PONVORY Ponesimod Kit

1 INDICATIONS AND USAGE PONVORY is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. PONVORY is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION Assessments are required prior to initiating PONVORY ( 2.1 ) Titration is required for treatment initiation ( 2.2 ) The recommended maintenance dosage is 20 mg taken orally once daily ( 2.2 ) First-dose monitoring is recommended for patients with sinus bradycardia, first- or second-degree [Mobitz type I] atrioventricular (AV) block, or a history of myocardial infarction or heart failure ( 2.3 )

2.1Assessments Prior to First Dose of PONVORY Before initiation of treatment with PONVORY, assess the following: Complete Blood Count Obtain a recent (i.e., within the last 6 months or after discontinuation of prior MS therapy) complete blood count (CBC), including lymphocyte count [see Warnings and Precautions (5.1) ] . Cardiac Evaluation Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist should be sought and first-dose monitoring is recommended [see Dosage and Administration (2.3) and Warnings and Precautions (5.2) ] .

Determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction [see Warnings and Precautions (5.2) and Drug Interactions (7.2 , 7.3) ] . Liver Function Tests Obtain recent (i.e., within the last 6 months) transaminase and bilirubin levels [see Warnings and Precautions (5.4) ] . Ophthalmic Evaluation Obtain an evaluation of the fundus, including the macula [see Warnings and Precautions (5.8) ] .

Current or Prior Medications with Immune System Effects If patients are taking anti-neoplastic, immunosuppressive, or immune-modulating therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with PONVORY [see Warnings and Precautions (5.1 , 5.10) and Drug Interactions (7.1) ] . Vaccinations Test patients for antibodies to varicella zoster virus (VZV) before initiating PONVORY; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with PONVORY [see Warnings and Precautions (5.1) ] .

If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of PONVORY.

2.2Recommended Dosage Maintenance Dosage After dose titration is complete (see Treatment Initiation ) , the recommended maintenance dosage of PONVORY is 20 mg taken orally once daily starting on Day 15. Administer PONVORY orally once daily. Swallow the tablet whole.

PONVORY can be taken with or without food. Treatment Initiation A starter pack must be used for patients initiating treatment with PONVORY [see How Supplied/Storage and Handling (16.1) ] . Initiate PONVORY treatment with a 14-day titration; start with one 2 mg tablet orally once daily and progress with the titration schedule as shown in Table 1 [see Warnings and Precautions (5.2) ] .

Table 1: Dose Titration Regimen Titration Day Daily Dose Days 1 and 2 2 mg Days 3 and 4 3 mg Days 5 and 6 4 mg Day 7 5 mg Day 8 6 mg Day 9 7 mg Day 10 8 mg Day 11 9 mg Days 12, 13, and 14 10 mg Maintenance Daily Dose Day 15 and thereafter 20 mg If dose titration is interrupted, missed dose instructions must be followed [see Dosage and Administration (2.4) ] .

2.3First Dose Monitoring in Patients with Certain Preexisting Cardiac Conditions Because initiation of PONVORY treatment results in a decrease in heart rate (HR), first-dose 4-hour monitoring is recommended for patients with sinus bradycardia [HR less than 55 beats per minute (bpm)], first- or second-degree [Mobitz type I] AV block, or a history of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in stable condition [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.2) ] .

First Dose 4-Hour Monitoring Administer the first dose of PONVORY in a setting where resources to appropriately manage symptomatic bradycardia are available. Monitor pat…

3 DOSAGE FORMS AND STRENGTHS PONVORY is available as round, biconvex, film-coated tablets for oral use. PONVORY contains ponesimod in the following dosage strengths (see Table 2 ): Table 2: Dosage Form and Strengths for PONVORY Tablet Strength Tablet Color Tablet Size Tablet Debossing 2 mg White 5.0 mm "2" on one side and an arch on the other side. 3 mg Red 5.0 mm "3" on one side and an arch on the other side.

4 mg Purple 5.0 mm "4" on one side and an arch on the other side. 5 mg Green 8.6 mm "5" on one side and an arch and an "A" on the other side. 6 mg White 8.6 mm " 6 " on one side and an arch and an "A" on the other side.

7 mg Red 8.6 mm "7" on one side and an arch and an "A" on the other side. 8 mg Purple 8.6 mm "8" on one side and an arch and an "A" on the other side. 9 mg Brown 8.6 mm " 9 " on one side and an arch and an "A" on the other side.

10 mg Orange 8.6 mm "10" on one side and an arch and an "A" on the other side. 20 mg Yellow 8.6 mm "20" on one side and an arch and an "A" on the other side. Tablets: 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, and 20 mg ( 3 )

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Administration Tell patients not to discontinue PONVORY without first discussing this with the prescribing healthcare provider. Advise patients to contact their healthcare provider if they accidently take more PONVORY than prescribed.

Instruct patients to administer tablets whole. Risk of Infections Inform patients that they may have an increased risk of infections, some of which could be life-threatening, when taking PONVORY and for 1 to 2 weeks after stopping it, and that they should contact their healthcare provider if they develop symptoms of infection [see Warnings and Precautions (5.1) ] . Advise patients that the use of some vaccines containing live virus (live attenuated vaccines) should be avoided during treatment with PONVORY, and PONVORY should be paused 1 to 2 weeks prior and until 4 weeks after a planned vaccination.

Recommend that patients postpone treatment with PONVORY for at least 1 month after VZV vaccination. Inform patients that prior or concomitant use of drugs that suppress the immune system may increase the risk of infection. Cardiac Effects Advise patients that initiation of PONVORY treatment results in transient decrease in heart rate [see Warnings and Precautions (5.2) ] .

Inform patients that to reduce this effect, dose titration is required. Advise patients that dose titration is also required if 4 or more consecutive daily doses are missed during treatment initiation or maintenance treatment [see Dosage and Administration (2.2 , 2.4) and Warnings and Precautions (5.2) ] . Inform certain patients with certain preexisting cardiac conditions that they will need to be observed in the doctor's office or other facility for at least 4 hours after the first dose and after reinitiation if treatment is interrupted or discontinued for certain periods [see Dosage and Administration (2.3) ] .

Respiratory Effects Advise patients that they should contact their healthcare provider if they experience new onset or worsening of dyspnea [see Warnings and Precautions (5.3) ] . Liver Injury Inform patients that PONVORY may increase liver enzymes. Advise patient that they should contact their healthcare provider if they experience any unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine during treatment [see Warnings and Precautions (5.4) ] .

Cutaneous Malignancies Inform patients that the risk of basal cell carcinoma is increased with the use of PONVORY and that cases of melanoma and squamous cell carcinoma have been reported. Advise patients that any suspicious skin lesions should be promptly evaluated. Advise patients to limit exposure to sunlight and ultraviolet light by wearing protective clothing and using a sunscreen with high protection factor [see Warnings and Precautions (5.6) ] .

Pregnancy and Fetal Risk Inform patients that, based on animal studies, PONVORY may cause fetal harm. Discuss with women of childbearing age whether they are pregnant, might be pregnant, or are trying to become pregnant. Advise women of childbearing potential of the need for effective contraception during treatment with PONVORY and for one week after stopping PONVORY.

Advise a female patient to immediately inform her healthcare provider if she is pregnant or planning to become pregnant [see Warnings and Precautions (5.7) ]. Macular Edema Advise patients that PONVORY may cause macular edema, and that they should contact their healthcare provider if they experience any changes in their vision while taking PONVORY [see Warnings and Precautions (5.8) ] . Inform patients with diabetes mellitus or a history of uveitis that their risk of macular edema is increased.

Posterior Reversible Encephalopathy Syndrome Advise patients to immediately report to their healthcare provider any symptoms involving sudden onset of severe headache, altered mental status, visual disturbances, or seizure. In…

MEDICATION GUIDE PONVORY ® (pon-VOR-ee) (ponesimod) tablets, for oral use This Medication Guide has been approved by the U.S. Food and Drug Administration. Approved: 09/2022 What is the most important information I should know about PONVORY?

PONVORY may cause serious side effects, including: Infections. PONVORY can increase your risk of serious infections that can be life-threatening and cause death. PONVORY lowers the number of white blood cells (lymphocytes) in your blood.

This will usually go back to normal within 1 to 2 weeks of stopping treatment. Your healthcare provider should review a recent blood test of your white blood cells before you start taking PONVORY. Call your healthcare provider right away if you have any of these symptoms of an infection during treatment with PONVORY and for 1 to 2 weeks after your last dose of PONVORY: fever tiredness body aches chills nausea vomiting headache with fever, neck stiffness, sensitivity to light, nausea, or confusion (these may be symptoms of meningitis, an infection of the lining around your brain and spine) Your healthcare provider may delay starting or may stop your PONVORY treatment if you have an infection.

Slow heart rate (bradycardia or bradyarrhythmia) when you start taking PONVORY. PONVORY can cause your heart rate to slow down, especially after you take your first dose. You should have a test to check the electrical activity of your heart called an electrocardiogram (ECG) before you take your first dose of PONVORY.

Only start your treatment with PONVORY using the Starter Pack. You must use the PONVORY Starter Pack to slowly increase the dose over a 14-day period to help reduce the effect of slowing of your heart rate. It is important to follow the recommended dosing instructions.

See " How should I take PONVORY ?" Call your healthcare provider if you experience the following symptoms of slow heart rate: dizziness lightheadedness feeling like your heart is beating slowly or skipping beats shortness of breath confusion chest pain tiredness Follow directions from your healthcare provider when starting PONVORY and when you miss a dose. See " How should I take PONVORY? " See " What are possible side effects of PONVORY? " for more information about side effects. What is PONVORY?

PONVORY is a prescription medicine that is used to treat relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is not known if PONVORY is safe and effective in children. Do not take PONVORY if you: have had a heart attack, chest pain called unstable angina, stroke or mini-stroke (transient ischemic attack or TIA), or certain types of heart failure in the last 6 months. have certain types of heart block or irregular or abnormal heartbeat (arrhythmia), unless you have a pacemaker.

Talk to your healthcare provider before taking PONVORY if you have any of these conditions, or do not know if you have any of these conditions. Before you take PONVORY, tell your healthcare provider about all of your medical conditions, including if you: have a fever or infection, or you are unable to fight infections due to a disease or taking medicines that weaken your immune system. have had chicken pox or have received the vaccine for chicken pox. Your healthcare provider may do a blood test for chicken pox virus.

You may need to get the full course of vaccine for chicken pox and then wait 1 month before you start taking PONVORY. have slow heart rate. have an irregular or abnormal heartbeat (arrhythmia). have a history of stroke. have heart problems, including a heart attack or chest pain. have breathing problems, including during your sleep (sleep apnea). have liver problems. have high blood pressure. had or now have a type of skin cancer called basal cell carcinoma (BCC), melanoma, or squamous cell carcinoma. have eye problems, especially an inflammation of the eye called uveitis. have diabetes. are pregnant…