Approved Drug Label (PDF)
8
Use in Specific Populations
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
A milk-only pharmacokinetic lactation study (n=5) demonstrated that ibrexafungerp is present in maternal milk and plasma. The estimated average daily infant dose of ibrexafungerp
from breast milk was <1% of the maternal weight-adjusted dose (see Data). There are no data on the effects of ibrexafungerp on the breastfed
infant, or the effects on milk production. The developmental and health
benefits of breastfeeding should be considered along with the mother's clinical
need for BREXAFEMME and any potential adverse
effects on the breast-fed child from
BREXAFEMME or from the underlying maternal condition.
Data
A milk-only pharmacokinetic
lactation study evaluated concentrations of ibrexafungerp in the plasma and
breast milk of 5 healthy lactating women, who were between 33 and 346 days
postpartum. Two oral doses of 300 mg of BREXAFEMME were administered 12 hours apart
for one day (600 mg total
daily dose). Ibrexafungerp was detected in breast milk at a mean (standard deviation) average
concentration (Cav) of 45.39 (13.669) ng/mL. The mean (standard deviation)
calculated daily infant dosage was 0.05 (0.06) mg/day which is <1% of the
maternal weight- adjusted dose. There are no data on infant exposure after
repeated maternal dosing of ibrexafungerp.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
What is the most important
information I should
know about BREXAFEMME?
BREXAFEMME may cause serious side effects, including:
Harm to your unborn baby. Treatment with BREXAFEMME during
pregnancy may cause harm to your unborn
baby. Women who can become pregnant may be asked by their healthcare
provider to take a pregnancy test before each treatment with BREXAFEMME. Women
who can become pregnant should use effective birth control throughout the
duration of treatment with BREXAFEMME and for 4 days after the last dose of BREXAFEMME. Talk to your healthcare
provider about birth control methods
that may be right for you.
…
Before you
take BREXAFEMME, tell your healthcare provider about all of your medical
conditions, including if you:
…
What are the possible side effects of BREXAFEMME?
See “What is the most important information I should know about BREXAFEMME?”
The most common side effects of BREXAFEMME include
headache, loose stools, nausea,
stomach pain, dizziness, vomiting, urinary tract
infection and tiredness (fatigue).
…
Approved Drug Label (PDF)
Boxed Warning
Newly added, as
follows:
WARNING: RISK OF
EMBRYO-FETAL TOXICITY
BREXAFEMME is
contraindicated in pregnancy because it may cause fetal harm based on findings
from animal reproductive studies [see
Contraindications (4) and Warnings and Precautions (5.1)].
For females of
reproductive potential, verify that the patient is not pregnant prior to
initiating BREXAFEMME treatment. Reassessing pregnancy status prior to each
dose is recommended when BREXAFEMME is used monthly for 6 months for reduction
in the incidence of recurrent vulvovaginal candidiasis (RVVC) [see Dosage and Administration (2.3),
Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].
Advise females of
reproductive potential to use effective contraception during treatment of
vulvovaginal candidiasis (VVC) and throughout the 6-month treatment period for
reduction in the incidence of RVVC with BREXAFEMME and, for 4 days after the
last dose [see Warnings and Precautions
(5.1) and Use in Specific Populations (8.3)].
5
Warnings and Precautions
5.1 Risk of Embryo-Fetal Toxicity
Additions and/or
revisions underlined:
… For females
of reproductive potential, verify that the patient is not pregnant prior to
initiating treatment with BREXAFEMME. Reassessment of pregnancy status prior
to each dose is recommended when BREXAFEMME is used monthly for 6 months for
reduction in the incidence of RVVC. Advise females of reproductive
potential to use effective contraception during treatment of VVC and
throughout the 6-month treatment period for reduction in the incidence of RVVC
with BREXAFEMME and, for 4 days after the last dose [see Use in Specific Populations (8.1, 8.3)].
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions
underlined:
Because clinical
trials are conducted under widely varying conditions, adverse reaction rates
observed in clinical trials of a drug cannot be directly compared to rates in
the clinical trials of another drug and may not reflect the rates observed in
practice.
Treatment of VVC
A total of 545
patients were exposed to BREXAFEMME in two clinical trials of post-menarchal
females with VVC (Trial 1 and Trial 2). The patients were treated
with BREXAFEMME 300 mg (two 150 mg tablets) twice a day, 12 hours apart, for
one day. The patients were 18 to 76 years of age (mean 34 years) …
Table 1. Adverse Reactions with Rates greater than or
equal to 2% in BREXAFEMME-Treated Patients with VVC in Trials 1 and 2
Other Adverse
Reactions
The following
adverse reactions occurred in < 2% of patients receiving BREXAFEMME in Trial
1 and Trial 2: dysmenorrhea, flatulence, back pain, elevated transaminases,
vaginal bleeding, rash/hypersensitivity reaction.
Reduction in the
Incidence of RVVC
A total of 130
patients were exposed to BREXAFEMME in a clinical trial of post-menarchal
females with RVVC (Trial 3). The patients were treated with BREXAFEMME 300 mg
(two 150 mg tablets) twice a day, 12 hours apart, for one day, monthly for six
consecutive months. The patients were 18 to 65 years of age (mean 34 years), of
which, 59% of patients were between 18 to 35 years, and 41% between 36 to 65
years. Ninety two percent (92%) were White, 7% were Black or African American,
and 1% were Asian. Nine percent (9%) of patients were of Hispanic or Latina
ethnicity.
The most
frequently reported adverse reactions are presented in Table 2.
There were no
serious adverse reactions and no patients discontinued treatment with
BREXAFEMME due to adverse reaction.
Table 2. Adverse Reactions with Rates greater than or
equal to 2% in BREXAFEMME-Treated Patients with RVVC in Trial 3
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
Risk Summary
Based on findings from animal studies, BREXAFEMME use is contraindicated
in pregnancy because it may cause fetal harm. In pregnant rabbits, oral
ibrexafungerp administered during organogenesis was associated with fetal malformations
including absent forelimb(s), absent hindpaw, absent ear pinna, and
thoracogastroschisis at dose exposures greater or equal to approximately 5
times the human exposure at the RHD …
8.3 Females and Males of Reproductive Potential
Additions and/or revisions underlined:
Based on animal data, BREXAFEMME may cause fetal harm when administered
to a pregnant female [see Use in Specific
Populations (8.1)].
Pregnancy Testing
For females of reproductive potential, verify that
the patient is not pregnant prior to initiating treatment with BREXAFEMME.
Reassessment of pregnancy status prior to each dose is recommended when
BREXAFEMME is used monthly for 6 months for reduction in the incidence of RVVC.
[see Dosage and Administration (2.3), Contraindications (4) and Use in Specific
Populations (8.1)].
Contraception
Females
For treatment of VVC, advise females of
reproductive potential to use effective contraception during treatment with
BREXAFEMME and for 4 days after the last dose.
For reduction in the incidence of RVVC, advise females of reproductive
potential to use effective contraception throughout the 6-month treatment
period with BREXAFEMME and, for 4 days after the last dose.
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of BREXAFEMME for treatment of VVC have been
established in post-menarchal pediatric females. BREXAFEMME is also
indicated for the reduction in the incidence of RVVC [see Indications and Usage (1.1)]. Use of BREXAFEMME in post-
menarchal pediatric patients is supported by evidence from adequate and
well-controlled studies of BREXAFEMME in adult non-pregnant women with
additional pharmacokinetic and safety data from post-menarchal pediatric
females [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3), and Clinical Studies (14.1)] …
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Newly added section; please refer to label for complete information.
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Advise the patient to read the FDA approved patient labeling (Medication
Guide) Risk of Embryo-Fetal Toxicity
Advise patients that BREXAFEMME is contraindicated in pregnancy since it may cause fetal harm
[see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
Inform females of
reproductive potential that their healthcare provider will verify that they are
not pregnant prior to initiating BREXAFEMME treatment.
Advise females of
reproductive potential that reassessing pregnancy status prior to each dose is
recommended when BREXAFEMME is used monthly for 6 months for reduction in the
incidence of RVVC
For treatment of VVC, advise
females of reproductive potential to use effective contraception while taking
BREXAFEMME and for 4 days after the last dose [see Use in Specific Populations (8.3)].
For reduction in the
incidence of RVVC, advise females of reproductive potential to use effective
contraception throughout the 6-month treatment period with BREXAFEMME and for 4
days after the last dose [see Use in
Specific Populations (8.3)].
Advise females to inform their healthcare provider of a known or
suspected pregnancy …
… Important Administration Instructions
For treatment of VVC, inform the patient that
each BREXAFEMME dose consists of two tablets. A total treatment course for
VVC is two doses taken approximately 12 hours apart and consists of a total
of four tablets.
For reduction in the incidence of RVVC, inform the patients that the
total treatment course is for six months. Each dose consists of two tablets
taken approximately 12 hours apart for a total daily dosage of four tablets,
taken monthly for six months. If the first
two tablets are taken in the morning, the second two tablets should be taken
that same day in the evening …
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