What are the risks associated with Levaquin (levofloxacin)?

Levaquin (Levofloxacin) Risks

Levofloxacin carries serious risks including tendon rupture, peripheral neuropathy, myasthenia gravis exacerbation, and central nervous system effects, with FDA black box warnings for tendinopathy and myasthenia gravis complications. 1

Musculoskeletal Risks

Tendinopathy and Tendon Rupture (Black Box Warning)

• Tendinitis and tendon rupture occur in all ages, most frequently affecting the Achilles tendon, with rates of 15-20 per 100,000 treated adult patients 2, 1
• Rupture can occur during treatment or up to several months after completion of therapy 1
• Levofloxacin specifically demonstrates higher propensity for tendon damage compared to other fluoroquinolones, with risk being exposure-dependent (higher doses and longer durations pose greater risk) 3
• A large retrospective study of 1 million Medicare beneficiaries found levofloxacin increased tendon rupture risk by 16% overall (HR=1.16), with 120% increased risk for Achilles tendon rupture specifically (HR=2.20) within 30 days of use 4
• Rotator cuff rupture risk increased by 16% (HR=1.16) with levofloxacin use 4

High-Risk Patient Populations for Tendinopathy

Patients at highest risk include: 2, 1, 3

• Age >60 years
• Concurrent corticosteroid therapy
• Kidney, heart, or lung transplant recipients
• Renal dysfunction
• History of rheumatoid arthritis or previous tendon disorders
• Strenuous physical activity

Management: Discontinue levofloxacin immediately if patient experiences pain, swelling, inflammation, or rupture of a tendon; advise rest and avoid exercise 1

Neurologic Risks

Peripheral Neuropathy

• Peripheral neuropathy may occur soon after initiation and can be irreversible 1
• Symptoms include pain, burning, tingling, numbness, and/or weakness 1
• Discontinue immediately if symptoms develop 1

Central Nervous System Effects

• Convulsions have been reported, particularly in patients with history of seizures 1
• Dizziness and lightheadedness may impair ability to operate machinery 1
• Persistent headache with or without blurred vision may indicate increased intracranial pressure 1
• Neurologic adverse events occurred in 3% of ciprofloxacin-treated patients in pediatric studies 2

Myasthenia Gravis Exacerbation (Black Box Warning)

• Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in myasthenia gravis patients 1
• Postmarketing reports include deaths and requirement for ventilatory support 1
• Avoid levofloxacin completely in patients with known myasthenia gravis 1

Cardiovascular Risks

QT Prolongation

• Levofloxacin can prolong the QT interval 1, 5
• Avoid in patients with: 1
  • Personal or family history of QT prolongation
  • Proarrhythmic conditions (hypokalemia, bradycardia, recent myocardial ischemia)
  • Concurrent use of Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic agents

Hypersensitivity and Allergic Reactions

• Serious and occasionally fatal hypersensitivity/anaphylactic reactions can occur, often following the first dose 1
• Reactions may include cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, angioedema, airway obstruction, bronchospasm, and acute respiratory distress 1
• Discontinue immediately at first appearance of skin rash or any sign of hypersensitivity 1

Hepatotoxicity

• Severe hepatotoxicity including acute hepatitis and fatal events have been reported 1
• Discontinue immediately if signs of liver injury develop: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, jaundice, light-colored stools, or dark urine 1

Gastrointestinal Effects

• Common adverse effects include gastrointestinal symptoms in 0.5-1.8% of patients 6
• Clostridioides difficile-associated diarrhea can occur, even 2+ months after last dose 1

Other Adverse Effects

• Cutaneous reactions occur in 0.2-0.4% of patients 6
• Glucose disturbances (hypo- or hyperglycemia) have been reported 5
• Phototoxicity potential exists, though lower than some other quinolones 7

Pediatric-Specific Concerns

• Not generally recommended for pediatric patients due to concerns about effects on bone and cartilage growth 6, 8
• Long-term follow-up studies showed musculoskeletal adverse events (arthropathy, peripheral neuropathy, abnormal bone development, scoliosis, walking difficulty, myalgia, tendon disorder) in 2% of levofloxacin-treated children at 5 years 2
• Reserve for drug-resistant organisms or specific severe infections where benefits clearly outweigh risks 6, 8

Drug Interactions

• Antacids containing aluminum/magnesium, sucralfate, iron supplements, multivitamins with zinc, and divalent cations markedly decrease absorption 6, 9, 1
• Administer these agents at least 2 hours before or after levofloxacin 6, 9, 1
• Cimetidine and probenecid decrease renal clearance but interactions are not clinically significant 10

Antimicrobial Resistance Concerns

• Levofloxacin should not be used as first-line agent for most bacterial infections and must be reserved for drug-resistant organisms, first-line drug intolerance, or specific severe infections 6
• Data suggest levofloxacin may promote fluoroquinolone resistance among S. pneumoniae and potentially drive class-wide resistance to P. aeruginosa 5
• E. coli resistance to fluoroquinolones ranges from 4-7% at major US tertiary care centers 6