Drug Action
Fingolimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the central nervous system.
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Drug reference
Fingolimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the central nervous system.
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Multiple sclerosis (initiated by a specialist) ▶BY MOUTH ▶Adult: 500 micrograms once daily
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Heart failure in the previous 6 months (New York Heart Association class III/IV). active malignancies. baseline QTc interval 500 milliseconds or greater. cerebrovascular disease (including transient ischaemic attack) in the previous 6 months. decompensated heart failure (requiring inpatient treatment) in the previous 6 months. increased risk for opportunistic infections (including immunosuppression). myocardial infarction in the previous 6 months. second- degree Mobitz type II atrioventricular block or third- degree AV block, or sick-sinus syndrome, if the patient does not have a pacemaker. severe active infection. severe cardiac arrhythmias requiring treatment with class Ia or class III anti-arrhythmic drugs. unstable angina in the previous 6 months
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Check varicella zoster virus status—consult product literature for further information. chronic obstructive pulmonary disease. elderly (limited information available). history of myocardial infarction. history of symptomatic bradycardia or recurrent syncope. patients receiving anti-arrhythmic or heart-rate lowering drugs, including beta-blockers and heart rate-lowering calcium-channel blockers (seek advice from cardiologist regarding switching to alternative drugs, or appropriate monitoring if unable to switch). pulmonary fibrosis. severe respiratory disease. severe sleep apnoea. significant QT prolongation (QTc greater than 470 milliseconds in women, or QTc greater than 450 milliseconds in men); if QTc 500 milliseconds or greater—see Contra-indications. susceptibility to QT- interval prolongation (including electrolyte disturbances). uncontrolled hypertension CAUTIONS, FURTHER INFORMATION ▶Washout period A washout period is recommended when switching treatment from some disease modifying therapies—consult product literature for further information. ▶Bradycardia and cardiac rhythm disturbance Fingolimod may cause transient bradycardia, atrioventricular conduction delays and heart block after the first dose. Fingolimod is not recommended in patients with the cardiovascular risks listed above unless the anticipated benefits outweigh the potential risks, and advice from a cardiologist (including monitoring advice) is sought before initiation.
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The manufacturer of Gilenya ® has provided a Prescriber’s checklist.
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NICE decisions ▶Fingolimod for the treatment of highly active relapsing- remitting multiple sclerosis (April 2012) NICE TA254 Fingolimod is recommended as an option for the treatment of highly active relapsing-remitting multiple sclerosis in adults, only if: . they have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with interferon beta, and . the manufacturer provides fingolimod with the discount agreed as part of the patient access scheme Patients currently receiving fingolimod whose disease does not meet the above criteria should be able to continue treatment until they and their clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta254 Scottish Medicines Consortium (SMC) decisions The Scottish Medicines Consortium has advised (September 2012) that fingolimod (Gilenya ®) is accepted for restricted use within NHS Scotland as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis despite treatment with interferon beta, with an unchanged or increased relapse rate or ongoing severe relapses, as compared to the previous year. This advice is contingent upon the continuing availability of the patient Immune system and malignant disease access scheme in NHS Scotland. The Scottish Medicines Consortium has advised (October 2014) that fingolimod (Gilenya ®) is accepted for restricted use within NHS Scotland as a single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis for adults with rapidly-evolving severe relapsing- remitting multiple sclerosis. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland, or a list price that is equivalent or lower. The Scottish Medicines Consortium has advised (April 2015) that fingolimod (Gilenya ®) is accepted for use within NHS Scotland as a single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis for adults with high disease activity despite treatment with at least one disease-modifying therapy. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland, or a list price that is equivalent or lower. All Wales Medicines Strategy Group (AWMSG) decisions The All Wales Medicines Strategy Group has advised (January 2017) that fingolimod (Gilenya ®) is recommended as an option for use within NHS Wales as a single disease- modifying therapy in highly active relapsing-remitting multiple sclerosis only in patients with rapidly-evolving severe relapsing-remitting multiple sclerosis defined by 2 or more disabling relapses in 1 year and with 1 or more gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) or a significant increase in T2 lesion load compared with a previous recent MRI, only if the manufacturer provides fingolimod with the discount agreed as part of the patient access scheme or where the list price is equivalent or lower. NHS restrictions NHS England Clinical Commissioning Policy NHS England (May 2014) has provided guidance on the use of fingolimod for the treatment of multiple sclerosis in England. An NHS England Clinical Commissioning Policy outlines the funding arrangements and the criteria for initiating and discontinuing this treatment option, see www.england.nhs. uk/commissioning/spec-services/npc-crg/group-d/d04/.
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MHRA/CHM ADVICE: FINGOLIMOD—NOT RECOMMENDED FOR PATIENTS AT KNOWN RISK OF CARDIOVASCULAR EVENTS. ADVICE FOR EXTENDED MONITORING FOR THOSE WITH SIGNIFICANT BRADYCARDIA OR HEART BLOCK AFTER THE FIRST DOSE AND FOLLOWING TREATMENT INTERRUPTION (JANUARY 2013) Fingolimod is known to cause transient bradycardias and heart block after the first dose—see Cautions, Contra- indications, and Monitoring for further information. MHRA/CHM ADVICE: FINGOLIMOD: NEW CONTRA-INDICATIONS IN RELATION TO CARDIAC RISK (DECEMBER 2017) Fingolimod can cause persistent bradycardia, which can increase the risk of serious cardiac arrhythmias. New contra-indications have been introduced for patients with pre-existing cardiac disorders—see Contra- indications for further information. MHRA/CHM ADVICE: MULTIPLE SCLEROSIS THERAPIES: SIGNAL OF REBOUND EFFECT AFTER STOPPING OR SWITCHING THERAPY (APRIL 2017) A signal of rebound syndrome in multiple sclerosis patients whose treatment with fingolimod was stopped or switched to other treatments has been reported in two recently published articles. The MHRA advise to be vigilant for such events and report any suspected adverse effects relating to fingolimod, or other treatments for multiple sclerosis, via the Yellow Card Scheme, while this report is under investigation. MHRA/CHM ADVICE: FINGOLIMOD: UPDATED ADVICE ABOUT RISK OF CANCERS AND SERIOUS INFECTIONS (DECEMBER 2017) Fingolimod has an immunosuppressive effect and can increase the risk of skin cancers and lymphoma. Following a recent EU review, the MHRA has recommended the following strengthened warnings: . re-assess the benefit-risk balance of fingolimod therapy in individual patients, particularly those with additional risk factors for malignancy—either closely monitor for skin cancers or consider discontinuation on a case-by-case basis . examine all patients for skin lesions before they start fingolimod and then re-examine at least every 6 to 12 months . advise patients to protect themselves against UV radiation exposure and seek urgent medical advice if they notice any skin lesions Immune system and malignant disease . refer patients with suspicious lesions to a dermatologist Fingolimod has also been associated with risk of fatal fungal infections and reports of progressive multifocal leukoencephalopathy (PML)—see Monitoring and Side effects for further information. MHRA/CHM ADVICE: FINGOLIMOD (GILENYA ®): INCREASED RISK OF CONGENITAL MALFORMATIONS; NEW CONTRA-INDICATION DURING PREGNANCY AND IN WOMEN OF CHILDBEARING POTENTIAL NOT USING EFFECTIVE CONTRACEPTION (SEPTEMBER 2019) An increased risk of major congenital malformations, including cardiac, renal, and musculoskeletal defects, has been associated with the use of fingolimod in pregnancy. Females of childbearing potential must use effective contraception during, and for 2 months after stopping, treatment. Healthcare professionals are advised that fingolimod is contra-indicated in pregnancy and that female patients should be informed of the risk of congenital malformations and given a pregnancy- specific patient reminder card. Pregnancy should be excluded before starting treatment, and pregnancy testing repeated at suitable intervals during treatment. Fingolimod should be stopped 2 months before planning a pregnancy. If a female taking fingolimod becomes pregnant, treatment should be stopped immediately, and the patient referred to an obstetrician for close monitoring. Exposed pregnancies should be enrolled on the pregnancy registry.
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→Appendix 1: fingolimod
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▶Common or very common Alopecia. arthralgia. asthenia. atrioventricular block. back pain. bradycardia. cough. decreased leucocytes. depression. diarrhoea. dizziness. dyspnoea. headaches. hypertension. increased risk of infection. myalgia. neoplasms. skin reactions. vision blurred. weight decreased ▶Uncommon Macular oedema. nausea. seizures. thrombocytopenia ▶Rare or very rare Posterior reversible encephalopathy syndrome (PRES) ▶Frequency not known Autoimmune haemolytic anaemia. haemophagocytic lymphohistiocytosis. peripheral oedema . progressive multifocal leukoencephalopathy (PML) SIDE-EFFECTS, FURTHER INFORMATION Basal-cell carcinoma Patients should be advised to seek medical advice if they have any signs of basal-cell carcinoma including skin nodules, patches or open sores that do not heal within weeks. Progressive multifocal leukoencephalopathy (PML) and other opportunistic infections Patients should be advised to seek medical attention if they have any signs of PML or any other infections. Suspension of treatment should be considered if a patient develops a severe infection, taking into consideration the risk-benefit.
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Manufacturer advises females of childbearing potential should use effective contraception during treatment and for 2 months after last treatment—see Important safety information for further information.
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Manufacturer advises avoid—teratogenic.
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Avoid.
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Manufacturer advises caution when initiating treatment in mild to moderate impairment; avoid in severe impairment.
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▶All patients receiving fingolimod should be monitored at treatment initiation, (first dose monitoring—before, during and after dose), and after treatment interruption (see note below); monitoring should include: ▶Pre-treatment . an ECG and blood pressure measurement before starting ▶During the first 6 hours of treatment . continuous ECG monitoring for 6 hours . blood pressure and heart rate measurement every hour ▶After 6 hours of treatment . a further 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. ▶If post-dose bradyarrhythmia-related symptoms occur, appropriate clinical management should be initiated and monitoring should be continued until the symptoms have resolved. If pharmacological intervention is required during the first-dose monitoring, overnight monitoring should follow, and the first-dose monitoring should then be repeated after the second dose. ▶If after 6 hours, the heart rate is less than 45 beats per minute, or the ECG shows new onset second degree or higher grade AV block, or a QTc interval of 500 milliseconds or greater, monitoring should be extended (at least overnight, until side-effect resolution). ▶The occurrence at any time of third degree AV block requires extended monitoring (at least overnight, until side-effect resolution). ▶In case of T-wave inversion, ensure there are no associated signs or symptoms of myocardial ischaemia—if suspected seek advice from a cardiologist. ▶Note ▶First dose monitoring as above should be repeated in all 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, treatment should be continued with the next dose as planned. ▶Manufacturer advises eye examination recommended 3–4 months after initiation of treatment (and before initiation of treatment in patients with diabetes or history of uveitis). ▶Manufacturer advises skin examination for skin lesions before starting treatment and then every 6 to 12 months thereafter or as clinically indicated. ▶Monitor hepatic transaminases before treatment, then every 3 months for 1 year, then periodically thereafter. ▶Monitor full blood count before treatment, at 3 months, then at least yearly thereafter and if signs of infection (interrupt treatment if lymphocyte count reduced)— consult product literature. ▶Monitor for signs and symptoms of haemophagocytic syndrome (including pyrexia, asthenia, hepato- splenomegaly and adenopathy—may be associated with hepatic failure and respiratory distress; also progressive cytopenia, elevated serum-ferritin concentrations, hypertriglyceridaemia, hypofibrinogenaemia, coagulopathy, hepatic cytolysis, hyponatraemia)—initiate treatment immediately. ▶Manufacturer advises to monitor routine MRI for lesions suggestive of progressive multifocal leukoencephalopathy (PML), particularly in patients considered at increased risk; monitor for signs and symptoms of new neurological dysfunction.
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There can be variation in the licensing of different medicines containing the same drug. Capsule ▶Gilenya (Novartis Pharmaceuticals UK Ltd) A Fingolimod (as Fingolimod hydrochloride) 250 microgram Gilenya 0.25mg capsules | 28 capsule P £1,470.00 Fingolimod (as Fingolimod hydrochloride) 500 microgram Gilenya 0.5mg capsules | 7 capsule P £367.50 | 28 capsule P £1,470.00 DT = £1,470.00
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Patient reminder card Patients should be given a patient reminder card. Female patients of childbearing potential should also be given a pregnancy-specific patient reminder card.
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500 micrograms once daily
First-line fragment. Read the complete Indications and Dose section above.
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