From the Guidelines
Quinolone antibiotics can cause severe adverse effects, including tendon damage, peripheral neuropathy, and QT interval prolongation, and their use should be approached with caution, especially in elderly patients, those taking corticosteroids, and patients with renal impairment, as evidenced by the British Thoracic Society guidelines 1.
Adverse Effects of Quinolones
The most serious adverse effects of quinolones include:
- Tendon damage, particularly Achilles tendon rupture
- Peripheral neuropathy
- Central nervous system effects, such as confusion, hallucinations, and seizures
- QT interval prolongation, which can lead to cardiac arrhythmias
- Photosensitivity reactions These adverse effects are more prevalent in certain patient populations, including:
- Elderly patients
- Patients taking corticosteroids
- Patients with renal impairment
Patient Guidance
Patients should be advised to stop the medication and seek medical attention if they experience:
- Tendon pain
- Weakness
- Numbness
- Tingling
- Significant mood changes while taking quinolones.
Specific Quinolones
Specific quinolones, such as ciprofloxacin, levofloxacin, and moxifloxacin, vary somewhat in their side effect profiles, with moxifloxacin carrying a higher risk of QT prolongation while ciprofloxacin more commonly causes tendon issues, as noted in the study published in Pediatrics 1.
FDA Warnings
The FDA has issued black box warnings regarding tendon rupture, peripheral neuropathy, and central nervous system effects associated with quinolone use, highlighting the importance of cautious use and monitoring, as discussed in the American Academy of Pediatrics report 1.
From the FDA Drug Label
17.3 Serious and Potentially Serious Adverse Reactions
Patients should be informed of the following serious adverse reactions that have been associated with levofloxacin or other fluoroquinolone use: Tendon Disorders: Patients should contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue levofloxacin treatment. Exacerbation of Myasthenia Gravis: Patients should inform their physician of any history of myasthenia gravis Patients should notify their physician if they experience any symptoms of muscle weakness, including respiratory difficulties. Hypersensitivity Reactions: Patients should be informed that levofloxacin can cause hypersensitivity reactions, even following the first dose Patients should discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction. Hepatotoxicity: Severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients taking levofloxacin Patients should inform their physician and be instructed to discontinue levofloxacin treatment immediately if they experience any signs or symptoms of liver injury including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements or dark colored urine Convulsions: Convulsions have been reported in patients taking fluoroquinolones, including levofloxacin. Patients should notify their physician before taking this drug if they have a history of convulsions. Neurologic Adverse Effects (e.g., Dizziness, Lightheadedness, Increased Intracranial Pressure): Patients should know how they react to levofloxacin before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination. Patients should notify their physician if persistent headache with or without blurred vision occurs Diarrhea: Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic If this occurs, patients should contact their physician as soon as possible. Peripheral Neuropathies: Patients should be informed that peripheral neuropathy has been associated with levofloxacin use. Symptoms may occur soon after initiation of therapy and may be irreversible If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, patients should immediately discontinue treatment and contact their physician Prolongation of the QT Interval: Patients should inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents
The quinolone adverse effects include:
- Tendon disorders: pain, swelling, or inflammation of a tendon, or weakness or inability to use one of the joints
- Exacerbation of myasthenia gravis: muscle weakness, including respiratory difficulties
- Hypersensitivity reactions: skin rash, hives, rapid heartbeat, difficulty in swallowing or breathing, angioedema
- Hepatotoxicity: severe hepatotoxicity, including acute hepatitis and fatal events
- Convulsions: history of convulsions
- Neurologic adverse effects: dizziness, lightheadedness, increased intracranial pressure
- Diarrhea: common problem caused by antibiotics, watery and bloody stools
- Peripheral neuropathies: pain, burning, tingling, numbness, and/or weakness
- Prolongation of the QT interval: personal or family history of QT prolongation or proarrhythmic conditions 2 Other serious side effects of quinolones include:
- Central nervous system effects: seizures, toxic psychoses, increased intracranial pressure
- Serious allergic reactions: allergic reactions can happen in people taking fluoroquinolones, even after only one dose
- Skin rash: skin rash may happen in people taking fluoroquinolones, even after only one dose
- Serious heart rhythm changes: QT prolongation and torsade de pointes
- Intestine infection: pseudomembranous colitis can happen with most antibiotics, including quinolones
- Changes in sensation and possible nerve damage: damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones 2, 3
From the Research
Quinolone Adverse Effects
- Quinolones are broad-spectrum antibiotics active primarily against aerobic gram-negative organisms, but they can have adverse effects such as central nervous system side effects, photosensitivity reactions, and gastrointestinal side effects 4.
- Trovafloxacin is associated with more adverse reactions than any other quinolone, and its gastrointestinal side effects are most frequent among the quinolones 4.
- Ciprofloxacin and trovafloxacin are associated with central nervous system side effects, while photosensitivity reactions may occur with sparfloxacin 4.
Tendinopathy Associated with Quinolones
- Fluoroquinolone antibiotics, including levofloxacin, have been associated with an increased risk of tendinopathy, including tendon rupture and tendinitis 5, 6, 7.
- The risk of tendinopathy appears to be exposure-dependent, with higher doses and longer durations of fluoroquinolone use being most commonly associated with tendon damage 5.
- Patient-specific risk factors for fluoroquinolone-associated tendinopathy include older age (older than 60 years), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation 5, 6, 7.
Comparison of Quinolone Adverse Effects
- Levofloxacin is preferred for general use because it has virtually no side effects, induces no resistance, and is the least expensive and most versatile quinolone currently available 4.
- However, levofloxacin has been associated with a higher risk of tendon damage compared to other fluoroquinolones, particularly ofloxacin and norfloxacin 5, 6, 7.
- The risk of tendon injury associated with fluoroquinolones can be increased by concomitant use of corticosteroids, and older age appears to be an additional risk factor for tendinopathy 6, 7.