FILOSIR

What it is

FILOSIR is a medicine containing the active ingredient fingolimod. Fingolimod is a sphingosine 1-phosphate receptor modulator. Fingolimod is metabolised by sphingosine kinase to the active metabolite fingolimod-phosphate, which binds to sphingosine 1-phosphate receptors located on lymphocytes and neural cells in the central nervous system.

Approved indications

— Treatment of adult and paediatric patients 10 years of age and above with relapsing forms of multiple sclerosis to reduce the frequency of relapses and to delay the progression of disability.

Dosing overview

In adults the recommended dose of FILOSIR 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 receive one 0.25 mg capsule daily taken orally, and paediatric patients with body weight > 40 kg receive one 0.5 mg capsule daily taken orally. On initiation of FILOSIR treatment, after the first dose, it is recommended that all patients be observed, with hourly pulse and blood pressure measurement, for a period of 6 hours for signs and symptoms of bradycardia, and all patients should have an electrocardiogram performed prior to dosing and at the end of the 6-hour monitoring period.

Key safety warnings

FILOSIR causes a dose-dependent reduction in peripheral lymphocyte count to 20–30% of baseline values and may therefore increase the risk of infections, including opportunistic infections, some serious in nature. Cases of cryptococcal infections, including cryptococcal meningitis, have been reported in the post-marketing setting after approximately 2–3 years of treatment, and cryptococcal meningitis may be fatal. Cases of progressive multifocal leukoencephalopathy have been reported in the post-marketing setting; PML is an opportunistic infection caused by JC virus which may be fatal or result in severe disability, and has occurred after approximately 2–3 years of treatment. Initiation of FILOSIR treatment results in a decrease in heart rate, with the decrease starting within an hour of the first dose and being maximal within 6 hours. Initiation of FILOSIR treatment has been associated with atrio-ventricular conduction delays, usually as first-degree atrio-ventricular blocks, and second-degree atrio-ventricular blocks, usually Mobitz type I, have been observed in less than 0.5% of patients receiving fingolimod 0.5 mg in clinical trials. Increased liver enzymes, mostly alanine aminotransaminase elevation, have been reported in multiple sclerosis patients treated with FILOSIR, with 3-fold or greater elevation in liver transaminases occurring in 8.5% of patients treated with fingolimod 0.5 mg during clinical trials. Clinically significant liver injury has been reported in patients treated with FILOSIR in the post-market setting including cases of acute liver failure requiring liver transplant. Rare cases of posterior reversible encephalopathy syndrome have been reported, with symptoms including sudden onset of severe headache, nausea, vomiting, altered mental status, visual disturbances and seizure, which may evolve into ischaemic stroke or cerebral haemorrhage. Cases of severe exacerbation of disease have been reported after stopping fingolimod in the post-marketing setting, generally observed within 12 weeks after stopping fingolimod, but also reported up to and beyond 24 weeks after fingolimod discontinuation.

Contraindications

FILOSIR is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalisation or Class III/IV heart failure; those with a history or presence of Mobitz Type II second-degree or third-degree atrioventricular block or sick sinus syndrome, unless the patient has a functioning pacemaker; those with a baseline QTc interval ≥ 500 ms; and those receiving concomitant treatment with Class Ia or Class III anti-arrhythmic drugs during FILOSIR initiation. FILOSIR should not be administered to patients with known hypersensitivity to fingolimod or any of the excipients.

PBS listing

No information regarding PBS listing is available in the provided source documents.

Regulatory history

FILOSIR fingolimod 0.5 mg capsule was first listed on the ARTG on 2011-02-01. The TGA approval date was 2011-01-19 for the treatment of Relapsing Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis with superimposed relapses to delay the progression of physical disability and reduce the frequency of relapse. FILOSIR fingolimod 0.25 mg capsule was first listed on the ARTG on 2019-04-12. FILOSIR is subject to additional monitoring in Australia, which will allow quick identification of new safety information.