Gepotidacin

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 augment the effect of other acetylcholinesterase inhibitors. Monitor for exaggerated neuromuscular blockade or excessive cholinergic effects [see Warnings and Precautions ( 5.2 )] . 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 [see Warnings and Precautions ( 5.2 )] .

7.4 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 [see Warnings and Precautions ( 5.1 )] .

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.