Zeposia

Treatment should be initiated under the supervision of a physician experienced in the management of multiple sclerosis (MS) or ulcerative colitis (UC). Posology The initial dose escalation regimen of ozanimod from Day 1 to Day 7 is required and shown below in Table 1.

92 mg ozanimod once daily, starting on Day 8. 92 mg once daily Re-initiation of therapy following treatment interruption The same dose escalation regimen described in Table 1 is recommended when treatment is interrupted for: • 1 day or more during the first 14 days of treatment.

• more than 7 consecutive days between Day 15 and Day 28 of treatment. • more than 14 consecutive days after Day 28 of treatment. If the treatment interruption is of shorter duration than the above, the treatment should be continued with the next dose as planned.

Special populations Adults over 55 years old and elderly population There are limited data available on RRMS patients > 55 years of age and on UC patients ≥ 65 years of age. No dose adjustment is needed in patients over 55 years of age.

2). Renal impairment No dose adjustment is necessary for patients with renal impairment. 2). Ozanimod was not evaluated in patients with severe hepatic impairment. 2). Paediatric population The safety and efficacy of Zeposia in children and adolescents aged below 18 years have not yet been established.

No data are available. 4 Method of administration Oral use. The capsules can be taken with or without food.

4%). Initiation of ozanimod may result in transient bradycardia that usually resolves by the end of the first week. 4). 1%) in the MS clinical studies. 4% of patients, in UC controlled clinical studies. The overall safety profile was similar for patients with multiple sclerosis and ulcerative colitis.

Tabulated list of adverse reactions The adverse reactions observed in patients treated with ozanimod in MS and UC clinical studies and from post-marketing experience including spontaneous case reports are listed below by system organ class (SOC) and frequency for all adverse reactions.

Within each SOC and frequency grouping, adverse reactions are presented in order of decreasing seriousness. 11 Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000).

4). 3% of patients on IFN β-1a IM. 1% of patients on IFN β-1a IM. The median time to elevation 3-fold the ULN was 6 months. The majority (79%) continued treatment with ozanimod with values returning to < 3-fold the ULN within approximately 2-4 weeks.

Ozanimod was discontinued for a confirmed elevation greater than 5-fold the ULN. 8% of patients on IFN beta-1a IM. 9% and no patients, respectively. 3% and no patients, respectively. In controlled and uncontrolled UC clinical studies, the majority (96%) of patients with ALT greater than 3-fold the ULN continued 12 treatment with ozanimod with values returning to less than 3-fold the ULN within approximately 2 to 4 weeks.

92 mg, and none in patients who received placebo in the controlled UC clinical studies. 4). 7 bpm in the UC clinical studies), returning towards baseline at Hour 6. With continued dose escalation, there were no clinically relevant HR decreases.

5% of patients treated with ozanimod versus 0% of patients treated with IFN β-1a IM on the day of treatment initiation (Day 1). 7% on IFN β-1a IM. 1). Patients who experienced bradycardia were generally asymptomatic. Heart rates below 40 beats per minute were not observed.

Bradyarrhythmia Initiation of treatment with ozanimod Prior to treatment initiation with ozanimod, an electrocardiogram (ECG) in all patients should be obtained to determine whether any pre-existing cardiac abnormalities are present.

In patients with certain pre-existing conditions, first-dose monitoring is recommended (see below). 2). 23 mg, the HR decrease started at Hour 4, with the greatest mean reduction at Hour 5, returning towards baseline at Hour 6. With continued dose escalation, there were no clinically relevant HR decreases.

Heart rates below 40 beats per minute were not observed. If necessary, the decrease in HR induced by ozanimod can be reversed by parenteral doses of atropine or isoprenaline. g. diltiazem and verapamil) because of the potential for additive effects on lowering HR.

Beta-blockers and calcium-channel blockers treatment can be initiated in patients receiving stable doses of ozanimod. 5). 3). Patients should be monitored with hourly pulse and blood pressure measurement during this 6-hour period. An ECG prior to and at the end of this 6-hour period is recommended.

Additional monitoring is recommended in patients if at hour 6 post-dose: • heart rate is less than 45 bpm 5 • heart rate is the lowest value post-dose, suggesting that the maximum decrease in HR may not have occurred yet • there is evidence of a new onset second-degree or higher AV block at the 6-hour post-dose ECG • QTc interval ≥ 500 msec In these cases, appropriate management should be initiated and observation continued until the symptoms/findings have resolved.

If medical treatment is required, monitoring should be continued overnight, and a 6-hour monitoring period should be repeated after the second dose of ozanimod. g. g. amiodarone, sotalol) antiarrhythmic medicinal products, which have been associated with cases of torsades de pointes in patients with bradycardia have not been studied with ozanimod.

1. 4). • Patients who in the last 6 months experienced myocardial infarction (MI), unstable angina, stroke, transient ischaemic attack (TIA), decompensated heart failure requiring hospitalisation or New York Heart Association (NYHA) Class III/IV heart failure.

• Patients with history or presence of second-degree atrioventricular (AV) block Type II or third- degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker. 4). • Active malignancies. • Severe hepatic impairment (Child-Pugh class C).

6).