if signs of liver injury develop: loss of appetite, nausea, vomiting, fever, weakness, right upper quadrant tenderness, jaundice, dark urine 1

Metabolic and Endocrine Effects

• Disrupted glucose metabolism with hypoglycemia in patients on hypoglycemic drugs 2, 8
• Monitor blood glucose regularly in diabetic patients 2

Dermatologic Reactions

• Rash, pruritus, and photosensitivity occur in 0.2-0.4% of patients 5
• Phototoxicity varies by agent, with caution necessary for intensive UV light exposure, especially with pefloxacin 9, 8
• Stevens-Johnson syndrome and toxic epidermal necrolysis (rare) 2

Hypersensitivity Reactions

• Serious and occasionally fatal anaphylactic reactions, often following first dose 1
• Cardiovascular collapse, hypotension/shock, seizure, loss of consciousness 1
• Angioedema (tongue, laryngeal, throat, facial swelling), airway obstruction, bronchospasm 1
• Discontinue immediately at first sign of skin rash or hypersensitivity 1

Hematologic Effects

• Agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia (uncommon) 2

Renal Toxicity

• Acute renal failure 8
• Crystallization-induced acute kidney failure more specific to ciprofloxacin and norfloxacin 8
• Dosage adjustment required when creatinine clearance <50 mL/minute for levofloxacin 5

Respiratory Effects

• Extrinsic allergic alveolitis (rare) 2

Risk Mitigation Strategies

Magnesium Supplementation

• The American College of Physical Medicine and Rehabilitation recommends considering magnesium supplementation during fluoroquinolone treatment if no contraindications exist 4, 3
• Mechanism relates to fluoroquinolones chelating magnesium and other divalent cations, affecting collagen synthesis 4, 3

Antioxidant Supplementation

• Vitamin E or coenzyme Q10 supplementation may be beneficial based on preliminary data showing protective effects against tendon damage 4
• Mitochondrial-targeted ubiquinone (MitoQ) demonstrates larger protective effects than untargeted ubiquinone 4

Drug Interactions to Avoid

• Separate antacids containing magnesium or aluminum, sucralfate, iron, multivitamins with zinc, and didanosine by at least 2 hours from fluoroquinolone administration 5, 1

Critical Management Pitfalls

• Do not delay discontinuation if tendon pain, swelling, or inflammation occurs—symptoms can appear within 2 hours or up to 6 months after stopping 4, 1
• Rest immediately at first sign of tendinitis; 50% of cases occur during sports participation 4
• Examine both Achilles tendons as bilateral involvement is common 4, 3
• Elderly patients' CNS symptoms (confusion, weakness, depression) are often mistakenly attributed to aging rather than drug toxicity 6
• Some adverse effects progress after discontinuation (tendinopathy, neuropathy) or may be irreversible (peripheral neuropathy) 1, 8
• For high-risk individuals (over 60 years, history of tendon disorders, neurological disorders, athletes), strongly consider alternative antibiotic classes when clinically appropriate 4, 3