- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of fingolimod.
Highly active relapsing and remitting MS after failure of prior therapy
Rapidly evolving severe relapsing remitting multiple sclerosis
Indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis in adults and children aged 10 years and older for:
Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy
Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by two or more disabling relapses in one year and with one or more gadolinium enhancing lesion on brain MRI or significant increase in T2 lesion load as compared to a previous recent MRI.
500micrograms once daily.
Children aged 10 years and older weighing less than or equal to 40kg
250micrograms once daily.
Children aged 10 years and older weighing greater than 40kg
500micrograms once daily.
Additional Dosage Information
Switching from another Disease Modifying Therapy
Beta-interferon or glatiramer acetate: Switch directly to fingolimod provided there are no signs of treatment related abnormalities.
Dimethyl fumarate: The washout period should be sufficient for complete blood count to recover before starting fingolimod.
Natalizumab: Elimination usually takes 2 to 3 months, caution is recommended due to concomitant immune effects when switching to fingolimod.
Teriflunomide: Elimination takes up to 2 years, washout period should be at least 3.5 months unless using accelerated washout procedure (for further details see relevant SPC), caution is recommended due to concomitant immune effects when switching to fingolimod.
Alemtuzumab: Switch to fingolimod is not recommended as duration of profound and prolonged immunosuppressive effects is unknown.
Children under 10 years
Concurrent ultraviolet light therapy
Decompensated cardiac failure
History of cardiac arrest
Long QT syndrome
New York Heart Association class III failure
Non-paced second degree atrioventricular block
Non-paced sinus node dysfunction
Non-paced third degree atrioventricular block
QTc interval greater than or equal to 500 msec
Serious cardiac arrhythmias
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Severe sleep apnoea
Sinoatrial exit block
Torsade de pointes
Transient ischaemic attack
Within 6 month of cerebrovascular accident
Within 6 months of a myocardial infarction
Precautions and Warnings
Children aged 10 to 12 years
Children with body weight under 40kg
Family history of long QT syndrome
Females of childbearing potential
History of immunosuppressant treatment
Patients over 65 years
Predisposition to syncope
Predisposition to uveitis
Chronic obstructive pulmonary disease
Congestive cardiac failure
History of hepatic impairment
History of myocardial infarction
History of torsade de pointes
Ischaemic heart disease
Mild hepatic impairment
QTc interval greater than 450 milliseconds in males
QTc interval greater than 460 milliseconds in female children
QTc interval greater than 470 milliseconds in female adults
Severe respiratory disease
Correct electrolyte disorders before treatment
Live virus vaccine should not be given for 2 months after treatment
Advise ability to drive/operate machinery may be affected by side effects
Before starting therapy ensure immunisations are up to date in children
Consider HPV vaccine before starting and continue related cancer screening
Female:Ensure information including a Patient Guide is received& understood
First dose may cause bradycardia and heart block
Monitoring of cardiovascular function essential after first dose
Perform skin examination prior to and every 6 to 12 months during treatment
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
A recent (within 3 months) MRI should be available prior to treatment
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure before starting treatment
Monitor hepatic function prior to treatment
Monitor serum transaminases before treatment
Perform ECG before treatment
Perform full blood count before treatment
Complete blood count should be done at month 3 then at least yearly
Consider monitoring ECG in patients at risk of QT prolongation
Extend monitoring if significant cardiac effects following first dose
If visual disturbances occur, perform ophthalmic evaluation
In cases of severe relapse, perform MRI to exclude tumefactive lesion
Increased monitoring required in patient at high risk of PML
Monitor bilirubin levels before treatment
Monitor blood pressure
Monitor blood pressure hourly for 6 hours after first dose
Monitor ECG for 6 hours after first dose
Monitor for JC virus antibodies before and six monthly during treatment
Monitor heart rate
Monitor hepatic function more frequently if AST/ALT between 3 and 5 x ULN
Monitor levels of hepatic enzymes and bilirubin
Monitor neurological function
Monitor ophthalmic function
Monitor patient closely during drug discontinuation for rebound effect
Monitor patients with cardiac disorders
Monitor serum electrolytes
Monitor transaminases/bilirubin at 1 month and every 3 months for 1 year
Monitor transaminases/bilirubin periodically until 2 months after treatment
Observe patient for at least 6 hours after first administration
Refer suspected myocardial ischaemia to a specialist
Refer suspicious skin lesions to a specialist
Regular pregnancy tests required during therapy
Repeat first dose monitoring following treatment interruption
Advise patient to report any blurred vision or any other eye symptoms
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report signs of basal-cell carcinoma
Advise patient to report symptoms of infection immediately
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
May reduce effectiveness of vaccinations during treatment
Risk of developing opportunistic infections
May affect results of some laboratory tests
Follow washout procedure when switching between disease modifying therapies
If treatment is stopped follow with a 6 week interval without therapy
Consider discontinuing if tumefactive lesion is suspected
Discontinue if AST/ALT between 3 to 5 x ULN and bilirubin is increased
Discontinue if macular oedema occurs
Discontinue if malignant lymphomas develop
Discontinue if meningitis or encephalitis occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if severe hepatic changes occur
Discontinue treatment if AST/ALT >5 times upper limit of normal
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Interrupt treatment if severe infection develops
Pregnancy confirmed: Discontinue this medication
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 2 months after treatment
Advise patient on possible rebound phenomena on withdrawal
Advise patient to avoid exposure to sunlight and UV rays during treatment
Give patient package leaflet and patient reminder card
For all patients, monitoring during the first 6 hours after first dose should include:
Pre-treatment ECG and blood pressure measurement before starting. During the first 6 hours of treatment Continuous ECG monitoring for 6 hours after first dose. Blood pressure and heart rate measurement every hour. After 6 hours of treatment ECG and blood pressure measurement. If heart rate at the end of the 6 hour period is at its lowest since fingolimod was first administered, monitoring should be extended by at least 2 hours and until heart rate increases.
In case of clinically important cardiac effects, monitoring should be extended (at least overnight) until resolved.
Criteria for extended monitoring
At any time during the 6 hour monitoring
Occurrence of symptomatic bradycardia.
New onset second degree atrioventricular block, Mobitz type II.
New onset third degree atrioventricular block.
At the 6 hour timepoint after the first dose
Heart rate less than 45 beats per minute in adults.
Heart rate less than 55 beats per minute in paediatric patients aged 12 years and over.
Heart rate less than 60 beats per minute in paediatric patients aged 10 to below 12 years.
New-onset second degree atrioventricular block, Mobitz type I or higher degree atrioventricular block.
QTc interval equal to or greater than 500 milliseconds.
Monitoring in patients requiring pharmacological intervention for symptoms related to bradycardia during first dose monitoring, should continue at least overnight and first dose monitoring should be repeated after the second dose.
Paediatric patients who start on 250microgram capsules and subsequently reach a stable body weight above 40 kg should be switched to 500microgram capsules. When switching from a 250microgram to 500microgram daily dose, it is recommended to repeat the same first dose monitoring as for treatment initiation.
First dose monitoring should be repeated in patients whose 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, repeated monitoring is not required and treatment should be continued with the next dose as planned.
If treatment is stopped, then a 6 week interval without therapy is required to clear fingolimod from the circulation. Starting other therapies during this time will result in concomitant exposure to fingolimod.
After discontinuation, lymphocyte counts progressively return to normal range within 1 to 2 months, therefore vigilance for infection should be continued throughout this period. Patients should be advised to report symptoms of infection during treatment, and for up to 2 months following discontinuation of treatment.
Ophthalmological evaluation is recommended in all patients every 3 to 4 months after treatment initiation. If visual disturbances occur, evaluation of the fundus, including the macula, should be carried out. Patients with history of uveitis and patients with diabetes mellitus are at increased risk of macular oedema. Ophthalmological evaluation prior to initiation and follow-up should be conducted.
If liver transaminases rise above 3 but less than 5 times the ULN without increase in serum bilirubin, more frequent monitoring should be instituted, including serum bilirubin and alkaline phosphatase (ALP) measurement to determine if further increases occur and to discern if an alternative aetiology of hepatic dysfunction is present. Treatment may be restarted after a benefit and risk assessment of the patient.
Cases of acute liver failure requiring liver transplant and clinically significant liver injury have been reported. Signs of liver injury, including elevated serum hepatic enzymes and total bilirubin, have occurred as early as ten days after first dose and reported after prolonged use.
Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.
Cases of cryptococcal meningitis have been reported in patients taking fingolimod, patients with signs and symptoms including headache accompanied by mental changes such as confusion, hallucinations and/or personality changes should undergo prompt evaluation. If cryptococcal meningitis is diagnosed fingolimod treatment should be suspended and appropriate treatment initiated.
Pregnancy and Lactation
Fingolimod is contraindicated during pregnancy.
The manufacturer states that fingolimod is associated with an increased risk of foetal malformations, including congenital heart disease. Renal and musculoskeletal abnormalities have also been reported. Fingolimod should be stopped 2 months before planning a pregnancy. Discontinue fingolimod if pregnancy occurs during treatment. Provide advice regarding the risk of harmful effects to the foetus associated with fingolimod treatment and perform ultrasonography examinations.
Fingolimod is contraindicated during breastfeeding.
Use of fingolimod when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of fingolimod in the breast milk, however presence in human breast milk is unknown.
Advise patient to avoid taking St John's wort concurrently.
Advise patient to report any signs of blurred vision or decreased visual acuity at any time, with particular attention to patients with diabetes mellitus and patients with history of uveitis.
Advise patient to report infection (such as meningitis or encephalitis) symptoms during therapy and for up to two months following discontinuation of therapy.
Advise patient to report signs of hepatic dysfunction e.g. malaise, jaundice, dark urine or abdominal pain. Advise patient to report any severe headache, nausea, vomiting, altered mental status, visual disturbances and seizures. Advise patient to report signs of basal-cell carcinoma.
Women of childbearing potential must use effective contraception during and up to 2 months after treatment. Provide pregnancy specific Patient Guide.
Advise patients not to drive or operate machinery if affected by side effects such as dizziness or drowsiness.
Abnormal liver function tests
Acute hepatic failure
Alanine aminotransferase increased
Aspartate aminotransferase increased
Basal cell carcinoma
Gamma glutamyl transferase (GGT) increased
Immune related haemolytic anaemia
Inversion of T wave
Peripheral vascular disorders
Posterior reversible encephalopathy syndrome (PRES)
Progressive multifocal leukoencephalopathy (PML)
Reduced neutrophil count
Squamous cell carcinoma
Effects on Laboratory Tests
Fingolimod reduces blood lymphocyte counts via re-distribution in secondary lymphoid organs therefore peripheral blood lymphocyte counts cannot be utilised to evaluate the lymphocyte subset status of a patient treated with fingolimod. Laboratory tests involving the use of circular mononuclear cells require larger blood volumes due to reduction in the number of circulating lymphocytes.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: June 2019
Summary of Product Characteristics: Gilenya 0.25mg tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2020.
Summary of Product Characteristics: Gilenya 0.5mg tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2020.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 September 2019
Already a member? Log in
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.