Norfloxacin (DB01059): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Norfloxacin is a first-generation synthetic antibiotic belonging to the fluoroquinolone class, characterized by its broad-spectrum, bactericidal activity against a range of Gram-positive and Gram-negative pathogens.[1] Its primary mechanism of action involves the inhibition of essential bacterial enzymes—DNA gyrase (topoisomerase II) and topoisomerase IV—which disrupts DNA replication, transcription, and repair, ultimately leading to bacterial cell death.[2] Historically, Norfloxacin's pharmacokinetic profile, particularly its high concentration in urine, established its principal clinical role in the treatment of urinary tract infections (UTIs), prostatitis, and certain gynecological infections.[1]

Despite its initial utility, the clinical application of Norfloxacin has been profoundly reshaped and curtailed by an evolving understanding of its safety profile. Post-marketing surveillance has revealed an association with disabling and potentially irreversible serious adverse reactions, prompting stringent warnings and restrictions from global regulatory bodies.[6] The U.S. Food and Drug Administration (FDA) has issued black box warnings—its most serious advisory—for Norfloxacin and other fluoroquinolones. These warnings highlight the risks of tendinitis and tendon rupture, irreversible peripheral neuropathy, central nervous system (CNS) effects, and the exacerbation of muscle weakness in patients with myasthenia gravis.[8]