Gepotidacin
FDA Drug Information • Also known as: Blujepa
- Brand Names
- Blujepa
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION BLUJEPA tablets contain gepotidacin mesylate, a triazaacenaphthylene antibacterial that inhibits bacterial DNA gyrase and topoisomerase IV. The chemical name is ( R )-2-((4-(((3,4-dihydro-2 H -pyrano[2,3- c ]pyridin-6-yl)methyl)amino)piperidin-1-yl)methyl)-1,2-dihydro-3 H ,8 H -2a,5,8a-triazaacenaphthylene-3,8-dione methanesulfonate dihydrate. The molecular formula is C 24 H 28 N 6 O 3 ●CH 4 O 3 S●2H 2 O and its molecular mass is 580.66. The structural formula is shown below. *stereogenic center Each BLUJEPA oral tablet contains gepotidacin 750 mg (equivalent to 910.7 mg of gepotidacin mesylate [anhydrous]). Inactive ingredients include colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide. Gepotidacin mesylate dihydrate chemical structure
What Is Gepotidacin Used For?
1 INDICATIONS AND USAGE BLUJEPA is a triazaacenaphthylene bacterial type II topoisomerase inhibitor indicated for the treatment of the following infections caused by susceptible microorganisms:
Uncomplicated urinary tract infections (uUTI) in female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg). ( 1.1 ) Uncomplicated urogenital gonorrhea in adult and pediatric patients 12 years of age and older weighing at least 45 kilograms who have limited or no alternative treatment options. Approval of this indication is based on limited clinical safety data for this indication. ( 1.2 , 6.1 ) Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of BLUJEPA and other antibacterial drugs, BLUJEPA should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. ( 1.3 ) 1.1 Treatment of Uncomplicated Urinary Tract Infections BLUJEPA is indicated in female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg) for the treatment of 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 Treatment of Uncomplicated Urogenital Gonorrhea BLUJEPA is indicated in adult and pediatric patients 12 years of age and older weighing at least 45 kilograms (kg) who have limited or no alternative options for the treatment of uncomplicated urogenital gonorrhea caused by susceptible strains of Neisseria gonorrhoeae. Approval of this indication is based on limited clinical safety data for BLUJEPA [see Adverse Reactions ( 6.1 )]. 1.3 Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of BLUJEPA and other antibacterial drugs, BLUJEPA should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.Dosage and Administration
2 DOSAGE AND ADMINISTRATION
uUTI: The recommended dosage of BLUJEPA is 1,500 mg (two 750 mg tablets) taken orally, twice daily (approximately 12 hours apart), for 5 days. ( 2.1 ) Uncomplicated Urogenital Gonorrhea: The recommended dosage of BLUJEPA is 3,000 mg (four 750 mg tablets) taken orally, followed by a second dose of 3,000 mg (four 750 mg tablets) approximately 12 hours later. ( 2.2 ) Administer BLUJEPA tablets after a meal to reduce the possibility of gastrointestinal intolerance. ( 2.3 ) 2.1 Recommended Dosage for Female Adult and Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kg for Uncomplicated UTI The recommended dosage of BLUJEPA is 1,500 mg (two 750 mg tablets) taken orally, twice daily (approximately 12 hours apart) for 5 days in female adult and pediatric patients 12 years of age and older with uncomplicated uUTI [see Dosage and Administration ( 2.3 )] . 2.2 Recommended Dosage for Adult and Pediatric Patients 12 Years of Age and Older Weighing at Least 45 kg for Uncomplicated Urogenital Gonorrhea The recommended dose of BLUJEPA is 3,000 mg (four 750 mg tablets) taken orally, followed by a second dose of 3,000 mg (four 750 mg tablets) approximately 12 hours later in adult and pediatric patients 12 years of age and older weighing at least 45 kg with uncomplicated urogenital gonorrhea [see Dosage and Administration ( 2.3 )]. Do not increase the dose, extend the duration of treatment, or reduce the interval between doses due to the risk of QTc interval prolongation [see Warnings and Precautions ( 5.1 )]. 2.3 Important Administration Instructions Administer BLUJEPA tablets after a meal to reduce the possibility of gastrointestinal intolerance [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 )] . 2.4 Recommendations Regarding Missed Dose(s) If a dose is missed, instruct patients to take the missed dose as soon as possible. For uUTI, do not double the dose to make up for a missed dose.Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling:
QTc Prolongation [see Warnings and Precautions ( 5.1 )] . Acetylcholinesterase Inhibition [see Warnings and Precautions ( 5.2 )] . Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] . Clostridioides difficile Infection [see Warnings and Precautions ( 5.4 )] . uUTI: The most common adverse reactions occurring in ≥1% of patients are diarrhea, nausea, abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis. ( 6.1 ) Uncomplicated Urogenital Gonorrhea: The most common adverse reactions occurring in ≥2% of patients are diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, soft feces, headache, fatigue, and hyperhidrosis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trial Experience in Patients with Uncomplicated UTI The safety of BLUJEPA was evaluated in 2 double‑blind, active‑controlled, randomized trials in female adult and pediatric patients 12 years of age and older with uUTI (Trial 1 and Trial 2). A total of 1,570 patients were treated with BLUJEPA and 1,558 patients were treated with nitrofurantoin (pooled safety populations for BLUJEPA and nitrofurantoin, respectively). Patients received treatment for a median duration of 5 days. In Trials 1 and 2 (pooled, intent-to-treat [ITT] population), the median age of patients treated with BLUJEPA was 49 (range 13 to 89) years; <1% were <18 years, 77% of patients were 18 to 64 years, 14% were 65 to 74 years, and 8% were ≥75 years. Patients were female (100%) and White (83%), Black or African American (7%), Asian (5%), or American Indian or Alaskan Native (4%); for ethnicity, 33% identified as Hispanic/Latino and 67% as non-Hispanic/Latino. The majority of patients were enrolled from the U.S. (55%). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation: In the pooled trials (Trials 1 and 2), serious adverse reactions occurred in 1/1,570 (<1%) uUTI patients treated with BLUJEPA and 1/1,558 (<1%) uUTI patients treated with nitrofurantoin. The serious adverse reaction reported with BLUJEPA was dysarthria. No adverse reaction led to death in either treatment group. In the pooled trials, adverse reactions leading to discontinuation of treatment occurred in 79/1,570 (5%) uUTI patients treated with BLUJEPA and 30/1,558 (2%) uUTI patients treated with nitrofurantoin. Adverse reactions occurring in >1% of patients leading to treatment discontinuation in patients treated with BLUJEPA included diarrhea (3%) and nausea (1%). Common Adverse Reactions: Table 1 lists the adverse reactions occurring in ≥1% of uUTI patients receiving BLUJEPA in the pooled trials (Trials 1 and 2). Table 1. Adverse Reactions Occurring in ≥1% of Uncomplicated Urinary Tract Infection Patients Treated with BLUJEPA (Trials 1 and 2 Pooled Data; Safety Population) a Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal tenderness, abdominal discomfort, and gastrointestinal pain. Adverse Reaction BLUJEPA N = 1,570 n (%) Nitrofurantoin N = 1,558 n (%) Diarrhea 258 (16) 51 (3) Nausea 146 (9) 64 (4) Abdominal pain a 60 (4) 34 (2) Flatulence 43 (3) 8 (<1) Headache 38 (2) 40 (3) Soft feces 37 (2) 8 (<1) Dizziness 29 (2) 19 (1) Vomiting 28 (2) 10 (<1) Vulvovaginal candidiasis 20 (1) 18 (1) Diarrhea: In Trials 1 and 2, diarrhea was reported in 258/1,570 (16%) uUTI patients receiving BLUJEPA; 11% mild, 5% moderate, and <1% severe. The diarrhea started within the first 2 days of...Drug Interactions
7 DRUG INTERACTIONS
CYP3A4 Inhibitors: Increase gepotidacin exposure. ( 7.1 ) Strong CYP3A4 inhibitors: Avoid concomitant use of BLUJEPA with strong CYP3A4 inhibitors. ( 5.1 , 7.1 ) Moderate CYP3A4 inhibitors: Avoid concomitant use of BLUJEPA with moderate CYP3A4 inhibitors in patients with uncomplicated urogenital gonorrhea. ( 5.1 , 7.1 ) CYP3A4 Inducers: Decrease gepotidacin exposure. ( 7.1 ) For uUTI: Avoid concomitant use of BLUJEPA with strong CYP3A4 inducers. ( 7.1 ) For uncomplicated urogenital gonorrhea: Avoid concomitant use of BLUJEPA with strong and moderate CYP3A4 inducers. ( 7.1 ) CYP3A4 Substrates: Avoid concomitant use of BLUJEPA with drugs that are extensively metabolized by CYP3A4 where minimal concentration changes may lead to serious adverse reactions. ( 7.2 ) Digoxin: Due to an increase in digoxin exposures, consider monitoring digoxin serum concentration, as appropriate, with concomitant administration of BLUJEPA. ( 7.2 ) 7.1 Effect of Other Drugs on BLUJEPA CYP3A4 Inhibitors Table 3. Recommendations for Concomitant Administration of CYP3A4 Inhibitors with BLUJEPA Indication Moderate CYP3A4 Inhibitors Strong CYP3A4 Inhibitors Uncomplicated UTI No dosage adjustment Avoid concomitant administration of BLUJEPA with strong inhibitors of CYP3A4 due to an increase in gepotidacin exposure [see Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.3 )]. Uncomplicated Urogenital Gonorrhea Avoid concomitant administration of BLUJEPA with moderate CYP3A4 inhibitors due to an increase in gepotidacin exposure [see Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.3 )]. Avoid concomitant administration of BLUJEPA with strong inhibitors of CYP3A4 due to an increase in gepotidacin exposure [see Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.3 )]. CYP3A4 Inducers Due to decreased gepotidacin exposures, avoid coadministration of BLUJEPA with CYP3A4 inducers as follows: Uncomplicated urinary tract infections: Avoid concomitant use of BLUJEPA with strong CYP3A4 inducers [see Clinical Pharmacology ( 12.3 )] . Uncomplicated urogenital gonorrhea: Avoid concomitant use of BLUJEPA with strong and moderate CYP3A4 inducers [see Clinical Pharmacology ( 12.3 )] . 7.2 Effect of BLUJEPA on Other Drugs CYP3A4 Substrates Avoid concomitant administration of BLUJEPA with drugs that are extensively metabolized by CYP3A4 where minimal concentration changes may lead to serious adverse reactions [see Clinical Pharmacology ( 12.3 )] . Digoxin Due to an increase in digoxin exposures, consider monitoring digoxin serum concentrations, as appropriate, with concomitant administration of BLUJEPA [see Clinical Pharmacology ( 12.3 )] . 7.3 Cholinergic/Anticholinergic Drugs As gepotidacin is an acetylcholinesterase inhibitor, there is potential for an exaggerated effect of concomitantly administered succinylcholine‑type neuromuscular blocking agents resulting in a delay in recovery of neuromuscular function. BLUJEPA may...Contraindications
4 CONTRAINDICATIONS BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 )] . A history of severe hypersensitivity to BLUJEPA. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Pregnancy Exposure Registry A pregnancy exposure registry will be established to monitor pregnancy outcomes in women exposed to BLUJEPA during pregnancy. Pregnant women exposed to BLUJEPA, and healthcare providers are encouraged to contact GlaxoSmithKline at 1‑888‑825‑5249. Risk Summary There are no available data on the use of BLUJEPA in pregnant women to evaluate for a drug‑associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In embryo‑fetal development studies in mice and rats, decreased fetal weights and increased fetal mortality (late resorptions) were observed at exposures less than the maximum recommended human dose (MRHD). In a mouse pre- and postnatal development study, there were no adverse developmental effects at exposures approximately equal to the MRHD (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage, in clinically recognized pregnancies, is 2% to 4% and 15% to 20%, respectively. Data Animal Data: Gepotidacin did not cause malformations when orally administered in embryo‑fetal development studies during organogenesis. Decreased fetal weights were seen in rats dosed orally with 450 mg/kg/day or greater (less than the MRHD based on AUC extrapolated from nonpregnant rats). Decreased fetal weights and increased late fetal resorptions were seen in mice at oral doses 500 mg/kg/day or greater (less than the MRHD based on AUC extrapolated from nonpregnant mice). In a pre- and post‑natal development study in mice given oral doses of up to 1,000 mg/kg/day (approximately equal to the MRHD), there were no gepotidacin effects on parturition, or post‑natal growth and development of the offspring.
Overdosage
10 OVERDOSAGE There is a risk of QTc prolongation with overdosage. Intermittent hemodialysis is not likely to substantially remove BLUJEPA from the systemic circulation. Consider contacting the Poison Help line (1‑800‑222‑1222) or a medical toxicologist for additional overdose management recommendations.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING BLUJEPA tablets are supplied as yellow, film-coated, capsule-shaped tablets debossed with “GS GU3” on one side and plain on the other side, containing 750 mg of gepotidacin. Bottle of 8 tablets (NDC 0173-0922-38). Bottle of 20 tablets (NDC 0173-0922-45). Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). [See USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.