What are the side effects of Ciprofloxacin (ciprofloxacin)?

Ciprofloxacin Side Effects

Ciprofloxacin carries FDA black box warnings for disabling and potentially permanent adverse effects involving tendons, muscles, joints, peripheral nerves, and the central nervous system, and should be reserved as a last-choice antibiotic when safer alternatives exist. 1

Most Serious Adverse Effects

Tendinopathy and Tendon Rupture

• Tendon rupture is the most concerning adverse effect, most frequently affecting the Achilles tendon and potentially requiring surgical repair 1
• Risk is substantially elevated in patients over 60 years, those taking corticosteroids, and transplant recipients (kidney, heart, or lung) 1
• Additional independent risk factors include strenuous physical activity, renal failure, and pre-existing tendon disorders like rheumatoid arthritis 2, 1
• Discontinue ciprofloxacin immediately at the first sign of tendon pain, swelling, or inflammation and advise complete rest 1
• Tendon rupture can occur during treatment or up to several months after completion 1

Peripheral Neuropathy

• Potentially permanent nerve damage affecting arms, hands, legs, or feet can develop 1
• Symptoms include pain, burning, tingling, numbness, or weakness in extremities 1
• Stop ciprofloxacin immediately if any neuropathy symptoms appear to prevent irreversible damage 1
• Recent case reports document fluoride-related toxicity from ciprofloxacin's fluorine atom causing neuropathies 3, 4

Central Nervous System Effects

• Seizures, increased intracranial pressure, and toxic psychosis have been reported 1
• CNS effects may occur after the first dose and include dizziness, confusion, tremors, hallucinations, depression, and rarely suicidal thoughts 1
• Use extreme caution in patients with epilepsy, severe cerebral arteriosclerosis, or other conditions that lower seizure threshold 1
• Discontinue immediately if CNS reactions occur 1

Cardiovascular Toxicity

• QT interval prolongation can lead to fatal dysrhythmias including torsade de pointes 2, 1
• Risk is highest in elderly patients, those with family history of QT prolongation, hypokalemia, or concurrent use of antiarrhythmic medications 1
• Stop treatment and seek immediate care if irregular heartbeat or fainting occurs 1

Common Adverse Effects

Gastrointestinal Effects

• Nausea, vomiting, diarrhea, and abdominal discomfort occur in 2-8% of patients 5
• The FDA label reports nausea in 0.5-1.8% and gastrointestinal disturbance as the most frequent side effect 6
• Clostridium difficile-associated diarrhea (pseudomembranous colitis) can occur during treatment or up to 2+ months after completion 1
• Seek immediate care for watery diarrhea, bloody stools, or persistent diarrhea with fever and cramping 1

Dermatologic Reactions

• Skin rash, pruritus, and photosensitivity occur in approximately 1% of patients 5
• Stop ciprofloxacin at the first sign of skin rash, as this may indicate a more serious hypersensitivity reaction 1
• Severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported 1
• Avoid sun exposure, tanning beds, and sunlamps; use sunscreen and protective clothing if sun exposure is unavoidable 1

Neurologic Effects (Non-Serious)

• Dizziness, insomnia, tremulousness, and headache occur in approximately 0.5-4% of patients 6, 5
• Do not drive or operate machinery until you know how ciprofloxacin affects you 1

Serious Hypersensitivity Reactions

• Anaphylactic reactions can occur after even a single dose 1
• Symptoms include hives, difficulty breathing/swallowing, facial/throat swelling, throat tightness, rapid heartbeat, or fainting 1
• Seek emergency treatment immediately with epinephrine, oxygen, IV steroids, and airway management as needed 1

Hepatotoxicity

• Acute liver failure, hepatitis, jaundice, and hepatic necrosis have been reported 1
• Stop ciprofloxacin immediately if yellowing of skin/eyes or dark urine develops 1

Metabolic Effects

• Hypoglycemia can occur, particularly when combined with oral antidiabetic agents like glyburide 1
• Monitor blood sugar closely in diabetic patients; antibiotic change may be necessary 1

Pediatric Considerations

• Arthropathy occurs in 9.3% of pediatric patients (ages 1-17) compared to 6.0% in controls 2
• Use only for specific FDA-approved indications in children under 18 years due to joint and cartilage concerns 1

Critical Drug Interactions

CYP1A2 Inhibition

• Ciprofloxacin inhibits CYP1A2, causing dangerous elevations of theophylline, tizanidine, clozapine, and other substrates 6, 2, 1
• Serious and fatal reactions including cardiac arrest, seizures, status epilepticus, and respiratory failure have occurred with concurrent theophylline use 1
• Monitor theophylline levels closely and reduce dose; consider alternative antibiotic if possible 6, 1
• Tizanidine is contraindicated with ciprofloxacin due to severe hypotension and sedation 6

Absorption Interference

• Multivalent cations (magnesium, aluminum, iron, calcium) in antacids, supplements, and dairy products drastically reduce ciprofloxacin absorption 6, 2
• Take ciprofloxacin at least 1-2 hours before or 4 hours after any products containing these cations 6

Other Significant Interactions

• Enhanced anticoagulant effects with warfarin 6
• Increased methotrexate toxicity 6
• Reduced clearance of IV lidocaine 6
• Increased levels of duloxetine, sildenafil, ropinirole, and pirfenidone 6

Overall Safety Profile

• Historical clinical trial data showed adverse effects in 9.3-10.2% of patients, with most reactions being mild to moderate 7, 8
• However, the FDA now emphasizes that fluoroquinolones can cause disabling and potentially permanent effects that may occur together and affect multiple body systems simultaneously 1
• Treatment discontinuation due to side effects occurs in approximately 1.5% of patients 7

Special Populations

Pregnancy and Lactation

• Avoid in pregnancy due to teratogenic effects and lack of established safety 6, 1
• Safety in lactating women has not been established 1

Renal Impairment

• Dose adjustment required when creatinine clearance is <50 mL/minute (reduce to 750-1000 mg three times weekly) 6
• Not removed by hemodialysis; no supplemental doses needed post-dialysis 6

Hepatic Disease

• Can be used with caution in liver disease as drug levels are not significantly affected, but increased monitoring is warranted 6