GEPOTIDACIN TAB
Clinical Criteria Summary
Document 865: Gepotidacin BLUJEPA in Cystitis Criteria May 2026
Exclusion Criteria
- History of QTc prolongation or relevant pre-existing cardiac disease or taking drugs that prolong the QTc interval
- Concomitant use of strong CYP3A4 inhibitors
- Severe renal impairment (eGFR <30 mL/min)
- Severe hepatic impairment (Child-Pugh Class C)
Inclusion Criteria
- Prescribed by a VA/VA Community Care infectious diseases specialist or locally designated expert
- Cystitis due to Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, or Enterococcus faecalis (men must have no signs of prostatitis)
Additional Inclusion Criteria (Microbiological/Clinical Response/Allergy)
- ONE of the following must be selected:
- Isolate is susceptible to gepotidacin and non-susceptible to all other appropriate oral antibiotics
- Isolate’s susceptibility to gepotidacin is not available and patient had an inadequate clinical and/or microbiological response to all other appropriate oral antibiotics
- Patient has severe hypersensitivity, contraindication, inadequate response, or intolerance to all other appropriate oral antibiotics
Additional Inclusion Criteria – Select If Applicable (Pregnancy & Lactation Counseling)
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
- For females who are lactating/providing breastmilk to an infant or planning to do so: Counseling provided on the risks vs benefits of treatment
Reference Examples (Per Document Footnotes)
- Other appropriate oral agents include: nitrofurantoin, beta-lactams, trimethoprim-sulfamethoxazole, fluoroquinolones (e.g., low-dose, 3-day course), fosfomycin tromethamine.
Document 866: Gepotidacin BLUJEPA in Gonorrhea Criteria May 2026
Exclusion Criteria
- History of QTc prolongation or relevant pre-existing cardiac disease or taking drugs that prolong the QTc interval
- Concomitant use of strong CYP3A4 inhibitors
- Severe renal impairment (eGFR <30 mL/min)
- Severe hepatic impairment (Child-Pugh Class C)
- Concomitant use of moderate CYP3A4 inhibitors or ≥2 of the following risk factors: weight between 45 and 60 kg, moderate renal impairment (eGFR 30 to 59 mL/min), or moderate hepatic impairment (Child-Pugh Class B)
Inclusion Criteria
- Prescribed by a VA/VA Community Care infectious diseases specialist or locally designated expert
- Uncomplicated urogenital gonorrhea
Additional Inclusion Criteria (Select ONE)
- Isolate is susceptible to gepotidacin and non-susceptible to all other appropriate oral antibiotics
- Isolate’s susceptibility to gepotidacin is not available and patient had an inadequate clinical and/or microbiological response to all other appropriate oral antibiotics
- Patient has severe hypersensitivity, contraindication, inadequate response, or intolerance to all other appropriate oral antibiotics
Additional Inclusion Criteria – Select If Applicable
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
- For females who are lactating/providing breastmilk to an infant or planning to do so: Counseling provided on the risks vs benefits of treatment
Clinical Notes & Definitions
- Patients unable to receive gentamicin injection (in combination with azithromycin) — including but not limited to those for whom gentamicin is medically inadvisable or traveling to a clinic for gentamicin injection is infeasible — may use gepotidacin as second-line therapy.
- Examples of other appropriate oral agents for gonorrhea: (1) ceftriaxone (or if ceftriaxone injection is infeasible, oral cefixime unless contraindicated) and (2) gentamicin + azithromycin.
Document 867: MON Gepotidacin BLUJEPA in Gonorrhea and Urinary Tract Infection Monograph May 2026
Indications
- Uncomplicated urogenital gonorrhea
- Females with uncomplicated urinary tract infections (uUTI) caused by certain susceptible pathogens
Patient Population & Eligibility
- Females with uUTI: Adult and pediatric patients 12 years of age or older weighing at least 40 kg
- Uncomplicated urogenital gonorrhea: Age ≥ 12 years; weight > 45 kg; suspected uncomplicated urogenital gonorrhea (including mucopurulent discharge); positive laboratory test for Neisseria gonorrhoeae, or both
- Use in males for uUTI is off-label and not studied; extrapolation to a primarily male VHA population with uUTI is uncertain
Susceptible Pathogens & Microbiology
- uUTI: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, Enterococcus faecalis
- Activity against extended-spectrum-beta-lactamase (ESBL) producing isolates resistant to common oral antibiotics such as fluoroquinolones (FQ)
- Gonorrhea: ceftriaxone-susceptible Neisseria gonorrhoeae
Dosage & Administration
- 2 tablets (1500 mg total) taken orally with or without food twice daily for 5 days
- Taking each dose after a meal may reduce the possibility of gastrointestinal intolerance
- No dose adjustment needed if CrCl ≥ 30 mL/min
- Not recommended if CrCl < 30 mL/min
Contraindications & Precautions
- History of severe hypersensitivity to gepotidacin
- Avoid in patients with a history of QTc prolongation or those with relevant pre-existing cardiac disease
- Avoid in patients taking drugs that prolong the QTc interval
- Avoid in patients taking strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP3A4 substrates
- Avoid in patients with severe renal impairment (eGFR <30 mL/min)
- Avoid in patients with severe hepatic impairment (Child-Pugh Class C)
- Consider monitoring digoxin serum concentrations due to potential increased exposure
Safety Considerations
- QTc prolongation: Dose and concentration-dependent prolongation observed; avoid in at-risk populations
- Acetylcholinesterase inhibition: Reversible AChEI activity observed; adverse events include dysarthria, pre-syncope, muscle spasms, diarrhea, nausea, vomiting, abdominal pain, hypersalivation, hyperhidrosis; severe effects may include atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope
- Hypersensitivity reactions: Include anaphylaxis
- Clostridioides difficile infection (CDI): Reported during or after therapy
- Adverse reactions >10%: Diarrhea
- Pregnancy/Lactation: No human data; decreased fetal weights and increased fetal mortality observed in mice/rats; likely transferred into human milk based on mouse studies
Place in Therapy & Criteria for Use
- Uncomplicated gonorrheal infection: Consider in consultation with an infectious disease specialist for third-line therapy in patients with inadequate response, documented non-susceptibility, or medical inadvisability to first-line therapy (ceftriaxone) AND second-line therapy (gentamicin + azithromycin). Oral cefixime may be used before considering gepotidacin in patients unable to take IM injections of ceftriaxone.
- Uncomplicated urinary tract infection: Consider in consultation with an infectious disease specialist for off-label use in males and on-label use in females who have inadequate response, documented non-susceptibility, or medical inadvisability to all preferred oral antibiotics (nitrofurantoin and TMP/SMZ) and alternative oral beta-lactam antibiotics (amoxicillin/clavulanate and a cephalosporin) and fluoroquinolones (low-dose, 3-day course).
- Uncomplicated urinary tract infection refers to simple cystitis without evidence of infection beyond the bladder in males or females, and without prostatitis in males.
- UpToDate recommends reserving gepotidacin for females with uUTI due to resistant uropathogens or allergies to standard agents, ideally with infectious diseases consultation, and makes no recommendation for use in males.