Gilenya

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 
 

Gilenya 0.25 mg hard capsules 

Gilenya 0.5 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Gilenya 0.25 mg hard capsules 

 

Each 0.25 mg capsule contains 0.25 mg fingolimod (as hydrochloride). 

 

Gilenya 0.5 mg hard capsules 

 

Each 0.5 mg capsule contains 0.5 mg fingolimod (as hydrochloride). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule 

 

Gilenya 0.25 mg hard capsules 

 

Capsule of 16 mm with ivory opaque cap and body, with black radial imprint “FTY 0.25mg” on cap 

and black radial band on body. 

 

Gilenya 0.5 mg hard capsules 

 

Capsule of 16 mm with bright yellow opaque cap and white opaque body; imprint with black ink, 

“FTY0.5 mg” on cap and two radial bands imprinted on the body with yellow ink. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Gilenya is indicated as single disease modifying therapy in highly active relapsing remitting multiple 

sclerosis for the following groups of adult patients and paediatric patients aged 10 years and older: 

 

- Patients with highly active disease despite a full and adequate course of treatment with at least 

one disease modifying therapy (for exceptions and information about washout periods see 

sections 4.4 and 5.1). 

or 

- Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more 

disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI 

or a significant increase in T2 lesion load as compared to a previous recent MRI. 

 

  



 

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4.2 Posology and method of administration 

 

The treatment should be initiated and supervised by a physician experienced in multiple sclerosis. 

 

Posology 

 
In adults, the recommended dose of fingolimod is one 0.5 mg capsule taken orally once daily. 

 

In paediatric patients (10 years of age and above), the recommended dose is dependent on body 

weight: 

- Paediatric patients with body weight ≤40 kg: one 0.25 mg capsule taken orally once daily. 

- Paediatric patients with body weight >40 kg: one 0.5 mg capsule taken orally once daily. 

 

Paediatric patients who start on 0.25 mg capsules and subsequently reach a stable body weight above 

40 kg should be switched to 0.5 mg capsules. 

 

When switching from a 0.25 mg to a 0.5 mg daily dose, it is recommended to repeat the same first 

dose monitoring as for treatment initiation. 

 

The same first dose monitoring as for treatment initiation is recommended when treatment is 

interrupted for: 

- 1 day or more during the first 2 weeks of treatment. 

- more than 7 days during weeks 3 and 4 of treatment. 

- more than 2 weeks after one month of treatment. 

If the treatment interruption is of shorter duration than the above, the treatment should be continued 

with the next dose as planned (see section 4.4). 
 

Special populations 

 

Elderly population 

Gilenya should be used with caution in patients aged 65 years and over due to insufficient data on 

safety and efficacy (see section 5.2). 

 

Renal impairment 

Fingolimod was not studied in patients with renal impairment in the multiple sclerosis pivotal studies. 

Based on clinical pharmacology studies, no dose adjustments are needed in patients with mild to 

severe renal impairment. 

 

Hepatic impairment 

Gilenya must not be used in patients with severe hepatic impairment (Child-Pugh class C) (see 

section 4.3). Although no dose adjustments are needed in patients with mild or moderate hepatic 

impairment, caution should be exercised when initiating treatment in these patients (see sections 4.4 

and 5.2). 

 

Paediatric population 

The safety and efficacy of fingolimod in children aged below 10 years have not yet been established. 

No data are available. There are very limited data available in children between 10–12 years old (see 

sections 4.4, 4.8 and 5.1). 

 

Method of administration 

 

This medicinal product is for oral use. 

 

Gilenya can be taken with or without food (see section 5.2). 

 

The capsules should always be swallowed intact, without opening them. 



 

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4.3 Contraindications 
 

- Immunodeficiency syndrome. 

- Patients with increased risk for opportunistic infections, including immunocompromised 

patients (including those currently receiving immunosuppressive therapies or those 

immunocompromised by prior therapies). 

- Severe active infections, active chronic infections (hepatitis, tuberculosis). 

- Active malignancies. 

- Severe liver impairment (Child-Pugh class C). 
- Patients who in the previous 6 months had myocardial infarction (MI), unstable angina pectoris, 

stroke/transient ischaemic attack (TIA), decompensated heart failure (requiring inpatient 

treatment), or New York Heart Association (NYHA) class III/IV heart failure (see section 4.4). 

- Patients with severe cardiac arrhythmias requiring anti-arrhythmic treatment with class Ia or 

class III anti-arrhythmic medicinal products (see section 4.4). 

- Patients with second-degree Mobitz type II atrioventricular (AV) block or third-degree AV 

block, or sick-sinus syndrome, if they do not wear a pacemaker (see section 4.4). 

- Patients with a baseline QTc interval ≥ 500 msec (see section 4.4). 

- During pregnancy and in women of childbearing potential not using effective contraception (see 

sections 4.4 and 4.6). 

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 
 

Bradyarrhythmia 

 

Initiation of treatment results in a transient decrease in heart rate and may also be associated with 

atrioventricular conduction delays, including the occurrence of isolated reports of transient, 

spontaneously resolving complete AV block (see sections 4.8 and 5.1). 

 
After the first dose, the decline in heart rate starts within one hour, and is maximal within 6 hours. 

This post-dose effect persists over the following days, although usually to a milder extent, and usually 

abates over the next weeks. With continued administration, the average heart rate returns towards 

baseline within one month. However individual patients may not return to baseline heart rate by the 

end of the first month. Conduction abnormalities were typically transient and asymptomatic. They 

usually did not require treatment and resolved within the first 24 hours on treatment. If necessary, the 

decrease in heart rate induced by fingolimod can be reversed by parenteral doses of atropine or 

isoprenaline. 

 

All patients should have an ECG and blood pressure measurement performed prior to and 6 hours after 

the first dose of Gilenya. All patients should be monitored for a period of 6 hours for signs and 

symptoms of bradycardia with hourly heart rate and blood pressure measurement. Continuous (real 

time) ECG monitoring during this 6 hour period is recommended. 

 
The same precautions as for the first dose are recommended when patients are switched from the 

0.25 mg to the 0.5 mg daily dose. 

 

Should post-dose bradyarrhythmia-related symptoms occur, appropriate clinical management should 

be initiated and monitoring should be continued until the symptoms have resolved. Should a patient 

require pharmacological intervention during the first-dose monitoring, overnight monitoring in a 

medical facility should be instituted and the first-dose monitoring should be repeated after the second 

dose of Gilenya. 

 



 

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If the heart rate at 6 hours is the lowest since the first dose was administered (suggesting that the 

maximum pharmacodynamic effect on the heart may not yet be manifest), monitoring should be 

extended by at least 2 hours and until heart rate increases again. Additionally, if after 6 hours, the heart 

rate is <45 bpm in adults, <55 bpm in paediatric patients aged 12 years and above, or <60 bpm in 

paediatric patients aged 10 to below 12 years, or the ECG shows new onset second degree or higher 

grade AV block or a QTc interval ≥500 msec, extended monitoring (at least overnight monitoring), 

should be performed, and until the findings have resolved. The occurrence at any time of third degree 

AV block should also lead to extended monitoring (at least overnight monitoring). 

 

The effects on heart rate and atrioventricular conduction may recur on re-introduction of fingolimod 

treatment depending on duration of the interruption and time since start of treatment. The same first 

dose monitoring as for treatment initiation is recommended when treatment is interrupted (see 

section 4.2). 

 

Very rare cases of T-wave inversion have been reported in adult patients treated with fingolimod. In 

case of T-wave inversion, the prescriber should ensure that there are no associated myocardial 

ischaemia signs or symptoms. If myocardial ischaemia is suspected, it is recommended to seek advice 

from a cardiologist. 

 

Due to the risk of serious rhythm disturbances or significant bradycardia, Gilenya should not be used 

in patients with sino-atrial heart block, a history of symptomatic bradycardia, recurrent syncope or 

cardiac arrest, or in patients with significant QT prolongation (QTc>470 msec [adult female], QTc 

>460 msec [paediatric female] or >450 msec [adult and paediatric male]), uncontrolled hypertension 

or severe sleep apnoea (see also section 4.3). In such patients, treatment with Gilenya should be 

considered only if the anticipated benefits outweigh the potential risks, and advice from a cardiologist 

sought prior to initiation of treatment in order to determine the most appropriate monitoring. At least 

overnight extended monitoring is recommended for treatment initiation (see also section 4.5). 

 

Fingolimod has not been studied in patients with arrhythmias requiring treatment with class Ia (e.g. 

quinidine, disopyramide) or class III (e.g. amiodarone, sotalol) antiarrhythmic medicinal products. 

Class Ia and class III antiarrhythmic medicinal products have been associated with cases of torsades de 

pointes in patients with bradycardia (see section 4.3). 

 

Experience with Gilenya is limited in patients receiving concurrent therapy with beta blockers, heart-

rate-lowering calcium channel blockers (such as verapamil or diltiazem), or other substances which 

may decrease heart rate (e.g. ivabradine, digoxin, anticholinesteratic agents or pilocarpine). Since the 

initiation of fingolimod treatment is also associated with slowing of the heart rate (see also section 4.8, 

Bradyarrhythmia), concomitant use of these substances during treatment initiation may be associated 

with severe bradycardia and heart block. Because of the potential additive effect on heart rate, 

treatment with Gilenya should not be initiated in patients who are concurrently treated with these 

substances (see also section 4.5). In such patients, treatment with Gilenya should be considered only if 

the anticipated benefits outweigh the potential risks. If treatment with Gilenya is considered, advice 

from a cardiologist should be sought regarding the switch to non heart-rate lowering medicinal 

products prior to initiation of treatment. If the heart-rate-lowering treatment cannot be stopped, 

cardiologist’s advice should be sought to determine appropriate first dose monitoring, at least 

overnight extended monitoring is recommended (see also section 4.5). 

 
QT interval 

 

In a thorough QT interval study of doses of 1.25 or 2.5 mg fingolimod at steady-state, when a negative 

chronotropic effect of fingolimod was still present, fingolimod treatment resulted in a prolongation of 

QTcI, with the upper limit of the 90% CI ≤13.0 ms. There is no dose- or exposure-response 

relationship of fingolimod and QTcI prolongation. There is no consistent signal of increased incidence 

of QTcI outliers, either absolute or change from baseline, associated with fingolimod treatment. 

 



 

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The clinical relevance of this finding is unknown. In the multiple sclerosis studies, clinically relevant 

effects on prolongation of the QTc-interval have not been observed but patients at risk for QT 

prolongation were not included in clinical studies. 

 

Medicinal products that may prolong QTc interval are best avoided in patients with relevant risk 

factors, for example, hypokalaemia or congenital QT prolongation. 

 

Immunosuppressive effects 

 

Fingolimod has an immunosuppressive effect that predisposes patients to an infection risk, including 

opportunistic infections that can be fatal, and increases the risk of developing lymphomas and other 

malignancies, particularly those of the skin. Physicians should carefully monitor patients, especially 

those with concurrent conditions or known factors, such as previous immunosuppressive therapy. If 

this risk is suspected, discontinuation of treatment should be considered by the physician on a case-by-

case basis (see also section 4.4 “Infections” and “Cutaneous neoplasms” and section 4.8 

“Lymphomas”). 

 

Infections 

 

A core pharmacodynamic effect of fingolimod is a dose-dependent reduction of the peripheral 

lymphocyte count to 20-30% of baseline values. This is due to the reversible sequestration of 

lymphocytes in lymphoid tissues (see section 5.1). 

 

Before initiating treatment with Gilenya, a recent complete blood count (CBC) (i.e. within 6 months or 

after discontinuation of prior therapy) should be available. Assessments of CBC are also 

recommended periodically during treatment, at month 3 and at least yearly thereafter, and in case of 

signs of infection. Absolute lymphocyte count <0.2x109/l, if confirmed, should lead to treatment 

interruption until recovery, because in clinical studies, fingolimod treatment was interrupted in 

patients with absolute lymphocyte count <0.2x109/l. 

 

Initiation of treatment with Gilenya should be delayed in patients with severe active infection until 

resolution. 

 

The immune system effects of Gilenya may increase the risk of infections, including opportunistic 

infections (see section 4.8). Effective diagnostic and therapeutic strategies should be employed in 

patients with symptoms of infection while on therapy. When evaluating a patient with a suspected 

infection that could be serious, referral to a physician experienced in treating infections should be 

considered. During treatment, patients should be instructed to report promptly symptoms of infection 

to their physician. 

 

Suspension of Gilenya should be considered if a patient develops a serious infection and consideration 

of benefit-risk should be undertaken prior to re-initiation of therapy. 

 

Elimination of fingolimod following discontinuation of therapy may take up to two months and 

vigilance for infection should therefore be continued throughout this period. Patients should be 

instructed to report symptoms of infection up to 2 months after discontinuation of fingolimod. 

 

Herpes viral infection 
Serious, life-threatening, and sometimes fatal cases of encephalitis, meningitis or meningoencephalitis 

caused by herpes simplex and varicella zoster viruses have occurred with Gilenya at any time during 

treatment. If herpes encephalitis, meningitis or meningoencephalitis occur, Gilenya should be 

discontinued and appropriate treatment for the respective infection should be administered. 

 



 

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Patients need to be assessed for their immunity to varicella (chickenpox) prior to Gilenya treatment. It 

is recommended that patients without a health care professional confirmed history of chickenpox or 

documentation of a full course of vaccination with varicella vaccine undergo antibody testing to 

varicella zoster virus (VZV) before initiating fingolimod therapy. A full course of vaccination for 

antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with 

Gilenya (see section 4.8). Initiation of treatment with fingolimod should be postponed for 1 month to 

allow full effect of vaccination to occur. 

 

Cryptococcal meningitis 

Cases of cryptococcal meningitis (a fungal infection), sometimes fatal, have been reported in the post-

marketing setting after approximately 2-3 years of treatment, although an exact relationship with the 

duration of treatment is unknown (see section 4.8). Patients with symptoms and signs consistent with 

cryptococcal meningitis (e.g. headache accompanied by mental changes such as confusion, 

hallucinations, and/or personality changes) should undergo prompt diagnostic evaluation. If 

cryptococcal meningitis is diagnosed, fingolimod should be suspended and appropriate treatment 

should be initiated. A multidisciplinary consultation (i.e. infectious disease specialist) should be 

undertaken if re-initiation of fingolimod is warranted. 

 

Progressive multifocal leukoencephalopathy 

Progressive multifocal leukoencephalopathy (PML) has been reported under fingolimod treatment 

since marketing authorisation (see section 4.8). PML is an opportunistic infection caused by John 

Cunningham virus (JCV), which may be fatal or result in severe disability. Cases of PML have 

occurred after approximately 2-3 years of monotherapy treatment without previous exposure to 

natalizumab. Although the estimated risk appears to increase with cumulative exposure over time, an 

exact relationship with the duration of treatment is unknown. Additional PML cases have occurred in 

patients who had been treated previously with natalizumab, which has a known association with PML. 

PML can only occur in the presence of a JCV infection. If JCV testing is undertaken, it should be 

considered that the influence of lymphopenia on the accuracy of anti-JCV antibody testing has not 

been studied in fingolimod-treated patients. It should also be noted that a negative anti-JCV antibody 

test does not preclude the possibility of subsequent JCV infection. Before initiating treatment with 

fingolimod, a baseline MRI should be available (usually within 3 months) as a reference. MRI 

findings may be apparent before clinical signs or symptoms. During routine MRI (in accordance with 

national and local recommendations), physicians should pay attention to PML suggestive lesions. MRI 

may be considered as part of increased vigilance in patients considered at increased risk of PML. 

Cases of asymptomatic PML based on MRI findings and positive JCV DNA in the cerebrospinal fluid 

have been reported in patients treated with fingolimod. If PML is suspected, MRI should be performed 

immediately for diagnostic purposes and treatment with fingolimod should be suspended until PML 

has been excluded. 

 

Human papilloma virus infection 

Human papilloma virus (HPV) infection, including papilloma, dysplasia, warts and HPV-related 

cancer, has been reported under treatment with fingolimod in the post-marketing setting. Due to the 

immunosuppressive properties of fingolimod, vaccination against HPV should be considered prior to 

treatment initiation with fingolimod taking into account vaccination recommendations. Cancer 

screening, including Pap test, is recommended as per standard of care. 

 
Macular oedema 

 

Macular oedema with or without visual symptoms has been reported in 0.5% of patients treated with 

fingolimod 0.5 mg, occurring predominantly in the first 3-4 months of therapy (see section 4.8). An 

ophthalmological evaluation is therefore recommended at 3-4 months after treatment initiation. If 

patients report visual disturbances at any time while on therapy, evaluation of the fundus, including 

the macula, should be carried out. 

 



 

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Patients with history of uveitis and patients with diabetes mellitus are at increased risk of macular 

oedema (see section 4.8). Fingolimod has not been studied in multiple sclerosis patients with 

concomitant diabetes mellitus. It is recommended that multiple sclerosis patients with diabetes 

mellitus or a history of uveitis undergo an ophthalmological evaluation prior to initiating therapy and 

have follow-up evaluations while receiving therapy. 

 

Continuation of treatment in patients with macular oedema has not been evaluated. It is recommended 

that Gilenya be discontinued if a patient develops macular oedema. A decision on whether or not 

therapy should be re-initiated after resolution of macular oedema needs to take into account the 

potential benefits and risks for the individual patient. 

 

Liver injury 

 

Increased hepatic enzymes, in particular alanine aminotransaminase (ALT) but also gamma 

glutamyltransferase (GGT) and aspartate transaminase (AST) have been reported in multiple sclerosis 

patients treated with fingolimod. Some cases of acute liver failure requiring liver transplant and 

clinically significant liver injury have also been reported. 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. In clinical trials, elevations 3-fold the 

upper limit of normal (ULN) or greater in ALT occurred in 8.0% of adult patients treated with 

fingolimod 0.5 mg compared to 1.9% of placebo patients. Elevations 5-fold the ULN occurred in 1.8% 

of patients on fingolimod and 0.9% of patients on placebo. In clinical trials, fingolimod was 

discontinued if the elevation exceeded 5 times the ULN. Recurrence of liver transaminase elevations 

occurred with rechallenge in some patients, supporting a relationship to fingolimod. In clinical studies, 

transaminase elevations occurred at any time during treatment although the majority occurred within 

the first 12 months. Serum transaminase levels returned to normal within approximately 2 months 

after discontinuation of fingolimod. 

 

Fingolimod has not been studied in patients with severe pre-existing hepatic injury (Child-Pugh class 

C) and should not be used in these patients (see section 4.3). 

 

Due to the immunosuppressive properties of fingolimod, initiation of treatment should be delayed in 

patients with active viral hepatitis until resolution. 

 

Recent (i.e. within last 6 months) transaminase and bilirubin levels should be available before 

initiation of treatment. In the absence of clinical symptoms, liver transaminases and serum bilirubin 

should be monitored at months 1, 3, 6, 9 and 12 on therapy and periodically thereafter until 2 months 

after Gilenya discontinuation. In the absence of clinical symptoms, if liver transaminases are greater 

than 3 but less than 5 times the ULN without increase in serum bilirubin, more frequent monitoring 

including serum bilirubin and alkaline phosphatase (ALP) measurement should be instituted to 

determine if further increases occur and in order to discern if an alternative aetiology of hepatic 

dysfunction is present. If liver transaminases are at least 5 times the ULN or at least 3 times the ULN 

associated with any increase in serum bilirubin, Gilenya should be discontinued. Hepatic monitoring 

should be continued. If serum levels return to normal (including if an alternative cause of the hepatic 

dysfunction is discovered), Gilenya may be restarted based on a careful benefit-risk assessment of the 

patient. 

 

Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, 

vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine, should have liver enzymes 

and bilirubin checked promptly and treatment should be discontinued if significant liver injury is 

confirmed. Treatment should not be resumed unless a plausible alternative aetiology for the signs and 

symptoms of liver injury can be established. 

 

Although there are no data to establish that patients with pre-existing liver disease are at increased risk 

of developing elevated liver function tests when taking Gilenya, caution in the use of Gilenya should 

be exercised in patients with a history of significant liver disease. 

 



 

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Blood pressure effects 

 

Patients with hypertension uncontrolled by medication were excluded from participation in 

premarketing clinical trials and special care is indicated if patients with uncontrolled hypertension are 

treated with Gilenya. 

 

In MS clinical trials, patients treated with fingolimod 0.5 mg had an average increase of approximately 

3 mmHg in systolic pressure, and approximately 1 mmHg in diastolic pressure, first detected 

approximately 1 month after treatment initiation, and persisting with continued treatment. In the two-

year placebo-controlled study, hypertension was reported as an adverse event in 6.5% of patients on 

fingolimod 0.5 mg and in 3.3% of patients on placebo. Therefore, blood pressure should be regularly 

monitored during treatment. 

 

Respiratory effects 

 

Minor dose-dependent reductions in values for forced expiratory volume (FEV1) and diffusion 

capacity for carbon monoxide (DLCO) were observed with fingolimod treatment starting at month 1 

and remaining stable thereafter. Gilenya should be used with caution in patients with severe 

respiratory disease, pulmonary fibrosis and chronic obstructive pulmonary disease (see section 4.8). 

 

Posterior reversible encephalopathy syndrome 

 

Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported at the 0.5 mg 

dose in clinical trials and in the post-marketing setting (see section 4.8). Symptoms reported included 

sudden onset of severe headache, nausea, vomiting, altered mental status, visual disturbances and 

seizure. Symptoms of PRES are usually reversible but may evolve into ischaemic stroke or cerebral 

haemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES 

is suspected, Gilenya should be discontinued. 

 

Prior treatment with immunosuppressive or immunomodulatory therapies 

 

There have been no studies performed to evaluate the efficacy and safety of fingolimod when 

switching patients from teriflunomide, dimethyl fumarate or alemtuzumab treatment to Gilenya. When 

switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action 

of the other therapy must be considered in order to avoid an additive immune effect whilst at the same 

time minimising the risk of disease reactivation. A CBC is recommended prior to initiating Gilenya to 

ensure that immune effects of the previous therapy (i.e. cytopenia) have resolved. 

 

Gilenya can generally be started immediately after discontinuation of interferon or glatiramer acetate. 

 

For dimethyl fumarate, the washout period should be sufficient for CBC to recover before treatment 

with Gilenya is started. 

 

Due to the long half-life of natalizumab, elimination usually takes up to 2-3 months following 

discontinuation. Teriflunomide is also eliminated slowly from the plasma. Without an accelerated 

elimination procedure, clearance of teriflunomide from plasma can take from several months up to 

2 years. An accelerated elimination procedure as defined in the teriflunomide summary of product 

characteristics is recommended or alternatively washout period should not be shorter than 3.5 months. 

Caution regarding potential concomitant immune effects is required when switching patients from 

natalizumab or teriflunomide to Gilenya. 

 

Alemtuzumab has profound and prolonged immunosuppressive effects. As the actual duration of these 

effects is unknown, initiating treatment with Gilenya after alemtuzumab is not recommended unless 

the benefits of such treatment clearly outweigh the risks for the individual patient. 

 

A decision to use prolonged concomitant treatment with corticosteroids should be taken after careful 

consideration. 



 

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Co-administration with potent CYP450 inducers 

 

The combination of fingolimod with potent CYP450 inducers should be used with caution. 

Concomitant administration with St John’s Wort is not recommended (see section 4.5). 

 

Malignancies 

 

Cutaneous malignancies 

Basal cell carcinoma (BCC) and other cutaneous neoplasms, including malignant melanoma, 

squamous cell carcinoma, Kaposi’s sarcoma and Merkel cell carcinoma, have been reported in patients 

receiving Gilenya (see section 4.8). Vigilance for skin lesions is warranted and a medical evaluation of 

the skin is recommended at initiation, and then every 6 to 12 months taking into consideration clinical 

judgement. The patient should be referred to a dermatologist in case suspicious lesions are detected. 

 

Since there is a potential risk of malignant skin growths, patients treated with fingolimod should be 

cautioned against exposure to sunlight without protection. These patients should not receive 

concomitant phototherapy with UV-B-radiation or PUVA-photochemotherapy. 

 

Lymphomas 

There have been cases of lymphoma in clinical studies and the post-marketing setting (see 

section 4.8). The cases reported were heterogeneous in nature, mainly non-Hodgkin’s lymphoma, 

including B-cell and T-cell lymphomas. Cases of cutaneous T-cell lymphoma (mycosis fungoides) 

have been observed. A fatal case of Epstein-Barr virus (EBV) positive B-cell lymphoma has also been 

observed. If lymphoma is suspected, treatment should be discontinued. 

 

Women of childbearing potential 

 

Due to risk to the foetus, fingolimod is contraindicated during pregnancy and in women of 

childbearing potential not using effective contraception. Before initiation of treatment, women of 

childbearing potential must be informed of this risk to the foetus, must have a negative pregnancy test 

and must use effective contraception during treatment and for 2 months after treatment discontinuation 

(see sections 4.3 and 4.6 and the information contained in the Physician Information Pack). 

 

Tumefactive lesions 

 

Rare cases of tumefactive lesions associated with MS relapse were reported in the post-marketing 

setting. In case of severe relapses, MRI should be performed to exclude tumefactive lesions. 

Discontinuation of treatment should be considered by the physician on a case-by-case basis taking into 

account individual benefits and risks. 

 

Return of disease activity (rebound) after fingolimod discontinuation 

 

In the post-marketing setting, severe exacerbation of disease has been observed rarely in some patients 

stopping fingolimod. This has generally been observed within 12 weeks after stopping fingolimod, but 

has also been reported up to 24 weeks after fingolimod discontinuation. Caution is therefore indicated 

when stopping fingolimod therapy. If discontinuation of fingolimod is deemed necessary, the 

possibility of recurrence of exceptionally high disease activity should be considered and patients 

should be monitored for relevant signs and symptoms and appropriate treatment initiated as required 

(see “Stopping therapy” below). 

 



 

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Stopping therapy 

 

If a decision is made to stop treatment with Gilenya a 6 week interval without therapy is needed, based 

on half-life, to clear fingolimod from the circulation (see section 5.2). Lymphocyte counts 

progressively return to normal range within 1-2 months of stopping therapy in most patients (see 

section 5.1) although full recovery can take significantly longer in some patients. Starting other 

therapies during this interval will result in concomitant exposure to fingolimod. Use of 

immunosuppressants soon after the discontinuation of Gilenya may lead to an additive effect on the 

immune system and caution is therefore indicated. 

 

Caution is also indicated when stopping fingolimod therapy due to the risk of a rebound (see “Return 

of disease activity (rebound) after fingolimod discontinuation” above). If discontinuation of Gilenya is 

deemed necessary, patients should be monitored during this time for relevant signs of a possible 

rebound. 
 

Interference with serological testing 

 
Since fingolimod reduces blood lymphocyte counts via re-distribution in secondary lymphoid organs, 

peripheral blood lymphocyte counts cannot be utilised to evaluate the lymphocyte subset status of a 

patient treated with Gilenya. Laboratory tests involving the use of circulating mononuclear cells 

require larger blood volumes due to reduction in the number of circulating lymphocytes. 

 

Paediatric population 

 

The safety profile in paediatric patients is similar to that in adults and the warnings and precautions for 

adults therefore also apply to paediatric patients. 

 

In particular, the following should be noted when prescribing Gilenya to paediatric patients: 

- Precautions should be followed at the time of the first dose (see “Bradyarrhythmia” above). The 

same precautions as for the first dose are recommended when patients are switched from the 

0.25 mg to the 0.5 mg daily dose. 

- In the controlled paediatric trial D2311, cases of seizures, anxiety, depressed mood and 

depression have been reported with a higher incidence in patients treated with fingolimod 

compared to patients treated with interferon beta-1a. Caution is required in this subgroup 

population (see “Paediatric population” in section 4.8). 

- Mild isolated bilirubin increases have been noted in paediatric patients on Gilenya. 

- It is recommended that paediatric patients complete all immunisations in accordance with 

current immunisation guidelines before starting Gilenya therapy (see “Infections” above). 

- There are very limited data available in children between 10–12 years old, less than 40 kg or at 

Tanner stage <2 (see sections 4.8 and 5.1). Caution is required in these subgroups due to very 

limited knowledge available from the clinical study. 

- Long-term safety data in the paediatric population are not available. 
 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Anti-neoplastic, immunomodulatory or immunosuppressive therapies 

 

Anti-neoplastic, immunomodulatory or immunosuppressive therapies should not be co-administered 

due to the risk of additive immune system effects (see sections 4.3 and 4.4). 

 

Caution should also be exercised when switching patients from long-acting therapies with immune 

effects such as natalizumab, teriflunomide or mitoxantrone (see section 4.4). In multiple sclerosis 

clinical studies the concomitant treatment of relapses with a short course of corticosteroids was not 

associated with an increased rate of infection. 

 



 

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Vaccination 

 

During and for up to two months after treatment with Gilenya vaccination may be less effective. The 

use of live attenuated vaccines may carry a risk of infections and should therefore be avoided (see 

sections 4.4 and 4.8). 

 

Bradycardia-inducing substances 

 

Fingolimod has been studied in combination with atenolol and diltiazem. When fingolimod was used 

with atenolol in an interaction study in healthy volunteers, there was an additional 15% reduction of 

heart rate at fingolimod treatment initiation, an effect not seen with diltiazem. Treatment with Gilenya 

should not be initiated in patients receiving beta blockers, or other substances which may decrease 

heart rate, such as class Ia and III antiarrhythmics, calcium channel blockers (such as verapamil or 

diltiazem), ivabradine, digoxin, anticholinesteratic agents or pilocarpine because of the potential 

additive effects on heart rate (see sections 4.4 and 4.8). If treatment with Gilenya is considered in such 

patients, advice from a cardiologist should be sought regarding the switch to non-heart-rate lowering 

medicinal products or appropriate monitoring for treatment initiation, at least overnight monitoring is 

recommended, if the heart-rate-lowering medication cannot be stopped. 

 

Pharmacokinetic interactions of other substances on fingolimod 

 

Fingolimod is metabolised mainly by CYP4F2. Other enzymes like CYP3A4 may also contribute to 

its metabolism, notably in the case of strong induction of CYP3A4. Potent inhibitors of transporter 

proteins are not expected to influence fingolimod disposition. Co-administration of fingolimod with 

ketoconazole resulted in a 1.7-fold increase in fingolimod and fingolimod phosphate exposure (AUC) 

by inhibition of CYP4F2. Caution should be exercised with substances that may inhibit CYP3A4 

(protease inhibitors, azole antifungals, some macrolides such as clarithromycin or telithromycin). 

 

Co-administration of carbamazepine 600 mg twice daily at steady-state and a single dose of 

fingolimod 2 mg reduced the AUC of fingolimod and its metabolite by approximately 40%. Other 

strong CYP3A4 enzyme inducers, for example rifampicin, phenobarbital, phenytoin, efavirenz and St. 

John’s Wort, may reduce the AUC of fingolimod and its metabolite at least to this extent. As this 

could potentially impair the efficacy, their co-administration should be used with caution. 

Concomitant administration with St. John’s Wort is however not recommended (see section 4.4). 

 

Pharmacokinetic interactions of fingolimod on other substances 

 

Fingolimod is unlikely to interact with substances mainly cleared by the CYP450 enzymes or by 

substrates of the main transporter proteins. 

 

Co-administration of fingolimod with ciclosporin did not elicit any change in the ciclosporin or 

fingolimod exposure. Therefore, fingolimod is not expected to alter the pharmacokinetics of medicinal 

products that are CYP3A4 substrates. 

 

Co-administration of fingolimod with oral contraceptives (ethinylestradiol and levonorgestrel) did not 

elicit any change in oral contraceptive exposure. No interaction studies have been performed with oral 

contraceptives containing other progestagens, however an effect of fingolimod on their exposure is not 

expected. 

 



 

13 

4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential/Contraception in females 

 

Fingolimod is contraindicated in women of childbearing potential not using effective contraception 

(see section 4.3). Therefore, before initiation of treatment in women of childbearing potential, a 

negative pregnancy test result must be available and counselling should be provided regarding the 

serious risk to the foetus. Women of childbearing potential must use effective contraception during 

treatment and for 2 months after discontinuation of Gilenya, since fingolimod takes approximately 

2 months to eliminate from the body after treatment discontinuation (see section 4.4). 

 

Specific measures are also included in the Physician Information Pack. These measures must be 

implemented before fingolimod is prescribed to female patients and during treatment. 

 

When stopping fingolimod therapy for planning a pregnancy the possible return of disease activity 

should be considered (see section 4.4). 

 
Pregnancy 

 

Based on human experience, post-marketing data suggest that use of fingolimod is associated with a 

2-fold increased risk of major congenital malformations when administered during pregnancy 

compared with the rate observed in the general population (2-3%; EUROCAT). 

 

The following major malformations were most frequently reported: 

- Congenital heart disease such as atrial and ventricular septal defects, tetralogy of Fallot 

- Renal abnormalities 

- Musculoskeletal abnormalities 

 

There are no data on the effects of fingolimod on labour and delivery. 

 

Animal studies have shown reproductive toxicity including foetal loss and organ defects, notably 

persistent truncus arteriosus and ventricular septal defect (see section 5.3). Furthermore, the receptor 

affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular 

formation during embryogenesis. 

 

Consequently, fingolimod is contraindicated during pregnancy (see section 4.3). Fingolimod should be 

stopped 2 months before planning a pregnancy (see section 4.4). If a woman becomes pregnant during 

treatment, fingolimod must be discontinued. Medical advice should be given regarding the risk of 

harmful effects to the foetus associated with treatment and ultrasonography examinations should be 

performed. 
 

Breast-feeding 

 

Fingolimod is excreted in milk of treated animals during lactation (see section 5.3). Due to the 

potential for serious adverse reactions to fingolimod in nursing infants, women receiving Gilenya 

should not breastfeed. 

 

Fertility 

 

Data from preclinical studies do not suggest that fingolimod would be associated with an increased 

risk of reduced fertility (see section 5.3). 
 

  



 

14 

4.7 Effects on ability to drive and use machines 
 

Fingolimod has no or negligible influence on the ability to drive and use machines. 

 

However, dizziness or drowsiness may occasionally occur when initiating treatment. On initiation of 

Gilenya it is recommended that patients be observed for a period of 6 hours (see section 4.4, 

Bradyarrhythmia). 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The most frequent adverse reactions (incidence ≥10%) at the 0.5 mg dose were headache (24.5%), 

hepatic enzyme increased (15.2%), diarrhoea (12.6%), cough (12.3%), influenza (11.4%), sinusitis 

(10.9%) and back pain (10.0%). 

 

Tabulated list of adverse reactions 

 

Adverse reactions reported in clinical trials and derived from post-marketing experience via 

spontaneous case reports or literature cases are shown below. Frequencies were defined using the 

following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to 

<1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the 

available data). Within each frequency grouping, adverse reactions are presented in the order of 

decreasing seriousness. 

 

Infections and infestations 

Very common: Influenza 

Sinusitis 

Common: Herpes viral infections 

Bronchitis 

Tinea versicolor 

Uncommon: Pneumonia 

Not known: Progressive multifocal leukoencephalopathy (PML)** 

Cryptococcal infections** 

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

Common: Basal cell carcinoma 

Uncommon: Malignant melanoma**** 

Rare: Lymphoma*** 

Squamous cell carcinoma**** 

Very rare: Kaposi’s sarcoma**** 

Not known Merkel cell carcinoma*** 

Blood and lymphatic system disorders 

Common: Lymphopenia 

Leucopenia 

Uncommon: Thrombocytopenia 

Not known: Autoimmune haemolytic anaemia*** 

Peripheral oedema*** 

Immune system disorders 

Not known: Hypersensitivity reactions, including rash, urticaria and angioedema 

upon treatment initiation*** 

Psychiatric disorders 

Common: Depression 

Uncommon: Depressed mood 



 

15 

Nervous system disorders 

Very common: Headache 

Common: Dizziness 

Migraine 

Uncommon: Seizure 

Rare: Posterior reversible encephalopathy syndrome (PRES)* 

Not known: Severe exacerbation of disease after fingolimod discontinuation*** 

Eye disorders 

Common: Vision blurred 

Uncommon: Macular oedema 

Cardiac disorders 

Common: Bradycardia 

Atrioventricular block 

Very rare: T-wave inversion*** 

Vascular disorders 

Common: Hypertension 

Respiratory, thoracic and mediastinal disorders 

Very common: Cough 

Common: Dyspnoea 

Gastrointestinal disorders 

Very common: Diarrhoea 

Uncommon: Nausea*** 

Hepatobiliary disorders 

Not known: Acute hepatic failure*** 

Skin and subcutaneous tissue disorders 

Common: Eczema 

Alopecia 

Pruritus 

Musculoskeletal and connective tissue disorders 

Very common: Back pain 

Common: Myalgia 

Arthralgia 

General disorders and administration site conditions 

Common: Asthenia 

Investigations 

Very common: Hepatic enzyme increased (increased alanine transaminase, gamma 

glutamyltransferase, aspartate transaminase) 

Common: Weight decreased*** 

Blood triglycerides increased 

Uncommon: Neutrophil count decreased 

* The frequency category was based on an estimated exposure of approximately 

10,000 patients to fingolimod in all clinical trials. 

** PML and cryptococcal infections (including cases of cryptococcal meningitis) have been 

reported in the post-marketing setting (see section 4.4). 

*** Adverse reactions from spontaneous reports and literature 

****  The frequency category and risk assessment were based on an estimated exposure of more 

than 24,000 patients to fingolimod 0.5 mg in all clinical trials. 

 

  



 

16 

Description of selected adverse reactions 

 

Infections 

In multiple sclerosis clinical studies the overall rate of infections (65.1%) at the 0.5 mg dose was 

similar to placebo. However, lower respiratory tract infections, primarily bronchitis and to a lesser 

extent herpes infection and pneumonia were more common in fingolimod-treated patients. Some cases 

of disseminated herpes infection, including fatal cases, have been reported even at the 0.5 mg dose. 

 

In the post-marketing setting, cases of infections with opportunistic pathogens, such as viral (e.g. 

varicella zoster virus [VZV], John Cunningham virus [JCV] causing Progressive Multifocal 

Leukoencephalopathy, herpes simplex virus [HSV]), fungal (e.g. cryptococci including cryptococcal 

meningitis) or bacterial (e.g. atypical mycobacterium), have been reported, some of which have been 

fatal (see section 4.4). 

 

Human papilloma virus (HPV) infection, including papilloma, dysplasia, warts and HPV-related 

cancer, has been reported under treatment with fingolimod in the post-marketing setting. Due to the 

immunosuppressive properties of fingolimod, vaccination against HPV should be considered prior to 

treatment initiation with fingolimod taking into account vaccination recommendations. Cancer 

screening, including Pap test, is recommended as per standard of care. 

 
Macular oedema 

In multiple sclerosis clinical studies macular oedema occurred in 0.5% of patients treated with the 

recommended dose of 0.5 mg and 1.1% of patients treated with the higher dose of 1.25 mg. The 

majority of cases occurred within the first 3-4 months of therapy. Some patients presented with blurred 

vision or decreased visual acuity, but others were asymptomatic and diagnosed on routine 

ophthalmological examination. The macular oedema generally improved or resolved spontaneously 

after discontinuation of treatment. The risk of recurrence after re-challenge has not been evaluated. 

 

Macular oedema incidence is increased in multiple sclerosis patients with a history of uveitis (17% 

with a history of uveitis vs. 0.6% without a history of uveitis). Gilenya has not been studied in 

multiple sclerosis patients with diabetes mellitus, a disease which is associated with an increased risk 

for macular oedema (see section 4.4). In renal transplant clinical studies in which patients with 

diabetes mellitus were included, therapy with fingolimod 2.5 mg and 5 mg resulted in a 2-fold increase 

in the incidence of macular oedema. 
 

Bradyarrhythmia 

Initiation of treatment results in a transient decrease in heart rate and may also be associated with 

atrioventricular conduction delays. In multiple sclerosis clinical studies the maximal decline in heart 

rate was seen within 6 hours after treatment initiation, with declines in mean heart rate of 12-13 beats 

per minute for fingolimod 0.5 mg. Heart rate below 40 beats per minute in adults, and below 50 beats 

per minute in paediatric patients, was rarely observed in patients on fingolimod 0.5 mg. The average 

heart rate returned towards baseline within 1 month of chronic treatment. Bradycardia was generally 

asymptomatic but some patients experienced mild to moderate symptoms, including hypotension, 

dizziness, fatigue and/or palpitations, which resolved within the first 24 hours after treatment initiation 

(see also sections 4.4 and 5.1). 

 

In multiple sclerosis clinical studies first-degree atrioventricular block (prolonged PR interval on 

ECG) was detected after treatment initiation in adult and paediatric patients. In adult clinical trials it 

occurred in 4.7% of patients on fingolimod 0.5 mg, in 2.8% of patients on intramuscular interferon 

beta-1a, and in 1.6% of patients on placebo. Second-degree atrioventricular block was detected in less 

than 0.2% adult patients on fingolimod 0.5 mg. In the post-marketing setting, isolated reports of 

transient, spontaneously resolving complete AV block have been observed during the six hour 

monitoring period following the first dose of Gilenya. The patients recovered spontaneously. The 

conduction abnormalities observed both in clinical trials and post-marketing were typically transient, 

asymptomatic and resolved within the first 24 hours after treatment initiation. Although most patients 



 

17 

did not require medical intervention, one patient on fingolimod 0.5 mg received isoprenaline for 

asymptomatic second-degree Mobitz I atrioventricular block. 

 

In the post-marketing setting, isolated delayed onset events, including transient asystole and 

unexplained death, have occurred within 24 hours of the first dose. These cases have been confounded 

by concomitant medicinal products and/or pre-existing disease. The relationship of such events to 

Gilenya is uncertain. 

 

Blood pressure 

In multiple sclerosis clinical studies fingolimod 0.5 mg was associated with an average increase of 

approximately 3 mmHg in systolic pressure and approximately 1 mmHg in diastolic pressure, 

manifesting approximately 1 month after treatment initiation. This increase persisted with continued 

treatment. Hypertension was reported in 6.5% of patients on fingolimod 0.5 mg and in 3.3% of 

patients on placebo. In the post-marketing setting, cases of hypertension have been reported within the 

first month of treatment initiation and on the first day of treatment that may require treatment with 

antihypertensive agents or discontinuation of Gilenya (see also section 4.4, Blood pressure effects). 
 

Liver function 

Increased hepatic enzymes have been reported in adult and paediatric multiple sclerosis patients 

treated with Gilenya. In clinical studies 8.0% and 1.8% of adult patients treated with fingolimod 

0.5 mg experienced an asymptomatic elevation in serum levels of ALT of ≥3x ULN (upper limit of 

normal) and ≥5x ULN, respectively. Recurrence of liver transaminase elevations has occurred upon re-

challenge in some patients, supporting a relationship to the medicinal product. In clinical studies, 

transaminase elevations occurred at any time during treatment although the majority occurred within 

the first 12 months. ALT levels returned to normal within approximately 2 months after 

discontinuation of treatment. In a small number of patients (N=10 on 1.25 mg, N=2 on 0.5 mg) who 

experienced ALT elevations ≥5x ULN and who continued on fingolimod therapy, the ALT levels 

returned to normal within approximately 5 months (see also section 4.4, Liver function). 
 

Nervous system disorders 

In clinical studies, rare events involving the nervous system occurred in patients treated with 

fingolimod at higher doses (1.25 or 5.0 mg) including ischaemic and haemorrhagic strokes and 

neurological atypical disorders, such as acute disseminated encephalomyelitis (ADEM)-like events. 

 

Cases of seizures, including status epilepticus, have been reported with the use of fingolimod in 

clinical studies and in the post-marketing setting. 

 

Vascular disorders 

Rare cases of peripheral arterial occlusive disease occurred in patients treated with fingolimod at 

higher doses (1.25 mg). 

 

Respiratory system 

Minor dose-dependent reductions in values for forced expiratory volume (FEV1) and diffusion 

capacity for carbon monoxide (DLCO) were observed with Gilenya treatment starting at month 1 and 

remaining stable thereafter. At month 24, the reduction from baseline values in percentage of predicted 

FEV1 was 2.7% for fingolimod 0.5 mg and 1.2% for placebo, a difference that resolved after treatment 

discontinuation. For DLCO the reductions at month 24 were 3.3% for fingolimod 0.5 mg and 2.7% for 

placebo (see also section 4.4, Respiratory effects). 

 

Lymphomas 

There have been cases of lymphoma of different varieties, in both clinical studies and the post-

marketing setting, including a fatal case of Epstein-Barr virus (EBV) positive B-cell lymphoma. The 

incidence of non-Hodgkin’s lymphoma (B-cell and T-cell) cases was higher in clinical trials than 

expected in the general population. Some T-cell lymphoma cases were also reported in the post-

marketing setting, including cases of cutaneous T-cell lymphoma (mycosis fungoides) (see also 

section 4.4, Malignancies). 



 

18 

 

Haemophagocytic syndrome 

Very rare cases of haemophagocytic syndrome (HPS) with fatal outcome have been reported in 

patients treated with fingolimod in the context of an infection. HPS is a rare condition that has been 

described in association with infections, immunosuppression and a variety of autoimmune diseases. 

 

Paediatric population 

 

In the controlled paediatric trial D2311 (see section 5.1), the safety profile in paediatric patients (10 to 

below 18 years of age) receiving fingolimod 0.25 mg or 0.5 mg daily was overall similar to that seen 

in adult patients. There were, nevertheless, more neurological and psychiatric disorders observed in 

the study. Caution is needed in this subgroup due to very limited knowledge available from the clinical 

study. 

 

In the paediatric study, cases of seizures were reported in 5.6% of fingolimod-treated patients and 

0.9% of interferon beta-1a-treated patients. 

 

Depression and anxiety are known to occur with increased frequency in the multiple sclerosis 

population. Depression and anxiety have also been reported in paediatric patients treated with 

fingolimod. 

 

Mild isolated bilirubin increases have been noted in paediatric patients on fingolimod. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Single doses up to 80 times the recommended dose (0.5 mg) were well tolerated in healthy adult 

volunteers. At 40 mg, 5 of 6 subjects reported mild chest tightness or discomfort which was clinically 

consistent with small airway reactivity. 

 

Fingolimod can induce bradycardia upon treatment initiation. The decline in heart rate usually starts 

within one hour of the first dose, and is steepest within 6 hours. The negative chronotropic effect of 

Gilenya persists beyond 6 hours and progressively attenuates over subsequent days of treatment (see 

section 4.4 for details). There have been reports of slow atrioventricular conduction, with isolated 

reports of transient, spontaneously resolving complete AV block (see sections 4.4 and 4.8). 

 

If the overdose constitutes first exposure to Gilenya, it is important to monitor patients with a 

continuous (real time) ECG and hourly measurement of heart rate and blood pressure, at least during 

the first 6 hours (see section 4.4). 

 

Additionally, if after 6 hours the heart rate is <45 bpm in adults, <55 bpm in paediatric patients aged 

12 years and above, or <60 bpm in paediatric patients aged 10 years to below 12 years, or if the ECG 

at 6 hours after the first dose shows second degree or higher AV block, or if it shows a QTc interval 

≥500 msec, monitoring should be extended at least for overnight and until the findings have resolved. 

The occurrence at any time of third degree AV block should also lead to extended monitoring 

including overnight monitoring. 

 

Neither dialysis nor plasma exchange results in removal of fingolimod from the body. 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

19 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Immunosuppressants, selective immunosuppressants, ATC code: 

L04AA27 

 

Mechanism of action 

 

Fingolimod is a sphingosine 1-phosphate receptor modulator. Fingolimod is metabolised by 

sphingosine kinase to the active metabolite fingolimod phosphate. Fingolimod phosphate binds at low 

nanomolar concentrations to sphingosine 1-phosphate (S1P) receptor 1 located on lymphocytes, and 

readily crosses the blood-brain barrier to bind to S1P receptor 1 located on neural cells in the central 

nervous system (CNS). By acting as a functional antagonist of S1P receptors on lymphocytes, 

fingolimod phosphate blocks the capacity of lymphocytes to egress from lymph nodes, causing a 

redistribution, rather than depletion, of lymphocytes. Animal studies have shown that this 

redistribution reduces the infiltration of pathogenic lymphocytes, including pro-inflammatory Th17 

cells, into the CNS, where they would be involved in nerve inflammation and nervous tissue damage. 

Animal studies and in vitro experiments indicate that fingolimod may also act via interaction with S1P 

receptors on neural cells. 

 

Pharmacodynamic effects 

 

Within 4-6 hours after the first dose of fingolimod 0.5 mg, the lymphocyte count decreases to 

approximately 75% of baseline in peripheral blood. With continued daily dosing, the lymphocyte 

count continues to decrease over a two-week period, reaching a minimal count of approximately 

500 cells/microlitre or approximately 30% of baseline. Eighteen percent of patients reached a minimal 

count below 200 cells/microlitre on at least one occasion. Low lymphocyte counts are maintained with 

chronic daily dosing. The majority of T and B lymphocytes regularly traffic through lymphoid organs 

and these are the cells mainly affected by fingolimod. Approximately 15-20% of T lymphocytes have 

an effector memory phenotype, cells that are important for peripheral immune surveillance. Since this 

lymphocyte subset typically does not traffic to lymphoid organs it is not affected by fingolimod. 

Peripheral lymphocyte count increases are evident within days of stopping fingolimod treatment and 

typically normal counts are reached within one to two months. Chronic fingolimod dosing leads to a 

mild decrease in the neutrophil count to approximately 80% of baseline. Monocytes are unaffected by 

fingolimod. 

 

Fingolimod causes a transient reduction in heart rate and decrease in atrioventricular conduction at 

treatment initiation (see sections 4.4 and 4.8). The maximal decline in heart rate is seen within 6 hours 

post dose, with 70% of the negative chronotropic effect achieved on the first day. With continued 

administration heart rate returns to baseline within one month. The decrease in heart rate induced by 

fingolimod can be reversed by parenteral doses of atropine or isoprenaline. Inhaled salmeterol has also 

been shown to have a modest positive chronotropic effect. With initiation of fingolimod treatment 

there is an increase in atrial premature contractions, but there is no increased rate of atrial 

fibrillation/flutter or ventricular arrhythmias or ectopy. Fingolimod treatment is not associated with a 

decrease in cardiac output. Autonomic responses of the heart, including diurnal variation of heart rate 

and response to exercise are not affected by fingolimod treatment. 

 

S1P4 could partially contribute to the effect but was not the main receptor responsible for the 

lymphoid depletion. The mechanism of action of bradycardia and vasoconstriction were also studied in 

vitro in guinea pigs and isolated rabbit aorta and coronary artery. It was concluded that bradycardia 

could be mediated primarily by activation of inward-rectifying potassium channel or G-protein 

activated inwardly rectifying K+ channel (IKACh/GIRK) and that vasoconstriction seems to be 

mediated by a Rho kinase and calcium dependent mechanism. 

 



 

20 

Fingolimod treatment with single or multiple doses of 0.5 and 1.25 mg for two weeks is not associated 

with a detectable increase in airway resistance as measured by FEV1 and forced expiratory flow rate 

(FEF) 25-75. However, single fingolimod doses ≥5 mg (10-fold the recommended dose) are associated 

with a dose-dependent increase in airway resistance. Fingolimod treatment with multiple doses of 0.5, 

1.25, or 5 mg is not associated with impaired oxygenation or oxygen desaturation with exercise or an 

increase in airway responsiveness to methacholine. Subjects on fingolimod treatment have a normal 

bronchodilator response to inhaled beta-agonists. 

 

Clinical efficacy and safety 

 

The efficacy of fingolimod has been demonstrated in two studies which evaluated once-daily doses of 

fingolimod 0.5 mg and 1.25 mg in adult patients with relapsing-remitting multiple sclerosis (RRMS). 

Both studies included adult patients who had experienced ≥2 relapses in the prior 2 years or ≥1 relapse 

during the prior year. Expanded Disability Status Score (EDSS) was between 0 and 5.5. A third study 

targeting the same adult patient population was completed after registration of Gilenya. 

 

Study D2301 (FREEDOMS) was a 2-year randomised, double-blind, placebo-controlled Phase III 

study of 1,272 patients (n=425 on 0.5 mg, 429 on 1.25 mg, 418 on placebo). Median values for 

baseline characteristics were: age 37 years, disease duration 6.7 years, and EDSS score 2.0. Outcome 

results are shown in Table 1. There were no significant differences between the 0.5 mg and the 

1.25 mg doses as regards either endpoint. 

 

Table 1 Study D2301 (FREEDOMS): main results 

 

 Fingolimod 

0.5 mg 

Placebo 

Clinical endpoints   

Annualised relapse rate (primary endpoint) 0.18** 0.40 

Percentage of patients remaining relapse-free at 

24 months 

70%** 46% 

Proportion with 3-month Confirmed Disability 

Progression† 

17% 24% 

Hazard ratio (95% CI) 0.70 (0.52, 0.96)*  

MRI endpoints   

Median (mean) number of new or enlarging T2 

lesions over 24 months 

0.0 (2.5)** 5.0 (9.8) 

Median (mean) number of Gd-enhancing lesions 

at month 24 

0.0 (0.2)** 0.0 (1.1) 

Median (mean) % change in brain volume over 

24 months 

-0.7 (-0.8)** -1.0 (-1.3) 

† Disability progression defined as 1-point increase in EDSS confirmed 3 months later 

** p<0.001, *p<0.05 compared to placebo 

All analyses of clinical endpoints were intent-to-treat. MRI analyses used evaluable dataset. 

 

Patients who completed the 24-month core FREEDOMS study could enter a dose-blinded extension 

study (D2301E1) and receive fingolimod. In total, 920 patients entered (n=331 continued on 0.5 mg, 

289 continued on 1.25 mg, 155 switched from placebo to 0.5 mg and 145 switched from placebo to 

1.25 mg). After 12 months (month 36), 856 patients (93%) were still enrolled. Between months 24 and 

36, the annualised relapse rate (ARR) for patients on fingolimod 0.5 mg in the core study who 

remained on 0.5 mg was 0.17 (0.21 in the core study). The ARR for patients who switched from 

placebo to fingolimod 0.5 mg was 0.22 (0.42 in the core study). 

 



 

21 

Comparable results were shown in a replicate 2-year randomised, double-blind, placebo-controlled 

Phase III study on fingolimod in 1,083 patients (n=358 on 0.5 mg, 370 on 1.25 mg, 355 on placebo) 

with RRMS (D2309; FREEDOMS 2). Median values for baseline characteristics were: age 41 years, 

disease duration 8.9 years, EDSS score 2.5. 

 

Table 2 Study D2309 (FREEDOMS 2): main results 

 

 Fingolimod 

0.5 mg 

Placebo 

Clinical endpoints   

Annualised relapse rate (primary endpoint) 0.21** 0.40 

Percentage of patients remaining relapse-free at 

24 months 

71.5%** 52.7% 

Proportion with 3-month Confirmed Disability 

Progression† 

25% 29% 

Hazard ratio (95% CI) 0.83 (0.61, 1.12)  

MRI endpoints   

Median (mean) number of new or enlarging T2 

lesions over 24 months 

0.0 (2.3)** 4.0 (8.9) 

Median (mean) number of Gd-enhancing lesions 

at month 24 

0.0 (0.4)** 0.0 (1.2) 

Median (mean) % change in brain volume over 

24 months 

-0.71 (-0.86)** -1.02 (-1.28) 

† Disability progression defined as 1-point increase in EDSS confirmed 3 months later 

** p<0.001 compared to placebo 

All analyses of clinical endpoints were intent-to-treat. MRI analyses used evaluable dataset. 

 
  



 

22 

Study D2302 (TRANSFORMS) was a 1-year randomised, double-blind, double-dummy, active 

(interferon beta-1a)-controlled Phase III study of 1,280 patients (n=429 on 0.5 mg, 420 on 1.25 mg, 

431 on interferon beta-1a, 30 µg by intramuscular injection once weekly). Median values for baseline 

characteristics were: age 36 years, disease duration 5.9 years, and EDSS score 2.0. Outcome results 

are shown in Table 3. There were no significant differences between the 0.5 mg and the 1.25 mg doses 

as regards study endpoints. 

 

Table 3 Study D2302 (TRANSFORMS): main results 

 

 Fingolimod 

0.5 mg 

Interferon beta-

1a, 30 μg 

Clinical endpoints   

Annualised relapse rate (primary endpoint) 0.16** 0.33 

Percentage of patients remaining relapse-free at 

12 months 

83%** 71% 

Proportion with 3-month Confirmed Disability 

Progression† 

6% 8% 

Hazard ratio (95% CI) 0.71 (0.42, 1.21)  

MRI endpoints   

Median (mean) number of new or enlarging T2 

lesions over 12 months 

0.0 (1.7)* 1.0 (2.6) 

Median (mean) number of Gd-enhancing lesions 

at 12 months 

0.0 (0.2)** 0.0 (0.5) 

Median (mean) % change in brain volume over 

12 months 

-0.2 (-0.3)** -0.4 (-0.5) 

† Disability progression defined as 1-point increase in EDSS confirmed 3 months later. 

* p<0.01,** p<0.001, compared to interferon beta-1a 

All analyses of clinical endpoints were intent-to-treat. MRI analyses used evaluable dataset. 

 

Patients who completed the 12-month core TRANSFORMS study could enter a dose-blinded 

extension (D2302E1) and receive fingolimod. In total, 1,030 patients entered, however, 3 of these 

patients did not receive treatment (n=356 continued on 0.5 mg, 330 continued on 1.25 mg, 167 

switched from interferon beta-1a to 0.5 mg and 174 from interferon beta-1a to 1.25 mg). After 

12 months (month 24), 882 patients (86%) were still enrolled. Between months 12 and 24, the ARR 

for patients on fingolimod 0.5 mg in the core study who remained on 0.5 mg was 0.20 (0.19 in the core 

study). The ARR for patients who switched from interferon beta-1a to fingolimod 0.5 mg was 0.33 

(0.48 in the core study). 

 

Pooled results of Studies D2301 and D2302 showed a consistent and statistically significant reduction 

in annualised relapse rate compared to comparator in subgroups defined by gender, age, prior multiple 

sclerosis therapy, disease activity or disability levels at baseline. 

 

Further analyses of clinical trial data demonstrate consistent treatment effects in highly active 

subgroups of relapsing remitting multiple sclerosis patients. 

 
  



 

23 

Paediatric population 

 

The efficacy and safety of once-daily doses of fingolimod 0.25 mg or 0.5 mg (dose selected based on 

body weight and exposure measurements) have been established in paediatric patients aged 10 to 

<18 years with relapsing-remitting multiple sclerosis. 

 

Study D2311 (PARADIGMS) was a double-blind, double-dummy, active-controlled study with 

flexible duration up to 24 months, with 215 patients 10 to <18 years old (n=107 on fingolimod, 108 on 

interferon beta-1a 30 µg by intramuscular injection once weekly). 

 

Median values for baseline characteristics were: age 16 years, median disease duration 1.5 years and 

EDSS score 1.5. The majority of patients were Tanner stage 2 or higher (94.4%) and were >40 kg 

(95.3%). Overall, 180 (84%) of patients completed the core phase on study drug (n=99 [92.5%] on 

fingolimod, 81 [75%] on interferon beta-1a). Outcome results are shown in Table 4. 

 

Table 4 Study D2311 (PARADIGMS): main results 

 

 Fingolimod 

0.25 mg or 0.5 mg 

Interferon beta-1a 

30 µg 

Clinical endpoints N=107 N=107# 

Annualised relapse rate (primary endpoint) 0.122** 0.675 

Percentage of patients remaining relapse-free at 

24 months 

85.7** 38.8 

MRI endpoints   

Annualised rate of the number of new or newly 

enlarging T2 lesions  

n=106 n=102 

Adjusted mean 4.393** 9.269 

Number of Gd-enhancing T1 lesions per scan up to 

month 24 

n=105 n=95 

Adjusted mean 0.436** 1.282 

Annualised rate of brain atrophy from baseline up to 

month 24 

n=96 n=89 

Least Square Mean -0.48* -0.80 

# One patient randomised to receive interferon beta-1a by intramuscular injection was unable to 

swallow the double-dummy medication and discontinued from study. The patient was 

excluded from the full analysis and safety set. 

* p<0.05, ** p<0.001, compared to interferon beta-1a. 

All analyses of clinical endpoints were on the full analysis set. 

 

5.2 Pharmacokinetic properties 
 

Pharmacokinetic data were obtained in healthy adult volunteers, in renal transplant adult patients and 

in multiple sclerosis adult patients. 
 

The pharmacologically active metabolite responsible for efficacy is fingolimod phosphate. 

 

Absorption 

 

Fingolimod absorption is slow (tmax of 12-16 hours) and extensive (≥85%). The apparent absolute oral 

bioavailability is 93% (95% confidence interval: 79-111%). Steady-state-blood concentrations are 

reached within 1 to 2 months following once-daily administration and steady-state levels are 

approximately 10-fold greater than with the initial dose. 

 

Food intake does not alter Cmax or exposure (AUC) of fingolimod. Fingolimod phosphate Cmax was 

slightly decreased by 34% but AUC was unchanged. Therefore, Gilenya may be taken without regard 

to meals (see section 4.2). 



 

24 

 

Distribution 

 

Fingolimod highly distributes in red blood cells, with the fraction in blood cells of 86%. Fingolimod 

phosphate has a smaller uptake in blood cells of <17%. Fingolimod and fingolimod phosphate are 

highly protein bound (>99%). 

 

Fingolimod is extensively distributed to body tissues with a volume of distribution of about 

1,200260 litres. A study in four healthy subjects who received a single intravenous dose of a 

radioiodolabelled analogue of fingolimod demonstrated that fingolimod penetrates into the brain. In a 

study in 13 male multiple sclerosis patients who received fingolimod 0.5 mg/day, the mean amount of 

fingolimod (and fingolimod phosphate) in seminal ejaculate, at steady-state, was approximately 

10,000 times lower than the oral dose administered (0.5 mg). 
 

Biotransformation 

 

Fingolimod is transformed in humans by reversible stereoselective phosphorylation to the 

pharmacologically active (S)-enantiomer of fingolimod phosphate. Fingolimod is eliminated by 

oxidative biotransformation catalysed mainly via CYP4F2 and possibly other isoenzymes and 

subsequent fatty acid-like degradation to inactive metabolites. Formation of pharmacologically 

inactive non-polar ceramide analogues of fingolimod was also observed. The main enzyme involved in 

the metabolism of fingolimod is partially identified and may be either CYP4F2 or CYP3A4. 

 

Following single oral administration of [14C] fingolimod, the major fingolimod-related components in 

blood, as judged from their contribution to the AUC up to 34 days post dose of total radiolabelled 

components, are fingolimod itself (23%), fingolimod phosphate (10%), and inactive metabolites (M3 

carboxylic acid metabolite (8%), M29 ceramide metabolite (9%) and M30 ceramide metabolite (7%)). 
 

Elimination 

 

Fingolimod blood clearance is 6.32.3 l/h, and the average apparent terminal half-life (t1/2) is 6-9 days. 

Blood levels of fingolimod and fingolimod phosphate decline in parallel in the terminal phase, leading 

to similar half-lives for both. 

 

After oral administration, about 81% of the dose is slowly excreted in the urine as inactive 

metabolites. Fingolimod and fingolimod phosphate are not excreted intact in urine but are the major 

components in the faeces, with amounts representing less than 2.5% of the dose each. After 34 days, 

the recovery of the administered dose is 89%. 
 

Linearity 

 

Fingolimod and fingolimod phosphate concentrations increase in an apparently dose proportional 

manner after multiple once-daily doses of 0.5 mg or 1.25 mg. 

 

  



 

25 

Characteristics in specific groups of patients 

 

Gender, ethnicity and renal impairment 

The pharmacokinetics of fingolimod and fingolimod phosphate do not differ in males and females, in 

patients of different ethnic origin, or in patients with mild to severe renal impairment. 
 

Hepatic impairment 

In subjects with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, and C), no 

change in fingolimod Cmax was observed, but fingolimod AUC was increased respectively by 12%, 

44%, and 103%. In patients with severe hepatic impairment (Child-Pugh class C), fingolimod-

phosphate Cmax was decreased by 22% and AUC was not substantially changed. The pharmacokinetics 

of fingolimod-phosphate were not evaluated in patients with mild or moderate hepatic impairment. 

The apparent elimination half-life of fingolimod is unchanged in subjects with mild hepatic 

impairment, but is prolonged by about 50% in patients with moderate or severe hepatic impairment. 

 

Fingolimod should not be used in patients with severe hepatic impairment (Child-Pugh class C) (see 

section 4.3). Fingolimod should be introduced cautiously in mild and moderate hepatic impaired 

patients (see section 4.2). 

 

Elderly population 

Clinical experience and pharmacokinetic information in patients aged above 65 years are limited. 

Gilenya should be used with caution in patients aged 65 years and over (see section 4.2). 
 

Paediatric population 

 

In paediatric patients (10 years of age and above), fingolimod-phosphate concentrations increase in an 

apparent dose proportional manner between 0.25 mg and 0.5 mg. 

 

Fingolimod-phosphate concentration at steady state is approximately 25% lower in paediatric patients 

(10 years of age and above) following daily administration of 0.25 mg or 0.5 mg fingolimod compared 

to the concentration in adult patients treated with fingolimod 0.5 mg once daily. 

 

There are no data available for paediatric patients below 10 years old. 

 

5.3 Preclinical safety data 
 

The preclinical safety profile of fingolimod was assessed in mice, rats, dogs and monkeys. The major 

target organs were the lymphoid system (lymphopenia and lymphoid atrophy), lungs (increased 

weight, smooth muscle hypertrophy at the bronchio-alveolar junction), and heart (negative 

chronotropic effect, increase in blood pressure, perivascular changes and myocardial degeneration) in 

several species; blood vessels (vasculopathy) in rats only at doses of 0.15 mg/kg and higher in a 2-year 

study, representing an approximate 4-fold margin based on the human systemic exposure (AUC) at a 

daily dose of 0.5 mg. 

 

No evidence of carcinogenicity was observed in a 2-year bioassay in rats at oral doses of fingolimod 

up to the maximally tolerated dose of 2.5 mg/kg, representing an approximate 50-fold margin based on 

human systemic exposure (AUC) at the 0.5 mg dose. However, in a 2-year mouse study, an increased 

incidence of malignant lymphoma was seen at doses of 0.25 mg/kg and higher, representing an 

approximate 6-fold margin based on the human systemic exposure (AUC) at a daily dose of 0.5 mg. 

 

Fingolimod was neither mutagenic nor clastogenic in animal studies. 

 

Fingolimod had no effect on sperm count/motility or on fertility in male and female rats up to the 

highest dose tested (10 mg/kg), representing an approximate 150-fold margin based on human 

systemic exposure (AUC) at a daily dose of 0.5 mg. 

 



 

26 

Fingolimod was teratogenic in the rat when given at doses of 0.1 mg/kg or higher. Drug exposure in 

rats at this dose was similar to that in patients at the therapeutic dose (0.5 mg). The most common 

foetal visceral malformations included persistent truncus arteriosus and ventricular septum defect. The 

teratogenic potential in rabbits could not be fully assessed, however an increased embryo-foetal 

mortality was seen at doses of 1.5 mg/kg and higher, and a decrease in viable foetuses as well as foetal 

growth retardation was seen at 5 mg/kg. Drug exposure in rabbits at these doses was similar to that in 

patients. 

 

In rats, F1 generation pup survival was decreased in the early postpartum period at doses that did not 

cause maternal toxicity. However, F1 body weights, development, behaviour, and fertility were not 

affected by treatment with fingolimod. 

 

Fingolimod was excreted in milk of treated animals during lactation at concentrations 2-fold to 3-fold 

higher than that found in maternal plasma. Fingolimod and its metabolites crossed the placental barrier 

in pregnant rabbits. 

 

Juvenile animal studies 

 

Results from two toxicity studies in juvenile rats showed slight effects on neurobehavioural response, 

delayed sexual maturation and a decreased immune response to repeated stimulations with keyhole 

limpet haemocyanin (KLH), which were not considered adverse. Overall, the treatment-related effects 

of fingolimod in juvenile animals were comparable to those seen in adult rats at similar dose levels, 

with the exception of changes in bone mineral density and neurobehavioural impairment (reduced 

auditory startle response) observed at doses of 1.5 mg/kg and higher in juvenile animals and the 

absence of smooth muscle hypertrophy in the lungs of the juvenile rats. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Gilenya 0.25 mg hard capsules 

 

Capsule fill 

Mannitol 

Hydroxypropylcellulose 

Hydroxypropylbetadex 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Yellow iron oxide (E172) 

 

Printing ink 

Shellac (E904) 

Black iron oxide (E172) 

Propylene glycol (E1520) 

Ammonia solution, concentrated (E527) 

 

  



 

27 

Gilenya 0.5 mg hard capsules 

 

Capsule fill 

Mannitol 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Yellow iron oxide (E172) 

 

Printing ink 

Shellac (E904) 

Ethanol, anhydrous 

Isopropyl alcohol 

Butyl alcohol 

Propylene glycol (E1520) 

Purified water 

Ammonia solution, concentrated (E527) 

Potassium hydroxide 

Black iron oxide (E172) 

Yellow iron oxide (E172) 

Titanium dioxide (E171) 

Dimethicone 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

Gilenya 0.25 mg hard capsules 

 

18 months 

 

Gilenya 0.5 mg hard capsules 

 

2 years 

 

6.4 Special precautions for storage 
 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

Gilenya 0.25 mg hard capsules 

 

PVC/PVDC/aluminium blister packs containing 28 hard capsules. 

PVC/PVDC/aluminium perforated unit dose blister packs containing 7x 1 hard capsules. 

 

  



 

28 

Gilenya 0.5 mg hard capsules 

 

PVC/PVDC/aluminium blister packs containing 28 or 98 hard capsules. 

PVC/PVDC/aluminium blister packs containing 7 or 28 hard capsules presented in wallets or 

multipacks containing 84 (3 packs of 28) hard capsules presented in wallets. 

PVC/PVDC/aluminium perforated unit dose blister packs containing 7x 1 hard capsules. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 
 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Gilenya 0.25 mg hard capsules 

 

EU/1/11/677/007-008 

 

Gilenya 0.5 mg hard capsules 

 

EU/1/11/677/001-006 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 17 March 2011 

Date of latest renewal: 23 November 2015 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

  

http://www.ema.europa.eu/


 

29 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



 

30 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

 Periodic safety update reports (PSURs) 

 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk management plan (RMP) 

 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 

activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 

marketing authorisation and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

 Additional risk minimisation measures 

 

Prior to launch of GILENYA in each Member State the Marketing Authorisation Holder (MAH) must 

agree about the content and format of the educational programme, including communication media, 

distribution modalities, and any other aspects of the programme, with the National Competent 

Authority (NCA). 

 

  



 

31 

The MAH shall ensure that in each Member State (MS) where GILENYA is marketed, all physicians 

who intend to prescribe GILENYA are provided with an updated Physician Information Pack, 

including: 

 

1. Summary of Product Characteristics (SmPC); 

2. Physician’s checklist for adult and pediatric patients, to consider prior to prescribing 

GILENYA, including information about the Pregnancy Exposure Registry; 

3. The Patient / Parent / Caregiver’s guide, to be provided to all patients, their parents (or legal 

representatives), and caregivers. 

4. The pregnancy-specific patient reminder card, to be provided to all patients, their parents (or 

legal representatives), and caregivers, as applicable. 

 

Physician’s checklist 

 

The physician’s checklist shall contain the following key messages: 

 

 Monitoring requirements at treatment initiation: 

Before first dose 

o Perform baseline ECG prior to the first dose of GILENYA; 

o Perform blood pressure measurement prior to the first dose of GILENYA; 

o Perform a liver function test prior to (within 6 months) treatment initiation; 

o Arrange ophthalmological assessment before starting GILENYA treatment in patients 

with diabetes mellitus or with a history of uveitis. 

o A negative pregnancy test result must be confirmed prior to starting treatment. 

 

Until 6 hours after first dose 

o Monitor the patient for 6 hours after the first dose of GILENYA has been administered 

for signs and symptoms of bradycardia, including hourly pulse and blood pressure 

checks. Continuous (real time) ECG monitoring is recommended; 

o Perform an ECG at the end of the 6-hour monitoring period. 

 

>6 to 8 hours after first dose 

o If, at the 6-hour time point, the heart rate is at the lowest value following the first dose, 

extend heart rate monitoring for at least 2 more hours and until the heart rate increases 

again. 

 

 Recommendation for re-initiating GILENYA therapy after treatment interruption: 

The same first dose monitoring as for treatment initiation is recommended when treatment is 

interrupted for: 

o One day or more during the first 2 weeks of treatment; 

o More than 7 days during weeks 3 and 4 of treatment; 

o More than 2 weeks after at least 1 month of treatment. 

 

 Recommendation for overnight monitoring after the first dose (or if the first dose monitoring 

applies during treatment re-initiation): 

o Extend heart rate monitoring for at least overnight in a medical facility and until 

resolution of findings in patients requiring pharmacological intervention during 

monitoring at treatment initiation/re-initiation. Repeat the first dose monitoring after the 

second dose of GILENYA; 

o Extend heart rate monitoring for at least overnight in a medical facility and until 

resolution of findings in patients: 

 With third degree AV block occurring at any time; 

 Where at the 6-hour time point: 

a. Heart rate <45 bpm, <55 bpm in paediatric patients aged 12 years old and 

above, or <60 bpm in pediatric patients 10 to below 12 years of age; 

b. New onset second degree or higher AV block; 

c. QTc interval 500 msec. 



 

32 

 

 GILENYA is contraindicated in patients with: 
o Known immunodeficiency syndrome; 

o Patients with increased risk for opportunistic infections, including immunocompromised 

patients (including those currently receiving immunosuppressive therapies or those 

immunocompromised by prior therapies); 

o Severe active infections, active chronic infections (hepatitis, tuberculosis); 

o Known active malignancies; 

o Severe liver impairment (Child-Pugh class C); 

o In the previous 6 months, myocardial infarction (MI), unstable angina pectoris, 

stroke/transient ischaemic attack (TIA), decompensated heart failure (requiring inpatient 

treatment), or New York Heart Association (NYHA) class III/IV heart failure; 

o Severe cardiac arrhythmias requiring anti-arrhythmic treatment with class Ia or class III 

anti-arrhythmic medicinal products; 

o Second-degree Mobitz type II atrioventricular (AV) block or third-degree AV block, or 

sick-sinus syndrome, if they do not wear a pacemaker; 

o Patients with a baseline QTc interval ≥500 msec; 

o Pregnant women and women of childbearing potential not using effective contraception; 

o Hypersensitivity to the active substance or to any of the excipients. 

 

 GILENYA is not recommended in patients with: 
o Sino-atrial heart block; 

o QTc prolongation >470 msec (adult females), QTc >460 msec (pediatric females) or 

>450 msec (adult and pediatric males); 

o History of cardiac arrest; 

o Severe sleep apnea; 

o History of symptomatic bradycardia; 

o History of recurrent syncope; 

o Uncontrolled hypertension. 

 

If GILENYA treatment is considered in these patients anticipated benefits must outweigh 

potential risks and a cardiologist must be consulted to determine appropriate monitoring, at least 

overnight extended monitoring is recommended. 

 

 GILENYA is not recommended in patients concomitantly taking medicines known to decrease 

the heart rate. If GILENYA treatment is considered in these patients anticipated benefits must 

outweigh potential risks and a cardiologist must be consulted to switch to non heart-rate-

lowering therapy or, if not possible, to determine appropriate monitoring. At least overnight 

extended monitoring is recommended. 
 

 GILENYA reduces peripheral blood lymphocyte counts. Peripheral lymphocyte count (CBC) 

should be checked in all patients prior to initiation (within 6 months or after discontinuation of 

prior therapy) and monitored during treatment with GILENYA. Treatment should be interrupted 

if lymphocyte count is confirmed as <0.2x109/L. The approved dosing of 0.5 mg once daily (or 

0.25 mg once daily in pediatric patients 10 years of age and above with a body weight of 

≤40 kg) when restarting Gilenya should be administered. Other dosing regimens have not been 

approved. 

 

  



 

33 

 GILENYA has an immunosuppressive effect that predisposes patients to an infection risk, 

including opportunistic infections that can be fatal, and increases the risk of developing 

lymphomas (including mycosis fungoides) and other malignancies, particularly those of the 

skin. Surveillance should include vigilance for both skin malignancies and mycosis fungoides. 

Physicians should carefully monitor patients, especially those with concurrent conditions or 

known factors, such as previous immunosuppressive therapy. If this risk is suspected, 

discontinuation of treatment should be considered by the physician on a case-by-case basis. 

 
o Treatment initiation in patients with severe active infection should be delayed until the 

infection is resolved. Suspension of treatment during serious infections should be 

considered. Anti-neoplastic, immunomodulatory or immunosuppressive therapies should 

not be co-administered due to the risk of additive immune system effects. For the same 

reason, a decision to use prolonged concomitant treatment with corticosteroids should be 

taken after careful consideration. 

 

o Vigilance for basal cell carcinoma and other cutaneous neoplasms including malignant 

melanoma, squamous cell carcinoma, Kaposi’s sarcoma and Merkel cell carcinoma is 

recommended, with skin examination prior to treatment initiation and then every 6 to 12 

months taking into consideration clinical judgement. Patients should be referred to a 

dermatologist if suspicious lesions are detected. Caution patients against exposure to 

sunlight without protection. These patients should not receive concomitant phototherapy 

with UV-B-radiation or PUVA-photochemotherapy. 

 

 Patients should be instructed to report signs and symptoms of infections immediately to their 

prescriber during and for up to two months after treatment with GILENYA. 

 
o Prompt diagnostic evaluation should be performed in patient with symptoms and signs 

consistent with cryptococcal meningitis; appropriate treatment, if diagnosed, should be 

initiated. 

Reports of cryptococcal meningitis (sometimes fatal) have been received after 

approximately 2-3 years of treatment, although an exact relationship with the duration of 

treatment is unknown. 

 

o Physicians should be vigilant for clinical symptoms or MRI findings suggestive of PML. 

If PML is suspected, treatment with GILENYA should be suspended until PML has been 

excluded. 

Cases of PML have occurred after approximately 2-3 years of monotherapy treatment 

although an exact relationship with the duration of treatment is unknown. 

 

o Specific recommendations regarding vaccination for patients initiating GILENYA 

treatment. Check varicella zoster virus (VZV) antibody status in patients without a 

healthcare professional confirmed history of chickenpox or documentation of a full 

course of varicella vaccination. If negative, a full course of vaccination with varicella 

vaccine is recommended and treatment initiation should be delayed for 1 month to allow 

full effect of vaccination to occur. 

 
o Human papilloma virus (HPV) infection, including papilloma, dysplasia, warts and HPV-

related cancer, has been reported in the post-marketing setting. Cancer screening, 

including Pap test, and vaccination for HPV-related cancer is recommended for patients, 

as per standard of care. 

 

 A full ophthalmological assessment should be considered: 

o 3-4 months after starting GILENYA therapy for the early detection of visual impairment 

due to drug-induced macular oedema; 

o During treatment with GILENYA in patients with diabetes mellitus or with a history of 

uveitis. 



 

34 

 

 GILENYA is teratogenic. It is contraindicated in women of childbearing potential (including 

female adolescents) not using effective contraception and in pregnant women. 

 

o A negative pregnancy test result must be confirmed prior to starting treatment, and it must 

be repeated at suitable intervals. 

 

o Women of child-bearing potential, including adolescent females, their parents (or legal 

representatives), and caregivers, should be counselled before treatment initiation and 

regularly thereafter about the serious risks of GILENYA to the foetus, facilitated by the 

pregnancy-specific patient reminder card. 

 

o Women of childbearing potential must use effective contraception during treatment and 

for two months following treatment discontinuation. 

 
o While on treatment, women must not become pregnant. If a woman becomes pregnant 

while on treatment, GILENYA must be discontinued. When stopping GILENYA therapy 

due to pregnancy or for planning a pregnancy, the possible return of disease activity 

should be considered. Medical advice should be given regarding the risk of harmful 

effects to the foetus associated with GILENYA treatment and ultrasonography 

examinations should be performed. 

 
o GILENYA must be stopped 2 months before planning a pregnancy. 

 

o Physicians are encouraged to enroll pregnant patients, or pregnant women may register 

themselves, in the GILENYA pregnancy registry. 

 

 Liver function should be monitored at months 1, 3, 6, 9 and 12 during GILENYA therapy and 

periodically thereafter; the approved dosing of 0.5 mg daily (or 0.25 mg once daily in pediatric 

patients 10 years of age and above with a body weight of ≤40 kg) should be administered. Other 

dosing regimens have not been approved. 

 

 In the post-marketing setting, severe exacerbation of disease has been observed rarely in some 

patients stopping GILENYA. The possibility of recurrence of exceptionally high disease 

activity should be considered. 

 

 Cases of seizure, including status epilepticus, have been reported. Physicians should be vigilant 

for seizures and especially in those patients with underlying conditions or with a pre-existing 

history or family history of epilepsy. 

 

 Physicians should reassess on an annual basis the benefit of GILENYA treatment versus risk in 

each patient, especially pediatric patients. 

 

 Physicians should provide patients/parents/caregivers with the patient/parents/caregiver guide 

and with the pregnancy-specific patient reminder card. 

 

The safety profile in pediatric patients is similar to adults and therefore the warnings and precautions 

in adults also apply for pediatric patients. 

 

  



 

35 

Specifically with pediatric patients, physicians should also: 

o Assess Tanner staging and measure height and weight as per standard of care; 

o Perform cardiovascular monitoring; 

o Take precautions when the first dose is administered / patients are switched from 0.25 to 

0.5 mg daily, due to the potential for bradyarrhythmia; 

o Monitor the patient for sign and symptoms of depression and anxiety; 

o Emphasize treatment compliance and misuse to patients, especially about treatment 

interruption and the importance of repeating cardiovascular monitoring; 

o Emphasize GILENYA immunosuppressive effects; 

o Consider a complete vaccination schedule before starting GILENYA; 

o Provide guidance on seizure monitoring. 

 

Patient / Parent / Caregiver guide 

 

The patient/parents/caregiver guide shall contain the following key messages: 

 What GILENYA is and how it works; 

 What multiple sclerosis is; 

 Patients should read the package leaflet thoroughly before starting treatment and should keep it 

in case they need to refer to it again during treatment; 

 Importance of reporting adverse reactions; 

 Patients should have a baseline ECG and blood pressure measurement prior to receiving the first 

dose of GILENYA; 

 Heart rate should be monitored for 6 or more hours after the first dose of GILENYA, including 

hourly pulse and blood pressure checks. Patients may be monitored with continuous ECG 

during the first 6 hours. An ECG at 6 hours should also be performed and, in some 

circumstances, monitoring may involve an overnight stay; 

 Patients should call their doctor in case of treatment interruption as the first dose monitoring 

may need to be repeated, depending on duration of interruption and time since starting of 

GILENYA treatment; 

 Patients should report immediately symptoms indicating low heart rate (such as dizziness, 

vertigo, nausea or palpitations) after the first dose of GILENYA; 

 GILENYA is not recommended in patients with cardiac disease or those taking medicines 

concomitantly known to decrease heart rate, and they should tell any doctor they see that they 

are being treated with GILENYA; 

 Signs and symptoms of infection, which should be immediately reported to the prescriber 

physician during and up to two months after GILENYA treatment; 

 The need to undergo cancer screening, including Pap test, and vaccination for HPV-related 

cancer, as per standard of care, will be assessed by the prescriber physician; 

 Any symptoms of visual impairment should be reported immediately to the prescriber during 

and for up to two months after the end of treatment with GILENYA; 

 GILENYA is teratogenic. Women of child-bearing potential, including adolescent females, 

should: 

o Be informed before treatment initiation and regularly thereafter by their physician about 

GILENYA’s serious risks to the foetus, and about the contraindication in pregnant 

women and in women of childbearing potential not using effective contraception, 

facilitated by the pregnancy-specific patient reminder card; 

o Have a negative pregnancy test before starting GILENYA; 

o Be using effective contraception during and for at least two months following 

discontinuation of GILENYA treatment; 

o Report immediately to the prescribing physician any (intended or unintended) pregnancy 

during and up to two months following discontinuation of GILENYA treatment; 

 A liver function test should be performed prior to treatment initiation; liver function monitoring 

should be performed at months 1, 3, 6, 9 and 12 during GILENYA therapy, and periodically 

thereafter; 



 

36 

 Skin cancers have been reported in multiple sclerosis patients treated with GILENYA. Patients 

should inform their doctor immediately if any skin nodules (e.g., shiny, pearly nodules), patches 

or open sores that do not heal within weeks are noted. Symptoms of skin cancer may include 

abnormal growth or changes of skin tissue (e.g., unusual moles) with a change in color, shape or 

size over time; 

 Seizure may occur. The doctor should be informed about a pre-existing history or family history 

of epilepsy; 

 Stopping GILENYA therapy may result in return of disease activity. The prescribing physician 

should decide whether and how the patient should be monitored after stopping GILENYA. 

 

Specifically for Pediatric patients: 

 

The following should be considered: 

 Physicians should assess Tanner staging and measure height and weight as per standard of care; 

 Precautions should be taken during the first dose of GILENYA and when patients are switched 

from 0.25 to 0.5 mg daily; 

 Depression and anxiety are known to occur with increased frequency in the multiple sclerosis 

population and have been reported also in pediatric patients treated with GILENYA; 

 Cardiac monitoring guidance; 

 Patients should ensure medication compliance and avoid misuse, especially treatment 

interruption, and repeat cardiac monitoring; 

 Signs and symptoms of infection; 

 Seizure monitoring guidance. 

 

Pregnancy-specific patient reminder card 

 

The pregnancy-specific patient reminder card shall contain the following key messages: 

 GILENYA is contraindicated during pregnancy and in women of childbearing potential not 

using effective contraception. 

 Doctors will provide counselling before treatment initiation and regularly thereafter regarding 

the teratogenic risk of GILENYA and required actions to minimise this risk. 

 Patients must use effective contraception while taking GILENYA. 

 A pregnancy test must be carried out and negative results verified by the doctor before starting 

treatment. It must be repeated at suitable intervals. 

 Patients will be informed by their doctor of the need for effective contraception while on 

treatment and for 2 months after discontinuation. 

 Doctors will provide counselling in the event of pregnancy and evaluation of the outcome of 

any pregnancy. 

 While on treatment, women must not become pregnant. If a woman becomes pregnant or wants 

to become pregnant, GILENYA must be discontinued. 

 Patients should inform their doctor straight away if there is worsening of multiple sclerosis after 

stopping treatment with GILENYA. 

 Women exposed to GILENYA during pregnancy are encouraged to join the pregnancy exposure 

registry that monitors outcomes of pregnancy. 

 

 Obligation to conduct post-authorisation measures 

 

The MAH shall complete, within the stated timeframe, the below measures: 

 

Description Due date 

Conduct of a prospective cohort study assessing the incidence of cardiovascular 

adverse events in patients starting GILENYA treatment for relapsing remitting 

multiple sclerosis based on a CHMP approved protocol. 

Final Study 

report by 30 

April 2021 

 

  



 

37 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

39 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.25 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.25 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 



 

40 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/008 28 capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

41 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.25 mg hard capsules 

fingolimod 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

  



 

42 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK CONTAINING SINGLE-UNIT-DOSE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.25 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.25 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 x 1 hard capsule 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 



 

43 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/007 7 x 1 hard capsule 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

44 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

SINGLE-UNIT-DOSE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.25 mg hard capsules 

fingolimod 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



 

45 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.5 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

98 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 



 

46 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/005 28 capsules 

EU/1/11/677/006 98 capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

47 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

  



 

48 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK – WALLET 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.5 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 hard capsules 

28 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

To open: While pressing tab 1 firmly, pull on tab 2. 

 

Week 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



 

49 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/002 7 capsules 

EU/1/11/677/003 28 capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 



 

50 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

51 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK CONTAINING WALLETS (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.5 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 84 (3 packs of 28) hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 



 

52 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/004 84 capsules (3 packs of 28) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

53 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK – WALLET (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.5 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

To open: While pressing tab 1 firmly, pull on tab 2. 

 

Week 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 



 

54 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/004 84 capsules (3 packs of 28) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



 

55 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS FOR WALLET 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg 

fingolimod 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

  



 

56 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK CONTAINING SINGLE-UNIT-DOSE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One capsule contains 0.5 mg fingolimod (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 x 1 hard capsule 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

Swallow each capsule whole 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store in the original package in order to protect from moisture. 

 

 



 

57 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/677/001 7 x 1 hard capsule 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

GILENYA 0.5 mg 

 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

58 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

SINGLE-UNIT-DOSE BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

GILENYA 0.5 mg hard capsules 

fingolimod 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



 

59 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



 

60 

Package leaflet: Information for the user 

 

Gilenya 0.25 mg hard capsules 

Gilenya 0.5 mg hard capsules 

fingolimod 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Gilenya is and what it is used for 

2. What you need to know before you take Gilenya 

3. How to take Gilenya 

4. Possible side effects 

5. How to store Gilenya 

6. Contents of the pack and other information 

 

1. What Gilenya is and what it is used for 

 

What Gilenya is 

Gilenya contains the active substance fingolimod. 

 

What Gilenya is used for 

Gilenya is used in adults and in children and adolescents (10 years of age and above) to treat 

relapsing-remitting multiple sclerosis (MS), more specifically in: 

- Patients who have failed to respond despite treatment with an MS treatment. 

or 

- Patients who have rapidly evolving severe MS. 

 

Gilenya does not cure MS, but it helps to reduce the number of relapses and to slow down the 

progression of physical disabilities due to MS. 

 

What is multiple sclerosis 

MS is a long-term condition that affects the central nervous system (CNS), comprised of the brain and 

spinal cord. In MS inflammation destroys the protective sheath (called myelin) around the nerves in 

the CNS and stops the nerves from working properly. This is called demyelination. 

 

Relapsing-remitting MS is characterised by repeated attacks (relapses) of nervous system symptoms 

that reflect inflammation within the CNS. Symptoms vary from patient to patient but typically involve 

walking difficulties, numbness, vision problems or disturbed balance. Symptoms of a relapse may 

disappear completely when the relapse is over, but some problems may remain. 

 

How Gilenya works 

Gilenya helps to protect against attacks on the CNS by the immune system by reducing the ability of 

some white blood cells (lymphocytes) to move freely within the body and by stopping them from 

reaching the brain and spinal cord. This limits nerve damage caused by MS. Gilenya also reduces 

some of the immune reactions of your body. 



 

61 

 

 

2. What you need to know before you take Gilenya 

 

Do not take Gilenya 

- if you have a lowered immune response (due to an immunodeficiency syndrome, a disease or 

to medicines that suppress the immune system). 

- if you have a severe active infection or active chronic infection such as hepatitis or 

tuberculosis. 

- if you have an active cancer. 

- if you have severe liver problems. 

- if, in the last 6 months, you have had heart attack, angina, stroke or warning of a stroke or 

certain types of heart failure. 

- if you have certain types of irregular or abnormal heartbeat (arrhythmia), including patients 

in whom the electrocardiogram (ECG) shows prolonged QT interval before starting Gilenya. 

- if you are taking or have recently taken medicine for irregular heartbeat such as quinidine, 

disopyramide, amiodarone or sotalol. 

- if you are pregnant or a woman of childbearing potential not using effective contraception. 

- if you are allergic to fingolimod or any of the other ingredients of this medicine (listed in 

section 6). 

If this applies to you or you are unsure, talk to your doctor before taking Gilenya. 

 

Warnings and precautions 

Talk to your doctor before taking Gilenya: 

- if you have severe breathing problems during sleep (severe sleep apnoea). 

- if you have been told you have an abnormal electrocardiogram. 

- if you suffer from symptoms of slow heart rate (e.g. dizziness, nausea, or palpitations). 

- if you are taking or have recently taken medicines that slow your heart rate (such as beta 

blockers, verapamil, diltiazem or ivabradine, digoxin, anticholinesteratic agents or pilocarpine). 

- if you have a history of sudden loss of consciousness or fainting (syncope). 

- if you plan to get vaccinated. 

- if you have never had chickenpox. 

- if you have or have had visual disturbances or other signs of swelling in the central vision 

area (macula) at the back of the eye (a condition known as macular oedema, see below), 

inflammation or infection of the eye (uveitis), or if you have diabetes (which can cause eye 

problems). 

- if you have liver problems. 

- if you have high blood pressure that cannot be controlled by medicines. 

- if you have severe lung problems or smoker’s cough. 

If any of these applies to you or you are unsure, talk to your doctor before taking Gilenya. 

 

Slow heart rate (bradycardia) and irregular heartbeat 

At the beginning of treatment or after taking the first dose of 0.5 mg when you switch from a 0.25 mg 

daily dose, Gilenya causes the heart rate to slow down. As a result, you may feel dizzy or tired, or be 

consciously aware of your heartbeat, or your blood pressure may drop. If these effects are severe, tell 

your doctor, because you may need treatment right away. Gilenya can also cause an irregular 

heartbeat, especially after the first dose. Irregular heartbeat usually returns to normal in less than one 

day. Slow heart rate usually returns to normal within one month. During this period, no clinically 

significant heart rate effects are usually expected. 

 



 

62 

Your doctor will ask you to stay at the surgery or clinic for at least 6 hours, with hourly pulse and 

blood pressure measurements, after taking the first dose of Gilenya or after taking the first dose of 

0.5 mg when you switch from a 0.25 mg daily dose, so that appropriate measures can be taken in the 

event of side effects that occur at the start of treatment. You should have an electrocardiogram 

performed prior to the first dose of Gilenya and after the 6-hour monitoring period. Your doctor may 

monitor your electrocardiogram continuously during that time. If after the 6-hour period you have a 

very slow or decreasing heart rate, or if your electrocardiogram shows abnormalities, you may need to 

be monitored for a longer period (at least 2 more hours and possibly overnight) until these have 

resolved. The same may apply if you are resuming Gilenya after a break in treatment, depending on 

both how long the break was and how long you had been taking Gilenya before the break. 

 

If you have, or if you are at risk for, an irregular or abnormal heartbeat, if your electrocardiogram is 

abnormal, or if you have heart disease or heart failure, Gilenya may not be appropriate for you. 

 

If you have a history of sudden loss of consciousness or decreased heart rate, Gilenya may not be 

appropriate for you. You will be evaluated by a cardiologist (heart specialist) to advise how you 

should start treatment with Gilenya, including overnight monitoring. 

 

If you are taking medicines that can cause your heart rate to decrease, Gilenya may not be appropriate 

for you. You will need to be evaluated by a cardiologist, who will check whether you can be switched 

to alternative medicine that does not decrease your heart rate in order to allow treatment with Gilenya. 

If such a switch is impossible, the cardiologist will advise how you should start treatment with 

Gilenya, including overnight monitoring. 

 

If you have never had chickenpox 

If you have never had chickenpox, your doctor will check your immunity against the virus that causes 

it (varicella zoster virus). If you are not protected against the virus, you may need a vaccination before 

you start treatment with Gilenya. If this is the case, your doctor will delay the start of treatment with 

Gilenya until one month after the full course of vaccination is completed. 

 

Infections 

Gilenya lowers the white blood cell count (particularly the lymphocyte count). White blood cells fight 

infection. While you are taking Gilenya (and for up to 2 months after you stop taking it), you may get 

infections more easily. Any infection that you already have may get worse. Infections could be serious 

and life-threatening. If you think you have an infection, have fever, feel like you have the flu, have 

shingles or have a headache accompanied by stiff neck, sensitivity to light, nausea, rash, and/or 

confusion or seizures (fits) (these may be symptoms of meningitis and/or encephalitis caused by a 

fungal or herpes viral infection), contact your doctor straight away, because it could be serious and 

life-threatening. 

 

If you believe your MS is getting worse (e.g. weakness or visual changes) or if you notice any new 

symptoms, talk to your doctor straight away, because these may be the symptoms of a rare brain 

disorder caused by infection and called progressive multifocal leukoencephalopathy (PML). PML is a 

serious condition that may lead to severe disability or death. Your doctor will consider performing an 

MRI scan to evaluate this condition and will decide whether you need to stop taking Gilenya. 

 

Human papilloma virus (HPV) infection, including papilloma, dysplasia, warts and HPV-related 

cancer, has been reported in patients treated with Gilenya. Your doctor will consider whether you need 

to have a vaccination against HPV before starting treatment. If you are a woman, your doctor will also 

recommend HPV screening. 

 

  



 

63 

Macular oedema 

Before you start Gilenya, if you have or have had visual disturbances or other signs of swelling in the 

central vision area (macula) at the back of the eye, inflammation or infection of the eye (uveitis) or 

diabetes, your doctor may want you to undergo an eye examination. 

 

Your doctor may want you to undergo an eye examination 3 to 4 months after starting Gilenya 

treatment. 

 

The macula is a small area of the retina at the back of the eye which enables you to see shapes, 

colours, and details clearly and sharply. Gilenya may cause swelling in the macula, a condition that is 

known as macular oedema. The swelling usually happens in the first 4 months of Gilenya treatment. 

 

Your chance of developing macular oedema is higher if you have diabetes or have had an 

inflammation of the eye called uveitis. In these cases your doctor will want you to undergo regular eye 

examinations in order to detect macular oedema. 

 

If you have had macular oedema, talk to your doctor before you resume treatment with Gilenya. 

 

Macular oedema can cause some of the same vision symptoms as an MS attack (optic neuritis). Early 

on, there may not be any symptoms. Be sure to tell your doctor about any changes in your vision. Your 

doctor may want you to undergo an eye examination, especially if: 

- the centre of your vision gets blurry or has shadows; 

- you develop a blind spot in the centre of your vision; 

- you have problems seeing colours or fine detail. 

 

Liver function tests 

If you have severe liver problems, you should not take Gilenya. Gilenya may affect your liver 

function. You will probably not notice any symptoms but if you notice yellowing of your skin 

or the whites of your eyes, abnormally dark urine (brown coloured), pain on the right side of 

your stomach area (abdomen), tiredness, feeling less hungry than usual or unexplained nausea 

and vomiting, tell your doctor straight away. 
If you get any of these symptoms after starting Gilenya, tell your doctor straight away. 

 

Before, during and after the treatment, your doctor will request blood tests to monitor your liver 

function. If your test results indicate a problem with your liver you may have to interrupt treatment 

with Gilenya. 

 

High blood pressure 

As Gilenya causes a slight elevation of blood pressure, your doctor may want to check your blood 

pressure regularly. 

 

Lung problems 

Gilenya has a slight effect on the lung function. Patients with severe lung problems or with smoker’s 

cough may have a higher chance of developing side effects. 

 

Blood count 

The desired effect of Gilenya treatment is to reduce the amount of white blood cells in your blood. 

This will usually go back to normal within 2 months of stopping treatment. If you need to have any 

blood tests, tell the doctor that you are taking Gilenya. Otherwise, it may not be possible for the doctor 

to understand the results of the test, and for certain types of blood test your doctor may need to take 

more blood than usual. 

 

Before you start Gilenya, your doctor will confirm whether you have enough white blood cells in your 

blood and may want to repeat a check regularly. In case you do not have enough white blood cells, 

you may have to interrupt treatment with Gilenya. 

 



 

64 

Posterior reversible encephalopathy syndrome (PRES) 

A condition called posterior reversible encephalopathy syndrome (PRES) has been rarely reported in 

MS patients treated with Gilenya. Symptoms may include sudden onset of severe headache, confusion, 

seizures and vision changes. Tell your doctor straight away if you experience any of these symptoms 

during your treatment with Gilenya, because it could be serious. 

 

Cancer 

Skin cancers have been reported in MS patients treated with Gilenya. Talk to your doctor straight 

away if you notice any skin nodules (e.g. shiny pearly nodules), patches or open sores that do not heal 

within weeks. Symptoms of skin cancer may include abnormal growth or changes of skin tissue (e.g. 

unusual moles) with a change in colour, shape or size over time. Before you start Gilenya, a skin 

examination is required to check whether you have any skin nodules. Your doctor will also carry out 

regular skin examinations during your treatment with Gilenya. If you develop problems with your 

skin, your doctor may refer you to a dermatologist, who after consultation may decide that it is 

important for you to be seen on a regular basis. 

 

A type of cancer of the lymphatic system (lymphoma) has been reported in MS patients treated with 

Gilenya. 

 

Exposure to the sun and protection against the sun 

Fingolimod weakens your immune system. This increases your risk of developing cancers, in 

particular skin cancers. You should limit your exposure to the sun and UV rays by: 

 wearing appropriate protective clothing. 

 regularly applying sunscreen with a high degree of UV protection. 

 

Unusual brain lesions associated with MS relapse 

Rare cases of unusually large brain lesions associated with MS relapse have been reported in patients 

treated with Gilenya. In case of severe relapse, your doctor will consider performing MRI to evaluate 

this condition and will decide whether you need to stop taking Gilenya. 

 

Switch from other treatments to Gilenya 

Your doctor may switch you directly from beta interferon, glatiramer acetate or dimethyl fumarate to 

Gilenya if there are no signs of abnormalities caused by your previous treatment. Your doctor may 

have to do a blood test in order to exclude such abnormalities. After stopping natalizumab you may 

have to wait for 2-3 months before starting treatment with Gilenya. To switch from teriflunomide, 

your doctor may advise you to wait for a certain time or to go through an accelerated elimination 

procedure. If you have been treated with alemtuzumab, a thorough evaluation and discussion with 

your doctor is required to decide if Gilenya is appropriate for you. 

 

Women of childbearing potential 

If used during pregnancy, Gilenya can harm the unborn baby. Before you start treatment with Gilenya 

your doctor will explain the risk to you and ask you to do a pregnancy test in order to ensure that you 

are not pregnant. Your doctor will give you a card which explains why you should not become 

pregnant while taking Gilenya. It also explains what you should do to avoid becoming pregnant while 

you are taking Gilenya. You must use effective contraception during treatment and for 2 months after 

stopping treatment (see section “Pregnancy and breastfeeding”). 

 

Worsening of MS after stopping Gilenya treatment 

Do not stop taking Gilenya or change your dose without talking to your doctor first. 

 

Tell your doctor straight away if you think your MS is getting worse after you have stopped treatment 

with Gilenya. This could be serious (see “If you stop taking Gilenya” in section 3, and also section 4, 

“Possible side effects”). 

 

  



 

65 

Elderly 

Experience with Gilenya in elderly patients (over 65 years) is limited. Talk to your doctor if you have 

any concerns. 

 

Children and adolescents 
Gilenya is not intended for use in children below 10 years old as it has not been studied in MS patients 

in this age group. 

 

The warnings and precautions listed above also apply to children and adolescents. The following 

information is particularly important for children and adolescents and their caregivers: 

- Before you start Gilenya, your doctor will check your vaccination status. If you have not had 

certain vaccinations, it may be necessary for you to be given them before Gilenya can be started. 

- The first time you take Gilenya, or when you switch from a 0.25 mg daily dose to a 0.5 mg daily 

dose, your doctor will monitor your heart rate and heartbeat (see “Slow heart rate (bradycardia) 

and irregular heartbeat” above). 

- If you experience convulsions or fits before or whilst taking Gilenya, let your doctor know. 

- If you suffer from depression or anxiety or if you become depressed or anxious while you are 

taking Gilenya, let your doctor know. You may need to be monitored more closely. 

 

Other medicines and Gilenya 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. Tell your doctor if you are taking any of the following medicines: 

 Medicines that suppress or modulate the immune system, including other medicines used 

to treat MS, such as beta interferon, glatiramer acetate, natalizumab, mitoxantrone, 

teriflunomide, dimethyl fumarate or alemtuzumab. You must not use Gilenya together with such 

medicines as this could intensify the effect on the immune system (see also “Do not take 

Gilenya”). 

 Corticosteroids, due to a possible added effect on the immune system. 

 Vaccines. If you need to receive a vaccine, seek your doctor’s advice first. During and for up to 

2 months after treatment with Gilenya, you should not receive certain types of vaccine (live 

attenuated vaccines) as they could trigger the infection that they were supposed to prevent. 

Other vaccines may not work as well as usual if given during this period. 

 Medicines that slow the heartbeat (for example beta blockers, such as atenolol). Use of 

Gilenya together with such medicines could intensify the effect on heartbeat in the first days 

after starting Gilenya. 

 Medicines for irregular heartbeat, such as quinidine, disopyramide, amiodarone or sotalol. 

You must not use Gilenya if you are taking such a medicine because it could intensify the effect 

on irregular heartbeat (see also “Do not take Gilenya”). 

 Other medicines: 

o protease inhibitors, anti-infectives such as ketoconazole, azole antifungals, clarithromycin 

or telithromycin. 

o carbamazepine, rifampicine, phenobarbital, phenytoin, efavirenz or St. John’s Wort 

(potential risk of reduced efficacy of Gilenya). 

 

  



 

66 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Pregnancy 

Do not use Gilenya during pregnancy, if you are trying to become pregnant or if you are a woman who 

could become pregnant and you are not using effective contraception. If Gilenya is used during 

pregnancy, there is a risk of harm to the unborn baby. The rate of congenital malformations observed 

in babies exposed to Gilenya during pregnancy is about 2 times the rate observed in the general 

population (in whom the rate of congenital malformations is about 2-3%). The most frequently 

reported malformations included cardiac, renal and musculoskeletal malformations. 

 

Therefore, if you are a woman of childbearing potential: 

- before you start treatment with Gilenya your doctor will inform you about the risk to an unborn 

baby and ask you to do a pregnancy test in order to ensure that you are not pregnant, 

and, 

- you must use effective contraception while taking Gilenya and for two months after you stop 

taking it to avoid becoming pregnant. Talk to your doctor about reliable methods of 

contraception. 

 

Your doctor will give you a card which explains why you should not become pregnant while taking 

Gilenya. 

 

If you do become pregnant while taking Gilenya, tell your doctor straight away. Your doctor will 

decide to stop treatment (see “If you stop taking Gilenya” in section 3, and also section 4, “Possible 

side effects”). Specialised pre-natal monitoring will be performed. 

 

Breast-feeding 

 

You should not breast-feed while you are taking Gilenya. Gilenya can pass into breast milk and 

there is a risk of serious side effects for the baby. 

 

Driving and using machines 

Your doctor will tell you whether your illness allows you to drive vehicles, including a bicycle, and 

use machines safely. Gilenya is not expected to have an influence on your ability to drive and use 

machines. 

 

However, at initiation of treatment you will have to stay at the doctor’s surgery or clinic for 6 hours 

after taking the first dose of Gilenya. Your ability to drive and use machines may be impaired during 

and potentially after this time period. 

 

 

  



 

67 

3. How to take Gilenya 
 

Treatment with Gilenya will be overseen by a doctor who is experienced in the treatment of multiple 

sclerosis. 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 

sure. 

 

The recommended dose is: 

 

Adults: 

The dose is one 0.5 mg capsule per day. 
 

Children and adolescents (10 years of age and above): 

The dose depends on body weight: 

 Children and adolescents with body weight equal to or below 40 kg: one 0.25 mg capsule per 

day. 

 Children and adolescents with body weight above 40 kg: one 0.5 mg capsule per day. 

Children and adolescents who start on one 0.25 mg capsule per day and later reach a stable body 

weight above 40 kg will be instructed by their doctor to switch to one 0.5 mg capsule per day. In this 

case, it is recommended to repeat the first-dose observation period. 

 

Do not exceed the recommended dose. 

 

Gilenya is for oral use. 

 

Take Gilenya once a day with a glass of water. Gilenya capsules should always be swallowed intact, 

without opening them. Gilenya can be taken with or without food. 

Taking Gilenya at the same time each day will help you remember when to take your medicine. 

 

If you have questions about how long to take Gilenya, talk to your doctor or your pharmacist. 

 

If you take more Gilenya than you should 

If you have taken too much Gilenya, call your doctor straight away. 

 

If you forget to take Gilenya 

If you have been taking Gilenya for less than 1 month and you forget to take 1 dose for a whole day, 

call your doctor before you take the next dose. Your doctor may decide to keep you under observation 

at the time you take the next dose. 

 

If you have been taking Gilenya for at least 1 month and have forgotten to take your treatment for 

more than 2 weeks, call your doctor before you take the next dose. Your doctor may decide to keep 

you under observation at the time you take the next dose. However, if you have forgotten to take your 

treatment for up to 2 weeks, you can take the next dose as planned. 

 

Never take a double dose to make up for a forgotten dose. 

 

  



 

68 

If you stop taking Gilenya 

Do not stop taking Gilenya or change your dose without talking to your doctor first. 

 

Gilenya will stay in your body for up to 2 months after you stop taking it. Your white blood cell count 

(lymphocyte count) may also remain low during this time and the side effects described in this leaflet 

may still occur. After stopping Gilenya you may have to wait for 6-8 weeks before starting a new MS 

treatment. 

 

If you have to restart Gilenya more than 2 weeks after you stop taking it, the effect on heart rate 

normally seen when treatment is first started may re-occur and you will need to be monitored at the 

doctor’s surgery or clinic for re-initiation of treatment. Do not restart Gilenya after stopping it for 

more than two weeks without seeking advice from your doctor. 

 

Your doctor will decide whether and how you need to be monitored after stopping Gilenya. Tell your 

doctor straight away if you think your MS is getting worse after you have stopped treatment with 

Gilenya. This could be serious. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Some side effects could be or could become serious 

Common (may affect up to 1 in 10 people) 

- Coughing with phlegm, chest discomfort, fever (signs of lung disorders) 

- Herpes virus infection (shingles or herpes zoster) with symptoms such as blisters, burning, 

itching or pain of the skin, typically on the upper body or the face. Other symptoms may be 

fever and weakness in the early stages of infection, followed by numbness, itching or red 

patches with severe pain 

- Slow heartbeat (bradycardia), irregular heart rhythm 

- A type of skin cancer called basal cell carcinoma (BCC) which often appears as a pearly nodule, 

although it can also take other forms 

- Depression and anxiety are known to occur with increased frequency in the MS population and 

have also been reported in paediatric patients treated with Gilenya. 

- Weight loss. 

 

Uncommon (may affect up to 1 in 100 people) 

- Pneumonia with symptoms such as fever, cough, difficulty breathing 

- Macular oedema (swelling in the central vision area of the retina at the back of the eye) with 

symptoms such as shadows or blind spot in the centre of the vision, blurred vision, problems 

seeing colours or details 

- Reduction in blood platelets which increases risk of bleeding or bruising 

- Malignant melanoma (a type of skin cancer which usually develops from an unusual mole). 

Possible signs of melanoma include moles which may change size, shape, elevation or colour 

over time, or new moles. The moles may itch, bleed or ulcerate 

- Convulsion, fits (more frequent in children and adolescents than in adults) 

 

  



 

69 

Rare (may affect up to 1 in 1,000 people) 

- A condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may 

include sudden onset of severe headache, confusion, seizures and/or vision disturbances 

- Lymphoma (a type of cancer that affects the lymph system) 

- Squamous cell carcinoma: a type of skin cancer which may present as a firm red nodule, a sore 

with crust, or a new sore on an existing scar 

 

Very rare (may affect up to 1 in 10,000 people) 

- Electrocardiogram anomaly (T-wave inversion) 

- Tumour related to infection with human herpes virus 8 (Kaposi’s sarcoma) 

 

Not known (frequency cannot be estimated from the available data) 

- Allergic reactions, including symptoms of rash or itchy hives, swelling of lips, tongue or face, 

which are more likely to occur on the day you start Gilenya treatment 

- Signs of liver disease (including liver failure), such as yellowing of your skin or the whites of 

your eyes (jaundice), nausea or vomiting, pain on the right side of your stomach area (abdomen), 

dark urine (brown coloured), feeling less hungry than usual, tiredness and abnormal liver 

function tests. In a very small number of cases, liver failure could lead to liver transplantation 

- Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). The 

symptoms of PML may be similar to an MS relapse. Symptoms might also arise that you might 

not become aware of by yourself, such as changes in mood or behaviour, memory lapses, speech 

and communication difficulties, which your doctor may need to investigate further to rule out 

PML. Therefore, if you believe your MS is getting worse or if you or those close to you notice 

any new or unusual symptoms, it is very important that you speak to your doctor as soon as 

possible 

- Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis with 

symptoms such as headache accompanied by stiff neck, sensitivity to light, nausea, and/or 

confusion 

- Merkel cell carcinoma (a type of skin cancer). Possible signs of Merkel cell carcinoma include 

flesh-coloured or bluish-red, painless nodule, often on the face, head or neck. Merkel cell 

carcinoma can also present as a firm painless nodule or mass. Long-term exposure to the sun 

and a weak immune system can affect the risk of developing Merkel cell carcinoma. 

- After Gilenya treatment is stopped, symptoms of MS can return and may become worse than 

they were before or during treatment. 

- Autoimmune form of anaemia (decreased amount of red blood cells) where red blood cells are 

destroyed (autoimmune haemolytic anaemia). 

 

If you experience any of these, tell your doctor straight away. 

 

Other side effects 

Very common (may affect more than 1 in 10 people) 

- Infection from flu virus with symptoms such as tiredness, chills, sore throat, aching in the joints 

or muscles, fever 

- Feeling of pressure or pain in the cheeks and forehead (sinusitis) 

- Headache 

- Diarrhoea 

- Back pain 

- Blood testing showing higher levels of liver enzymes 

- Cough 

 

  



 

70 

Common (may affect up to 1 in 10 people) 

- Ringworm, a fungal infection of the skin (tinea versicolor) 

- Dizziness 

- Severe headache often accompanied by nausea, vomiting and sensitivity to light (migraine) 

- Low level of white blood cells (lymphocytes, leucocytes) 

- Weakness 

- Itchy, red, burning rash (eczema) 

- Itching 

- Blood fat (triglycerides) level increased 

- Hair loss 

- Breathlessness 

- Depression 

- Blurred vision (see also the section on macular oedema under “Some side effects could be or 

could become serious”) 

- Hypertension (Gilenya may cause a mild increase in blood pressure) 

- Muscle pain 

- Joint pain 

 

Uncommon (may affect up to 1 in 100 people) 

- Low level of certain white blood cells (neutrophils) 

- Depressed mood 

- Nausea 

 

Rare (may affect up to 1 in 1,000 people) 

- Cancer of the lymphatic system (lymphoma) 

 

Not known (frequency cannot be estimated from the available data) 

- Peripheral swelling 

 

If any of these affects you severely, tell your doctor 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Gilenya 
 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton and blister foil after 

“EXP”. The expiry date refers to the last day of that month. 

Do not store above 25ºC. 

Store in the original package in order to protect from moisture. 

Do not use this medicine if you notice that the pack is damaged or shows signs of tampering. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help to protect the environment. 

 

 

  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

71 

6. Contents of the pack and other information 

 

What Gilenya contains 
- The active substance is fingolimod. 

 

Gilenya 0.25 mg hard capsules 

- Each capsule contains 0.25 mg fingolimod (as hydrochloride). 

- The other ingredients are: 

Capsule fill: mannitol, hydroxypropylcellulose, hydroxypropylbetadex, magnesium stearate. 

Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172). 

Printing ink: shellac (E904), black iron oxide (E172), propylene glycol (E1520), ammonia 

solution, concentrated (E527). 

 

Gilenya 0.5 mg hard capsules 

- Each capsule contains 0.5 mg fingolimod (as hydrochloride). 

- The other ingredients are: 

Capsule fill: mannitol, magnesium stearate. 

Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172). 

Printing ink: shellac (E904), ethanol anhydrous, isopropyl alcohol, butyl alcohol, propylene 

glycol (E1520), purified water, ammonia solution, concentrated (E527), potassium hydroxide, 

black iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), dimethicone. 

 

What Gilenya looks like and contents of the pack 

Gilenya 0.25 mg hard capsules have an ivory opaque body and cap. “FTY 0.25mg” is imprinted on the 

cap with black ink and a black radial band on the body. 

 

Gilenya 0.5 mg hard capsules have a white opaque body and bright yellow opaque cap. “FTY0.5mg” 

is imprinted on the cap with black ink and two bands are imprinted on the body with yellow ink. 

 

Gilenya 0.25 mg capsules are available in packs containing 7 or 28 capsules. Not all pack sizes may be 

marketed in your country. 

 

Gilenya 0.5 mg capsules are available in packs containing 7, 28 or 98 capsules or in multipacks 

containing 84 capsules (3 packs of 28 capsules). Not all pack sizes may be marketed in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

  



 

72 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



 

73 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

74 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX IV 

 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 

OF THE MARKETING AUTHORISATION(S) 



 

75 

Scientific conclusions 

 

Taking into account the PRAC Assessment Report on the PSUR for fingolimod, the scientific 

conclusions of CHMP are as follows: 

 

Data has been presented on liver injury requiring transplant from spontaneous reports, including one 

case with a close temporal relationship with fingolimod, and on herpes zoster/herpes simplex 

infections with fingolimod where 9 new cases of VZV infection with visceral or CNS dissemination 

and 3 new cases of Herpes simplex infection with visceral or CNS dissemination were reported, 

adding up to 50 and 20 cumulative cases, respectively. Among these 70 cumulative cases, there were 

20 cases of meningoencephalitis, 9 cases of encephalitis and 3 cases of meningitis. 

 

In view of these data, the PRAC agrees that the information should be reflected in the section 4.4 and 

4.8 of the SmPC and accordingly in sections 2 and 4 of the PL. 

 

The CHMP agrees with the scientific conclusions made by the PRAC. 

 

Grounds for the variation to the terms of the marketing authorisation(s) 

 

On the basis of the scientific conclusions for fingolimod the CHMP is of the opinion that the benefit-

risk balance of the medicinal product(s) containing fingolimod is unchanged subject to the proposed 

changes to the product information. 

 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)