8.1 Pregnancy
Additions and/or revisions underlined:
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.
8.2 Lactation
Additions and/or revisions underlined:
…
Data
Gepotidacin concentrations in milk have not been measured
directly in animals.
However, in a pre- and
post-natal development study when gepotidacin was orally administered to maternal mice during pregnancy
and lactation, at all tested doses, gepotidacin was detected in the plasma
of their nursing offspring (with dosing 200
mg/kg/day or greater,
which was expected
to result in maternal exposures as low as 0.2-times the MHRD as extrapolated from exposures in
nonpregnant mice).
8.3 Pediatric Use
Additions and/or revisions underlined:
Uncomplicated UTI
The
safety and effectiveness of BLUJEPA for the treatment of uUTI have been
established 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) [see Clinical Pharmacology (12.3),
Clinical Studies (14.1)]. 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 [see Adverse Reactions (6.1), Clinical
Studies (14.1)].
The safety
and effectiveness of BLUJEPA have not been established for
the treatment of uncomplicated UTI
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 [see Indications and Usage (1.1)]. 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 [see Clinical Pharmacology (12.3), Clinical Studies (14.2)]. The
safety profile of BLUJEPA was similar between pediatric healthy volunteers 12
to <18 years of age (n = 12) who received two 3,000 mg doses compared to
adults [see Adverse Reactions (6.1)].
The safety
and effectiveness of BLUJEPA have not been established for the treatment
of uncomplicated urogenital
gonorrhea in pediatric patients less than 12 years of age or weighing less than
45 kg.
8.5
Geriatric Use
Additions and/or revisions underlined:
Uncomplicated UTI
Of the total number
of patients who received treatment
with BLUJEPA in the uUTI studies (Trials
1 and 2), 226 (14%) were 65
to less than 75 years of age and 127 (8%) were 75 years of age and older [see Clinical Studies (14.1)]. No overall
differences in safety or effectiveness
of BLUJEPA were observed between
patients 65 years of age and older and younger adult patients, but greater
sensitivity of some older individuals cannot be ruled out.
BLUJEPA
is known to be substantially excreted by the kidney, and the risk of adverse
reactions to this drug may be greater
in patients with impaired renal
function [see Warnings and Precautions (5.1),
Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Uncomplicated Urogenital Gonorrhea
Trial 3 did not include sufficient numbers of subjects
aged 65 years and older to determine
whether they respond
differently from younger subjects.
8.6
Renal Impairment
Additions and/or revisions underlined:
For Patients with uUTI or Uncomplicated Urogenital Gonorrhea
No 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 (5.1),
Clinical Pharmacology (12.3)].
Additional Recommendations for Patients
with Uncomplicated Urogenital Gonorrhea
For patients
with uncomplicated urogenital gonorrhea and moderate
renal impairment (eGFR
30 to 59 mL/min), avoid
use of BLUJEPA when additional risk factors for increased gepotidacin exposure
are present [see Warnings and Precautions
(5.1)].
8.7
Hepatic Impairment
Additions and/or
revisions underlined:
For Patients
with uUTI or Uncomplicated Urogenital Gonorrhea
No 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 (5.1), Clinical Pharmacology (12.3)].
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