Gilenya

Fingolimod HCl

Single disease-modifying therapy for adult patients & paed patients ≥10 yr w/ highly active relapsing-remitting multiple sclerosis despite full & adequate course of treatment w/ at least 1 disease-modifying therapy; or w/ rapidly evolving severe relapsing-remitting multiple sclerosis defined by ≥2 disabling relapses in 1 yr, & w/ ≥1 Gadolinium-enhancing lesions on brain MRI or significant increase in T2 lesion load as compared to previous recent MRI.

Adult 0.5 mg once daily. Paed patient ≥10 yr weighing >40 kg 0.5 mg once daily, weighing ≤40 kg 0.25 mg once daily. Paed patients who start on 0.25 mg cap & subsequently reach a stable body wt >40 kg should be switched to 0.5 mg cap.

May be taken with or without food: Swallow whole, do not open cap.

Hypersensitivity. Immunodeficiency syndrome. Patients w/ increased risk for opportunistic infections, including immunocompromised patients. Severe active infections, active chronic infections eg, hepatitis, TB. Active malignancies. Patients who, in the previous 6 mth, had MI, unstable angina pectoris, stroke/transient ischaemic attack, decompensated heart failure (requiring inpatient treatment), or NYHA class III/IV heart failure. Patients w/ severe cardiac arrhythmias requiring anti-arrhythmic treatment w/ class Ia or III anti-arrhythmic medicinal products; 2nd degree Mobitz type II AV block or 3rd degree AV block, or sick sinus syndrome, w/o pacemaker; baseline QTc interval ≥500 msec. Severe liver impairment (Child-Pugh class C). Women of childbearing potential not using effective contraception. Pregnancy.

Risk of bradyarrhythmia, QTc interval prolongation, & BP effects. Measure ECG & BP prior to & 6 hr after the 1st dose of Gilenya. Regularly monitor BP during treatment. Do not use in patients w/ SA heart block, history of symptomatic bradycardia, recurrent syncope or cardiac arrest, significant QT prolongation, uncontrolled HTN, or severe sleep apnoea. Risk of infections (herpes viral infection, cryptococcal meningitis, progressive multifocal leukoencephalopathy, HPV infection). Assess CBC before treatment initiation, periodically during treatment, at mth 3, & at least yrly thereafter, & in case of signs of infection. Delay treatment initiation in patients w/ severe active infection until resolution. A full course of vaccination w/ varicella vaccine for Ab -ve patients is recommended prior to commencing Gilenya treatment, w/ treatment initiation being postponed for 1 mth to allow full effect of vaccination to occur. Consider vaccination against HPV prior to treatment initiation. Reports of macular oedema w/ or w/o visual symptoms, w/ risk being increased in patients w/ DM & history of uveitis. Reports of increased hepatic enzymes. Delay treatment initiation in patients w/ active viral hepatitis until resolution. Monitor liver transaminases & serum bilirubin at mth 1, 3, 6, 9, & 12 on therapy & periodically thereafter until 2 mth after treatment discontinuation if clinical symptoms of hepatic dysfunction are absent. Reports of rare cases of posterior reversible encephalopathy syndrome. Potential risk of malignant skin growths. Medical evaluation of skin is recommended at treatment initiation & then every 6-12 mth. Caution against exposure to sunlight w/o protection. Do not receive concomitant phototherapy w/ UVB radiation or PUVA photochemotherapy. Risk of lymphoma. Reports of rare cases of tumefactive lesions associated w/ multiple sclerosis relapse. Risk of rebound after treatment discontinuation. Allow a 6-wk interval w/o therapy to clear fingolimod from circulation if stopping treatment. Interference w/ lab tests involving use of circulating mononuclear cells. Prior treatment w/ immunosuppressive or immunomodulatory therapies. Concomitant use w/ potent CYP450 inducers. Not recommended w/ St. John's wort. Patients w/ severe resp disease, pulmonary fibrosis, & COPD; history of significant liver disease; mild or moderate hepatic impairment; elderly ≥65 yr. Women of childbearing potential must use effective contraception during treatment & for 2 mth after treatment discontinuation. Discontinue treatment 2 mth before planning a pregnancy, or if a woman becomes pregnant during treatment. Women receiving Gilenya should not breastfeed. Paed population: Safety & efficacy in childn <10 yr have not yet been established. Limited data available in childn 10-12 yr, <40 kg, or at Tanner stage <2. Reports of seizures, anxiety, depressed mood, & depression. Mild isolated bilirubin increases. Complete all immunisations before treatment initiation.

Flu, sinusitis; headache; cough; diarrhoea; back pain; increased hepatic enzyme (increased ALT, γ-glutamyltransferase, AST). Herpes viral infections, bronchitis, tinea versicolor; basal cell carcinoma; lymphopenia, leucopenia; depression; dizziness, migraine; blurred vision; bradycardia, AV block; HTN; dyspnoea; eczema, alopecia, pruritus; myalgia, arthralgia; asthenia; decreased wt, increased blood triglycerides.

Risk of additive immune system effects w/ antineoplastic, immunomodulatory, or immunosuppressive therapies. Exercise caution when switching patients from long-acting therapies w/ immune effects eg, natalizumab, teriflunomide, mitoxantrone. Vaccination may be less effective during & for up to 2 mth after Gilenya treatment. Risk of infections w/ live attenuated vaccines. Potential additive effects on heart rate w/ β-blockers, class Ia & III antiarrhythmics, Ca channel blockers, ivabradine, digoxin, anticholinesteratic agents, pilocarpine. Increased AUC w/ CYP3A4 inhibitors eg, PIs, azole antifungals, clarithromycin, telithromycin. Reduced AUC w/ strong CYP3A4 inducers eg, carbamazepine, rifampicin, phenobarb, phenytoin, efavirenz, St. John's wort.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants

L04AE01 - fingolimod ; Belongs to the class of sphingosine-1-phosphate (S1P) receptor modulators. Used as immunosuppressants.

P₁S₁S₃