Broad-spectrum fluoroquinolone
Levofloxacin is an antibiotic (fluoroquinolone) used to treat respiratory, urinary, skin and other bacterial infections. It is effective, but can cause serious and sometimes irreversible side effects on tendons, nerves and the central nervous system — it should only be used when there is no alternative.
Also known as: Tavanic, Levaquin
Combining Levofloxacin with Ibuprofen (NSAID) increases the risk of seizures by lowering the seizure threshold.
Fluoroquinolones, such as levofloxacin, antagonise GABA receptors, lowering the seizure threshold; NSAIDs (ibuprofen) can potentiate this effect, increasing the risk of seizures, especially in patients with epilepsy, brain injury or renal impairment. The levofloxacin label and the Portuguese Prontuário Terapêutico advise against the combination in predisposed patients. If the antibiotic is needed, prefer an alternative analgesic or monitor closely; warn the patient about neurological symptoms (dizziness, confusion, tremor) and stop at any sign.
Levofloxacin + ibuprofen: increased risk of CNS stimulation and seizures. Avoid in patients with epilepsy or a history of seizures.
NSAIDs and quinolones may lower the seizure threshold (central interference, notably with GABA); combined use adds these effects and increases the seizure risk, especially in patients with epilepsy or predisposition.
Watch for neurological symptoms (dizziness, tremor, behavioral changes) and prodromal seizure signs.
Any seizure or suspicion thereof requires discontinuation and urgent neurological evaluation.
Prefer an alternative antibiotic in patients with epilepsy/a history of seizures; if the combination is necessary, monitor very closely.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c6c117c-9d91-48f4-9aaa-ee70b99218c2 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Levofloxacin with Amiodarone increases the risk of QT prolongation and ventricular arrhythmias (e.g. torsades de pointes).
Levofloxacin prolongs the QT interval (hERG blockade) and amiodarone does too; the effect is additive and the torsades de pointes risk increases, especially in women, the elderly, and with hypokalaemia, bradycardia or heart disease. In patients on chronic amiodarone, prefer an antibiotic without QT effects (e.g. beta-lactams) when coverage is adequate. If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Levofloxacin + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG.
Levofloxacin prolongs the ECG QT interval and Amiodarone is a class III antiarrhythmic with an additive effect; together they raise the risk of serious ventricular arrhythmias.
Monitor the ECG (QT interval), electrolytes (potassium/magnesium) and symptoms such as palpitations or syncope.
Syncope, palpitations, a very prolonged QT or arrhythmia require discontinuation and urgent evaluation.
Avoid the combination in patients at risk (hypokalemia, long QT, bradycardia); if unavoidable, monitor the ECG.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c6c117c-9d91-48f4-9aaa-ee70b99218c2 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Antacids with cations (aluminium, magnesium, calcium) and iron/zinc supplements significantly reduce Levofloxacin absorption, compromising its efficacy.
Levofloxacin, like other fluoroquinolones, forms insoluble chelates with di- and trivalent cations (aluminium, magnesium, calcium) of antacids, reducing oral bioavailability and risking therapeutic failure. The levofloxacin label recommends administering the antibiotic at least 2 hours before or 2 hours after antacids containing magnesium or aluminium (the same applies to sucralfate, iron and zinc). This spacing should be checked at prescription and dispensing, especially in outpatients, to ensure antibiotic efficacy.
Antacids + levofloxacin: cations (Al, Mg, Ca) chelate levofloxacin and reduce absorption. Administer levofloxacin 2 hours before or 2 hours after antacids.
Bi/trivalent cations chelate quinolones in the gut, forming insoluble complexes that reduce levofloxacin bioavailability.
Ensure the dosing interval is respected and monitor the clinical response to the antibiotic.
Treatment failure with persistent signs of infection after concurrent dosing.
Give levofloxacin at least 2 hours before or 2–4 hours after antacids, iron/zinc supplements or calcium preparations.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c6c117c-9d91-48f4-9aaa-ee70b99218c2 ; approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c72f0736-ee20-45b4-baf0-b80f1e3fa9cb — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Levofloxacin may potentiate the anticoagulant effect of Warfarin, raising the INR and the bleeding risk.
Levofloxacin, like other fluoroquinolones, can potentiate warfarin by reducing the gut flora producing vitamin K and by inhibiting cytochrome P450 isoenzymes (CYP1A2 and CYP3A4), although its inhibition potential is lower than ciprofloxacin's. Reports exist of INR elevation and bleeding. The INR should be monitored during and after the antibiotic course and the warfarin dose adjusted; the risk is higher in the elderly and in patients with reduced hepatic or renal function.
Levofloxacin can increase the effect of warfarin (enzyme inhibition + gut flora). Monitor the INR during and after the antibiotic.
Quinolones (including levofloxacin) may prolong prothrombin time in patients on oral anticoagulants through metabolic inhibition and possible gut flora changes.
Monitor the INR and bleeding signs during and after therapy.
Bleeding or an elevated INR require urgent medical evaluation.
Monitor the INR and adjust the warfarin dose; inform the patient of the bleeding risk.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c6c117c-9d91-48f4-9aaa-ee70b99218c2 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Levofloxacin reduces caffeine clearance (CYP1A2 inhibition), potentiating its stimulant effects.
Limit caffeine intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=857f256c-88ac-4f73-9815-c2724edf2f1e
Calcium in dairy may reduce levofloxacin absorption when taken together.
Separate dairy intake 2 hours before or 6 hours after dosing.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=857f256c-88ac-4f73-9815-c2724edf2f1e
Levofloxacin prolongs the QT interval and increases the risk of ventricular arrhythmias in at-risk patients.
Avoid in QT prolongation or with QT-prolonging drugs; monitor ECG.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=857f256c-88ac-4f73-9815-c2724edf2f1e
Fluoroquinolones can cause tendinopathy and tendon rupture, especially in the elderly, with corticosteroids or renal impairment.
Stop at the first sign of tendon pain; avoid in patients with a history of quinolone tendinopathy.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=857f256c-88ac-4f73-9815-c2724edf2f1e
Fluoroquinolones cause arthropathy in young animals; use in pregnancy is generally avoided.
Avoid in pregnancy unless no safe alternative exists.
Excreted into breast milk; avoid while breastfeeding.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=857f256c-88ac-4f73-9815-c2724edf2f1e
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Broad-spectrum bactericidal fluoroquinolone that inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, blocking DNA replication, transcription and repair. Active against Gram-negatives (including Pseudomonas aeruginosa) and Gram-positives; linear and predictable pharmacokinetics by oral and intravenous routes.
Levofloxacin binds to the DNA-enzyme complexes of bacterial topoisomerases (DNA gyrase and topoisomerase IV), stabilising the cleavage complex and preventing DNA religation — bacterial replication is interrupted. The primary target differs between Gram-negatives (gyrase) and Gram-positives (topoisomerase IV).
Levofloxacin is rapidly and essentially completely absorbed orally, with an absolute bioavailability of ~99% (500 mg and 750 mg tablets). Peak plasma concentrations occur 1–2 hours after dosing; food delays the peak ~1 hour and decreases it ~14% (without clinical relevance). The volume of distribution is 74–112 L.
Levofloxacin is minimally metabolised (~5%): it undergoes little biotransformation and is excreted mainly unchanged in urine by glomerular filtration and tubular secretion. Renal excretion accounts for most elimination — the dose must be adjusted in renal impairment.
The elimination half-life is ~6.3–8.8 hours in patients with normal renal function (longer in renal impairment: 27 hours with CrCl 20–49 mL/min; 35 hours with CrCl <20 mL/min). Steady state is reached within 48 hours of daily dosing.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
