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Gepotidacin (Blujepa)

Gepotidacin (Blujepa) photo pending

Top 5 Points

There are many things to know, but following FDA approval my top 5 things to know about gepotidacin include:

  1. Oral only, for women with uncomplicated UTI caused by certain bacteria (includes E. coli)
  2.  Gastrointestinal side effects may be an issue, but taking after a meal may help
  3. Beware drug-drug interactions with CYP3A4 that can impact gepotidacin concentrations
  4. Beware QTc prolongation
  5. Has a mechanism like the fluoroquinolones, but is not a fluoroquinolone. Is is a first-in-class triazaacenaphthylene antibacterial (try to say that 3x fast!)

KEY POINTS

  • Gepotidacin is triazaacenaphthylene antibacterial that works by interfering with bacterial DNA synthesis by inhibiting type II topoisomerase (includes topoisomerase II [DNA gyrase] and topoisomerase IV
    • Similar mechanism of action as fluoroquinolones, but structurally different than fluoroquinolones
  • Gepotidacin was FDA-approved on 25 March 2025 for the treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kg with uncomplicated urinary tract infection caused by one of the following susceptible bacteria
    • E. coli
    • Klebsiella pneumoniae
    • Citrobacter freundii complex
    • Staphylococcus saprophyticus
    • Enterococcus faecalis
  • Dosed 1500 mg (two 750 mg tablets) taken orally twice a day for 5 days
    • Administration after a meal can reduce GI intolerance
    • No renal dose adjustments, but not recommended to use if eGFR is below 30 mL/min or dialysis
    • No hepatic dose adjustments, but not recommended to use with severe hepatic impairment
    • Provided in a bottle of 20 tablets to be stored at room temperature
  • Holds warnings for:
    • QTc prolongation
    • Acetylcholinesterase inhibition
    • Hypersensitivity reaction
    • Clostridium difficile infection
  • The most common side effects are: diarrhea (16% in trial data), nausea (9% in trial data), abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis
  • Beware drug-drug interactions with CYP3A4 inducers, inhibitors, and substrates which may alter gepotidacin concentrations
  • Has a warning about use with digoxin
  • 31% of the dose is excreted into the urine (20% was unchanged drug)
  • Listed as an option in the UTI WikiGuidelines (see link below)
  • Studied against nitrofurantoin for uncomplicated UTI, with similar efficacy results
  • Has been studied for use to treat uncomplicated urogenital gonorrhoea
  • Has activity against bacteria not listed in the FDA approval, but lacks clinical data establishing efficacy
  • Despite the name having “blu” in it, the tablets are yellow in color
  • GlaxoSmithKline owns gepotidacin
  • No pricing available yet, likely to be expensive

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