Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, including the brain, spinal cord, and optic nerves. The body mistakenly attacks and damages the protective coating of (myelin) that helps to insulate nerves. The inflammation disrupts the flow of information and nerve signals. Symptoms from MS vary widely and have patterns of relapse (temporary worsening of symptoms) and remission.
MS is treated with disease-modifying treatments (DMTs) to prevent relapses and manage symptoms. DMTs will not eliminate relapses but should slow progression or worsening of your MS over time. Most medicines for treating MS require an injection; however, oral medicines, like Zeposia, provide an easier treatment option.
How Zeposia Works
Zeposia is part of a newer class of medicines called sphingosine-1-phosphate (S1P) receptor modulators. These medicines work by targeting immune cells, called lymphocytes. These cells play a key role in the inflammatory process. S1P medicines prevent the release of lymphocytes from the lymph nodes, which reduces the inflammation. The decreased inflammation reduces the attack on the protective covering (myelin sheath) of nerve fibers in the brain. This leads to less relapses or slower progression of your MS.
How Should I Take This Medicine?
Zeposia is an oral capsule taken daily. You will receive a 7-day starter pack. The dose will increase over those 7 days and may be changed by your health care provider if you have liver problems. It is important to take it as prescribed by your health care provider.
The capsule is swallowed whole with or without food. If you miss a dose during the first 2 weeks, talk with your healthcare provider. You will need to get a new starter pack.
Blood tests including a complete blood count and liver function tests are required before starting. Let your health care provider know if you had any of these tests in the past 6 months. An electrocardiogram (EKG), a common test to monitor your heart, will also be done. If you have a history of certain eye diseases (macular edema or uveitis) or diabetes, you will need to have an eye exam before starting.
Let your health care provider if you have had chickenpox or the chickenpox vaccine. If not, blood tests or the varicella vaccine may be required before starting treatment.
What Studies of Zeposia Were Done?
Two studies (SUNBEAM and RADIANCE) were completed to see if Zeposia was safe and effective for relapsing MS compared with interferon (IFN) beta-1a, which is a standard treatment for MS.
Everyone had a diagnosis of relapsing-remitting MS and had experienced at least one relapse in the past 1-2 years, had an Expanded Disability Status Scale (EDSS) from 0 to 5, and brain lesions on MRI. The EDSS tool looks at disability in people with MS and tracks changes over time. Scores of less than 5 represent mild to moderate disease. People with primary progressive MS were not included in these studies. The SUNBEAM study treated people until the last enrolled participant was treated for 12 months. The RADIANCE study treated people for 24 months. The efficacy was measured by the annual relapse rate (ARR) over the treatment period (SUNBEAM) and 24 months (RADIANCE). This means that the group with a higher ARR had more relapses and symptoms. The studies also measured the number of total and new lesions on MRI, time to worsening in disability (at least 1 point increase in EDSS), and percent of people with worsened disability.
People in the studies received either Zeposia 0.92 milligrams orally or INF 30 milligrams injected in the muscle. Those taking Zeposia completed a dose titration, where they started at a lower dose and increased to the full dose after 7 days. The characteristics of the studies are listed in the table below. Almost all the people were white, with a little more than half being female. The average age was 35.
MS Disease Values | SUNBEAM | RADIANCE |
Time since MS symptoms started (mean) | 6.9 years | 6.6 years |
EDSS Score (mean) | 2.5 | 2.5 |
Percent treated with nonsteroid therapy | 31% | 29% |
Number of relapses in the prior year (mean) | 1.3 | 1.3 |
Percent with lesions on MRI scans | 48% | 43% |
What Benefits Were Seen in the Studies?
The ARR was lower in people taking Zeposia compared with people using INF, with a higher percentage of people without a relapse with Zeposia. This means that more people were less likely to have a relapse during treatment or the time to the next relapse was longer when taking Zeposia compared to INF. There was also a lower number of new or worsening brain lesions in people taking Zeposia.
SUNBEAM (12+ months) | RADIANCE (24 months) | |||
Zeposia | INF | Zeposia | INF | |
Annualized relapse rate | 0.18 | 0.35 | 0.17 | 0.28 |
People without a relapse | 78% | 66% | 76% | 64% |
Number or new or worsening lesions (mean) | 1.47 | 2.84 | 1.84 | 3.18 |
The worsening of disability at 3 and 6 months results were combined from the SUNBEAM and RADIANCE trials. The percentage of people with worsening disability scores was similar in all the groups.
SUNBEAM + RADIANCE | ||
3 months | ||
Zeposia | INF | |
Percent worsened disability: 3-month | 7.6% | 7.8% |
Percent worsened disability: 6-month | 5.8% | 4.0% |
Your results may differ from what was seen in clinical studies. You and your health care provider should determine if the benefits outweigh any potential risks.
How Long Does Zeposia Take to Work?
After a few months, you may see improvements in frequency of symptoms of your relapses. This means that you may function better in daily activities because of the following benefits.
- Decrease in the number of relapses over time
- Less symptoms or shorter duration of your relapses
- Slowed progression, like fewer new or growing lesions on your MRI scans
- Day-to-day symptoms, like tiredness, numbness, or vision changes, may be less
- Ability to maintain daily activities in your family or social life
The long-term goal is to slow progression, so it is important for you to track your symptoms and relapses and review them with your health care provider.
Are There Any Reasons Why I Should Not Take Zeposia?
Make sure your health care provider is aware of all your past or current health conditions. You should not take it if you have any of the following conditions.
Slow or irregular heartbeats or rhythms. When first started, Zeposia may slow the way your heart’s electrical system works. Some people may experience a slower heart rate or a change in their heart rhythm for a short period of time. This usually resolves as your body adjusts to the medicine. Before starting, your health care provider will check your heart rhythm with an electrocardiogram (EKG).
It is important to tell your health care provider if you have or have had any of the following heart problems or take any medicines that affect your heart rate.
- History of stroke or transient ischemic attack (TIA), heart attack, chest pain (unstable angina) or certain types of heart failure within the past 6 months
- History of unusual or abnormal heart beats (arrhythmias) without use of a pacemaker
Sleeping problems. Severe problems sleeping (sleep apnea) can cause drops in oxygen levels, irregular heartbeat, and slowing of your heart rate. If your sleep apnea is not treated, your health care provider may wait to start Zeposia until treatment is started. If your sleep apnea is controlled, your health care provider may monitor your heart more closely.
Medicines that affect monoamine oxidase-B enzyme. Medicines, like Zeposia, that affect the monoamine oxidase-B enzyme (MAO-B) can cause extremely high blood pressure. See the Interactions section and talk to your health care provider if you are taking one of these medicines before starting Zeposia.
How Can I Prevent and Manage Side Effects?
The most common side effects are infections. Zeposia increases your risk for infections since it blocks the lymphocytes from producing inflammation. You may see more common colds, flu, or urinary tract infections. There is also a risk of more serious infections, like shingles or rare brain infections. The best way to prevent infection is to reduce your exposure to germs by washing your hands and avoiding people who are sick. You should work with your health care provider to determine the right vaccinations and timing of those with Zeposia. Call your health care provider if you have the following symptoms of infection:
- Fever or chills
- Body aches
- Cough
- Tiredness
- Persistent headache
- Confusion
- Vision changes
- Painful rash
When starting, you may experience sudden drops in blood pressure when standing up from a seated or lying position (orthostatic hypotension). To help prevent this, be careful not to get up too quickly. If you feel dizzy, sit or lie down right away until the dizziness stops, then take your time getting up again. Tell your health care provider right away if you have any of the following symptoms of orthostatic hypotension:
- Dizziness, feeling lightheaded, or fainting upon standing
- Blurred vision
- Confusion
- Feeling weak
Other side effects include high blood pressure, back pain, headache, and painful or frequent urination.
These are not all of the side effects. Talk with your health care provider if you are having symptoms that bother you. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088. In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.
What Types of Interactions Can Happen?
Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vaccines, vitamins/minerals, herbal products, and other supplements you are using.
Medicines that affect your immune system may cause an increase in the effect on your immune system while taking Zeposia or changing to another medicine for your MS. Taking two immune-suppressing medicines at the same time may decrease your body’s ability to fight infection, heal, or increase cancer risk in rare cases. Tell your health care provider if you are taking or have taken any of the following medicines. They may closely monitor your immune system or make changes to the medicines you are taking:
- An anti-neoplastic medicine, which is used to treat cancers
- A non-corticosteroid immunosuppressant, which is a medicine that targets different building blocks of the immune system
- An immune-modulating medicine, which is a medicine that controls and retrains your immune system
Medicines that affect monoamine oxidase-B enzyme. Enzymes break down chemicals in your body. Monoamine oxidase-B (MAO-B) enzymes break down certain chemicals, or neurotransmitters, that affect your mood, behavior, and blood pressure. Zeposia can inhibit MAO-B, which may cause increased levels of these chemicals. You could have extremely high blood pressure. Tell your health care provider if you are taking or have recently taken any of the following:
- A monoamine oxidase inhibitor (MAOI), which is a medicine used for depression or Parkinson’s disease. MAOIs and Zeposia should not be taken together or within 14 days.
- Opioid medicines used to treat pain, like meperidine, methadone, or tramadol
- Selective serotonin reuptake inhibitors (SSRIs), used to treat depression, like citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
- Tricyclic antidepressants like amitriptyline and nortriptyline
- Serotonin and norepinephrine reuptake inhibitors (SNRIs), used to treat depression, like desvenlafaxine, duloxetine, and venlafaxine
If you measure your blood pressure and the top number (systolic) is 180 or higher or the bottom number (diastolic) is 120 or higher, get medical attention right away. Increases in blood pressure may not be noticeable, but look out for any of the following symptoms of severely high blood pressure:
- Sudden severe headache
- Chest pain
- Dizziness or confusion
- Trouble breathing
- Nausea/vomiting
- Blurry or other changes to vision
- Anxiety
- Buzzing in the ears
- Nosebleed
- Feeling of skipped heartbeats
Medicines that change your heart rate. Taking both a calcium channel blocker and beta-blocker during treatment may cause more lowering of your heart rate. Examples include amlodipine, atenolol, metoprolol, or verapamil. Talk with your health care provider or a cardiologist before starting treatment. During treatment, monitor your heart rate and call your health care provider if you have signs of low heart rate, including dizziness, feeling lightheaded or faint, feeling weak or tired, or confusion. If you feel faint or dizzy, lie down.
Vaccines. Certain vaccines may not work or may increase your risk of infection. It is best to avoid live or live-attenuated vaccines during treatment. These vaccines contain weakened pieces of the virus that may cause infections when your immune system is reduced. Examples include measles-mumps-rubella (MMR), nasal flu, and chickenpox vaccines. If you need a vaccination, you should get it at least 1 month before starting or 3 months after stopping treatment. Talk with your health care provider about the right timing of any vaccines.
Changes to blood levels of your medicine. Several medicines can affect the blood levels of Zeposia. This may increase the risk of side effects or can cause it to not work as well. The following medicines should be avoided. Talk with your health care provider if you are taking any of these medicines:
- A strong CYP2C8 inhibitor, like gemfibrozil, which may increase the blood levels and cause more side effects
- A strong CYP2C8 inducer, like rifampin, which may decrease the blood levels and decrease the effects of the medicine
This is not a complete list of medicines that may interact with Zeposia. Tell your pharmacist or health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them determine if there are any interactions or if you need a dosage adjustment.
What Should I Know About Stopping Treatment?
After stopping Zeposia, it does not leave your body immediately. It can take up to 3 months to fully clear your system. The level of medication will slowly decrease over those months. You could still experience some benefits and side effects during this time. As the medicine decreases, your symptoms of MS may return or become worse. Contact your health care provider right away if you experience worsening symptoms of MS.
Before stopping treatment, talk to your health care provider about the following:
- Use of effective birth control for at least 3 months
- Continued monitoring of your heart, liver function, and white blood cells
- Timing of live or live-attenuated vaccines
- Timing to start any other immune-suppressing medicine
Getting Your Specialty Medicine: What to Expect
Your primary care provider or rheumatologist will prescribe Zeposia. It is a specialty medicine, which is a high-cost medication that is taken for rare, complex, or chronic diseases. It may require a different process than picking up a prescription at your local pharmacy. This process helps you stay on track with your treatment. The manufacturer has a program to help support the process, or your insurance company may require a specific pharmacy.
Here are some differences that you may expect.
Insurance approval. Your insurance may require approval for using this medicine, also called prior authorization. The insurer reviews the prescription from your health care provider to make sure it is covered and the process that needs to be followed.
Specialty pharmacy. You may be required to use a specialty pharmacy to get your medicine each month. These pharmacies work with your health care provider and insurance company, help with instructions on how to take and store the medicine, monitor side effects, and track refills. This pharmacy will also send work with you on how to get you the medicine. Your health care provider will work with you and your insurance company on which pharmacy to use and the information that will be provided.
Monitoring for side effects. You will be required to complete blood tests and other monitoring while on treatment. The specialty pharmacy or other health care provider will help plan and track this with you.
Cost assistance. There is a co-pay assistance program from the manufacturer that may allow you to pay $0 for your prescription. Whether you are eligible depends on whether you have prescription insurance and what type of insurance you have. You can find out more at www.zeposia.com/multiple-sclerosis/support-program-for-patients or by calling 833-937-6742.
