Gepotidacin mesylate is a triazaacenaphthylene antibiotic that inhibits bacterial type II topoisomerase.1
Uncomplicated Urinary Tract Infections
Gepotidacin mesylate is used for treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kg with uncomplicated urinary tract infections (uUTI) caused by the following susceptible microorganisms: Escherichia coli , Klebsiella pneumoniae , Citrobacter freundii complex, Staphylococcus saprophyticus , and Enterococcus faecalis .1, 2, 5
Gepotidacin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.1
The current indication for gepotidacin mesylate in the treatment of uUTI caused by susceptible bacteria is based on results from 2 multicenter, randomized, parallel-group, double-blind, double-dummy, noninferiority studies (Trial 1 and Trial 2).1, 2, 5 A total of 3,136 female patients with uUTI were randomized in these trials.1 Both trials compared gepotidacin 1500 mg (administered orally twice daily with food for 5 days) to nitrofurantoin 100 mg (administered orally twice daily for 5 days).1, 2, 5
Patients had at least 2 symptoms consistent with uUTI (dysuria, frequency, urgency, or lower abdominal pain) with evidence of urinary nitrite or pyuria.1 Patients were excluded if they had any medical condition or presentation suggestive of a complicated UTI or an upper UTI (e.g., pyelonephritis, urosepsis).1, 5 Efficacy was assessed as a composite of clinical cure and microbiological response at the test-of-cure (TOC) visit (study days 10 to 13) in the microbiological intent-to-treat nitrofurantoin-susceptible (micro-ITTS) population, which included all patients who received at least 1 dose of study medication and had at least 1 baseline qualifying uropathogen (≥105colony-forming units [CFU]/mL), and excluded patients with organisms not susceptible to nitrofurantoin.1, 2, 5 Clinical cure was defined as resolution of all signs and symptoms of acute cystitis present at baseline and no new signs and symptoms without the patient receiving other systemic antimicrobials.1, 5 Microbiological response was defined as having all qualifying uropathogens found at baseline at ≥105 CFU/mL reduced to <103 CFU/mL without the patient receiving other systemic antimicrobials.1, 5
In Trial 1, the micro-ITTS population included 634 female patients with uUTI (336 in the gepotidacin group and 298 in the nitrofurantoin group).1 The median age of patients was 54 years; 57% were >50 years of age and 40% had a history of recurrent infection.1 In Trial 2, the micro-ITTS population included 567 female patients with uUTI (292 in the gepotidacin group and 275 in the nitrofurantoin group).1 The median age of patients was 51 years; 52% were >50 years of age and 41% had a history of recurrent infection.1 Composite response in the gepotidacin and nitrofurantoin groups was 51.8% (174/336) and 47% (140/298), respectively, in Trial 1.1, 2 Composite response in the gepotidacin and nitrofurantoin groups was 58.9% (172/292) and 44% (121/275), respectively, in Trial 2.1, 2 Both trials demonstrated noninferiority of gepotidacin to nitrofurantoin for composite response.1, 2, 5
Clinical practice guidelines on the management of uUTIs have been published by the Infectious Diseases Society of America (IDSA) and other experts.4, 6, 7 These guidelines generally recommend the use of nitrofurantoin, trimethoprim-sulfamethoxazole (TMP/SMX), fosfomycin, and pivmecillinam as appropriate treatment options for acute uncomplicated cystitis.4, 6, 7 The choice of antibiotic should be individualized and based on local practice and susceptibility patterns; drug availability and costs; and patient-specific factors.3, 4, 6, 7 Gepotidacin is not discussed because the drug was approved after guideline publication.4
Administer gepotidacin orally; administration after a meal is recommended to reduce the possibility of GI intolerance.1, 2
If a dose is missed, instruct patients to take the missed dose as soon as possible.1 Do not double the dose to make up for a missed dose.1
Store the tablets at 20-25ºC (excursions permitted between 15-30ºC).1
Dosage of gepotidacin mesylate is expressed in terms of gepotidacin.1
The recommended dosage of gepotidacin for the treatment of an uncomplicated urinary tract infection in female adult and pediatric patients 12 years of age and older weighing at least 40 kg is 1500 mg (two 750-mg tablets) twice daily (approximately 12 hours apart) for 5 days.1, 2
No dosage adjustments are required for patients with mild or moderate hepatic impairment (Child-Pugh Class A/B).1, 2 Avoid use of gepotidacin in patients with severe hepatic impairment (Child-Pugh Class C) due to increased exposure and risk of QT interval corrected for rate (QTC) prolongation.1, 2
No dosage adjustments are required for patients with mild renal impairment (eGFR 60 to 89 mL/minute) or moderate renal impairment (eGFR 30 to 59 mL/minute).1, 2 Avoid use of gepotidacin in patients with severe renal impairment or kidney failure (eGFR <30 mL/minute), including those receiving dialysis, due to increased exposure and risk of QTCprolongation.1, 2
The manufacturer makes no specific dosage recommendations for geriatric patients.1, 2
Dose and concentration-dependent prolongation of the QT interval corrected for rate (QTC) has been observed with gepotidacin.1
Avoid gepotidacin in patients with a history of QTC interval prolongation or those with relevant pre-existing cardiac disease, patients taking antiarrhythmic agents, or other medications that may potentially prolong the QTc interval.1
Due to an increase in gepotidacin exposure and the risk of QTc interval prolongation, avoid concomitant administration of gepotidacin in patients receiving therapy with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole), patients with severe hepatic impairment (Child-Pugh Class C), and patients with severe renal impairment (eGFR <30 mL/minute).1 If administration of gepotidacin cannot be avoided in these patients, monitor and correct serum electrolyte abnormalities and collect an ECG prior to administration and during treatment, as clinically indicated.1, 3
Acetylcholinesterase Inhibition
Gepotidacin is a reversible acetylcholinesterase inhibitor in in vitro laboratory studies.1 Adverse reactions including dysarthria, presyncope, muscle spasms, diarrhea, nausea, vomiting, abdominal pain, hypersalivation, and hyperhidrosis, which are potentially attributed to acetylcholinesterase inhibition, have been observed in clinical trials.1 Increased cholinergic effects can be associated with severe adverse reactions including atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope.1 Monitor patients with medical conditions that may be exacerbated by acetylcholinesterase inhibition.1
Gepotidacin, as an acetylcholinesterase inhibitor, may exaggerate the neuromuscular effects of succinylcholine-type muscle relaxation during anesthesia.1 Gepotidacin may exaggerate the effects of other acetylcholinesterase inhibitors.1 Monitor patients for exaggerated neuromuscular blockade or excessive cholinergic effects.1
Because gepotidacin may antagonize the effects of systemic anticholinergic medications or non-depolarizing neuromuscular blocking agents, monitor patients if gepotidacin is concomitantly administered with these medications.1, 3
Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving gepotidacin.1 Prior to initiating therapy, carefully inquire about previous hypersensitivity reactions; previous hypersensitivity is a contraindication to use of the drug.1 If an allergic reaction occurs during therapy, discontinue gepotidacin and administer appropriate treatment.1
Clostridioides difficile Infection
Clostridioides difficile (C. difficile) infection (CDI) has been reported for nearly all systemic antibacterial agents, including gepotidacin mesylate, and may range in severity from mild diarrhea to fatal colitis.1 Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile .1
C. difficile produces toxins A and B, which contribute to the development of CDI.1 Hypertoxin producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.1 CDI must be considered in all patients who present with diarrhea following antibacterial drug use.1 Careful medical history is necessary since CDI has been reported to occur over 2 months after the administration of antibacterial agents.1
If CDI is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued.1 Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.1
Development of Drug-resistant Bacteria
Prescribing gepotidacin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.1
A pregnancy exposure registry will be established to monitor pregnancy outcomes in women exposed to gepotidacin mesylate during pregnancy.1 Pregnant women exposed to gepotidacin, and healthcare providers are encouraged to contact GlaxoSmithKline at 1-888-825-5249.1
There are no available data on the use of gepotidacin in pregnant women to evaluate for a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1
In embryofetal development studies in mice and rats, decreased fetal weights and increased fetal mortality (late resorptions) were observed at exposures about 0.8-to-1-times the maximum recommended human dose (MRHD).1 In a mouse pre- and postnatal development study, there were no adverse developmental effects at exposures of approximately 3-times the MRHD.1
There are no data on the presence of gepotidacin in human milk, its effects on the breastfed child, or on milk production.1 Based on a study in lactating mice, gepotidacin is likely transferred into milk.1 When a drug is present in animal milk, it is likely that the drug will be present in human milk.1 The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for gepotidacin and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.1
The safety and effectiveness of gepotidacin for the treatment of uncomplicated urinary tract infections (uUTI) have been established in female pediatric patients 12 years of age and older, weighing at least 40 kg.1 Use of gepotidacin in these patients is supported by evidence from adequate and well-controlled studies in female adult and pediatric patients 12 years of age and older with uUTI and additional pharmacokinetic data in pediatric patients (12 to <18 years of age).1 The safety profile of gepotidacin in female pediatric patients 12 years of age and older was similar to female adults with uUTI treated with the drug.1
The safety and effectiveness of gepotidacin have not been established in pediatric patients <12 years of age or weighing <40 kg.1
Of the total number of patients who received treatment with gepotidacin in the uUTI studies (Trials 1 and 2), 226 (14%) were 65 to <75 years of age and 127 (8%) were ≥75 years of age.1 No overall differences in safety or effectiveness of gepotidacin were observed between patients ≥65 years of age and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.1
Gepotidacin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.1
No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh Class A/B).1 Avoid use of gepotidacin in patients with severe hepatic impairment (Child-Pugh Class C) due to increased exposure and the risk of QTc prolongation.1
No dosage adjustment is required in patients with mild (eGFR 60 to 89 mL/minute) or moderate renal impairment (eGFR 30 to 59 mL/minute).1 Avoid use of gepotidacin in patients with severe renal impairment or kidney failure (eGFR <30 mL/minute), including those receiving dialysis, due to increased exposure and the risk of QTc prolongation.1
The most common adverse reactions occurring in ≥1% of patients are diarrhea, nausea, abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis.1, 2
Gepotidacin is a potential substrate of cytochrome P-450 (CYP) 3A4, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, and MATE2-K.1, 2 Gepotidacin is a reversible inhibitor of CYP3A4.2 Gepotidacin is not an inducer of CYP1A2, 2B6, or 3A4.1 Gepotidacin is not a substrate of the hepatic organic anion transporting polypeptides (OATPs) 1B1, 1B3, and 2B1, organic anion transporters (OATs) OAT1, OAT2, and OAT3, and organic cation transporters (OCTs) OCT2 and OCT3.1 Gepotidacin inhibited MATE1 and MATE2-K.1, 2
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
CYP3A4 inhibitors: Avoid concomitant administration of gepotidacin mesylate with strong inhibitors of CYP3A4.1, 2
CYP3A4 inducers: Avoid concomitant administration of gepotidacin with strong inducers of CYP3A4.1, 2
CYP3A4 substrates: Avoid concomitant administration of gepotidacin with drugs that are extensively metabolized by CYP3A4 and have a narrow therapeutic index.1
Drugs Associated with QT Prolongation
Due to an increased risk of QTcprolongation, avoid concomitant administration of gepotidacin mesylate with other medications that have the potential to prolong the QTc interval.1
Cholinergic/Anticholinergic Drugs
There is a potential for an exaggerated effect of concomitantly administered succinylcholine-type neuromuscular blocking agents resulting in a delay in recovery of neuromuscular function.1 Gepotidacin mesylate may augment the effect of other acetylcholinesterase inhibitors (e.g., donepezil).1 Monitor for exaggerated neuromuscular blockade or excessive cholinergic effects.1 There is potential for an antagonistic effect with systemic anticholinergic medications (e.g., benztropine, oxybutynin) or non-depolarizing neuromuscular blocking agents.1
Concomitant administration of a single 0.5 mg dose of digoxin with two 3000-mg doses of gepotidacin (not an FDA-labeled dosage), given 12 hours apart, resulted in a 1.5-fold increase in the digoxin maximum concentration (Cmax), a 1.1-fold increase in the digoxin AUC (0-infinity), and a delayed digoxin time to maximum plasma concentration (Tmax).1, 2 Due to an increase in digoxin exposures, consider monitoring digoxin serum concentrations, as appropriate, with concomitant administration of gepotidacin.1
Concomitant administration of itraconazole 200 mg per day for 3 days and a single 1500-mg dose of gepotidacin results in an increase in the Cmax of gepotidacin of approximately 1.4-fold and AUC of approximately 1.5-fold.1
Concomitant administration of a single dose of midazolam 2 mg with gepotidacin [2 doses of 3000 mg, given 12 hours apart (not an FDA-labeled dosage)] resulted in a 1.9-fold increase in midazolam AUC (0-infinity).1, 2
Concomitant administration of gepotidacin 1500 mg with rifampin 600 mg once daily for 7 days resulted in a decrease of 52% in gepotidacin plasma AUC (0-infinity).1, 2
Gepotidacin mesylate is a triazaacenaphthylene antibacterial that inhibits Type II topoisomerases including bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, thereby inhibiting DNA replication.1, 2 Gepotidacin has bactericidal activity against pathogens as determined by time-kill studies.1 In vitro studies demonstrated a gepotidacin post-antibiotic effect ranging from 1.8 to 2.2 hours for E. coli , 1 to >6.6 hours for K. pneumoniae , 1.4 to 3 hours for P. mirabilis , 1 to 2.6 hours for C. freundii , 2.7 to 4.3 hours for S. saprophyticus , and 1.2 to 2.7 hours for E. faecalis at 5 times the MIC.1, 2
The bioavailability of gepotidacin is approximately 45%.1 Time to maximum concentration is approximately 2 hours.2 A standard and moderate fat meal had no clinically significant effect on pharmacokinetics.1 The plasma protein binding is approximately 25 to 41%, while 25 to 33% is bound to alpha-1-glycoprotein.1, 2 The half-life is 9.3 hours.1, 2 Gepotidacin is metabolized primarily by oxidative metabolism mediated by CYP3A4, producing several circulating metabolites.1, 2 The major metabolite is M4, which is approximately 11% of circulating drug-related materials.1, 2 Gepotidacin is excreted approximately 52% (30% unchanged drug) in feces and approximately 31% (20% unchanged drug) in urine.1, 2 The major route of elimination for absorbed gepotidacin is in the urine.1
Gepotidacin mesylate has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections:1
Gram-positive bacteria: Enterococcus faecalis , Staphylococcus saprophyticus. 1
Gram-negative bacteria: Citrobacter freundii , Escherichia coli , Klebsiella pneumoniae .1
The following in vitro data are available, but their clinical significance is unknown.1 At least 90% of the following bacteria exhibit an in vitro MIC less than or equal to the susceptible breakpoint for gepotidacin against isolates of similar genus or organism group.1 However, the efficacy of gepotidacin in treating clinical infections caused by the following bacteria has not been established in adequate and well-controlled clinical trials: Citrobacter koseri , Klebsiella aerogenes , Klebsiella oxytoca/Raoltella ornithinolytica , Morganella morganii , Proteus mirabilis , and Providencia rettgeri .1
During clinical studies, gepotidacin demonstrated activity against some isolates of the following multilocus sequence typing (MLST) for E. coli : ST10, ST131, ST1193, ST69, ST95, and ST73.1
Although no clear mechanisms of resistance have been identified for gepotidacin mesylate, potential mechanisms that may impact gepotidacin activity are gepotidacin-specific alterations of DNA gyrase (gyrA , gyrB ) and/or topoisomerase IV (parC , parE ) gene targets, plasmid-mediated quinolone resistance genes (especially qnr ), and efflux.1, 2 The following amino acids may be important for gepotidacin activity GyrA P35, V44, D82, A175, GyrB D426, P445, and ParC D79 as shown through studies with isogenic mutants in E. coli and K. pneumoniae .1 A single target-specific mutation may not significantly impact gepotidacin activity.1 The relationship between gepotidacin and fluoroquinolone susceptibility does not appear to include amino acid substitutions in GyrA and ParC that are known to reduce fluoroquinolone susceptibility in E. coli .1 Gepotidacin activity against E. coli and K. pneumoniae is unrelated to beta-lactam resistance mechanisms.1
The frequency of resistance development to gepotidacin due to spontaneous mutations in the gram-negative and gram-positive uropathogens tested in vitro at 10 times MIC ranged from 10-9 to 10-10.1
Target-specific cross-resistance with other classes of antibacterial drugs has not been identified; therefore, isolates resistant to other drugs may be susceptible to gepotidacin.1 However, isolates of Enterobacterales with ≥4-fold increases in gepotidacin MIC have been identified in vitro and in clinical studies.1
In in vitro studies, no antagonism against Enterobacterales or gram-positive isolates was observed for gepotidacin in combination with multiple antibacterial drugs, including fluoroquinolones, sulfonamides, cephalosporins, macrolides, tetracyclines, aminoglycosides, glycopeptides, carbapenems, nitrofurantoin, monobactams, and oxazolidinones.1, 2
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 750 mg (of gepotidacin) | Blujepa® | GlaxoSmithKline |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions December 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. GlaxoSmithKline LLC. Blujepa®(gepotidacin) ORAL prescribing information. 2025 Mar.
2. Food and Drug Administration. Center for Drug Evaluation and Research. Application number:218230Orig1s000. Integrated Review. Created 2023 November. From FDA website.
3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number:218230Orig1s000. Risk Assessment and Risk Mitigation Review(s). Created 2025 March. From FDA website.
4. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52(5):e103-e120.
5. Wagenlehner F, Perry CR, Hooton TM, Scangarella-Oman NE, Millns H, Powell M, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet 2024;403:741-55.
6. Nelson Z, Aslan AT, Beahm NP et al. Guidelines for the prevention, diagnosis, and management of urinary tract infections in pediatrics and adults: A WikiGuidelines Group Consensus Statement. JAMA Netw Open. 2024 Nov 4;7(11):e2444495. doi: 10.1001/jamanetworkopen.2024.44495. Erratum in: JAMA Netw Open. 2024 Dec 2;7(12):e2453497. doi: 10.1001/jamanetworkopen.2024.53497. PMID: 39495518.
7. Anger J, Lee U, Ackerman AL et al. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU Guideline. J Urol. 2019 Aug;202(2):282-289. doi: 10.1097/JU.0000000000000296. Epub 2019 Jul 8. Update in: J Urol. 2022 Oct;208(4):754-756. doi: 10.1097/JU.0000000000002888. PMID: 31042112.