"Section Title","Title","Description","Appl No","Appl Type","Drug Name","Active Ingredient","Sub No","Sub Type","URL","URL Text"
"Warnings and Precautions","","
Section has
undergone some re-formatting; additions and/or revisions underlined:
5.1 Bradyarrhythmia
and Atrioventricular Blocks
… In some patients, heart rate decrease during the
second period is more pronounced than the decrease observed in the first 6
hours. Heart rates below 40 beats per minute in adults, and below 50 beats
per minute in pediatric patients occurred rarely. In controlled clinical trials in adult
patients …
… With continued dosing, the heart rate returns to
baseline within 1 month of chronic treatment. Clinical data indicate effects
of GILENYA on heart rate are maximal after the first dose although milder
effects on heart rate may persist for, on average, 2 to 4 weeks after
initiation of therapy at which time heart rate generally returns to baseline.
Physicians should continue to be alert to patient reports of cardiac symptoms.
Atrioventricular
Blocks
Initiation of GILENYA treatment has resulted in
transient AV conduction delays. In controlled clinical trials in adult
patients, first-degree …
5.2 Infections
Following In controlled trials, “in adult patients” is
added throughout subsection.
5.4 Macular Edema
5.5 Possible Reversible Encephalopathy Syndrome
5.6 Respiratory Effects
5.7 Liver Injury
Following In controlled trials, “in adult patients” is
added throughout these subsections.
5.10 Cutaneous Malignancies
Additions and/or revisions underlined:
… In two-year
placebo-controlled trials in adult patients, the incidence of BCC was 2%
in patients on GILENYA 0.5 mg and 1% in patients on placebo. Melanoma and
Merkel cell carcinoma have been reported … ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Adverse Reactions","6.1 Clinical Trials Experience","
Additions and/or revisions underlined:
Adults
In clinical trials
…
Table 1 lists
adverse reactions in clinical studies in adults that occurred in …
Table 1: Adverse Reactions Reported in Adult
Studies 1 and 3 (Occurring in greater than or equal to1% of Patients and
Reported for GILENYA 0.5 mg at greater than or equal to1% Higher Rate than for
Placebo)
Adverse reactions
of seizure, dizziness, pneumonia …
Addition of the following:
Seizure
Cases of seizures
have been reported with the use of GILENYA in clinical trials and in the
postmarketing setting in adults. In adult clinical trials, the rate of seizures
was 0.9% in GILENYA-treated patients and 0.3% in placebo-treated patients. It
is unknown whether these events were related to the effects of multiple
sclerosis alone, to GILENYA, or to a combination of both.
Pediatric Patients
10 Years of Age and Older
In the controlled
pediatric trial (Study 4), the safety profile in pediatric patients receiving
GILENYA 0.25 mg or 0.5 mg daily was similar
to that seen in adult patients.
In the pediatric
study, cases of seizures were reported in 5.6% of GILENYA-treated patients and
0.9% of interferon beta- 1a-treated patients. ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Drug Interactions","7.3 Vaccines","
Additions and/or revisions underlined:
because of the
risk of infection. It is recommended that pediatric patients, if possible, be
brought up to date with all immunizations in agreement with current
immunization guidelines prior to initiating GILENYA therapy. ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Use in Specific Populations","8.1 Pregnancy","
Additions and/or revisions underlined:
Pregnancy Exposure
Registry
There is a
pregnancy exposure registry that monitors pregnancy outcomes in women exposed
to GILENYA
during pregnancy. Physicians are encouraged …
Risk Summary
Newly added information:
There are no
adequate data on the developmental risk associated with the use of GILENYA in
pregnant women. In oral studies conducted in rats and rabbits, fingolimod
demonstrated developmental toxicity, including an increase in malformations (rats)
and embryolethality, when given to pregnant animals. In rats, the highest
no-effect dose was less than the recommended human dose of 0.5 mg/day on a body
surface area (mg/m2) basis. The most common fetal visceral malformations in
rats were persistent truncus arteriosus and ventricular septal defect. The
receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to
be involved in vascular formation during embryogenesis.
In the US, general
population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%,
respectively. The background risk of major birth defects and miscarriage for
the indicated population is unknown.
Data
Animal Data
… ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Use in Specific Populations","8.2 Lactation","
Additions and/revisions underlined:
Risk Summary
There are no data
on the presence of fingolimod in human milk, the effects on the
breastfed infant, or the effects of the drug on milk production. Fingolimod is excreted in the milk of
treated rats. The developmental and health benefits of breastfeeding should
be considered along with the mother’s clinical need for GILENYA and any
potential adverse effects on the breastfed infant from GILENYA or
from the underlying maternal condition. ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Use in Specific Populations","8.3 Females and Males of Reproductive Potential","
Newly added information
Contraception
Before initiation
of GILENYA treatment, women of childbearing potential should be counselled on
the potential for a serious risk to the fetus and the need for effective
contraception during treatment with GILENYA. Since it takes approximately 2
months to eliminate the compound from the body after stopping treatment, the
potential risk to the fetus may persist and women should use effective
contraception during this period. ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Use in Specific Populations","8.4 Pediatric Use","
Additions and/or revisions underlined:
Safety and effectiveness
of GILENYA for the treatment of relapsing forms of multiple sclerosis in pediatric
patients 10 to less than 18 years of age were established in one randomized,
double-blind clinical study in 215 patients (GILENYA equals 107; intramuscular
interferon (IFN) beta-1a equals 108).
In the controlled
pediatric study, the safety profile in pediatric patients (10 to less than 18
years of age) receiving GILENYA 0.25 mg or 0.5 mg daily was similar to that
seen in adult patients. In the pediatric study, cases of seizures were reported
in 5.6% of GILENYA treated patients and 0.9% of interferon beta-1a treated
patients.
It is recommended
that pediatric patients if possible, complete all immunizations in accordance
with current immunization guidelines prior to initiating GILENYA therapy.
Safety and
effectiveness of GILENYA in pediatric patients below the age of 10
years have not been established.
Juvenile Animal
Toxicity Data
In a study in
which fingolimod (0.3, 1.5, or 7.5 mg/kg/day) …
… This effect had
not fully recovered by 6-8 weeks after the end of treatment.
Overall, a
no-effect dose for adverse developmental effects in juvenile animals was not
identified. ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","PATIENT COUNSELING INFORMATION","
Additions and/or revisions underlined:
Cardiac Effects
… at least 6 hours
after the first dose, after reinitiation if treatment is
interrupted or discontinued for certain periods, and after the dosage is
increased.
Addition of the following:
Posterior Reversible
Encephalopathy Syndrome
Advise patients to
immediately report to their healthcare provide any symptoms involving sudden
onset of severe headache, altered mental status, visual disturbances, or
seizure. Inform patients that delayed
treatment could lead to permanent neurological sequelae.
","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","MEDICATION GUIDE","
This section has been reformatted; please refer to
label for complete information. ","022527","NDA","GILENYA","FINGOLIMOD","24","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s024lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.3 Progressive Multifocal Leukoencephalopathy","
Additions and/or
revisions underlined:
…
If PML is confirmed, treatment with GILENYA should
be discontinued.
Immune reconstitution inflammatory syndrome (IRIS)
has been reported in patients treated with S1P receptor modulators, including
GILENYA, who developed PML and subsequently discontinued treatment. IRIS
presents as a clinical decline in the patient’s condition that may be rapid,
can lead to serious neurological complications or death, and is often associated
with characteristic changes on MRI. The time to onset of IRIS in patients with
PML was generally within a few months after S1P receptor modulator
discontinuation. Monitoring for development of IRIS and appropriate treatment
of the associated inflammation should be undertaken. ","022527","NDA","GILENYA","FINGOLIMOD","38","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022527s038lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.9 Severe Increase in Disability After Stopping GILENYA","
Additions and/or
revisions underlined:
…
After stopping GILENYA in the setting of PML,
monitor for development of immune reconstitution inflammatory syndrome
(PML-IRIS) [see Warnings and Precautions (5.3)]. ","022527","NDA","GILENYA","FINGOLIMOD","38","SUPPL ","https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022527s038lbl.pdf","Approved Drug Label"
"Contraindications","n/a","
(additions
underlined)
…
- cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III
anti-arrhythmic drugs
… ","022527","NDA","GILENYA","FINGOLIMOD","26","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s26lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.6 Respiratory Effects","
(subsection
revised, additions underlined)
Dose-dependent
reductions in forced expiratory volume
over 1 second (FEV1) and diffusion lung
capacity for carbon monoxide (DLCO) were
observed in patients treated with GILENYA as early as 1 month after treatment
initiation. In 2-year placebo-controlled trials
in adult patients, the reduction from baseline in the percent of
predicted values for FEV1 at the time of last assessment on drug was 2.8% for
GILENYA 0.5 mg and 1.0% for placebo. For DLCO, the reduction from baseline in percent of predicted values at the time
of last assessment on drug was 3.3% for GILENYA
0.5
mg and 0.5% for placebo. The changes in FEV1 appear to be reversible after treatment discontinuation. There is insufficient information
to determine the reversibility of
the decrease of DLCO after drug discontinuation. In MS placebo-controlled trials in adult patients, dyspnea was
reported in 9% of patients receiving GILENYA
0.5 mg and 7% of patients receiving
placebo. Several patients discontinued
GILENYA because of unexplained dyspnea during the extension (uncontrolled) studies. GILENYA has not been tested in MS
patients with compromised respiratory
function.
Spirometric evaluation
of respiratory function and evaluation of DLCO should be performed
during therapy with GILENYA if clinically
indicated. ","022527","NDA","GILENYA","FINGOLIMOD","26","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s26lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.11 Malignancies","
(additions
underlined)
…
Lymphoma
Cases
of lymphoma, including both T-cell and
B-cell types and CNS lymphoma, have occurred in patients receiving GILENYA. The
reporting rate of non-Hodgkin lymphoma
with GILENYA is greater than that expected in the general population adjusted by age, gender, and region. Cutaneous T-cell lymphoma (including mycosis fungoides) has also been reported with GILENYA in the
postmarketing setting. ","022527","NDA","GILENYA","FINGOLIMOD","26","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s26lbl.pdf","Approved Drug Label"
"Adverse Reactions","6.2 Postmarketing Experience","
(subsection
added)
The
following adverse reactions have been
identified during postapproval use of
GILENYA. Because these reactions are reported voluntarily from a population of uncertain size, it is
not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.
Infections:
infections including cryptococcal infections, progressive multifocal leukoencephalopathy
Musculoskeletal and connective tissue disorders:
arthralgia, myalgia
Nervous
system disorders: posterior reversible
encephalopathy syndrome , seizures, including
status epilepticus
Neoplasms,
benign, malignant, and unspecified (incl cysts and polyps): melanoma, Merkel cell carcinoma, and cutaneous T cell
lymphoma (including mycosis
fungoides)
Skin
and subcutaneous tissue disorders: hypersensitivity ","022527","NDA","GILENYA","FINGOLIMOD","26","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s26lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","MEDICATION GUIDE","
(minor
revisions to the Medication Guide were included to correspond to the new PI
language, please refer to label) ","022527","NDA","GILENYA","FINGOLIMOD","26","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s26lbl.pdf","Approved Drug Label"
"Warnings and Precautions","","
Newly added subsection:
5.9 Severe Increase in Disability after Stopping
GILENYA
Severe increase in
disability accompanied by multiple new lesions on MRI has been reported after
discontinuation of GILENYA in the postmarketing setting. Patients in most of
these reported cases did not return to the functional status they had before
stopping GILENYA. The increase in disability generally occurred within 12 weeks
after stopping GILENYA but was reported up to 24 weeks after GILENYA
discontinuation.
Monitor patients
for development of severe increase in disability following discontinuation of
GILENYA and begin appropriate treatment as needed. ","022527","NDA","GILENYA","FINGOLIMOD","27","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s027lbl.pdf","Approved Drug Label"
"Adverse Reactions","","
Addition to the bulleted line listing:
- Severe
Increase in Disability after Stopping GILENYA ","022527","NDA","GILENYA","FINGOLIMOD","27","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s027lbl.pdf","Approved Drug Label"
"Use in Specific Populations","8.1 Pregnancy","
Addition of the following:
Clinical
Considerations
The possibility of
severe increase in disability should be considered in women who discontinue or
are considering discontinuation of GILENYA because of pregnancy or planned
pregnancy. In many of the cases in which increase in disability was reported
after stopping GILENYA, patients had stopped GILENYA because of pregnancy or
planned pregnancy. ","022527","NDA","GILENYA","FINGOLIMOD","27","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s027lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","PATIENT COUNSELING INFORMATION","
Addition of the following:
Severe Increase in
Disability after Stopping GILENYA
Inform patients
that severe increase in disability has been reported after discontinuation of
GILENYA. Advise patients to contact their physician if they develop worsening
symptoms of MS following discontinuation of GILENYA. ","022527","NDA","GILENYA","FINGOLIMOD","27","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022527s027lbl.pdf","Approved Drug Label"
"Warnings and Precautions","Liver Injury"," Clinically significant liver injury has occurred in
patients treated with Gilenya in the postmarketing setting. Signs of
liver injury, including
markedly elevated
serum hepatic enzymes
and elevated total bilirubin, have occurred as
early as ten days after the first dose and
have also been reported after prolonged
use. Cases of acute liver failure requiring liver transplant have
been reported.
In 2-year placebo-controlled clinical trials in
adult patients, elevation
of liver enzymes
(ALT, AST and GGT) to 3-
fold the upper limit of normal (ULN) or greater occurred in 14% of patients
treated with GILENYA
0.5 mg and 3% of patients
on placebo.
Elevations 5-fold the ULN
or greater occurred in
4.5% of patients
on GILENYA and 1% of patients on placebo. The
majority of elevations occurred within 6 to 9
months. In clinical trials,
GILENYA was discontinued if the elevation
exceeded 5 times the ULN. Serum transaminase levels returned
to normal within approximately 2 months
after discontinuation of GILENYA.
Recurrence of liver transaminase
elevations occurred with rechallenge in some patients.
Prior to starting treatment with GILENYA (within 6 months), obtain serum transaminases (ALT and AST)
and total bilirubin levels.
Obtain transaminase levels and total bilirubin levels periodically until two months after GILENYA discontinuation.
Patients should be monitored
for signs
and symptoms of any hepatic
injury. Measure liver transaminase and bilirubin levels
promptly in patients who
report symptoms that may indicate
liver injury, including
new or worsening fatigue, anorexia,
right upper abdominal discomfort,
dark urine, or jaundice.
In this clinical context,
if the patient is found
to have
an alanine aminotransferase (ALT) greater than three times the
reference range with serum total bilirubin
greater than two times the
reference range,
treatment with
GILENYA treatment should
be interrupted. Treatment should
not
be resumed if a plausible alternative etiology for the signs
and symptoms cannot be
established, because these patients
are at risk for severe
drug-induced liver injury.
Because GILENYA exposure is doubled in patients
with severe hepatic impairment, these patients
should be closely monitored, as the risk of adverse
reactions is greater. ","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"Warnings and Precautions","Posterior Reversible Encephalopathy Syndrome"," Additions and/or revisions
underlined:
There have been
rare cases of posterior
reversible encephalopathy syndrome (PRES) reported
in adult patients receiving GILENYA.
Symptoms reported included sudden onset of severe headache,
altered mental status, visual disturbances,
and seizure. Symptoms of PRES
are usually reversible
but
may evolve into ischemic
stroke or cerebral
hemorrhage. Delay in diagnosis
and treatment may lead to permanent neurological sequelae.
If
PRES is suspected, GILENYA should be discontinued. ","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"Warnings and Precautions","Respiratory Effects"," Additions and/or revisions
underlined:
Dose-dependent reductions in forced expiratory volume over 1
second (FEV1) and
diffusion lung capacity
for carbon monoxide
(DLCO) were observed in
patients treated with GILENYA as early
as 1 month after treatment
initiation. In 2-year placebo-controlled
trials in adult patients, the reduction
from baseline in the percent of predicted values for FEV1
at the time of last assessment on drug was
2.8% for GILENYA
0.5 mg and 1.0% for placebo. For DLCO,
the reduction from baseline
in percent of predicted
values at the time of
last assessment on drug was
3.3% for GILENYA 0.5 mg and 0.5% for placebo. The
changes in FEV1 appear to be
reversible after treatment discontinuation. There is insufficient information to determine the reversibility of the decrease of DLCO after drug discontinuation. In MS placebo-controlled trials in adult patients, dyspnea was reported in 9% of patients receiving GILENYA 0.5 mg and 7% of patients
receiving placebo.
Several patients discontinued
GILENYA because of unexplained dyspnea during the extension
(uncontrolled) studies.
GILENYA has not been tested
in MS patients with compromised respiratory function.
Spirometric evaluation of respiratory function and evaluation of DLCO should be performed during
therapy with GILENYA
if clinically indicated. ","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"Adverse Reactions","Clinical Trials Experience"," Table Number 1: Newly added table; please refer to label for complete
information ","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"Adverse Reactions","Postmarketing Experience"," Additions and/or revisions
underlined:
The following adverse reactions
have been identified during
postapproval use
of
GILENYA. Because these reactions are reported voluntarily from a population of uncertain
size, it is not always
possible to reliably estimate their frequency
or establish a causal relationship to drug exposure.
Hepatobiliary Disorders: Liver injury ","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","PATIENT COUNSELING INFORMATION"," Additions and/or revisions
underlined:
Hepatic Effects
Inform patients
that GILENYA may cause liver injury. Advise patients
that they should
contact their physician if they have
any unexplained nausea, vomiting, abdominal pain, fatigue,
anorexia, or jaundice and/or dark urine. ","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","Medication Guide"," GILENYA can cause
your heart rate to slow down,
especially after you take your first dose. You will have a test,
called an electrocardiogram (ECG), to check the electrical activity of your heart before you take your first dose of GILENYA.
What is GILENYA?
GILENYA is a prescription medicine used to treat relapsing forms of multiple
sclerosis (MS),
to include clinically isolated syndrome, relapsing-remitting disease,
and active secondary progressive disease, in adults and children 10 years of age and older.
What are possible side effects of GILENYA? GILENYA can cause serious side effects, including: - liver damage. GILENYA may cause liver damage. Your doctor should
do blood tests to check your liver before you start taking GILENYA and periodically during
treatment. Call your doctor right away if you have any of the following symptoms of liver damage. . .
","022527","NDA","GILENYA","FINGOLIMOD","30","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s029s030lbl.pdf","Approved Drug Label"
"Contraindications","n/a"," Patients who have had a hypersensitivity reaction to fingolimod or any
of the excipients in GILENYA. Observed reactions include rash, urticaria
and angioedema upon treatment initiation ","022527","NDA","GILENYA","FINGOLIMOD","18","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022527s018lbl.pdf","Approved Drug Label"
"Warnings and Precautions",""," Human Papilloma Virus (HPV) Infection
(Newly added
subsection)
Human papilloma virus (HPV) infections, including papilloma,
dysplasia, warts, and HPV-related cancer, have
been reported in patients
treated with GILENYA in the postmarketing setting.
Vaccination against HPV should be
considered prior to treatment initiation
with GILENYA, taking into account
vaccination recommendations. Cancer screening,
including Papanicolaou (Pap) test, is recommended
as per standard of care for patients using an immunosuppressive therapy.
Fetal Risk
(Additions and/or
revisions underlined)
Based on findings
from animal studies, GILENYA may cause fetal harm when
administered to a pregnant woman. In animal reproduction studies conducted in rats and
rabbits, developmental toxicity
was observed with administration of fingolimod at doses less
than the recommended human dose. Advise pregnant
women and females of reproductive potential of the
potential risk to a fetus.
Because it takes approximately 2 months
to eliminate
GILENYA from the body,
advise females of reproductive potential to use effective
contraception to avoid
pregnancy during and for 2 months after stopping GILENYA treatment [see Use in
Specific Populations (8.1, 8.3)].
Tumefactive Multiple
Sclerosis
(Newly added
subsection)
MS relapses with tumefactive demyelinating lesions on
imaging have been observed during GILENYA therapy
and after GILENYA
discontinuation in the postmarketing setting. Most reported
cases of tumefactive MS in patients
receiving Gilenya
have occured within the first 9
months after GILENYA
initiation, but tumefactive MS may occur at any point during treatment. Cases
of tumefactive
MS have
also been reported within the
first 4 months after Gilenya discontinuation. Tumefactive
MS should be considered when a severe MS
relapse occurs during
GILENYA treatment, especially during initiation,
or
after discontinuation of GILENYA, prompting imaging evaluation and initiation
of appropriate treatment.
Malignancies
(Additions and/or revisions
underlined)
Cutaneous Malignancies
Melanoma, squamous
cell carcinoma and Merkel cell carcinoma
have been reported
with GILENYA in the postmarketing setting. ","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"Adverse Reactions",""," (Additions and/or revisions
underlined)
The following
serious adverse reactions are described
elsewhere in labeling:
·
Tumefactive Multiple Sclerosis [see Warnings
and Precautions (5.10)]
Postmarketing Experience
(Additions and/or revisions
underlined)
The following adverse reactions have been identified during
postapproval use of GILENYA. Because these reactions are reported voluntarily
from a population of uncertain size, it is not always possible to reliably
estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: Hemolytic anemia
and thrombocytopenia Hepatobiliary Disorders: Liver injury [see Warnings
and Precautions (5.5)]
Infections: infections including cryptococcal infections
[see Warnings and Precautions (5.2)], human papilloma virus (HPV) infection,
including papilloma, dysplasia, warts and HPV-related cancer [see Warnings and
Precautions (5.2)], progressive multifocal leukoencephalopathy [see
Warnings and Precautions (5.3)] ","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"Use in Specific Populations","Pregnancy"," (Newly added
information)
Based on findings from animal studies, GILENYA may cause
fetal harm when administered to a pregnant woman. Data from prospective reports
to the Gilenya Pregnancy Registry (GPR) are currently not sufficient to allow
for an adequate assessment of the drug-associated risk for birth defects and
miscarriage in humans.
Advise pregnant women of the potential risk to a fetus.
In females planning to become pregnant, GILENYA should be
stopped 2 months before planned conception. ","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"Use in Specific Populations","Lactation"," Risk Summary
(Newly added information)
When a drug is present in animal milk, it is likely that the drug will be present in
human milk. ","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"Use in Specific Populations","Females and Males of Reproductive Potential"," (Newly added
subsection)
Pregnancy Testing
The pregnancy status of females of reproductive potential
should be verified prior to starting treatment with GILENYA [see Use in Specific
Populations (8.1)]. ","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","PATIENT COUNSELING INFORMATION"," (Newly added
information)
• Advise pregnant women and females of reproductive
potential of the potential risk to a fetus. Advise females to
inform their healthcare provider of a known or suspected
pregnancy [see Warnings and Precautions (5.8) and Use
in Specific Populations (8.1, 8.3)].
• Advise female patients of reproductive potential to use
effective contraception during treatment with GILENYA
and for two months after the final dose [see Use in Specific
Populations (8.3)]. ","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","MEDICATION GUIDE"," (Newly added
information)
Pregnancy. Please consult your doctor before getting
pregnant. You should avoid becoming pregnant while
taking Gilenya or in the two months after you stop taking it
because of the risk of harm to the baby.
Human Papilloma Virus (HPV). Due to risk of HPV infection
please consult your doctor for routine pap smear.
-You should stop taking GILENYA 2 months before trying to become pregnant.
","022527","NDA","GILENYA","FINGOLIMOD","31","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022527s031lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.2 Infections","
(additions underlined)
Risk of Infections
GILENYA causes a dose-dependent reduction in
peripheral lymphocyte count to 20%–30% of baseline values because of reversible
sequestration of lymphocytes in lymphoid tissues. GILENYA may therefore
increase the risk of infections, some serious in nature.Life-threatening and
fatal infections have occurred in association with GILENYA.
… ","022527","NDA","GILENYA","FINGOLIMOD","22","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022527s022lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.3 Progressive Multifocal Leukoencephalopathy","
(additions underlined)
Cases of progressive multifocal leukoencephalopathy
(PML) have occurred in patients with MS who received GILENYA in the
postmarketing setting. PML is an opportunistic viral infection of the brain
caused by the JC virus (JCV) that typically only occurs in patients who are
immunocompromised, and that usually leads to death or severe disability. PML has
occurred in patients who had not been treated previously with natalizumab,
which has a known association with PML, were not taking any other
immunosuppressive or immunomodulatory medications concomitantly, and did not
have any ongoing systemic medical conditions resulting in compromised
immune system function. The majority of cases have occurred in patients
treated with GILENYA for at least 2 years. The relationship between the risk of
PML and the duration of treatment is unknown.
…
MRI findings may be apparent before clinical signs
or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of
JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms
specific to PML, have been reported in patients treated with MS medications
associated with PML, including GILENYA.
Many of these patients subsequently became symptomatic with PML.
Therefore, monitoring with MRI for signs that may be consistent with PML may be
useful, and any suspicious findings should lead to further investigation to
allow for an early diagnosis of PML, if present. Lower PML-related mortality
and morbidity have been reported following discontinuation of another MS
medication associated with PML in patients with PML who were initially
asymptomatic compared to patients with PML who had characteristic clinical
signs and symptoms at diagnosis. It is
not known whether these differences are due to early detection and
discontinuation of MS treatment or due to differences in disease in these
patients. ","022527","NDA","GILENYA","FINGOLIMOD","22","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022527s022lbl.pdf","Approved Drug Label"
"Warnings and Precautions","5.10 Cutaneous Malignancies","
(additions underlined)
The risk of basal cell carcinoma (BCC) and melanoma is increased
in patients treated with GILENYA. In two-year placebo-controlled trials,
the incidence of BCC was 2% in patients on GILENYA 0.5 mg and 1% in patients on
placebo. Melanoma has been reported with GILENYA in the postmarketing
setting. Periodic skin examination is
recommended for all patients, particularly those with risk factors for skin
cancer. Providers and patients are
advised to monitor for suspicious skin lesions. If a suspicious skin lesion is
observed, it should be promptly evaluated. As usual for patients with
increased risk for skin cancer, exposure to sunlight and ultraviolet light
should be limited by wearing protective clothing and using a sunscreen with a
high protection factor. ","022527","NDA","GILENYA","FINGOLIMOD","22","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022527s022lbl.pdf","Approved Drug Label"
"Adverse Reactions","n/a","
(addition/revision
underlined)
…
- Cutaneous Malignancies
… ","022527","NDA","GILENYA","FINGOLIMOD","22","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022527s022lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","PATIENT COUNSELING INFORMATION","
(additions underlined)
…
Risk of Infections
Inform patients that they may have an increased
risk of infections, some of which could be life-threatening, when
taking GILENYA, and that they should contact their physician if they develop
symptoms of infection. Advise patients that the use of some vaccines should be
avoided during treatment with GILENYA and for 2 months after discontinuation.
…
Cutaneous Malignancies
Advise patients that basal cell carcinoma and
melanoma are associated with use of GILENYA. Advise patients that any
suspicious skin lesions should be promptly evaluated. Advise patients to
limit exposure to sunlight and ultraviolet light by wearing protective clothing
and using a sunscreen with a high protection factor. ","022527","NDA","GILENYA","FINGOLIMOD","22","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022527s022lbl.pdf","Approved Drug Label"
"MG/PCI/PI (Medication Guide/Patient Counseling Information/Package Insert)","MEDICATION GUIDE","
(additions underlined)
What
are possible side effects of GILENYA?
…
- skin cancers including basal cell carcinoma
(BCC) and melanoma. Talk to your doctor if you notice any skin nodules
(e.g., shiny pearly nodules), patches or open sores that do not heal within
weeks, or unusual moles, which may present as a change in color,
shape, or size over time. These may
be signs of skin cancer.
… ","022527","NDA","GILENYA","FINGOLIMOD","22","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022527s022lbl.pdf","Approved Drug Label"
"Warnings and Precautions",""," Risk of Infections
-In the postmarketing setting, serious infections with opportunistic pathogens including viruses (e.g., John Cunningham virus (JCV), herpes simplex viruses 1 and 2, varicella-zoster virus), fungi (e.g., cryptococci), and bacteria (e.g., atypical mycobacteria) have been reported with GILENYA. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and appropriate treatment. Herpes Viral Infections
-Cases of Kaposi’s sarcoma have been reported in the postmarketing setting. Kaposi’s sarcoma is an angioproliferative disorder that is associated with infection with human herpes virus 8 (HHV-8). Patients with symptoms or signs consistent with Kaposi’s sarcoma should be referred for prompt diagnostic evaluation and management. Progressive Multifocal Leukoencephalopathy
-Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients with MS who received GILENYA in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in patients who had not been treated previously with natalizumab, which has a known association with PML, and who were also not taking any immunosuppressive or immunomodulatory medications concomitantly. The patients had no other ongoing identified systemic medical conditions resulting in compromised immune system function, although one patient had a history of cancer treated with chemotherapy several years prior to taking Gilenya. The cases have occurred in patients treated with GILENYA for at least 2 years. The relationship between the risk of PML and the duration of treatment is unknown. Liver Injury
-Cases of liver injury with hepatocellular and/or cholestatic hepatitis have been reported with GILENYA in the postmarketing setting. Basal Cell Carcinoma
-Basal cell carcinoma (BCC) is associated with use of GILENYA. In two-year placebo-controlled trials the incidence of BCC was 2% in patients on GILENYA 0.5 mg and 1% in patients on placebo [see Adverse reactions (6)]. Providers and patients are advised to monitor for suspicious skin lesions. If a suspicious skin lesion is observed, it should be promptly evaluated. Hypersensitivity Reactions
-Hypersensitivity reactions, including rash, urticaria, and angioedema have been reported with GILENYA in the postmarketing setting. GILENYA is contraindicated in patients with history of hypersensitivity to fingolimod or any of its excipients ","022527","NDA","GILENYA","FINGOLIMOD","18","SUPPL ","http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022527s018lbl.pdf","Approved Drug Label"