Formulary
Fingolimod: Indications, Dosing, Side Effects and Interactions
Fingolimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the...
MedNext Academy | 8 min read
Fingolimod: Indications, Dosing, Side Effects and Interactions
Fingolimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the...
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.
Indications and dose
**Multiple sclerosis (initiated by a specialist)**
- **Adult** (By Mouth): 500 micrograms once daily.
**Multiple sclerosis (initiated by a specialist) for fingolimod**
- **Child 10-17 years (body-weight up to 40 kg)** (By mouth): 250 micrograms once daily.
- **Child 10-17 years (body-weight 40 kg and above)** (By mouth): 500 micrograms once daily.
Cautions
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.
Contraindications
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; heart failure in the previous 6 months (New York Heart Association class III/IV); increased risk for opportunistic infections (including immunosuppression); myocardial infarction in the previous 6 months; seconddegree Mobitz type II atrioventricular block or thirddegree AV block, or sicksinus 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
Side effects
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; hepatic disorders; 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.
Interactions
**Other interactions (15):**
- 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.
- Vaccination During and for up to two months after treatment with fingolimod vaccination may be less effective.
- 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...
- Treatment with fingolimod 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...
Pregnancy
Important safety information For fingolimod 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 contraindications 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 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 contraindication 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. MHRA/CHM advice: Fingolimod ( Gilenya ): updated advice about the risks of serious liver injury and herpes meningoencephalitis (January 2021) A European review of safety data identified 7 cases of clinically significant liver injury that developed between 10 days and 5 years of starting fingolimod, including 3 reports of acute hepatic failure requiring liver transplantation. The guidance for monitoring liver function and criteria for discontinuation have been strengthened to minimise the risks of liver injury. Liver function tests including serum bilirubin should be performed before starting and during treatment at months 1, 3, 6, 9, and 12, then periodically thereafter until 2 months after discontinuation. In the absence of clinical symptoms, if liver transaminases (AST or ALT) exceed: 3 times the upper limit of normal (ULN) but less than 5 times the ULN without increase in serum bilirubin, liver function tests should be monitored more frequently; 5 times the ULN or at least 3 times the ULN with any increase in serum bilirubin, fingolimod should be discontinued; treatment may be restarted when serum levels have returned to normal, after careful benefit-risk assessment of the underlying cause. In the presence of clinical symptoms suggestive of hepatic dysfunction, liver function tests should be checked promptly and fingolimod discontinued if significant liver injury is confirmed; further treatment may be restarted after recovery, only if an alternative cause of hepatic dysfunction is established. The review also considered reported cases of herpes zoster/herpes simplex infections with visceral or CNS dissemination (e.g. herpes meningoencephalitis), some of which were fatal. Healthcare professionals are reminded to continue to be vigilant for infections with fingolimod. Patients should be advised to seek urgent medical attention if they develop any signs or symptoms of liver injury or brain infection (during fingolimod treatment and for 8 weeks after the last dose in the case of the latter).
Breast feeding
Avoid.
Hepatic impairment
Manufacturer advises caution when initiating treatment in mild to moderate impairment; avoid in severe impairment.
Medicinal forms
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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