Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Embryo-Fetal
Toxicity
Additions and/or
revisions underlined:
Based
on data from animal reproduction studies, FILSPARI may cause fetal harm when
administered to a pregnant patient and is contraindicated for use during
pregnancy. The available human data for endothelin receptor antagonists do not
establish the presence or absence of fetal harm related to the use of FILSPARI.
Counsel patients who can become pregnant of the potential risk to a fetus.
Exclude pregnancy before initiating treatment with FILSPARI. Advise patients
who can become pregnant to use effective contraception prior to initiation of
treatment, during treatment, and for two weeks after discontinuation of
treatment with FILSPARI. Advise pre-pubertal females and/or their
guardian(s) of the fetal risk and the need to use effective contraception once
they reach reproductive potential.
.
. .
6
Adverse Reactions
6.1 Clinical
Trials Experience
Extensive
changes; please refer to label for complete information
7
Drug Interactions
7.5 CYP2B6, 2C9,
and 2C19 Substrates
Additions and/or
revisions underlined:
Monitor for efficacy of concurrently administered
CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance
with the Prescribing Information.
Sparsentan is a weak inducer of CYP2B6 and
2C9, and a moderate inducer of 2C19. Sparsentan decreases exposure of
these substrates [see Clinical Pharmacology (12.3)], which may reduce
efficacy related to these substrates.
7.6 P-gp
Substrates
Additions and/or
revisions underlined:
Monitor for adverse reactions and consider dose
reduction of P-gp substrates with narrow therapeutic indices when
co-administered with FILSPARI. FILSPARI is a weak P-gp inhibitor.
Co-administration of FILSPARI may increase plasma concentrations of
P-gp substrate drugs [see Clinical
Pharmacology (12.3)].
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or
revisions underlined:
The safety and effectiveness of FILSPARI for
reducing proteinuria in FSGS have been established in pediatric patients aged 8
years and older. Use of FILSPARI for this indication is supported by evidence
from an adequate and well-controlled trial that enrolled 35 pediatric patients
aged 9 years and older [see Dosage and
Administration (2.4), Adverse Reactions (6.1), Clinical Pharmacology (12.3),
Clinical Studies (14.2)].
The safety and effectiveness of FILSPARI in
pediatric patients less than 8 years of age with FSGS have not been
established.
The safety and effectiveness of FILSPARI in
pediatric patients with IgAN have not been established.
8.5 Geriatric Use
Additions and/or
revisions underlined:
Of the total number of subjects in the clinical
studies of FILSPARI, 37 (8.3%) were
65 and older. No overall differences in safety or
effectiveness were observed between these subjects and younger subjects.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or
revisions underlined:
.
. .
Embryo-Fetal
Toxicity
.
. .
Advise
pre-pubertal females and/or their guardian(s) of the fetal risk and the need to
use effective contraception once they reach reproductive potential.
.
. .
Dosing
Advise
patients to take the full daily dose with water prior to the morning or evening
meal. Patients who cannot swallow whole tablets can crush and suspend the
tablet(s) in half cup of water, mix and orally administer the entire prepared
suspension immediately after preparation. If any portion of the tablet is left
in the cup, add a small amount of additional water, swirl to mix and swallow
immediately. Do not store the solution for later use [see Dosage and Administration (2.5)]. Instruct patients to take
the dose before the same meal each day. If a dose is missed, take the next
dose at the regularly scheduled time. Do not take double or extra doses [see Dosage and Administration (2.5)].
MEDICATION GUIDE
Additions and/or
revisions underlined:
.
. .
If you are the
parent or caregiver of a female child who started taking FILSPARI tablets
before reaching puberty, you should check your child regularly to see if they
are developing signs of puberty. Tell their healthcare provider right away if
you notice that your child is developing breast buds or pubic hair. Their
healthcare provider should decide if your child has reached puberty. Your child
may reach puberty before having their first menstrual period.
.
. .
FILSPARI
is a prescription medicine used to:
lower protein in
the urine in adults and children aged 8 years and older with a kidney disease
called focal segmental glomerulosclerosis (FSGS) who do not have a condition
called nephrotic syndrome.
It
is not known if FILSPARI is safe and effective in children less than 8 years
of age with FSGS. It is not known if FILSPARI is safe and effective in children
with IgAN.
. . .
Take FILSPARI tablets
whole with water before your
morning or evening meal.
Take your dose of
FILSPARI before the same meal
each day.
If you cannot
swallow the tablet whole, you may crush FILSPARI and mix it in water only right
before you take it. Do not mix FILSPARI with other liquids.
Crush the FILSPARI tablet in a clean pill crusher or
mortar and pestle.
Mix the crushed FILSPARI in half a cup of water. The
crushed medicine will not completely dissolve in the water.
Drink all of the mixture right away.
If any of the pieces are left in the cup, add a little
more water to the cup, swirl to mix, and drink right away.
Do not store the mixed solution for later use.
.
. .
Approved Drug Label (PDF)
Boxed Warning
Additions and/or
revisions underlined:
…
Embryo-Fetal Toxicity
FILSPARI is contraindicated for
use during pregnancy because it may cause fetal harm if used by pregnant
patients. Therefore, in patients who can become pregnant, exclude
pregnancy prior to initiation of FILSPARI. Advise use of effective
contraception before the initiation of treatment, during treatment, and for two
weeks after discontinuation of treatment with FILSPARI. When pregnancy
is detected, discontinue FILSPARI as soon as possible [see Dosage
and Administration (2.3), Contraindications (4), Warnings and Precautions (5.3),
Use in Specific Populations (8.1, 8.3)].
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or
revisions underlined:
Risk Summary
Based
on data from animal reproductive toxicity studies, FILSPARI may cause
fetal harm, including birth defects and fetal death, when administered to a
pregnant patient and is contraindicated during pregnancy [see Contraindications (4)]. Available
data from reports of pregnancy in clinical trials with FILSPARI are
insufficient to identify a drug- associated risk of major birth defects,
miscarriage, or other adverse maternal or fetal outcomes. Available data
from postmarketing reports and published literature over decades of use with
ERA in the same class as FILSPARI have not identified an increased risk of
fetal harm; however, these data are limited. Methodological limitations of
these postmarketing reports and published literature include lack of a control
group; limited information regarding dose, duration, and timing of drug
exposure; and missing data. These limitations preclude establishing a reliable
estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA
use. In animal reproduction studies, oral administration of sparsentan to pregnant rats throughout organogenesis at 10-times the maximum
recommended human dose (MRHD) in mg/day caused teratogenic effects in rats, including craniofacial
malformations, skeletal abnormalities, increased embryo- fetal lethality, and
reduced fetal weights (see Data). Advise
pregnant patients of the potential risk to the fetus.
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 2-4% and 15-20%, respectively.
…
8.3 Females and
Males of Reproductive Potential
Additions and/or
revisions underlined:
Based
on data from animal reproductive toxicity studies, FILSPARI may cause
fetal harm, including birth defects and fetal death,
when administered to a pregnant
patient and is contraindicated during pregnancy [see Contraindications (4), Use in
Specific Populations (8.1)].
Pregnancy Testing
Exclude pregnancy before
initiating FILSPARI
in females of reproductive potential. The patient should contact their physician immediately for
pregnancy testing if onset of menses is delayed or pregnancy is suspected. If
the pregnancy test is positive, the physician and patient should discuss
the risks to their pregnancy and the fetus.
Contraception
Patients who can become pregnant who
are using FILSPARI must use an effective method of contraception prior to initiation of treatment, during
treatment, and for two
weeks after discontinuation of treatment with FILSPARI to prevent pregnancy
[see Warnings and Precautions (5.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Extensive
changes; please refer to label for complete information
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
Advise patients to read the FDA-approved patient labeling (Medication Guide). Restricted Access
Advise the patient that FILSPARI is only available
through a restricted access program called the FILSPARI REMS because of the risk of hepatotoxicity, and that FILSPARI
is available only from certified pharmacies that are enrolled in the
FILSPARI REMS.
As a component of the FILSPARI REMS,
prescribers must review the contents of the FILSPARI Medication Guide with the
patient before initiating FILSPARI and patients must sign the FILSPARI
REMS Patient Enrollment Form to confirm
that they understand the risks of FILSPARI.
Instruct patients of the risk of hepatotoxicity associated with FILSPARIHepatotoxicity
Advise patients with symptoms
suggesting hepatotoxicity (nausea,
vomiting, right upper quadrant pain, fatigue, anorexia,
jaundice, dark urine, fever, or itching) to immediately stop taking FILSPARI
and seek medical attention [see Dosage
and Administration
(2.2, 2.4, 2.6), Warnings
and Precautions (5.1)].
Discuss with the patient
the requirement to measure serum aminotransferases every 3
months [see Dosage and Administration (2.2, 2.6), Warnings
and Precautions (5.1, 5.2)].
Embryo-Fetal Toxicity
Counsel patients
who can become
pregnant about the need to use effective methods of
contraception prior to treatment with FILSPARI, during treatment, and for two
weeks after treatment discontinuation. Patients who can become pregnant should
have a negative pregnancy test prior to initiation of treatment
with FILSPARI [see Dosage and
Administration (2.3), Contraindications (4), Warnings and Precautions (5.3), Use in Specific Populations (8.1, 8.3)].
…
Approved Drug Label (PDF)
Boxed Warning
BOX WARNING
Additions and/or
revisions underlined:
…
Hepatotoxicity
Some Endothelin
Receptor Antagonists (ERAs) have caused elevations of aminotransferases,
hepatotoxicity, and liver failure. In clinical studies, elevations in
aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal
(ULN) have been observed in up to 3.5% of FILSPARI-treated patients,
including cases confirmed with rechallenge.
…
5
Warnings and Precautions
5.1 Hepatotoxicity
Additions and/or
revisions underlined:
Elevations in ALT or AST of at least 3-fold ULN have
been observed in up to 3.5% of FILSPARI-treated patients, including
cases confirmed with rechallenge [see
Adverse Reactions (6.1)]. While no concurrent elevations in bilirubin
greater than 2-times ULN or cases of liver failure were observed in
FILSPARI-treated patients in clinical trials, some endothelin receptor
antagonists have caused elevations of aminotransferases, hepatotoxicity, and
liver failure. To reduce the risk of potential serious hepatotoxicity, measure
serum aminotransferase levels and total bilirubin prior to initiation of
treatment and monthly for the first 12 months, then every 3 months during
treatment [see Dosage and Administration
(2.2)].
6
Adverse Reactions
6.1 Clinical
Trials Experience
Extensive changes to table 2; please refer to label
for complete information
Additions and/or revisions underlined:
Laboratory Tests
Initiation of FILSPARI may cause an initial small
decrease in estimated glomerular filtration rate (eGFR) that occurs within the
first 4 weeks of starting therapy and then stabilizes.
The incidence of a hemoglobin decrease >2 g/dL
compared to baseline and below the lower limit of normal was greater for the
FILSPARI arm (19%) compared to the irbesartan arm (13%). This
decrease is thought to be in part due to hemodilution. There were no treatment
discontinuations due to anemia or hemoglobin decrease in the PROTECT study.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions
and/or revisions underlined:
Liver problems.
- FILSPARI can cause
changes in liver tests. Liver failure was not observed in people treated with
FILSPARI in clinical studies, but some medicines that are like
FILSPARI can cause liver failure.
…
Stop
taking FILSPARI and get medical help right away if you develop any of the
following signs of liver problems during treatment with FILSPARI:
…
Patients
who can become pregnant must use effective birth control before starting
treatment with FILSPARI, during treatment with FILSPARI, and for 1 month
after stopping FILSPARI because the medicine may still be in your body.
…
What
is FILSPARI?
FILSPARI
is a prescription medicine used to slow kidney function decline in
adults with a kidney disease called primary immunoglobulin A nephropathy
(IgAN), who are at risk for their disease getting worse.
…
Ask
your healthcare provider or pharmacist if you are not sure if you take
one of these medicines.
Before taking
FILSPARI, tell your healthcare provider about all of your medical conditions, including
if you:
- are breastfeeding or plan to breastfeed. It is not
known if FILSPARI passes into your breast milk. Do not breastfeed during
treatment with FILSPARI. Talk to your healthcare provider about the best way to
feed your baby during treatment with FILSPARI.
Tell your
healthcare provider about all the medicines you take, including
prescription and over-the-counter medicines, vitamins, herbal supplements, and
grapefruit. FILSPARI and other medicines may affect each other and cause side
effects. Do not start any new medicine until you check with your healthcare
provider.
Especially tell
your healthcare provider if you take:
nonsteroidal
anti-inflammatory drugs (NSAIDs)
potassium-containing
medicines, potassium supplements, or salt substitutes containing potassium
blood
pressure medicines
- H2 receptor blocker medicine or proton pump inhibitor
(PPI) medicine
Ask your healthcare provider or pharmacist
if you are not sure if you take one of these medicines.
How should I take FILSPARI?
- FILSPARI
will be provided to you by a certified pharmacy. Your healthcare provider will
give you complete details.
- Take
FILSPARI exactly as your healthcare provider tells you to take it. Do not stop
taking FILSPARI unless your healthcare provider tells you.
- Your
healthcare provider may change your dose, temporarily stop, or permanently stop
treatment with FILSPARI if you develop side effects.
- Take FILSPARI whole with water before your
morning or evening meal. Take your dose before the same meal each day.
- If
you miss a dose, take the next dose at the regularly scheduled time. Do not
take 2 doses at the same time or take extra doses.
- If you take an antacid, take FILSPARI 2 hours before
or 2 hours after you take your antacid.
- If
you take too much FILSPARI, call your healthcare provider or go to the nearest
hospital emergency room right away.
…
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