gepotidacin 750 MG Oral Tablet [Blujepa]

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 • 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.

WARNINGS AND PRECAUTIONS • QTc Prolongation: • Avoid use of BLUJEPA in patients with a history of QTc prolongation, or with relevant pre‑existing cardiac disease, or in patients receiving drugs that prolong the QTc interval. ( 5.1 ) • Due to an increase in gepotidacin exposure and the risk of QTc interval prolongation, avoid use of BLUJEPA in patients who have any of the following risk factors: ( 5.1 , 7.1 , 8.6 , 8.7 ) • Concomitant use of strong CYP3A4 inhibitors • Severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min) • Severe hepatic impairment (Child-Pugh Class C) • Additionally, avoid BLUJEPA in uncomplicated urogenital gonorrhea patients, who have any of the following risk factors for increased gepotidacin exposure: ( 5.1 , 7.1 , 8.6 , 8.7 ) • Concomitant use of moderate CYP3A4 inhibitors • Two or more of the following risk factors: Body weight between 45 kilograms and 60 kilograms, Moderate renal impairment (eGFR 30 to 59 mL/min), Moderate hepatic impairment (Child-Pugh Class B) • 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 ) • 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 ) • Clostridioides difficile Infection (CDI): CDI has been reported with nearly all systemic antibacterial agents, including BLUJEPA. Evaluate patients who develop diarrhea. ( 5.4 ) 5.1 QTc Prolongation A dose and concentration-dependent prolongation of the QTc interval has been observed with BLUJEPA [see Clinical Pharmacology ( 12.2 )]. 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 ( 7.4 )]. Due to an increase in gepotidacin exposure (C max ), and the risk of QTc interval prolongation, avoid BLUJEPA in patients who have any of the following risk factors [see Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.6 , 8.7 )]: • Concomitant use of strong CYP3A4 inhibitors • Severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min) • Severe hepatic impairment (Child-Pugh Class C) Additionally, avoid BLUJEPA in uncomplicated urogenital gonorrhea patients who also have any of the following risk factors for increased gepotidacin exposure [see Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.6 , 8.7 )]: • Concomitant use of moderate CYP3A4 inhibitors • Two or more of the following risk factors: o Body weight between 45 kg and 60 kg o Moderate renal impairment (eGFR 30 to 59 mL/min) o Moderate hepatic impairment (Child ‑ Pugh Class B) 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. 5.2 Acetylcholinesterase Inhibition BLUJEPA is a reversible acetylcholinesterase inhibitor in in vitro laboratory studies. Adverse reactions including dysarthria, syncope, 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 ( 6.1 )] . Increased cholinergic effects can be associated with severe adverse reactions including atrioventricular block, bradycardia, bronchospasm, and seizures/convulsions. 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 ( 7.3 )] . 5.3 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA [see Adverse Reactions ( 6.1 )] . BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA [see Contraindications ( 4 )]. 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. 5.4 Clostridioides difficile Infection Clostridioides 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 ( 6 )] . Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDI. Hypertoxin producing isolates of C. difficile cause 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. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.5 Development of Drug-Resistant Bacteria Prescribing BLUJEPA 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 [see Indications and Usage ( 1.3 )] .

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 )

Mechanism of Action BLUJEPA is an antibacterial drug [see Microbiology ( 12.4 )] .