Quinolones are bactericidal antimicrobials that act by inhibiting type II topoisomerase (DNA gyrase) and topoisomerase IV, enzymes essential for bacterial DNA replication, transcription, repair, and recombination. In the UK, only fluoroquinolones are in clinical use, all containing a fluorine substituent on the central ring. These drugs share the suffix “-oxacin”, including ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and delafloxacin. The following article will describe indications, pharmacokinetics, cautions and contraindications, adverse effects and drug interactions for fluoroquinolones. adobe stock Fig 1: Mechanisms of action of antimicrobials Spectrum of Activity and Indications Fluoroquinolones are broad-spectrum agents: Ciprofloxacin → potent against Gram-negative bacteria (e.g., Pseudomonas aeruginosa, Salmonella spp.) but weaker against Gram-positive organisms and inactive against most anaerobes. Should not be used as a sole agent against treatment of severe infections that may be due to gram positive or anaerobic bacteria. Levofloxacin → the active S (-) enantiomer of the racemic drug ofloxacin (ofloxacin is a mixture of both R (-) and S (-) enantiomers). Indications: urinary tract infections, pneumonia, exacerbation of COPD, and skin infections. ⚠️ MHRA advises fluoroquinolones should only be used when other commonly recommended antibiotics are inappropriate, due to the potential for long lasting or fatal adverse effects Resistance to fluoroquinolones can occur through mutations in regions of DNA-gyrase and/or topoisomerase IV (known as Quinolone-Resistance Determining Regions (QRDRs)), efflux pump mechanisms of resistance and permeation barriers. Pharmacokinetic Parameters Quinolones have excellent oral bioavailability and are generally only metabolised to small extents. The following table summarises the key pharmacokinetic parameters for quinolones: Drug Absorption Distribution Metabolism Excretion Ciprofloxacin tablets (PO) F = 70–80%, Tmax 1–2 h. Oral 500 mg ≈ IV 400 mg Good tissue penetration, 20–30% protein bound Low concentrations of metabolites are present which have lower antimicrobial activity Moderate CYP1A2 inhibitor No dose adjustment required in hepatic impairment. Largely excreted renally as unchanged compound; dose reduction required in renal impairment. Half life 4-7 hours Ofloxacin tablets (PO) Tmax <1 hour 25% protein bound Minimal 80–90% renal excretion (unchanged) Excretion may be reduced in patients with severe liver dysfunction Half life 5.7-7 hours Levofloxacin tablets (PO) F = 99–100%, Tmax 1–2 h Css within 48 hours 30-40% protein bound Wide tissue distribution, poor CSF penetration <5% metabolism >85% renal excretion Dose should be reduced in renal impairment Half life 6-8 hours Moxifloxacin tablets (PO) F = 91% Tmax = 0.5-4 hours 40-42% protein bound (mainly albumin) Rapid distribution to extravascular spaces Phase II metabolism (inactive metabolites) 35% renal, 60% faecal No dose adjustment required in renal impairment Terminal half life 12 hours (half life once reached equilibrium) Delafloxacin tablets (PO) Tmax ~1 h, unaffected by food Css = 5 days Well distributed 85% protein bound (mainly albumin) No change in pharmacokinetics in obesity ~10% metabolites, no CYP interactions 50% renal, 48% faecal No dosage adjustment required in hepatic impairment or mild – severe renal impairment. Not recommended in ESRD. Half life 14 hours Cautions and Adverse Effects Cautions ⚠️ MHRA safety concerns (potentially life-altering or fatal): Reduction in seizure threshold: convulsions may occur as a result of the use of quinolones, the risk increases if taking NSAIDs like fenbufen at the same time or other drugs that lower the seizure threshold such as theophylline. Tendon damage and rupture: can occur within 48 hours of commencing treatment to months after stopping. Quinolones are contraindicated in patients with previous tendon disorders related to quinolone use Age >60 years and corticosteroid use may increase risk Quinolones should be stopped if tendonitis occurs Increased risk of aortic aneurysm and dissection Small risk of heart valve regurgitation Suicidal thoughts and behaviour Can occur even after first dose Other cautions for use of fluoroquinolones also include: QT prolongation (especially with hypokalaemia, hypomagnesaemia, cardiac disease, concomitant drugs that prolong QT) May affect blood glucose: hyper- or hypo-glycaemia, more common with oral hypoglycaemic agent such as sulfonylureas or insulin G6PD deficiency → haemolysis risk with ciprofloxacin Exacerbate myasthenia gravis (due to neuromuscular blockade) Photosensitivity with ciprofloxacin and ofloxacin – avoid strong sunlight and UV rays during treatment and 48 hours afterwards (lower risk with levofloxacin; rare with moxifloxacin; not reported with delafloxacin) MRSA is likely to be co-resistant towards fluoroquinolones apart from delafloxacin Levofloxacin and ofloxacin may cause false positive results of urinary opiates Levofloxacin may give false-negative results in the diagnosis of TB Adverse events Alongside serious adverse events are described above, fluoroquinolones most commonly cause nausea and diarrhoea. Further listed adverse events include: Ciprofloxacin & delafloxacin → crystalluria Moxifloxacin → renal impairment (↑ creatinine, urea) Hepatic necrosis/failure Peripheral neuropathy Psychiatric effects (hallucinations, suicidal thoughts) Dermatological: Stevens–Johnson syndrome, TEN Superinfections (e.g., thrush, C. difficile) Created in BioRender. Boucher, M. (2025) https://BioRender.com/ydwlen2 Fig 2: MHRA alerts with fluoroquinolones Contraindications Some contraindications have already been described in the caution section above, other contraindications for the use of fluoroquinolones also include the following: Paediatrics (<18 years) – cartilage toxicity risk Levofloxacin and delafloxacin are contraindicated in those <18 years old, in pregnancy and breast-feeding women. Moxifloxacin is contraindicated in those < 18 years old as efficacy and safety has not been established. Moxifloxacin is contraindicated in patients with impaired hepatic function (child pugh C) and/or liver transaminase levels >5x upper limit due to limited experience in this patient cohort. Interactions Fluoroquinolones should be used cautiously with drugs that increase the risk of side effects: QT prolonging drugs (e.g., TCAs, macrolides, antipsychotics) Drugs that lower seizure threshold (e.g. theophylline) Fluoroquinolones chelate with cations leading to reduction in absorption, the interacting substances vary for each drug and are described below: Ciprofloxacin should only be taken 1-2 hours before or 4 hours after calcium (including milk, yoghurt, calcium fortified orange juice), magnesium, aluminium, iron, sevelamer, lanthanum, sucralfate and antacids Ofloxacin should not be taken within 2 hours of iron salts, zinc, magnesium or aluminium containing antacids and didanosine* Levofloxacin can be taken irrespective of meal times, however should be taken at least 2 hours before or after iron, zinc, magnesium or aluminium containing antacids, didanosine* and sucralfate. Calcium has minimal impact on levofloxacin absorption. Moxifloxacin should not be taken within 6 hours of antacids containing magnesium or aluminum, didanosine*, sucralfate, iron or zinc preparations. Delafloxacin should be taken at least 2 hours before or 6 hours after antacids containing aluminium/magnesium, sucralfate, iron, zinc or didanosine*. *Any buffered anti-retroviral tablet containing magnesium or aluminium as the buffering agent will interact. Warfarin: potentiated effect → INR monitoring CYP1A2 inhibition (ciprofloxacin): ↑ levels of theophylline, tizanidine (contraindicated), clozapine, duloxetine, ropinirole and agomelatine Phenytoin: serum level ↑ or ↓ by ciprofloxacin Ciprofloxacin may increase levels of ropinirole, clozapine, sildenafil, duloxetine, lidocaine and zolpidem Caution with drugs that affect tubular renal secretion (e.g. probenecid, cimetidine, furosemide and methotrexate) ↑ ofloxacin, ciprofloxacin and levofloxacin levels ↑ toxicity of methotrexate Ofloxacin may ↑ glibenclamide level Charcoal ↓ absorption of moxifloxacin and can be used in moxifloxacin overdose References Ciprofloxacin 750mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) accessed 9/2/25 Ciprofloxacin | Drugs | BNF | NICE accessed 9/2/25 Ofloxacin 200 mg Tablets – Summary of Product Characteristics (SmPC) – (emc) accessed 10/2/25 Ofloxacin | Drugs | BNF | NICE accessed 12/2/25 Levofloxacin 250mg tablets – Summary of Product Characteristics (SmPC) – (emc). Last updated on emc: 08 Mar 2021. Accessed 10/02/25 Levofloxacin | Drugs | BNF | NICE Accessed 12/2/25 Moxifloxacin 400 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) Last updated on emc: 15 Aug 2024. Accessed 12/2/25 Moxifloxacin | Drugs | BNF | NICE accessed 12/2/25 Quofenix 450 mg tablets – Summary of Product Characteristics (SmPC – (emc) Last updated on emc: 15 Jan 2025. Accessed 12/2/25 Delafloxacin | Drugs | BNF | NICE accessed 12/2/25 Do you think you’re ready? Take the quiz below Pro Feature - Quiz Quinolones Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article