Pronunciation:

si-PON-i-mod

Brand Names:

• Mayzent

Dosage Forms:

• Tablet

Classifications:

Therapeutic—

Immune Modulator

Pharmacologic—

Sphingosine 1-Phosphate Receptor Modulator

Uses of This Medicine:

Siponimod is used to treat the relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. This medicine will not cure MS, but it may slow some of the disabling effects and decrease the number of relapses of the disease.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of siponimod in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of siponimod in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Levoketoconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Adagrasib
• Adenovirus Vaccine
• Alemtuzumab
• Alfuzosin
• Amiodarone
• Amisulpride
• Amitriptyline
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asciminib
• Asenapine
• Astemizole
• Atazanavir
• Atenolol
• Azithromycin
• Bacillus of Calmette and Guerin Vaccine, Live
• Bedaquiline
• Bepridil
• Betaxolol
• Bisoprolol
• Buprenorphine
• Buserelin
• Carbamazepine
• Carvedilol
• Chloroquine
• Chlorpromazine
• Cholera Vaccine, Live
• Ciprofloxacin
• Cisapride
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clothiapine
• Clozapine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Dasatinib
• Degarelix
• Delamanid
• Dengue Tetravalent Vaccine, Live
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dexmedetomidine
• Digoxin
• Diltiazem
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Dronedarone
• Droperidol
• Ebastine
• Efavirenz
• Encorafenib
• Entrectinib
• Enzalutamide
• Eribulin
• Erythromycin
• Escitalopram
• Esmolol
• Etrasimod
• Famotidine
• Felbamate
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Formoterol
• Foscarnet
• Fosphenytoin
• Fostemsavir
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Gepirone
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Influenza Virus Vaccine, Live
• Inotuzumab Ozogamicin
• Itraconazole
• Ivabradine
• Ivosidenib
• Ketoconazole
• Labetalol
• Lapatinib
• Leuprolide
• Levofloxacin
• Lofexidine
• Lumefantrine
• Macimorelin
• Measles Virus Vaccine, Live
• Mefloquine
• Mesoridazine
• Methadone
• Methotrimeprazine
• Metoprolol
• Metronidazole
• Mifepristone
• Mirtazapine
• Mizolastine
• Mobocertinib
• Moricizine
• Moxifloxacin
• Mumps Virus Vaccine, Live
• Nadolol
• Nafarelin
• Nebivolol
• Nelfinavir
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Ozanimod
• Pacritinib
• Paliperidone
• Panobinostat
• Papaverine
• Paroxetine
• Pasireotide
• Pazopanib
• Penbutolol
• Pentamidine
• Perphenazine
• Phenobarbital
• Pimavanserin
• Pimozide
• Pindolol
• Pipamperone
• Piperaquine
• Pitolisant
• Poliovirus Vaccine, Live
• Ponesimod
• Posaconazole
• Primidone
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Propranolol
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Quizartinib
• Ranolazine
• Relugolix
• Ribociclib
• Rifampin
• Risperidone
• Ritonavir
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Saquinavir
• Selpercatinib
• Sertindole
• Sertraline
• Sevoflurane
• Smallpox Monkeypox Vaccine, Live Non-Replicating
• Smallpox Vaccine
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sparfloxacin
• Sulpiride
• Sultopride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Telaprevir
• Telavancin
• Telithromycin
• Terfenadine
• Tetrabenazine
• Thioridazine
• Tocilizumab
• Tolterodine
• Toremifene
• Trazodone
• Triclabendazole
• Trimipramine
• Triptorelin
• Typhoid Vaccine, Live
• Vandetanib
• Vardenafil
• Varicella Virus Vaccine, Live
• Vemurafenib
• Venlafaxine
• Verapamil
• Vilanterol
• Vinflunine
• Voclosporin
• Voriconazole
• Vorinostat
• Yellow Fever Vaccine
• Ziprasidone
• Zoster Vaccine, Live
• Zotepine
• Zuclopenthixol

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina (chest pain), unstable (within the last 6 months) or
• Heart attack (within the last 6 months) or
• Heart failure (Class III or IV) (within the last 6 months) or
• Heart rhythm problems (eg, Mobitz type II second-degree, third-degree heart block, sick sinus syndrome), without a pacemaker or
• Stroke, including transient ischemic attack (within the last 6 months)—Should not be used in patients with these conditions.

• Asthma or
• Bradycardia (slow heartbeat), history of or
• Chronic obstructive pulmonary disease (COPD) or
• Fainting, recurrent, history of or
• Hypertension (high blood pressure) or
• Liver disease, or history of or
• Skin cancer, or history of—Use with caution. May make these conditions worse.

• CYP2C9 genotype—Use with caution. Patients with certain types of genotype can increase the levels of siponimod in the body, which can cause unwanted effects. Your doctor will check for this genotype before you use this medicine.

• Diabetes or
• Uveitis (eye swelling), history of or
• Weak immune system—Use with caution. May increase risk for more serious side effects.

• Infection—May decrease your body's ability to fight infections.

• Infection, severe—Should be treated first before using this medicine.

Proper Use of This Medicine:

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

If you are using this medicine and have certain heart conditions, your doctor may want you to stay in the medical facility for at least 6 hours after the first dose of this medicine and after starting it again if you miss 1 or more doses.

Swallow the tablet whole. Do not split, crush, or chew it. You may take this medicine with or without food.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For relapsing forms of multiple sclerosis:
    • Adults—Dose is based on your genotype and must be determined by your doctor.
      • For genotypes *1/*1, *1/*2, or *2/*2—At first, you will need to take this medicine with a 5-day titration schedule with your 12-tablet starter pack. 0.25 milligram (mg) once a day for Days 1 and 2, 0.5 mg (two 0.25 mg tablet) once on Day 3, 0.75 mg (three 0.25 mg tablet) once on Day 4, and 1.25 mg (five 0.25 mg tablet) once on Day 5. Then, a maintenance dose of 2 mg once a day starting on Day 6.
      • For genotypes *1/*3 or *2/*3—At first, you will need to take this medicine with a 4-day titration schedule with your 7-tablet starter pack. 0.25 milligram (mg) once a day for Days 1 and 2, 0.5 mg (two 0.25 mg tablet) once on Day 3, and 0.75 mg (three 0.25 mg tablet) once on Day 4. Then, a maintenance dose of 1 mg once a day starting on Day 5.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

Call your doctor or pharmacist for instructions.

• If you miss a dose after the initial dose titration, take it as soon as you remember, then go back to your regular dosing schedule.
• If you miss 1 or more doses during the initial dose titration, you will need to restart the medicine.
• If you miss a dose for 4 days in a row, you will need to restart the dose titration.

Storage—

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the unopened medicine in the refrigerator. Do not freeze. You may store the opened medicine in its original container at room temperature for up to 3 months after opening. Do not refrigerate after opening.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for any unwanted effects. Your doctor will also check your skin for any changes before and during treatment with this medicine.

Symptoms of your MS may return and become worse after stopping treatment with this medicine. Do not stop using this medicine without checking first with your doctor.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment with this medicine and for 10 days after the last dose. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may increase your risk of developing infections, including a herpes infection or a serious brain infection called meningitis or progressive multifocal leukoencephalopathy. Avoid being near people who are sick or have infections while you are using this medicine. Wash your hands often. Also tell your doctor if you have ever had an infection that would not go away or an infection that kept coming back.

Siponimod may cause a rare condition called immune reconstitution inflammatory syndrome (IRIS). This may occur after a person stops receiving this medicine after developing PML during treatment. Tell your doctor right away if you have an inflammatory reaction to an infection that includes mild burning, stinging, or tingling of the skin, or a feeling of heat, redness, or swelling of the skin.

Check with your doctor right away if blurred vision, difficulty with reading, or any other change in vision occurs during or after treatment. Your doctor may want your eyes be checked by an ophthalmologist (eye doctor).

This medicine may cause heart rhythm problems. Tell your doctor right away if you get dizzy or lightheaded, have a fast, slow, or irregular heartbeat, or feel like fainting.

Tell your doctor right away if you have a cough, trouble breathing, chest tightness, or any type of breathing problem with this medicine. These could be symptoms of a serious lung problem.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Your doctor will check your blood pressure on a regular basis while you are using this medicine. Tell your doctor right away if you have a severe headache, lightheadedness, or changes in your vision.

This medicine may increase your risk of having skin cancer (eg, basal cell carcinoma, melanoma, squamous cell carcinoma). Tell your doctor right away if you notice any skin nodules, patches, or open sores that do not quickly heal. Avoid exposure to sunlight. Wear sunscreen with a high sun protection factor. Do not use sunlamps or tanning beds.

Tell your doctor right away if you have seizures, headache, confusion, vision problems, unusual drowsiness, tiredness, or weakness. These could be symptoms of a serious nervous system problem called posterior reversible encephalopathy syndrome (PRES).

While you are being treated with siponimod, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. You should not receive a live vaccine during treatment with this medicine and for 4 weeks after the last dose. Do not use this medicine 1 week before and for 4 weeks after receiving a live vaccine. Siponimod may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine within the last several months. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bloating or swelling of the face, arms, hands, lower legs, or feet

blurred vision

chest pain or discomfort

fast, slow, or irregular heartbeat

headache

lightheadedness, dizziness, or fainting

nervousness

pounding in the ears

rapid weight gain

tingling of the hands or feet

unusual tiredness or weakness

unusual weight gain or loss

Less common

Anxiety

change in the size, shape, or color of existing mole

change in vision

chills

confusion

cough

difficulty in speaking

double vision

fever

hoarseness

inability to move the arms, legs, or facial muscles

inability to speak

lower back or side pain

mole that leaks fluid or bleeds

nausea

new mole

numbness or tingling in the face, arms or legs

pain or discomfort in the arms, jaw, back, or neck

painful blisters on the trunk of the body

painful or difficult urination

persistent non-healing sore

pink growth

pounding, slow heartbeat

reddish patch or irritated area

seizures

shiny bump

slow speech

sweating

tremor

trouble speaking, thinking, or walking

trouble breathing

vomiting

white, yellow, or waxy scar-like area

incidence not known

Back pain

drowsiness

fever

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Arm or leg pain

diarrhea

falls

Less common

Lack or loss of strength

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.