Blujepa From GSK

The FDA recently approved gepotidacin oral tablets (Blujepa; GSK) for the treatment of uncomplicated urinary tract infections (UTIs) caused by Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis in girls and women 12 years and older who weigh at least 40 kg. The approval also states that to reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, gepotidacin should be used only to treat uncomplicated UTIs that are proven or strongly suspected to be caused by bacteria.¹

Image credit: Sherry Young | stock.adobe.com

Uncomplicated UTIs affect more than half of all women in their lifetime, with approximately 30% experiencing at least 1 recurrence. Up to 16 million women in the US are affected by uncomplicated UTIs each year.²

PHARMACOLOGY AND PHARMACOKINETICS

Gepotidacin is a triazaacenaphthylene antibacterial that inhibits type 2 topoisomerases, including bacterial topoisomerase 2 and topoisomerase 4, resulting in the inhibition of DNA replication. It reaches maximum concentration 2 hours after oral administration and has an elimination half-life of 9.3 hours. Age, body weight, race, and sex have not been shown to have a clinically relevant effect on gepotidacin exposure.¹

DOSAGE AND ADMINISTRATION

The recommended dose of gepotidacin is 1500 mg orally twice daily for 5 days. The medication should be taken after a meal to reduce gastrointestinal intolerance. If a dose is missed, it should be taken as soon as possible, but not doubled. Gepotidacin is supplied as 750-mg tablets.¹

CLINICAL TRIALS

Gepotidacin was evaluated for efficacy in 2 double-blind, double- dummy, multicenter, noninferiority, parallel-group trials: EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144). A total of 3136 female patients with uncomplicated UTIs were randomly assigned to receive either gepotidacin 1500 mg orally twice daily with food for 5 days or nitrofurantoin 100 mg orally twice daily for 5 days. The primary end point for both trials was the combined clinical and microbiological response at the test-of-cure visit on days 10 to 13 in patients with uropathogens that were susceptible to nitrofurantoin. Both trials found gepotidacin to be noninferior to nitrofurantoin.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with gepotidacin is contraindicated in patients with a history of severe hypersensitivity to the medication or any of its components.

Gepotidacin should not be used in patients with a history of QTc prolongation or relevant preexisting cardiac disease, or in patients using medications that prolong the QTc interval. It should not be used in patients with severe hepatic or renal impairment or coadministered with strong CYP3A4 inducers or strong CYP3A4 inhibitors. Concomitant use with agents that are extensively metabolized by CYP3A4 and have a narrow therapeutic window should be avoided.^1,2

Because gepotidacin is a reversible acetylcholinesterase (AChE) inhibitor, it may antagonize the effects of systemic anticholinergic medications or nondepolarizing neuromuscular-blocking agents. Adverse effects such as dysarthria have been reported. Patients with medical conditions that may be exacerbated by AChE inhibition and patients receiving succinylcholine-type neuromuscular-blocking agents, nondepolarizing neuromuscular-blocking agents, or systemic anticholinergic medications should be monitored. If a hypersensitivity reaction occurs, the medication should be discontinued, and supportive measures should be initiated.

Clostridioides difficile infection has been reported with almost all systemic antibacterial agents and should be considered in patients who present with diarrhea after antibacterial use. Concomitant use of gepotidacin with digoxin may require additional monitoring of digoxin serum concentration. The use of gepotidacin in pregnancy and breastfeeding has not been evaluated. It has not been studied in patients younger than 12 years or who weigh less than 40 kg.^1,2

The most common adverse reactions are abdominal pain, diarrhea, dizziness, flatulence, headache, nausea, soft feces, vomiting, and vulvovaginal candidiasis.¹

REFERENCES

1. Blujepa. Prescribing information. GSK; 2025. Accessed April 1, 2025. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Blujepa/pdf/BLUJEPA-PI-MG.PDF

2. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and pediatric patients 12 years of age and older. News release. GSK. March 25, 2025. Accessed April 1, 2025. https://us.gsk.com/en-us/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections-uutis-in-female-adults-and-pediatric-patients-12-years-of-age-and-older/