Drug Safety-related Labeling Changes (SrLC)

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GILENYA (NDA-022527)

(FINGOLIMOD)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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12/26/2019 (SUPPL-31)

Approved Drug Label (PDF)

5 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.

6 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)]

8 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)].

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.

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.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

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.

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)].

08/16/2019 (SUPPL-30)

Approved Drug Label (PDF)

5 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.

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.

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.

6 Adverse Reactions

Clinical Trials Experience

Table Number 1: Newly added table; please refer to label for complete information

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

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

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. . .

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.

01/11/2019 (SUPPL-26)

Approved Drug Label (PDF)

4 Contraindications

(additions underlined)

  • cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs

5 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.

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.

6 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

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(minor revisions to the Medication Guide were included to correspond to the new PI language, please refer to label)

10/26/2018 (SUPPL-27)

Approved Drug Label (PDF)

5 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.

6 Adverse Reactions

Addition to the bulleted line listing:

  • Severe Increase in Disability after Stopping GILENYA

8 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.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

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.

05/11/2018 (SUPPL-24)

Approved Drug Label (PDF)

5 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 …

6 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.

7 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.

8 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

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.

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.

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.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

This section has been reformatted; please refer to label for complete information.

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.

 

12/15/2017 (SUPPL-22)

Approved Drug Label (PDF)

5 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.

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.

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.

6 Adverse Reactions

(addition/revision underlined)

  • Cutaneous Malignancies

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

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.

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.

02/19/2016 (SUPPL-18)

Approved Drug Label (PDF)

4 Contraindications

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

5 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

 

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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