What is the FDA‑approved indication, oral dosing regimen, adverse effects, contraindications, and alternative oral agents for Blujepa (gepotidacin) in a patient aged ≥12 years and weighing ≥40 kg with uncomplicated urinary tract infection?

Gepotidacin (Blujepa) for Uncomplicated Urinary Tract Infections

FDA-Approved Indication

Gepotidacin is FDA-approved for the treatment of uncomplicated urinary tract infections (uUTIs) caused by susceptible isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis in female adult and pediatric patients aged ≥12 years and weighing ≥40 kg. 1

Oral Dosing Regimen

The recommended dose is gepotidacin 1,500 mg orally twice daily for 5 days. 2, 3

• Gepotidacin should be administered with food to decrease gastrointestinal-related adverse effects 4
• The 5-day twice-daily regimen was selected based on pharmacokinetic/pharmacodynamic modeling and phase III clinical trial data demonstrating non-inferiority to nitrofurantoin 2, 3

Mechanism of Action and Clinical Efficacy

• Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that selectively inhibits bacterial DNA replication through a novel mechanism—it simultaneously targets both DNA gyrase (GyrA) and topoisomerase IV (ParC) 2, 4
• This distinct mechanism of action confers activity against multidrug-resistant uropathogens, including fluoroquinolone-resistant strains 4
• In phase III trials (EAGLE-2 and EAGLE-3), gepotidacin demonstrated non-inferiority to nitrofurantoin for the treatment of uUTIs in females aged ≥12 years 3, 4

Antimicrobial Susceptibility Profile

Gepotidacin demonstrates exceptionally low resistance rates across common uropathogens, making it particularly valuable for multidrug-resistant infections:

• Among Enterobacterales isolates, resistance ranges from 0-6.8% 5
• Resistance among ESBL-producing Enterobacterales is 0-0.6% 5
• Resistance is 0% among multidrug-resistant (MDR) E. coli, K. pneumoniae, and Proteus mirabilis isolates 5
• Gepotidacin retains activity against uropathogens resistant to ampicillin, amoxicillin-clavulanic acid, fluoroquinolones, fosfomycin, nitrofurantoin, and trimethoprim-sulfamethoxazole 5
• For Gram-positive uropathogens, susceptibility is 99.2-100% for Enterococcus faecalis and 66.7-100% for Staphylococcus saprophyticus 5

Adverse Effects

The most common adverse effects are gastrointestinal in nature: 4

• Nausea, diarrhea, and abdominal discomfort are the predominant side effects 4
• Administering gepotidacin with food significantly reduces gastrointestinal adverse effects 4

Contraindications and Drug Interactions

• Gepotidacin has several potential drug-drug interactions that require careful evaluation 4
• The drug is contraindicated in patients with known hypersensitivity to gepotidacin or any component of the formulation 4

Alternative Oral Agents for Uncomplicated UTI

When gepotidacin is not appropriate, alternative oral agents for uUTI in patients ≥12 years include:

First-Line Alternatives:

• Nitrofurantoin 100 mg orally twice daily for 5 days (the comparator in gepotidacin trials) 3, 4
• Trimethoprim-sulfamethoxazole 160/800 mg orally twice daily for 3 days (when local resistance <20%) 6
• Fosfomycin 3,000 mg orally as a single dose for patients ≥12 years 7

Fluoroquinolone Options (when local resistance <10%):

• Ciprofloxacin 500 mg orally twice daily for 3 days 6
• Levofloxacin 250 mg orally once daily for 3 days 6

Beta-Lactam Alternatives:

• Cefpodoxime 200 mg orally twice daily for 10 days 6
• Ceftibuten 400 mg orally once daily for 10 days 6
• Amoxicillin-clavulanate 875/125 mg orally twice daily for 7 days (when susceptible) 6

Clinical Positioning

Gepotidacin represents an important addition to the therapeutic arsenal for uUTIs because:

• It offers a novel mechanism of action that circumvents existing resistance mechanisms 4
• It maintains activity against multidrug-resistant uropathogens, including those resistant to fluoroquinolones and other commonly used agents 5, 4
• It provides an oral option for patients with infections caused by organisms resistant to traditional first-line agents 4

Critical Pitfalls to Avoid

• Do not use gepotidacin for complicated UTIs or pyelonephritis—it is FDA-approved only for uncomplicated UTIs 1
• Do not prescribe gepotidacin without food—this significantly increases gastrointestinal adverse effects 4
• Do not use gepotidacin in patients <12 years or weighing <40 kg—safety and efficacy have not been established in this population 1
• Do not assume gepotidacin is appropriate for male patients—FDA approval is limited to female patients only 1