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Fluoroquinolones: Pharmacology, Side Effects and Contraindications

• Fluoroquinolones: general pharmacology
• Fluoroquinolones: ciprofloxacin
• Fluoroquinolones: levofloxacin
• Fluoroquinolones: ofloxacin

Classification of fluoroquinolones:

Fluoroquinolones have a broad spectrum of activity against Gram-negative pathogens, including Pseudomonas. Depending on the classification, they also have antibacterial activity against atypical bacteria (mycoplasma, chlamydia) and Gram-positive pathogens (staphylococci, streptococci, legionella). Enterococci are not covered.

• Group 1: oral fluoroquinolones with the indication urinary tract infection: norfloxacin.
• Group 2: parenterally applicable fluoroquinolones with a broad indication: ciprofloxacin, ofloxacin.
• Group 3: Fluoroquinolones with improved efficacy against Gram-positive and atypical bacteria: levofloxacin.
• Group 4: Fluoroquinolones with improved efficacy against Gram-positive, atypical pathogens and anaerobic bacteria: moxifloxacin.

Mechanism of Action:

Fluoroquinolones are bactericidal; they interfere with bacterial DNA synthesis by inhibiting the bacterial type II topoisomerase (DNA gyrase). The partial effect of fluoroquinolones on human topoisomerases may cause severe side effects.

Indications for Fluoroquinolones:

Due to their side effects, fluoroquinolones should only be prescribed for strict indications and without equivalent alternatives. Urological indications for fluoroquinolones are severe or complicated bacterial urinary tract infections (acute pyelonephritis, prostatitis, or epididymitis), urosepsis, treatment of gonorrhea (with proven sensitivity), or severe soft tissue infections. No indications for fluoroquinolones are self-limiting or mild infections (such as uncomplicated urinary tract infections), prevention of recurrent urinary tract infections, non-bacterial (chronic) prostatitis, or prophylactic perioperative use.

Pharmacokinetics of Fluoroquinolones:

• Fluoroquinolones have a good bioavailability after oral administration.
• A high volume of distribution and protein binding below 40% lead to a good tissue penetration.
• Low metabolization and mainly unchanged renal elimination. Exception moxifloxacin: hepatic conjugation and excretion of metabolites via urine and feces.

Side Effects of Fluoroquinolones:

Numerous warnings have been published regarding the side effects of fluoroquinolones (BfArM, EMA or FDA), as some serious side effects can lead to long-lasting and possibly irreversible patient impairment.

Gastrointestinal tract:

Nausea, vomiting, diarrhea, pseudomembranous colitis.

CNS:

Neurotoxic side effects with headache, dizziness, insomnia, psychosis to seizures, depression, fatigue, impaired memory and impaired vision, hearing, smell and taste.

Skin:

Allergic skin reactions, very rarely severe. Photosensitization.

Musculoskeletal system:

Cartilage damage, tendinitis, tendon rupture, myalgia, muscle weakness, arthralgia, and abnormal gait.

Cardiovascular system:

QT prolongation with dangerous arrhythmias, increased risk of aortic aneurysm and its rupture.

Blood:

Rare changes in blood count.

Contraindications to Fluoroquinolones:

• Pregnancy and lactation
• Increased risk for seizures.
• Severe chronic kidney disease
• QT-prolongation
• Caution in children: cartilage damage

Interactions:

• No oral administration of fluoroquinolones with iron preparations or antacids containing magnesium or aluminum, as otherwise absorption is prevented.
• Inhibition of degradation and, thus, increase in the concentration of ciclosporin, oral anticoagulants, theophylline, methotrexate, and glibenclamide.

References

Rote Hand-Brief des BfArM bezüglich der Risiken von Fluorchinolonen.

EMA Warning: https://www.ema.europa.eu/en/news/fluoroquinolone-antibiotics-reminder-measures-reduce-risk-long-lasting-disabling-potentially-irreversible-side-effects

FDA Warning regarding fluoroquinolone antibiotics: https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics

Simon und Stille 1997 SIMON, C. ; STILLE, W.: Antibiotika-Therapie in Klinik und Praxis.
9. Auflage.
Stuttgart New York : Schattauer, 1997

  Deutsche Version: Fluoroquinolone (Gyrasehemmer)