Gepotidacin Dosing and Clinical Use
Gepotidacin 1,500 mg orally twice daily for 5 days is the FDA-approved regimen for uncomplicated urinary tract infections in female patients ≥12 years weighing ≥40 kg when first-line agents are unsuitable. 1, 2
FDA-Approved Indication and Dosing
Gepotidacin is approved for uncomplicated UTIs caused by susceptible isolates of E. coli, K. pneumoniae, C. freundii complex, S. saprophyticus, and E. faecalis in female adult and pediatric patients aged ≥12 years weighing ≥40 kg. 1
The standard dose is 1,500 mg orally twice daily for 5 days. 3, 4, 2
Steady-state plasma concentrations are achieved by day 3 of therapy, with urinary trough concentrations of 322-352 μg/mL maintained from day 3 onward. 4
Efficacy Data
In the EAGLE-2 trial, gepotidacin achieved therapeutic success (combined clinical and microbiological cure) in 50.6% of patients versus 47.0% with nitrofurantoin, demonstrating non-inferiority. 2
In the EAGLE-3 trial, gepotidacin achieved therapeutic success in 58.5% of patients versus 43.6% with nitrofurantoin, demonstrating both non-inferiority and superiority. 2
For uncomplicated urogenital gonorrhea, gepotidacin successfully treated 96% (66/69) of patients in phase 2 studies, though this indication is not yet FDA-approved. 5
Renal and Hepatic Adjustments
No specific renal or hepatic dose adjustments are provided in the available evidence. The phase 2a and phase 3 trials did not report dose modifications based on organ dysfunction, suggesting the standard dose was used across all enrolled patients. 4, 2 However, formal pharmacokinetic studies in patients with renal or hepatic impairment have not been published in the provided evidence.
Contraindications and Safety Profile
The most common adverse event is diarrhea, occurring in 14-18% of patients, typically mild to moderate in severity. 2
No life-threatening or fatal events occurred in the phase 3 trials involving over 3,000 patients. 2
Gepotidacin had an acceptable safety profile with no treatment-limiting adverse events in phase 2a evaluation. 4
Specific contraindications are not detailed in the available evidence, though standard precautions for novel antibiotics would apply (e.g., known hypersensitivity to the drug or its components).
Clinical Context and Positioning
Gepotidacin represents a first-in-class triazaacenaphthylene antibiotic with a distinct mechanism of action—inhibiting bacterial DNA replication through balanced inhibition of DNA gyrase (GyrA) and topoisomerase IV (ParC). 3, 1
This unique mechanism provides activity against common uropathogens, including drug-resistant phenotypes, making it valuable when first-line agents (nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin) are unsuitable due to resistance or intolerance. 2
The drug achieves high urinary concentrations with AUC₀₋₂₄/MIC ratios ranging from 1,292 to 121,698 in urine, well above the threshold needed for bacterial eradication. 4
Important Clinical Caveats
Gepotidacin is currently approved only for female patients; efficacy and safety in male patients with UTI have not been established. 1, 2
The drug is approved only for uncomplicated UTIs; it should not be used for complicated UTIs, pyelonephritis, or other systemic infections without additional evidence. 1
Both EAGLE trials were stopped early for efficacy after interim analysis, which may limit long-term safety data. 2
Therapeutic success rates (50-58%) were lower than historical cure rates for first-line agents, likely reflecting the stringent composite endpoint requiring both complete symptom resolution and microbiological eradication to <10³ CFU/mL. 2
Gonorrhea Context (Investigational)
For uncomplicated urogenital gonorrhea, gepotidacin remains investigational and is not FDA-approved for this indication. 5
Phase 2 data showed 96% efficacy, and further phase 3 studies are underway. 5
If approved, gepotidacin would provide an oral alternative when ceftriaxone is unsuitable, addressing the critical need for novel gonorrhea treatments amid rising antimicrobial resistance. 5