FYNEFTA

What it is

FYNEFTA is fingolimod hydrochloride available in 0.25 mg and 0.5 mg hard capsules.

Approved indications —

Relapsing forms of multiple sclerosis in adult and paediatric patients aged 10 years and above, to reduce the frequency of relapses and to delay the progression of disability.

Dosing overview

In adults, the recommended dose is one 0.5 mg capsule taken orally once daily. In paediatric patients aged 10 years and above, the dose depends on body weight: one 0.25 mg capsule daily for those weighing 40 kg or less, and one 0.5 mg capsule daily for those weighing more than 40 kg. FYNEFTA can be taken with or without food. On initiation of FYNEFTA treatment, all patients should be observed with hourly pulse and blood pressure measurement for 6 hours after the first dose for signs and symptoms of bradycardia, and should have an electrocardiogram performed prior to dosing and at the end of the 6-hour monitoring period.

Key safety warnings

**Infections.** FYNEFTA causes a dose-dependent reduction in peripheral lymphocyte count to 20–30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues, 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 after approximately 2–3 years of treatment, and cryptococcal meningitis may be fatal; patients with symptoms and signs consistent with cryptococcal infections should undergo prompt diagnostic evaluation. Cases of progressive multifocal leukoencephalopathy (PML) have been reported after approximately 2–3 years of treatment; PML is an opportunistic infection caused by JC virus which may be fatal or result in severe disability. **Bradyarrhythmia.** Initiation of fingolimod treatment results in a decrease in heart rate, with the decrease starting within an hour of the first dose and reaching maximum within 6 hours. In patients receiving FYNEFTA 0.5 mg, the decrease in heart rate averages approximately 8 beats per minute. Some patients experienced mild to moderate symptoms, including hypotension, dizziness, fatigue, and/or palpitations. **Macular oedema.** Macular oedema can occur with or without visual symptoms, and an ophthalmologic evaluation should be performed before starting FYNEFTA and at 3–4 months after treatment initiation. Patients with diabetes mellitus or a history of uveitis are at increased risk of macular oedema. **Liver function.** Increased liver enzymes, mostly alanine aminotransaminase (ALT) elevation, have been reported in multiple sclerosis patients treated with fingolimod, with 3-fold or greater elevation in liver transaminases occurring in 8.5% of patients treated with FYNEFTA 0.5 mg. 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. **Skin cancers.** 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. Periodic skin examination is recommended for all patients, and healthcare professionals and patients are advised to monitor for suspicious skin lesions before initiating treatment and regularly during treatment with FYNEFTA. **Rebound disease activity.** 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 fingolimod discontinuation.

Contraindications

FYNEFTA 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. It 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. FYNEFTA 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 FYNEFTA initiation. FYNEFTA should not be administered to patients with known hypersensitivity to fingolimod or any of the excipients.

PBS listing

Information regarding PBS listing, strength(s) listed, item count, restriction type, and ex-manufacturer price is not provided in the source documents.

Regulatory history

FYNEFTA fingolimod 0.5 mg capsule was first listed on the ARTG on 1 February 2011, and the 0.25 mg capsule variant was first listed on 12 April 2019. The TGA approved fingolimod on 19 January 2011 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.