Ponvory

Treatment should be initiated under the supervision of a physician experienced in the management of multiple sclerosis. 5). Treatment starts with one 2 mg tablet orally once daily on day 1 and dose-escalation progresses with the titration schedule outlined in Table 1.

2, “Re-initiation of therapy following treatment interruption during dose titration or maintenance period”). 2, Treatment initiation), the recommended maintenance dose is one 20 mg tablet taken orally once daily. Re-initiation of therapy following treatment interruption during dose titration or maintenance period - if less than 4 consecutive doses are missed, resume treatment with the first missed dose.

- if 4 or more consecutive doses are missed, reinitiate treatment with day 1 (2 mg) of the titration regimen (new treatment initiation pack). The same first dose monitoring as for treatment initiation is recommended when 4 or more consecutive doses of ponesimod are missed during the titration or maintenance periods.

Special populations Elderly population Clinical studies of ponesimod did not include patients aged 65 years and older. Ponesimod should be prescribed with caution in patients aged 65 years and over due to the lack of data on safety and efficacy.

2). 2). 2). Paediatric population The safety and efficacy of Ponvory in children and adolescents aged less than 18 years have not been established. No data are available. Method of administration Ponesimod should be administered orally once daily.

2).

9%) and upper respiratory tract infection (11%). Tabulated list of adverse reactions Adverse reactions reported with ponesimod in controlled clinical trials and uncontrolled extension trials are ranked by frequency, with the most frequent reactions first.

Frequencies were defined using the following convention: 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); very rare (<1/10,000); not known (cannot be estimated from the available data).

6% of patients receiving teriflunomide 14 mg. Patients who experienced bradycardia were generally asymptomatic. Bradycardia resolved in all patients without intervention and did not require discontinuation of ponesimod treatment. On day 1, 3 patients treated with ponesimod had asymptomatic post-dose HR below or equal to 40 bpm; all 3 patients had baseline HRs below 55 bpm.

15 Initiation of ponesimod treatment has been associated with transient AV conduction delays that follow a similar temporal pattern as the observed decrease in HR during dose titration. 2% of patients receiving teriflunomide 14 mg in the OPTIMUM study.

No second-degree AV blocks, Mobitz type I (Wenckebach), were observed in OPTIMUM. The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, resolved without intervention, and did not require discontinuation of ponesimod treatment.

1% respectively). Nasopharyngitis and viral infections were more common in ponesimod-treated patients. 9% of patients receiving teriflunomide 14 mg. 8%). 2 × 109/L while remaining on treatment with ponesimod. 1% of ponesimod-treated patients compared to none of the patients receiving teriflunomide 14 mg.

5% of patients receiving, teriflunomide 14 mg, respectively. 1% in patients receiving teriflunomide 14 mg. The majority of elevations occurred within 6 or 12 months of starting treatment. ALT levels returned to normal after discontinuation of ponesimod.

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

In patients with certain pre-existing conditions, first-dose monitoring is recommended (see below). 2). After the first dose of ponesimod, the decrease in HR typically begins within an hour and reaches its nadir within 2-4 hours. The HR typically recovers to baseline levels 4-5 hours after administration.

The mean decrease in HR on day 1 of dosing (2 mg) was 6 bpm. With up-titration after day 1, the decrease in HR is less pronounced with no further post-dose decrease in HR observed after day 3. 5). For patients receiving a stable dose of a beta-blocker, the resting HR should be considered before introducing ponesimod treatment.

If the resting HR is greater than 55 bpm under chronic beta-blocker treatment, ponesimod can be introduced. If resting HR is less than or equal to 55 bpm, beta-blocker treatment should be interrupted until the baseline HR is greater than 55 bpm.

5). Beta-blocker treatment can be initiated in patients receiving stable doses of ponesimod. 1). Administer the first dose of ponesimod in a setting where resources to appropriately manage symptomatic bradycardia are available. Monitor patients for 4 hours after the first dose for signs and symptoms of bradycardia with a minimum of hourly pulse and blood pressure measurements.

Obtain an ECG in these patients at the end of the 4-hour observation period. Additional monitoring after 4-hours is recommended if any of the following abnormalities are present (even in the absence of symptoms), continue monitoring until the abnormality resolves: - HR 4 hours postdose is less than 45 bpm - HR 4 hours postdose is at the lowest value postdose, suggesting that the maximum pharmacodynamic effect on the heart may not have occurred - The ECG 4 hours postdose shows new onset second-degree or higher AV block 7 If postdose symptomatic bradycardia, bradyarrhythmia, or conduction related symptoms occur, or if ECG 4 hours post-dose shows new onset second degree or higher AV block or QTc greater than or equal to 500 msec, initiate appropriate management, begin continuous ECG monitoring, and continue monitoring until the symptoms have resolved if no pharmacological treatment is required.

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

4). - Severe active infections, active chronic infections. - Active malignancies. - Moderate or severe hepatic impairment (Child-Pugh class B and C, respectively). 6).