Gepotidacin is a first‑in‑class oral antibiotic, marketed in the US as Blujepa, that inhibits bacterial DNA gyrase and topoisomerase IV via a binding site distinct from fluoroquinolones, giving it activity against many uropathogens and Neisseria gonorrhoeae, including some resistant strains.
Approved in the US for uncomplicated UTIs in females ≥12 years and ≥40 kg caused by susceptible E. coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.
Approved for uncomplicated urogenital gonorrhea in patients ≥45 kg, where it was non‑inferior to ceftriaxone plus azithromycin in a phase 3 trial
Phase 3 UTI trials (EAGLE‑2/3) showed non‑inferiority and, in one trial, superiority versus nitrofurantoin, with acceptable safety and tolerability.
Mechanism of action and resistance
Chemically, gepotidacin is a triazaacenaphthylene topoisomerase inhibitor that blocks DNA replication by binding to GyrA (DNA gyrase) and ParC (topoisomerase IV) at a site between the scissile DNA bonds.
Its dual, well‑balanced targeting of both enzymes and distinct binding mode mean single target mutations that confer fluoroquinolone resistance often do not abolish gepotidacin activity.
Formulation: oral tablets containing 750 mg gepotidacin (≈910.7 mg gepotidacin mesylate) per tablet.
Typical UTI regimen: 1,500 mg orally (two 750 mg tablets) every 12 hours for 5 days in patients ≥12 years and ≥40 kg; administration with food is recommended to mitigate GI effects.
Large apparent plasma protein binding, with elimination via feces (~52%, ~30% unchanged) and urine (~31%, ~20% unchanged).
Exposure increases with renal impairment and with severe hepatic impairment, which may necessitate dose adjustment or avoidance per labeling.
Metabolized partly via CYP3A4; strong CYP3A4 inhibitors increase, and strong inducers decrease, gepotidacin exposure.
At higher concentrations it can inhibit certain transporters and increase exposure to substrates such as digoxin and midazolam, so co‑medication review is required.
Gepotidacin showed an overall acceptable safety profile with no drug‑related life‑threatening or fatal events; most adverse events were mild to moderate.
Most common adverse reactions are gastrointestinal (nausea, diarrhea, abdominal pain), generally manageable and reduced when taken with food.
Prescribing information includes warnings regarding QT prolongation risk, liver enzyme elevations, and use in significant renal or hepatic impairment, so ECG and lab monitoring may be appropriate in higher‑risk patients.