Fluoroquinolone antibacterials
ATC code: J01MA02 (Ciprofloxacin)
Inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV – blocking bacterial DNA replication and transcription. Active against gram-negative flora (E. coli, Pseudomonas, Klebsiella), some gram-positive organisms (Staphylococcus aureus), and atypicals. A moderate inhibitor of CYP1A2 and a weaker inhibitor of CYP3A4 – a source of clinically significant interactions. Chelation with divalent and trivalent cations (Mg2+, Ca2+, Fe2+, Al3+) markedly reduces absorption. black-box warnings in older adults: tendinitis, tendon rupture, aortic aneurysm, QT prolongation.
First line
First-line for complicated urinary tract infections and pyelonephritis in adults. Not recommended as first-line for uncomplicated cystitis – nitrofurantoin, fosfomycin, or TMP-SMX are preferred. warns of serious adverse effects and advises reserving fluoroquinolones for uncomplicated infections only when no alternatives exist.
First line
First-line for severe traveler's diarrhea with fever or bloody stools. Mild cases are managed with rehydration and loperamide. Short course of 1–3 days. Rising resistance in Southeast Asia limits efficacy; azithromycin is the alternative for that region.
Second line
Ciprofloxacin is not first-line for community-acquired pneumonia. It is used only when Pseudomonas aeruginosa is suspected – typically in patients with structural lung disease. For standard CAP, respiratory fluoroquinolones – levofloxacin or moxifloxacin – are preferred.
Calcium forms insoluble chelate complexes with fluoroquinolones in the GI lumen; ciprofloxacin absorption drops 30–50%. Separate doses by at least 2 hours: fluoroquinolone 2 hours before or 6 hours after calcium.
Source: FDA: Cipro (ciprofloxacin) prescribing information (2021)
Dairy products contain calcium, which binds fluoroquinolones in the gut and reduces absorption by 30–50%. Do not take ciprofloxacin with milk, yogurt, or cheese – separate by at least 2 hours.
Source: FDA: Cipro (ciprofloxacin) prescribing information (2021)
8 pairs found. Sorted from critical to minor.
Mechanism
Additive QT prolongation: amiodarone strongly blocks IKr potassium channels and ciprofloxacin does the same more mildly. Risk of torsades de pointes. black-box warning for all fluoroquinolones regarding QT prolongation (2016 update).
Management
Avoid the combination where possible. If ciprofloxacin is essential, obtain an ECG at baseline and on day 2–3 and keep potassium above 4.0 mmol/L and magnesium in the upper-normal range. Alternatives are non-fluoroquinolone antibiotics where susceptibility allows.
Boxed warning
FDA black box: fluoroquinolones cause potentially irreversible serious adverse effects – tendinitis and tendon rupture, peripheral neuropathy, CNS effects. Also increased risk of aortic dissection. Do not prescribe for uncomplicated infections when alternatives exist.
FDA category C. Animal studies show cartilage damage. Contraindicated in pregnancy. Used only for life-threatening infections with no alternatives.
ciprofloxacin is evaluated for the following indications with varying evidence strength: Urinary tract infection (evidence tier A), Traveler's diarrhea (evidence tier B), Community-acquired pneumonia (evidence tier C). See the full indication matrix with dosing and citations above on this page.
Common side effects of ciprofloxacin (≥ 1 in 100): Nausea, Diarrhea, Headache, Insomnia. See the Safety section for uncommon and serious reactions.
FDA category C. FDA category C. Animal studies show cartilage damage. Contraindicated in pregnancy. Used only for life-threatening infections with no alternatives.
ciprofloxacin is contraindicated in: Hypersensitivity to fluoroquinolones; Concomitant tizanidine use; Age under 18 (except in specific indications). Full list in the Safety section.
FDA black box: fluoroquinolones cause potentially irreversible serious adverse effects – tendinitis and tendon rupture, peripheral neuropathy, CNS effects. Also increased risk of aortic dissection. Do not prescribe for uncomplicated infections when alternatives exist.
Mechanism
Additive QT prolongation: sertraline modestly and ciprofloxacin modestly. In older patients with additional factors (hypokalemia, bradycardia, female sex), torsades de pointes risk increases. Ciprofloxacin also weakly inhibits CYP enzymes, potentially raising sertraline concentration slightly.
Management
Obtain a baseline ECG when prescribing ciprofloxacin to a patient on sertraline. Keep potassium above 4.0 mmol/L. If QTc exceeds 500 ms, switch to a non-fluoroquinolone antibiotic.
Sources
Mechanism
Ципрофлоксацин ингибирует CYP1A2, повышая концентрацию теофиллина и риск судорог, тахикардии, желудочковых нарушений ритма.
Management
Снизить дозу теофиллина на 30–50% и контролировать уровень в плазме.
Mechanism
Dual mechanism: 1) ciprofloxacin is a moderate CYP1A2 inhibitor and weak CYP3A4 inhibitor, raising R-warfarin concentration; 2) elimination of gut flora reduces vitamin K2 synthesis. INR rises 3–7 days after antibiotic initiation; in some patients by 1–2 units or more (Stockley's Drug Interactions; review by Glasheen et al., J Gen Intern Med, 2005).
Management
Check INR on days 3 and 7 of the course and again 7–10 days after completion. For courses ≥ 5 days, pre-emptively reduce the warfarin dose by 15–25 %. If feasible, choose an antibiotic with less INR impact (e.g. a cephalosporin where susceptibility allows).
Sources
Mechanism
Older experimental data suggested that NSAIDs combined with fluoroquinolones increase CNS excitability and seizure risk (via fluoroquinolone-mediated GABA-A receptor antagonism with possible NSAID potentiation). Clinically meaningful seizure frequency is rare but the risk is elevated in older patients, CKD, and prior epilepsy.
Management
In patients without epilepsy and with normal eGFR, the combination is acceptable, particularly at antiplatelet aspirin doses. With prior epilepsy or eGFR below 30 mL/min, choose a non-fluoroquinolone.
Sources
Mechanism
In 10–15 % of patients, gut flora (mainly Eubacterium lentum) metabolize part of digoxin into inactive products. Ciprofloxacin eliminates this flora – digoxin concentration may rise in these patients. Ciprofloxacin also weakly inhibits P-glycoprotein.
Management
For ciprofloxacin courses ≥ 5 days in a digoxin-treated patient, check digoxin level and ECG at 3–5 days. Target concentration is 0.5–0.9 ng/mL in HF.
Sources
Mechanism
Fluoroquinolones disrupt glucose homeostasis – they can cause both hypoglycemia (especially in older patients on glucose-lowering therapy) and hyperglycemia. The mechanism is unclear; suggested mechanism is blockade of ATP-sensitive K+ channels in β-cells. black-box warning from 2018 regarding severe hypoglycemia with fluoroquinolones.
Management
During ciprofloxacin in a metformin-treated patient, self-monitor glucose twice daily. For tachycardia, sweating, tremor, or confusion, immediately check glucose and treat hypoglycemia if needed. Where possible, choose a non-fluoroquinolone antibiotic in T2D patients.
Sources
Mechanism
Ciprofloxacin is better absorbed in an acidic gastric environment. Omeprazole raises gastric pH – ciprofloxacin bioavailability falls by roughly 20–30 %. Additionally, Al/Mg-containing antacids (often used concurrently) chelate ciprofloxacin and reduce absorption further.
Management
If a PPI is necessary, take ciprofloxacin 2 hours before or 6 hours after the PPI and any antacids/calcium/iron products. For severe infections, consider IV ciprofloxacin.
Sources