FINGOLIMOD SANDOZ

What it is

FINGOLIMOD is available as 0.25 mg and 0.5 mg hard capsules, each containing fingolimod hydrochloride.

Approved indications

— Treatment of adult and paediatric patients of 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 FINGOLIMOD is one 0.5 mg capsule taken orally once daily. In paediatric patients aged 10 years and above, the recommended dose depends on body weight: paediatric patients with body weight ≤40 kg receive one 0.25 mg capsule daily, whilst paediatric patients with body weight >40 kg receive one 0.5 mg capsule daily. FINGOLIMOD can be taken with or without food. On initiation of FINGOLIMOD treatment, all patients are recommended to be observed with hourly pulse and blood pressure measurement for 6 hours for signs and symptoms of bradycardia, with an electrocardiogram performed prior to dosing and at the end of the 6-hour monitoring period.

Key safety warnings

FINGOLIMOD causes a dose-dependent reduction in peripheral lymphocyte count and may 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, and cryptococcal meningitis may be fatal, so patients with symptoms consistent with cryptococcal infections should undergo prompt diagnostic evaluation. Cases of progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by JC virus which may be fatal or result in severe disability, have been reported after approximately 2–3 years of treatment. Physicians should be vigilant for clinical symptoms or MRI findings suggestive of PML, and if PML is suspected, FINGOLIMOD treatment should be suspended until PML has been excluded. Initiation of fingolimod treatment results in a decrease in heart rate starting within an hour of the first dose and maximal within 6 hours, averaging approximately 8 beats per minute for the 0.5 mg dose. Initiation has been associated with atrio-ventricular conduction delays, with second-degree atrio-ventricular blocks observed in less than 0.5% of patients, typically transient and asymptomatic, usually not requiring treatment and resolving within 24 hours. Increased liver enzymes, mostly alanine aminotransaminase (ALT) elevation, have been reported, with 3-fold or greater elevation 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 fingolimod in the post-market setting including cases of acute liver failure requiring liver transplant. Macular oedema can occur with or without visual symptoms, and an ophthalmologic evaluation should be performed before starting FINGOLIMOD and at 3–4 months after treatment initiation. Patients with diabetes mellitus or a history of uveitis are at increased risk of macular oedema and should undergo ophthalmologic evaluation prior to initiating therapy and have regular follow-up evaluations. Skin cancers including basal cell carcinoma, malignant melanoma, squamous cell carcinoma, Kaposi's sarcoma and Merkel cell carcinoma have been reported in patients receiving fingolimod, and patients should be cautioned against exposure to sunlight without protection. Cases of severe exacerbation of disease have been reported after stopping fingolimod, generally observed within 12 weeks after stopping but also reported up to and beyond 24 weeks after discontinuation.

Contraindications

FINGOLIMOD 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. FINGOLIMOD is contraindicated in patients with 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. FINGOLIMOD is contraindicated in patients with baseline QTc interval ≥500 ms and in those receiving concomitant treatment with Class Ia or Class III anti-arrhythmic drugs during FINGOLIMOD initiation. FINGOLIMOD should not be administered to patients with known hypersensitivity to fingolimod or any of the excipients.

Regulatory history

FINGOLIMOD was first listed on the ARTG on 9 September 2020, with three registered variants (FINGOLIMOD RAN, FINGOLIMOD RBX, and FINGOLIMOD SUN), each containing fingolimod 500 microgram capsules.