Blujepa
(Gepotidacin)Blujepa Prescribing Information
BLUJEPA is a triazaacenaphthylene bacterial type II topoisomerase inhibitor indicated for the treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg) with uncomplicated urinary tract infections (uUTI) caused by the following susceptible microorganisms:
BLUJEPA is indicated for the treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg) with uncomplicated urinary tract infections (uUTI) caused by the following susceptible microorganisms:
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. (
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.
• 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 Recommended Dosage for Female Adult and Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kgThe recommended dosage of BLUJEPA is 1,500 mg (two 750 mg tablets) taken orally, twice daily (approximately 12 hours apart) for 5 days. Administer BLUJEPA tablets after a meal to reduce the possibility of gastrointestinal intolerance
[see Adverse Reactions , and Clinical Pharmacology ].• Administer BLUJEPA tablets after a meal to reduce the possibility of gastrointestinal intolerance. ()2.1 Recommended Dosage for Female Adult and Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kgThe recommended dosage of BLUJEPA is 1,500 mg (two 750 mg tablets) taken orally, twice daily (approximately 12 hours apart) for 5 days. Administer BLUJEPA tablets after a meal to reduce the possibility of gastrointestinal intolerance
[see Adverse Reactions , and Clinical Pharmacology ].
Each film coated tablet of BLUJEPA contains 750 mg of gepotidacin. BLUJEPA tablets are yellow, capsule shaped, and debossed with “GS GU3” on one side and plain on the other side.
• Renal Impairment: Avoid use of BLUJEPA in patients with severe renal impairment with eGFR <30 mL/min, including those receiving dialysis. ()8.6 Renal ImpairmentNo dosage adjustment is required in patients with mild renal impairment (eGFR 60 to 89 mL/min) or moderate renal impairment (eGFR 30 to 59 mL/min). Avoid use of BLUJEPA in patients with severe renal impairment or kidney failure (eGFR <30 mL/min), including those receiving dialysis, due to increased exposure to gepotidacin and the risk of QTc prolongation
[see Warnings and Precautions , and Clinical Pharmacology ].• Hepatic Impairment: Avoid use of BLUJEPA in patients with severe hepatic impairment (Child-Pugh Class C). ()8.7 Hepatic ImpairmentNo dosage adjustment is required in patients with mild or moderate hepatic impairment (Child‑Pugh Class A/B). Avoid use of BLUJEPA in patients with severe hepatic impairment (Child‑Pugh Class C) due to increased exposure to gepotidacin and the risk of QTc prolongation
[see Warnings and Precautions , and Clinical Pharmacology ].
BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA
Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA
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.
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%).
In the pooled trials (Trials 1 and 2), serious adverse reactions occurred in 1/1,570 (<1%) patient treated with BLUJEPA and 1/1,558 (<1%) patient 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%) of patients treated with BLUJEPA and 30/1,558 (2%) of 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%).
Table 1lists the adverse reactions occurring in ≥1% of patients receiving BLUJEPA in the pooled trials (Trials 1 and 2).
| aAbdominal 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 paina | 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) |
• QTc Prolongation: Avoid use of BLUJEPA in patients with a history of QTc prolongation, or with relevant pre-existing cardiac disease, and in patients receiving drugs that prolong the QTc interval. Due to an increase in BLUJEPA exposure, avoid concomitant administration of BLUJEPA with strong CYP3A4 inhibitors and in patients with severe hepatic impairment (Child-Pugh Class C) and in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min). ()5.1 QTc ProlongationA dose and concentration-dependent prolongation of the QTc interval has been observed with BLUJEPA
[see Clinical Pharmacology ].Avoid BLUJEPA 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
[see Drug Interactions ].Due to an increase in gepotidacin exposure (Cmax) and the risk of QTc interval prolongation, avoid concomitant administration of BLUJEPA with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole), in patients with severe hepatic impairment (Child‑Pugh Class C), or in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min)
[see Drug Interactions , and Use in Specific Populations ].If administration of BLUJEPA 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.
• Acetylcholinesterase inhibition: Dysarthria and other adverse reactions have been reported in patients receiving BLUJEPA. Monitor patients with underlying medical conditions that may be exacerbated by acetylcholinesterase inhibition and patients receiving succinylcholine-type neuromuscular blocking agents, systemic anticholinergic medications, or non-depolarizing neuromuscular blocking agents. ()5.2 Acetylcholinesterase InhibitionBLUJEPA is a reversible acetylcholinesterase inhibitor in in vitro laboratory studies. 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
[see Adverse Reactions ]. Increased cholinergic effects can be associated with severe adverse reactions including atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope. Monitor patients with medical conditions that may be exacerbated by acetylcholinesterase inhibition.BLUJEPA, as an acetylcholinesterase inhibitor, may exaggerate the neuromuscular effects of succinylcholine‑type muscle relaxation during anesthesia. BLUJEPA may exaggerate the effects of other acetylcholinesterase inhibitors. Monitor patients for exaggerated neuromuscular blockade or excessive cholinergic effects.
Because BLUJEPA may antagonize the effects of systemic anticholinergic medications or non‑depolarizing neuromuscular blocking agents, monitor patients if BLUJEPA is concomitantly administered with these medications
[see Drug Interactions ].• Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA. If an allergic reaction to BLUJEPA occurs, discontinue the drug and institute appropriate supportive measures. ()5.3 Hypersensitivity ReactionsHypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA
[see Adverse Reactions ]. BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA[see Contraindications ].Before therapy with BLUJEPA is instituted, carefully inquire about previous hypersensitivity reactions to BLUJEPA. If an allergic reaction to BLUJEPA occurs, discontinue the drug and institute appropriate supportive measures.• Clostridioides difficile Infection(CDI): CDI has been reported with nearly all systemic antibacterial agents, including BLUJEPA. Evaluate patients who develop diarrhea. ()5.4Clostridioides difficileInfectionClostridioides difficile (C. difficile)infection (CDI) has been reported for nearly all systemic antibacterial agents, including BLUJEPA, and may range in severity from mild diarrhea to fatal colitis[see Adverse Reactions ]. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth ofC. difficile.C. difficileproduces toxins A and B which contribute to the development of CDI. Hypertoxin producing isolates ofC. difficilecause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDI must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDI has been reported to occur over 2 months after the administration of antibacterial agents.If CDI is suspected or confirmed, ongoing antibacterial drug use not directed against
C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment ofC. difficile, and surgical evaluation should be instituted as clinically indicated.