Blujepa Drug Information

Important Administration Instructions Administer

BLUJEPA tablets after a meal to reduce the possibility of gastrointestinal intolerance.

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.

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. The majority of patients were enrolled from the U.S. (55%). The serious adverse reaction reported with BLUJEPA was dysarthria.

No adverse reaction led to death in either treatment group. Adverse reactions occurring in >1% of patients leading to treatment discontinuation in patients treated with BLUJEPA included diarrhea (3%) and nausea (1%). Table 1.

The diarrhea started within the first 2 days of treatment for the majority of patients and the median duration of diarrhea was 4 days. Adverse Reactions Occurring in Less than 1% of uUTI Patients Receiving BLUJEPA in Trials 1 and 2 (Pooled): Gastrointestinal Disorders: Abdominal distension, dyspepsia (includes epigastric discomfort, eructation) Nervous System Disorders: Presyncope, dysarthria Infections and Infestations: Clostridioides difficile infection Musculoskeletal and Connective Tissue Disorders: Muscle spasms Vascular Disorders: Hot flush Cardiac Disorders: Tachycardia Eye Disorders: Blurred vision Ear and Labyrinth Disorders: Vertigo General Disorders and Administration Site Disorders: Fatigue Investigations: Alanine aminotransferase/aspartate aminotransferase increased Skin and Subcutaneous Tissue: Rash, hyperhidrosis Immune System Disorders: Hypersensitivity reactions Select Adverse Reactions Occurring in uUTI Patients Receiving BLUJEPA in Phase 1 and 2 Clinical Studies: Gastrointestinal Disorders: Hypersalivation (with oral daily doses ranging from 100 mg to 6,000 mg, which includes not approved doses) Clinical Trial Experience in Patients with Uncomplicated Urogenital Gonorrhea The safety of BLUJEPA was evaluated in a randomized, active‑controlled trial (Trial 3) comparing BLUJEPA to ceftriaxone and azithromycin in adult and pediatric patients 12 years of age and older with uncomplicated urogenital gonorrhea. A total of 309 patients received at least one dose of BLUJEPA (safety population).

Overall, patients randomized to receive BLUJEPA treatment were predominately male (89%) and White (74%). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation: No serious adverse reactions occurred in uncomplicated urogenital gonorrhea patients treated with BLUJEPA in Trial 3. Adverse reactions leading to discontinuation of treatment occurred in 3/309 (<1%) of uncomplicated urogenital gonorrhea patients treated with BLUJEPA.

Common Adverse Reactions: Table 2 lists the adverse reactions occurring in ≥2% of uncomplicated urogenital gonorrhea patients receiving BLUJEPA in Trial 3. Table 2. Most episodes of diarrhea started on the same day as dosing, with few diarrhea episodes after day 2.

The median duration was 2 days. Discontinuation of BLUJEPA due to diarrhea was reported in 1/309 (<1%) uncomplicated urogenital gonorrhea patients.

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. Uncomplicated Urogenital Gonorrhea Avoid concomitant administration of BLUJEPA with moderate CYP3A4 inhibitors due to an increase in gepotidacin exposure.

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. • Uncomplicated urogenital gonorrhea: Avoid concomitant use of BLUJEPA with strong and moderate CYP3A4 inducers.

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. Digoxin Due to an increase in digoxin exposures, consider monitoring digoxin serum concentrations, as appropriate, with concomitant administration of BLUJEPA.

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 augment the effect of other acetylcholinesterase inhibitors. Monitor for exaggerated neuromuscular blockade or excessive cholinergic effects.

There is potential for an antagonistic effect with systemic anticholinergic medications or non‑depolarizing neuromuscular blocking agents. Consider the potential for this interaction if BLUJEPA is administered concomitantly with anticholinergic medications.

Drugs that Prolong the QTc Interval Due to the increased risk of QTc prolongation, avoid concomitant administration of BLUJEPA with other medications that have the potential to prolong the QTc interval.

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 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.

Pediatric Use Uncomplicated UTI The safety and effectiveness of BLUJEPA for the treatment of uUTI have been established for the treatment of uncomplicated UTI in female pediatric patients 12 years of age and older, weighing at least 40 kg. Use of BLUJEPA in these patients is supported by evidence from adequate and well‑controlled studies of BLUJEPA 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). The safety profile of BLUJEPA in female pediatric patients 12 years of age and older was similar to female adults with uUTI treated with BLUJEPA.

The safety and effectiveness of BLUJEPA have not been established in pediatric patients less than 12 years of age or weighing less than 40 kg. Uncomplicated Urogenital Gonorrhea The safety and effectiveness of BLUJEPA for the treatment of uncomplicated urogenital gonorrhea have been established in pediatric patients 12 years of age and older weighing at least 45 kg who have limited or no alternative treatment options. Use of BLUJEPA in these patients is supported by evidence from an adequate and well‑controlled study (Trial 3) in adult and pediatric patients with uncomplicated urogenital gonorrhea weighing at least 45 kg, and additional pharmacokinetic analyses showing similar drug exposure levels for pediatric patients (12 to <18 years of age) compared with adults.

BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA. A history of severe hypersensitivity to BLUJEPA.

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.