Zeposia: Uses, Dosage & Side Effects
An oral S1P receptor modulator for the treatment of relapsing multiple sclerosis and moderately to severely active ulcerative colitis in adults
Zeposia (ozanimod) is a prescription sphingosine 1-phosphate (S1P) receptor modulator used for the treatment of relapsing forms of multiple sclerosis (RRMS) with active disease and moderately to severely active ulcerative colitis in adults. It works by reducing the number of lymphocytes that can leave lymph nodes and migrate to sites of inflammation in the brain, spinal cord, or gut. Zeposia is taken orally once daily at a maintenance dose of 0.92 mg, following a mandatory 7-day dose titration to minimize cardiac effects. Clinical trials have demonstrated that Zeposia significantly reduces annualized relapse rates in MS and induces clinical remission in ulcerative colitis, while maintaining a favorable overall safety profile.
Quick Facts: Zeposia
Key Takeaways
- Zeposia (ozanimod) is an oral S1P receptor modulator approved for two distinct conditions: relapsing-remitting multiple sclerosis (RRMS) with active disease in adults, and moderately to severely active ulcerative colitis in adults who have had an inadequate response to prior therapies.
- Treatment requires a mandatory 7-day dose titration (0.23 mg for 4 days, then 0.46 mg for 3 days) before reaching the maintenance dose of 0.92 mg once daily, to reduce the risk of bradycardia at treatment initiation.
- In the SUNBEAM and RADIANCE Part B trials for MS, Zeposia demonstrated significant reductions in annualized relapse rates compared with interferon beta-1a, along with reductions in brain MRI lesion activity.
- Zeposia works by blocking lymphocyte emigration from lymph nodes, reducing the number of circulating lymphocytes that can reach and damage the central nervous system (in MS) or the intestinal wall (in ulcerative colitis).
- Key monitoring requirements include pre-treatment ECG, liver function tests, complete blood count, and varicella immunity verification. Women of childbearing potential must use effective contraception during treatment and for 3 months after discontinuation.
What Is Zeposia and What Is It Used For?
Zeposia contains the active substance ozanimod, which belongs to a class of medicines known as sphingosine 1-phosphate (S1P) receptor modulators. S1P receptors are found on the surface of lymphocytes (a type of white blood cell that plays a central role in immune responses) and on various other cell types throughout the body. Ozanimod binds with high affinity and selectivity to two specific subtypes of these receptors: S1P receptor 1 (S1P1) and S1P receptor 5 (S1P5). This selective binding profile distinguishes Zeposia from earlier S1P receptor modulators such as fingolimod, which binds to four of the five S1P receptor subtypes.
Under normal physiological conditions, S1P1 receptors on lymphocytes play a critical role in regulating the movement of these cells between lymphoid tissues (such as lymph nodes and the spleen) and the peripheral blood. Lymphocytes require S1P1 receptor signaling to exit lymph nodes and enter the bloodstream. By binding to and internalizing S1P1 receptors on lymphocytes, ozanimod blocks this signaling pathway, effectively trapping lymphocytes within the lymph nodes. This results in a reversible reduction in the number of lymphocytes circulating in the peripheral blood, typically by approximately 45% from baseline when measured at trough drug levels.
The reduction in circulating lymphocytes has important therapeutic implications for both multiple sclerosis and ulcerative colitis. In both diseases, activated lymphocytes play a central role in driving the inflammatory processes that cause tissue damage. By reducing the pool of lymphocytes available to migrate to sites of inflammation, Zeposia helps protect tissues from immune-mediated damage while preserving the overall architecture and function of the immune system. Importantly, the lymphocyte reduction is reversible: lymphocyte counts typically return to normal within approximately 3 months of discontinuing treatment, as the S1P1 receptors are re-expressed and lymphocytes regain their ability to exit lymph nodes.
Multiple Sclerosis
Zeposia is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) who have active disease. Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) in which the immune system, including T lymphocytes and B lymphocytes, mistakenly attacks the myelin sheath that protects nerve fibers in the brain and spinal cord. This demyelination disrupts the transmission of nerve signals and can lead to a wide range of neurological symptoms, including numbness, weakness, visual disturbances, fatigue, cognitive difficulties, and problems with balance and coordination.
In relapsing-remitting MS, the most common form of the disease, patients experience episodes of neurological worsening (relapses or exacerbations) followed by periods of partial or complete recovery (remissions). Over time, however, repeated attacks can lead to accumulated neurological disability. The goal of disease-modifying therapy in RRMS is to reduce the frequency and severity of relapses, slow the accumulation of disability, and reduce the formation of new inflammatory lesions in the brain and spinal cord as seen on magnetic resonance imaging (MRI).
Zeposia was evaluated in two pivotal phase III clinical trials for RRMS:
- SUNBEAM (Study 1): This randomized, double-blind, active-controlled trial enrolled 1,346 patients with RRMS and compared Zeposia 0.92 mg once daily with intramuscular interferon beta-1a (Avonex) 30 mcg once weekly over a minimum treatment period of 12 months. Zeposia demonstrated a statistically significant 48% relative reduction in the annualized relapse rate (ARR) compared with interferon beta-1a (ARR: 0.181 versus 0.350). Zeposia also showed significant reductions in the number of new or enlarging T2 lesions and gadolinium-enhancing lesions on brain MRI.
- RADIANCE Part B (Study 2): This randomized, double-blind, active-controlled trial enrolled 1,313 patients with RRMS and compared Zeposia 0.92 mg with intramuscular interferon beta-1a 30 mcg weekly over 24 months. Zeposia achieved a statistically significant 38% relative reduction in ARR compared with interferon beta-1a (ARR: 0.172 versus 0.276). MRI outcomes were also significantly improved with Zeposia.
Ulcerative Colitis
Zeposia is also indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response to, or were intolerant to either conventional therapy or a biologic agent. Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation and ulceration of the mucosal lining of the colon and rectum. Symptoms include bloody diarrhea, abdominal pain, urgency, and fatigue. The disease follows a relapsing-remitting course and can significantly impair quality of life.
In ulcerative colitis, Zeposia works by the same mechanism: reducing the number of circulating lymphocytes that can migrate to the intestinal wall and participate in the inflammatory response. By reducing lymphocyte infiltration into the colonic mucosa, Zeposia helps to decrease inflammation, promote mucosal healing, and alleviate symptoms.
The efficacy of Zeposia in ulcerative colitis was demonstrated in the TRUE NORTH trial, a phase III, randomized, double-blind, placebo-controlled study that included both an induction phase (10 weeks) and a maintenance phase (up to 52 weeks). Results showed that a significantly greater proportion of patients receiving Zeposia achieved clinical remission at both week 10 (induction) and week 52 (maintenance) compared with placebo. Zeposia also demonstrated superiority over placebo for endoscopic improvement and corticosteroid-free remission.
Zeposia is one of the few oral medications approved for both relapsing multiple sclerosis and ulcerative colitis. This dual indication reflects the central role that lymphocyte trafficking plays in the pathogenesis of both conditions and makes Zeposia a particularly relevant treatment option for patients who may have both conditions or who prefer the convenience of an oral medication over injectable or infused therapies.
What Should You Know Before Taking Zeposia?
Contraindications
Zeposia must not be used in the following situations:
- Allergy to ozanimod or any excipient: If you are allergic to ozanimod hydrochloride or any of the other ingredients (including microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate, or components of the capsule shell), do not take Zeposia.
- Severely compromised immune system: Patients with conditions that cause severe immunodeficiency should not use Zeposia, as the additional reduction in lymphocyte count could increase the risk of serious infections.
- Recent cardiovascular events: Zeposia is contraindicated in patients who have experienced a myocardial infarction (heart attack), unstable angina, stroke, transient ischemic attack (TIA), or decompensated heart failure requiring hospitalization within the past 6 months.
- Certain cardiac arrhythmias: Patients with certain types of irregular or abnormal heart rhythm (arrhythmia), including Mobitz type II second-degree or third-degree atrioventricular (AV) block, or sick sinus syndrome without a functioning pacemaker, must not use Zeposia. Your doctor will perform an electrocardiogram (ECG) before starting treatment.
- Severe active infection: Patients with severe active infections, including hepatitis B or C or active tuberculosis, should not start Zeposia until the infection has been adequately treated and resolved.
- Active malignancy: Zeposia should not be used in patients with active cancer, except for basal cell carcinoma of the skin.
- Severe hepatic impairment: Patients with severe liver problems (Child-Pugh class C) must not take Zeposia.
- Pregnancy without contraception: Women of childbearing potential who are not using effective contraception must not take Zeposia, as the drug may cause harm to the developing fetus.
Warnings and Precautions
Zeposia can cause a transient decrease in heart rate (bradycardia) and atrioventricular (AV) conduction delays when treatment is first initiated. This is why a 7-day dose titration is required. Patients with certain pre-existing cardiac conditions, including resting heart rate below 55 bpm, second-degree AV block (Mobitz type I), or a history of myocardial infarction or heart failure, may require first-dose monitoring for at least 6 hours after the initial dose, with hourly pulse and blood pressure measurements and continuous ECG monitoring.
Before and during treatment with Zeposia, your doctor should be informed about the following conditions, which may require additional monitoring or precautions:
- Slow heart rate or heart rate-lowering medications: If you have a slow heart rate at rest or are currently taking beta-blockers, calcium channel blockers, or other heart rate-lowering medications, the risk of bradycardia at treatment initiation may be increased. Your doctor may need to monitor you more closely.
- Severe untreated sleep apnea: Patients with severe obstructive sleep apnea that has not been treated should inform their doctor, as this may increase the risk of cardiac effects.
- Liver problems: Elevated liver enzymes have been reported with Zeposia. Your doctor will check your liver function before starting treatment and periodically during treatment. If you develop unexplained nausea, vomiting, right-sided abdominal pain, fatigue, loss of appetite, or yellowing of the skin or eyes (jaundice) during treatment, contact your doctor immediately.
- Infections: Zeposia reduces the number of lymphocytes in the blood, which may increase susceptibility to infections. If you have an active infection, your doctor may delay the start of treatment. During treatment, and for up to 3 months after stopping, you may be more prone to infections. Report any signs of infection to your doctor promptly.
- Low lymphocyte count: Your doctor will monitor your blood counts before and during treatment. If your lymphocyte count falls below a certain threshold, your doctor may temporarily or permanently discontinue Zeposia.
- Varicella (chickenpox) immunity: If you have never had chickenpox or are unsure about your immunity, your doctor will test for varicella zoster virus (VZV) antibodies before starting treatment. If you are not immune, vaccination against VZV is recommended at least 1 month before starting Zeposia.
- Vaccinations: Live attenuated vaccines should be avoided during treatment with Zeposia and for 3 months after stopping treatment, as the vaccines may be less effective and there is a risk of infection from the vaccine strain.
- Macular edema: Zeposia may cause macular edema (swelling of the central part of the retina), which can cause blurred vision. Patients with a history of uveitis, diabetes mellitus, or prior macular edema are at increased risk and should have an ophthalmological examination before starting treatment and during treatment.
- Progressive multifocal leukoencephalopathy (PML): PML is a rare but serious brain infection caused by the JC virus that can occur in patients taking immunomodulatory therapies. If you or others notice worsening of your MS symptoms, or any new or unfamiliar neurological symptoms such as progressive weakness, clumsiness, memory loss, or confusion, contact your doctor immediately.
- Posterior reversible encephalopathy syndrome (PRES): If you experience severe headache, confusion, seizures, or visual loss during treatment, seek immediate medical attention, as these symptoms may indicate PRES.
- Blood pressure: Zeposia may increase blood pressure. Your doctor may want to monitor your blood pressure regularly during treatment.
- Skin cancer risk: Because Zeposia modulates the immune system, there may be an increased risk of skin cancer. Limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and applying sunscreen with a high sun protection factor (SPF) regularly.
- Pulmonary effects: Small reductions in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO) have been observed. Patients with severe pre-existing lung disease, such as pulmonary fibrosis or chronic obstructive pulmonary disease (COPD), should be monitored.
Pregnancy and Breastfeeding
Zeposia must not be used during pregnancy or by women of childbearing potential who are not using effective contraception. Ozanimod may cause harm to the developing fetus. A pregnancy test is required before starting treatment, and effective contraception must be used during treatment and for at least 3 months after the last dose. If you become pregnant during treatment, inform your doctor immediately.
Animal reproductive studies have demonstrated adverse effects on fetal development with ozanimod, including embryonic lethality and skeletal abnormalities at exposures similar to or lower than those achieved at the recommended human dose. Based on these findings and the mechanism of action of the drug, there is a potential risk of fetal harm in humans. Women of childbearing potential must use effective contraception during treatment with Zeposia and for at least 3 months after stopping treatment, because the drug and its active metabolites may remain in the body for some time after the last dose.
Before starting treatment, your doctor will explain the risks to the unborn child and ask you to take a pregnancy test to confirm that you are not pregnant. You will receive a patient card explaining why you should not become pregnant while taking Zeposia and what steps to take to prevent pregnancy. If you discover that you are pregnant while taking Zeposia, stop the medication and inform your doctor immediately. Specialized prenatal monitoring will be arranged.
Zeposia should not be used during breastfeeding. Ozanimod and its metabolites may pass into breast milk, and there is a risk of serious adverse effects in the breastfed infant. The decision to breastfeed during Zeposia treatment should be discussed with your doctor, weighing the benefits of breastfeeding against the benefits of treatment.
Children and Adolescents
Zeposia is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of ozanimod have not been established in this age group, and there are currently no clinical data to support its use in pediatric patients.
Driving and Operating Machinery
Zeposia has no or negligible effect on the ability to drive and operate machinery. Based on its pharmacological properties and known adverse reaction profile, it is unlikely to impair these abilities.
How Does Zeposia Interact with Other Drugs?
Unlike many monoclonal antibody therapies, Zeposia is a small molecule that is extensively metabolized in the body, primarily by cytochrome P450 3A4 (CYP3A4), aldehyde dehydrogenase (ALDH), and aldehyde oxidase (AO). It also forms two major active metabolites, CC112273 and CC1084037, which contribute significantly to the overall pharmacological activity. Because of this metabolic profile, Zeposia has the potential for clinically relevant drug-drug interactions with medications that affect these enzymatic pathways or that have additive pharmacological effects.
Before starting Zeposia, you should inform your doctor about all medications you are currently taking, have recently taken, or may be planning to take. The following drug interactions are of particular clinical importance:
| Drug / Drug Class | Interaction Type | Clinical Significance |
|---|---|---|
| Immunosuppressants (e.g., ciclosporin, azathioprine, 6-mercaptopurine) | Additive immunosuppression | Increased risk of infections; avoid concomitant use or use with caution. When switching from other immunosuppressants, consider wash-out periods. |
| Other MS therapies (e.g., alemtuzumab, natalizumab, interferon beta, dimethyl fumarate, glatiramer, teriflunomid, mitoxantrone) | Additive immunosuppression | Increased risk of additive immune effects. Adequate wash-out periods required when switching between therapies. |
| Beta-blockers (e.g., atenolol, metoprolol, propranolol) | Additive bradycardia | Increased risk of slow heart rate at treatment initiation. Enhanced cardiac monitoring may be required. |
| Calcium channel blockers (e.g., diltiazem, verapamil) | Additive bradycardia | Increased risk of slow heart rate and AV conduction delays. Enhanced cardiac monitoring may be required. |
| MAO inhibitors (e.g., phenelzine, selegiline) | Pharmacodynamic interaction | Risk of hypertensive crisis due to the MAO-B inhibitory activity of an ozanimod metabolite. Concomitant use is contraindicated or requires extreme caution. |
| Gemfibrozil (CYP2C8 inhibitor) | Increased exposure to active metabolite | Co-administration increases exposure to the active metabolite CC112273. Concomitant use is not recommended. |
| Clopidogrel (CYP2C8 inhibitor) | Increased exposure to active metabolite | May increase levels of CC112273. Use with caution. |
| Rifampicin (strong CYP3A4/P-gp inducer) | Decreased ozanimod exposure | Reduces efficacy of Zeposia by lowering ozanimod plasma levels. Concomitant use is not recommended. |
| Live attenuated vaccines | Reduced vaccine efficacy / infection risk | Avoid live vaccines during treatment and for 3 months after stopping Zeposia. Inactivated vaccines may be given but efficacy may be reduced. |
One notable interaction unique to ozanimod relates to its metabolite CC112273, which possesses MAO-B inhibitory activity. Although the degree of MAO-B inhibition at therapeutic doses is generally considered modest, co-administration with MAO inhibitors (such as phenelzine for depression or selegiline for Parkinson's disease) could theoretically increase the risk of a hypertensive crisis, particularly if combined with tyramine-rich foods. Patients should inform their doctor if they are taking any MAO inhibitors before starting Zeposia.
When switching to Zeposia from other MS disease-modifying therapies, adequate wash-out periods must be observed to minimize the risk of additive immunosuppressive effects. The duration of the wash-out period depends on the half-life and mechanism of action of the previous therapy. For example, patients switching from natalizumab typically require a wash-out of 2–3 months, while those switching from alemtuzumab may need monitoring of lymphocyte counts for 6 months or more. Your neurologist will determine the appropriate timing based on your specific situation.
What Is the Correct Dosage of Zeposia?
Dose Titration (Days 1–7)
When starting Zeposia, all patients must follow a mandatory 7-day dose titration regimen to minimize the risk of transient bradycardia (slow heart rate) that can occur with S1P receptor modulators. A special starter pack is provided for this purpose, containing the appropriate capsules for the first 7 days of treatment:
| Treatment Day | Daily Dose | Capsule Color | Notes |
|---|---|---|---|
| Days 1–4 | 0.23 mg ozanimod | Light gray | Take one capsule daily |
| Days 5–7 | 0.46 mg ozanimod | Light gray and orange | Take one capsule daily |
| Day 8 onward | 0.92 mg ozanimod | Orange | Maintenance dose, once daily |
Adults (Maintenance Dose)
Standard Adult Dosage
After completing the 7-day titration, the recommended maintenance dose is 0.92 mg once daily, taken orally. The capsules should be swallowed whole and can be taken with or without food. Try to take Zeposia at approximately the same time each day to maintain consistent drug levels in the body.
Patients with Hepatic Impairment
For patients with mild or moderate chronic liver problems (Child-Pugh class A or B), no dose adjustment is required during the titration phase. However, for the maintenance phase, your doctor may reduce the dose to 0.92 mg every other day in patients with moderate hepatic impairment (Child-Pugh class B). Zeposia is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).
Children and Adolescents
Pediatric Use
Zeposia is not approved for use in patients under 18 years of age. Safety and efficacy have not been established in this age group.
Elderly Patients
Elderly Use
Limited clinical data are available for patients over 55 years of age. No dose adjustment is specifically recommended for elderly patients, but caution is advised, particularly regarding cardiac monitoring at treatment initiation, given the higher prevalence of cardiovascular disease in older adults.
Missed Dose
The instructions for managing a missed dose depend on when during treatment the dose was missed:
- During the first 14 days: If you miss one or more doses during the first 14 days of treatment, contact your doctor. You may need to restart the dose titration from the beginning using a new starter pack.
- After the first 14 days: If you miss a dose, take it as soon as you remember. If you have missed the dose for the entire day, skip the missed dose and take the next dose at your usual time. Do not take a double dose to compensate for a forgotten dose.
If treatment is interrupted for certain durations, the dose titration must be repeated:
- 1 or more days missed during the first 14 treatment days
- More than 7 consecutive days missed between day 15 and day 28
- More than 14 consecutive days missed after day 28
Overdose
If you have taken more Zeposia than prescribed, contact your doctor or go to a hospital emergency department immediately. Bring the medicine packaging and this information with you. There is no specific antidote for ozanimod overdose. The most important clinical concern with overdose would be prolonged bradycardia and AV conduction delays. Standard supportive measures should be employed, and continuous cardiac monitoring is recommended until symptoms resolve.
Do not stop taking Zeposia without first discussing with your doctor. After stopping Zeposia, the drug and its active metabolites remain in the body for approximately 3 months. During this time, your lymphocyte count may remain low and the side effects described in this article may still occur. If you have MS, there is a risk of disease reactivation or rebound after stopping S1P receptor modulators. If you feel that your MS is worsening after stopping Zeposia, inform your doctor immediately.
What Are the Side Effects of Zeposia?
Like all medicines, Zeposia can cause side effects, although not everybody gets them. The side effects are listed below by frequency category according to standard medical classification. Understanding the potential side effects of Zeposia, their frequency, and which ones require immediate medical attention is important for safe use of this medication.
Contact your doctor or seek emergency medical care immediately if you experience: signs of a serious infection (high fever, severe headache with neck stiffness); sudden severe headache with confusion, seizures, or visual loss; progressive weakness, clumsiness, or memory loss; yellowing of the skin or eyes (jaundice); or blurred or decreased vision.
Very Common
May affect more than 1 in 10 people
- Upper respiratory tract infections (nasopharyngitis, pharyngitis, rhinitis, laryngitis) caused by viruses
- Low levels of a type of white blood cell called lymphocytes (lymphopenia)
Common
May affect up to 1 in 10 people
- Sore throat (pharyngitis)
- Viral respiratory infection (signs of lung infection)
- Herpes zoster (shingles)
- Herpes simplex or cold sores (oral herpes)
- Headache
- Slow heart rate (bradycardia)
- Elevated blood pressure (hypertension)
- Low blood pressure (hypotension)
- Urinary tract infection
- Swelling of the ankles and feet due to fluid retention (peripheral edema)
- Elevated liver enzymes or bilirubin levels in blood tests (sign of liver problems) or yellowing of skin/eyes (jaundice, hyperbilirubinemia)
- Reduced lung function that may cause shortness of breath
Uncommon
May affect up to 1 in 100 people
- Allergic reaction (may include skin rash, hives)
- Blurred vision due to macular edema (swelling in the central part of the retina)
Rare
May affect up to 1 in 1,000 people
- Progressive multifocal leukoencephalopathy (PML) – a rare, serious brain infection
- Liver damage (hepatotoxicity)
Cardiac Effects at Treatment Initiation
Bradycardia (slow heart rate) is a known pharmacological effect of S1P receptor modulators, including Zeposia. In clinical trials, the maximum mean decrease in heart rate from baseline was approximately 1.2 beats per minute on day 1 of treatment (with the 0.23 mg dose), occurring at approximately 5 hours post-dose. The heart rate typically returns to baseline within 24 hours and does not recur with continued daily dosing. This effect is mitigated by the dose titration regimen, which is why it is critical to follow the titration schedule carefully and not skip directly to the maintenance dose.
Liver Effects
Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) — liver enzymes measured in routine blood tests — have been reported in patients taking Zeposia. In clinical trials, ALT or AST elevations of 5 times or more the upper limit of normal occurred in approximately 1% of patients. Most elevations were asymptomatic and reversible upon dose reduction or discontinuation. Your doctor will perform liver function tests before starting treatment, at months 1, 3, 6, 9, and 12 during treatment, and periodically thereafter. If liver enzyme levels rise significantly, treatment may need to be interrupted or stopped.
Infections
Because Zeposia reduces the number of circulating lymphocytes, patients may be more susceptible to infections, including viral respiratory infections, herpes zoster (shingles), herpes simplex, and urinary tract infections. During treatment and for up to 3 months after stopping Zeposia, remain vigilant for signs and symptoms of infection and report them to your doctor promptly. Serious infections, including opportunistic infections, have been reported with S1P receptor modulators as a class.
How Should You Store Zeposia?
Proper storage of Zeposia is important to ensure the medication remains effective and safe throughout the treatment period. Follow these storage guidelines:
- Temperature: Store at or below 25°C (77°F). Do not freeze.
- Packaging: Keep the capsules in the original blister packaging to protect from moisture. Do not remove capsules from the blister until you are ready to take them.
- Children: Keep Zeposia out of the sight and reach of children.
- Expiration date: Do not use Zeposia after the expiration date (EXP) printed on the blister and carton. The expiration date refers to the last day of that month.
- Damaged packaging: Do not use the medication if the packaging appears damaged or shows signs of tampering.
- Disposal: Do not throw unused medicines in the drain or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. These measures help to protect the environment.
What Does Zeposia Contain?
Active Ingredient
The active substance in Zeposia is ozanimod, present as ozanimod hydrochloride. It is available in three strengths:
- Zeposia 0.23 mg hard capsule: Each capsule contains 0.23 mg of ozanimod (as hydrochloride). Light gray opaque capsule, 14.3 mm long, printed with “OZA” on the cap and “0.23 mg” on the body in black ink.
- Zeposia 0.46 mg hard capsule: Each capsule contains 0.46 mg of ozanimod (as hydrochloride). Orange opaque cap and light gray body, 14.3 mm long, printed with “OZA” on the cap and “0.46 mg” on the body in black ink.
- Zeposia 0.92 mg hard capsule: Each capsule contains 0.92 mg of ozanimod (as hydrochloride). Orange opaque capsule, 14.3 mm long, printed with “OZA” on the cap and “0.92 mg” on the body in black ink.
Inactive Ingredients
Capsule contents: Microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, and magnesium stearate.
Capsule shell (0.23 mg): Gelatin, titanium dioxide (E171), yellow iron oxide (E172), black iron oxide (E172), and red iron oxide (E172).
Capsule shell (0.46 mg): Gelatin, titanium dioxide (E171), yellow iron oxide (E172), black iron oxide (E172), and red iron oxide (E172).
Capsule shell (0.92 mg): Gelatin, titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172).
Printing ink: Black iron oxide (E172), shellac (E904), propylene glycol (E1520), concentrated ammonia solution (E527), and potassium hydroxide (E525).
Sodium and Potassium Content
Each Zeposia capsule contains less than 1 mmol (23 mg) of sodium and less than 1 mmol (39 mg) of potassium, meaning it is essentially “sodium-free” and “potassium-free.” This is relevant for patients on restricted sodium or potassium diets.
Pack Sizes
Zeposia is available in the following pack sizes:
- Starter pack (titration pack): Wallet pack containing 7 hard capsules: 4 × 0.23 mg capsules and 3 × 0.46 mg capsules, for the first 7 days of treatment.
- Maintenance packs: Packs containing 28 × 0.92 mg hard capsules or 98 × 0.92 mg hard capsules.
Not all pack sizes may be marketed in all countries.
Frequently Asked Questions About Zeposia
Zeposia (ozanimod) is an oral sphingosine 1-phosphate (S1P) receptor modulator. It is approved for two conditions: relapsing-remitting multiple sclerosis (RRMS) with active disease in adults, and moderately to severely active ulcerative colitis in adults who have not responded adequately to, or are intolerant of, prior therapies. Zeposia works by preventing certain immune cells (lymphocytes) from leaving lymph nodes, thereby reducing the inflammation that drives both conditions.
Zeposia requires a 7-day dose titration because S1P receptor modulators can cause a transient decrease in heart rate (bradycardia) when treatment is first started. By gradually increasing the dose from 0.23 mg (days 1–4) to 0.46 mg (days 5–7) and then to the maintenance dose of 0.92 mg (day 8 onward), the cardiac effects are minimized. This titration is mandatory for all patients, and a special starter pack is provided.
No. Zeposia may cause harm to the developing fetus and must not be used during pregnancy. Women of childbearing potential must use effective contraception during treatment and for at least 3 months after stopping Zeposia. A pregnancy test is required before starting treatment. If you are planning to become pregnant, discuss with your doctor first — you will need to stop Zeposia and wait at least 3 months before trying to conceive.
If you miss a dose during the first 14 days, contact your doctor as you may need to restart the titration. If you miss a dose after the first 14 days, take it as soon as you remember. If you have forgotten the entire day, skip it and take the next dose at your usual time. Do not double up. If treatment is interrupted for an extended period (more than 7 consecutive days during days 15–28, or more than 14 consecutive days after day 28), you will need to restart from the titration pack.
Zeposia (ozanimod) is a selective S1P1 and S1P5 receptor modulator, which distinguishes it from fingolimod (Gilenya), the first S1P modulator approved for MS, which binds to four of the five S1P receptor subtypes. This greater selectivity may contribute to a more favorable side effect profile, including less pronounced cardiac effects at initiation. Other S1P modulators include siponimod (Mayzent) and ponesimod (Ponvory). Each has a distinct pharmacological profile, dosing schedule, and approved indication(s). Your neurologist or gastroenterologist can help determine which option is most appropriate for your situation.
Before starting Zeposia, your doctor will typically order: an electrocardiogram (ECG) to check your heart rhythm, a complete blood count to assess lymphocyte levels, liver function tests (ALT, AST, bilirubin), a varicella zoster virus (VZV) antibody test to confirm chickenpox immunity, and for women of childbearing potential, a pregnancy test. An eye examination is recommended for patients with diabetes or a history of uveitis. Depending on your medical history, additional cardiac monitoring on the first day of treatment may be required.
References & Sources
This article is based on the following peer-reviewed sources and regulatory documents. All medical claims are supported by Level 1A evidence where applicable.
- European Medicines Agency (EMA). Zeposia (ozanimod) – Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/en/medicines/human/EPAR/zeposia
- U.S. Food and Drug Administration (FDA). Zeposia (ozanimod) – Prescribing Information. Revised 2024. Available at: FDA Prescribing Information
- Comi G, Kappos L, Selmaj KW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009–1020. doi:10.1016/S1474-4422(19)30239-X
- Cohen JA, Comi G, Selmaj KW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021–1033. doi:10.1016/S1474-4422(19)30238-8
- Sandborn WJ, Feagan BG, D'Haens G, et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2021;385(14):1280–1291. doi:10.1056/NEJMoa2033617
- American Academy of Neurology (AAN). Practice Guideline: Disease-Modifying Therapies for Adults with Multiple Sclerosis. 2024.
- European Crohn's and Colitis Organisation (ECCO). Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. 2024.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
Medical Editorial Team
Medical Content
Written by the iMedic Medical Editorial Team – specialists in neurology, gastroenterology, and clinical pharmacology
Medical Review
Reviewed by the iMedic Medical Review Board according to EMA, FDA, and international clinical guidelines
Evidence Standard
Level 1A evidence from systematic reviews and randomized controlled trials (SUNBEAM, RADIANCE, TRUE NORTH)
Independence
No pharmaceutical company sponsorship or advertising. Independent medical editorial content with no commercial funding
Last reviewed: | Next scheduled review: July 2026 | Content version: 1.0