Velsipity (Etrasimod)
Sphingosine-1-phosphate (S1P) receptor modulator for ulcerative colitis
Velsipity (etrasimod) is a once-daily oral sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderate to severe active ulcerative colitis in adults and adolescents aged 16 years and older. It works by preventing inflammatory lymphocytes from reaching the colon, thereby reducing inflammation and symptoms of the disease.
Quick Facts
Key Takeaways
- Velsipity is a once-daily oral tablet for moderate to severe ulcerative colitis in adults and adolescents 16 years and older who have not responded to or cannot tolerate other treatments.
- An ECG is required before starting treatment because Velsipity can cause a temporary decrease in heart rate and heart rhythm disturbances at initiation.
- Velsipity is contraindicated in pregnancy and women of childbearing potential must use effective contraception during treatment and for at least 14 days after stopping.
- The most common side effect is lymphopenia (low lymphocyte counts), which is part of the drug's mechanism of action but increases infection risk.
- If treatment is interrupted for 7 or more consecutive days, the first-dose monitoring precautions (taking with food, possible ECG) may need to be repeated.
What Is Velsipity and What Is It Used For?
Velsipity contains the active substance etrasimod, which represents a significant advancement in the treatment of ulcerative colitis (UC). Ulcerative colitis is a chronic inflammatory bowel disease that affects the lining of the large intestine (colon) and rectum, causing symptoms such as bloody diarrhea, abdominal pain, urgency, and fatigue. The disease follows an unpredictable course with periods of flares and remission, and it can substantially impair quality of life.
As an S1P receptor modulator, etrasimod selectively targets S1P receptors 1, 4, and 5. Its primary mechanism of action involves preventing lymphocytes (a type of white blood cell central to the inflammatory response) from traveling out of lymph nodes and into the bloodstream. Lymphocytes are key drivers of the intestinal inflammation seen in ulcerative colitis. By reducing the number of circulating lymphocytes that would otherwise migrate to the colon and perpetuate the inflammatory cycle, etrasimod helps to reduce bowel inflammation and the associated symptoms of the disease.
Velsipity is typically prescribed when patients have had an inadequate response to, lost response to, or were intolerant of conventional therapies (such as aminosalicylates, corticosteroids, or immunomodulators) or biologic agents. The approval of etrasimod was supported by the ELEVATE UC 52 and ELEVATE UC 12 phase 3 clinical trials, which demonstrated significant improvements in clinical remission, endoscopic improvement, and symptom reduction compared to placebo.
Unlike some other treatments for ulcerative colitis that require infusions or injections, Velsipity offers the convenience of a once-daily oral tablet, which may improve adherence and patient preference. The drug was approved by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) in 2023, marking it as one of the newer targeted therapies available for moderate to severe UC.
What Should You Know Before Taking Velsipity?
Starting treatment with Velsipity requires a thorough medical assessment. Because etrasimod affects the immune system and can influence heart function, your prescribing physician will need to conduct several evaluations before you begin therapy. Understanding the contraindications, warnings, and precautions associated with this medication is essential for safe and effective treatment.
Contraindications
You must not take Velsipity if any of the following apply to you:
- You are allergic to etrasimod or any of the other ingredients in the tablet
- You have a severely weakened immune system (immunodeficiency)
- You have had a heart attack, unstable angina, stroke, transient ischemic attack (TIA), or certain types of severe heart failure in the past 6 months
- You have certain types of heart rhythm disorders (arrhythmias) – your doctor will check your heart before starting treatment
- You have a serious active infection or a chronic infection such as hepatitis or tuberculosis
- You have active cancer
- You have severe liver problems
- You are pregnant or a woman of childbearing potential not using effective contraception
Warnings and Precautions
Talk to your doctor or pharmacist before taking Velsipity if you have any of the following conditions or risk factors:
Heart rate and rhythm effects: Velsipity can cause a temporary decrease in heart rate (bradycardia) and other heart rhythm disturbances when treatment is first started. Before initiating therapy, your doctor will perform an electrocardiogram (ECG). You may feel dizzy, fatigued, or become aware of your heartbeat, and your blood pressure may drop. If you have certain pre-existing heart conditions, your doctor may need to monitor you for at least the first 4 hours after your initial dose, measuring your pulse and blood pressure hourly. If treatment is interrupted for 7 or more consecutive days, ECG monitoring and the with-food requirement may be necessary again when restarting.
High blood pressure: Velsipity may increase blood pressure. Your doctor will want to monitor your blood pressure regularly during treatment, and appropriate antihypertensive therapy may be initiated or adjusted as needed.
Infections: Velsipity lowers the levels of lymphocytes in your blood, which is part of its mechanism of action but also means your ability to fight infections may be reduced. While taking Velsipity (and for approximately 2 weeks after stopping), you may be more susceptible to infections, and existing infections may worsen. Contact your doctor immediately if you develop signs of infection such as fever, flu-like symptoms, shingles, or symptoms suggestive of meningitis (headache with stiff neck, light sensitivity, nausea, rash, confusion, or seizures).
Progressive multifocal leukoencephalopathy (PML): Cases of PML have been reported with similar S1P receptor modulators. PML is a rare but serious viral brain infection that can cause severe disability or death. Symptoms include visual disturbances, increasing weakness, clumsiness, memory loss, and confusion. If you develop any of these symptoms, contact your doctor immediately.
Macular edema: Velsipity can cause swelling in the macula (the central part of the retina). The risk is higher if you have diabetes, uveitis, or other eye conditions. Your doctor will check your vision before starting treatment and regularly during therapy. Even without risk factors, an eye examination is recommended within 3 to 4 months of starting treatment. Report any changes in vision promptly, especially blurred vision, shadows, blind spots, or light sensitivity.
Cancer risk: Because Velsipity suppresses the immune system, there is an increased risk of developing cancers, particularly skin cancer. Limit sun and UV light exposure, wear protective clothing, and apply sunscreen regularly. Report any suspicious skin changes to your doctor promptly.
Posterior reversible encephalopathy syndrome (PRES): This rare condition involves swelling in the brain with symptoms such as headache, visual changes, decreased awareness, confusion, and seizures. Seek immediate medical attention if these symptoms develop.
Vaccinations: Vaccines may be less effective during Velsipity treatment. Ensure your vaccinations are up to date before starting therapy. Live vaccines should be given at least 4 weeks before initiating treatment, or at least 2 weeks after stopping Velsipity. Inactivated vaccines can generally be given during treatment, though their effectiveness may be reduced.
Liver function: Velsipity may affect liver function. Your doctor will perform blood tests to monitor your liver before, during, and after treatment. Contact your doctor if you develop symptoms of liver injury, such as yellowing of the skin or eyes, dark urine, right-sided abdominal pain, unexplained fatigue, or nausea and vomiting.
Lung problems: Velsipity may affect lung function. Patients with severe lung conditions such as pulmonary fibrosis, asthma, or chronic obstructive pulmonary disease (COPD) have a higher risk of respiratory side effects.
Pregnancy and Breastfeeding
Velsipity can cause harm to an unborn baby and must not be used during pregnancy. Women of childbearing potential must use effective contraception during treatment and for at least 14 days after stopping Velsipity. A pregnancy test is required before starting treatment. If you become pregnant while taking Velsipity, stop the medication and contact your doctor immediately.
You should not breastfeed while taking Velsipity, as etrasimod may pass into breast milk and could cause side effects in the nursing infant.
Children and Adolescents
Velsipity should not be given to children or adolescents under 16 years of age, as it has not been studied in this age group. For adolescents aged 16 and older, the same dose as for adults is used.
How Does Velsipity Interact with Other Drugs?
Drug interactions with Velsipity can arise through pharmacodynamic effects (where two drugs affect the same biological pathway) or pharmacokinetic effects (where one drug affects how the other is metabolized). Because etrasimod modulates the immune system and affects heart rate, particular caution is required when combining it with drugs that have similar effects.
Major Interactions
| Drug / Drug Class | Type of Interaction | Clinical Significance |
|---|---|---|
| Beta-blockers (e.g., metoprolol, atenolol) | Additive bradycardia | Both drugs can slow heart rate; combined use may cause clinically significant bradycardia. Enhanced first-dose cardiac monitoring may be required. |
| Calcium channel blockers (e.g., diltiazem, verapamil) | Additive bradycardia | Heart-rate-lowering calcium channel blockers may amplify Velsipity's effects on heart rhythm. Close cardiac monitoring recommended. |
| Antiarrhythmic drugs (e.g., amiodarone, flecainide) | Additive cardiac effects | These drugs affect heart rhythm and should generally not be co-administered with Velsipity without specialist supervision. |
| Fluconazole and other CYP2C8 inhibitors | Increased etrasimod levels | Fluconazole and similar drugs can increase the blood concentration of etrasimod, increasing the risk of side effects. Co-administration is not recommended. |
| Rifampicin, enzalutamide and other CYP inducers | Decreased etrasimod levels | Strong enzyme inducers reduce etrasimod blood levels, potentially making the treatment less effective. Co-administration is not recommended. |
| Live vaccines | Immunosuppression risk | Live vaccines may trigger the infection they are meant to prevent. Give live vaccines at least 4 weeks before starting or 2 weeks after stopping Velsipity. |
Other Interactions
Immunosuppressive therapies: Using other immunosuppressive drugs alongside Velsipity may result in an additive effect on the immune system, increasing the risk of infections. When switching from other UC treatments, your doctor will usually advise stopping those treatments (with the possible exception of corticosteroids and mesalazine) before starting Velsipity. An appropriate washout period may be necessary to reduce the risk of overlapping immunosuppression.
Hormonal contraceptives: Velsipity may slightly increase the levels of hormones released from certain oral contraceptive pills. While you will still be protected from pregnancy, the risk of experiencing hormonal contraceptive side effects may be marginally higher. Discuss any new side effects with your doctor.
Tell your doctor or pharmacist about all medicines you take, have recently taken, or plan to take, including over-the-counter drugs, supplements, and herbal products. Your doctor will assess potential interactions and advise you accordingly.
What Is the Correct Dosage of Velsipity?
Treatment with Velsipity should be initiated and supervised by a physician experienced in the management of ulcerative colitis. The dosing regimen is straightforward, but there are important considerations regarding how to take the medication, what to do if doses are missed, and precautions that apply when restarting after an interruption.
Adults and Adolescents (16 years and older)
Standard Dosage
Dose: 2 mg once daily
Route: Oral (swallow tablet whole with water)
First 3 days: Must be taken with food
After day 3: May be taken with or without food
Important: Do not split, crush, or chew the tablet, as this may alter absorption.
| Patient Group | Recommended Dose | Special Considerations |
|---|---|---|
| Adults (18+ years) | 2 mg once daily | ECG before first dose; take with food for first 3 days |
| Adolescents (16–17 years) | 2 mg once daily | Same as adults; supervised by specialist |
| Children (<16 years) | Not recommended | Safety and efficacy not established |
| Elderly (≥65 years) | 2 mg once daily | No dose adjustment required; limited clinical experience |
| Mild to moderate hepatic impairment | 2 mg once daily | No dose adjustment required; monitor liver function |
| Severe hepatic impairment | Contraindicated | Do not use |
| Renal impairment | 2 mg once daily | No dose adjustment required |
Missed Dose
If you forget to take a dose of Velsipity, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for a forgotten one. Taking the medication at the same time each day can help establish a routine and reduce the likelihood of missing doses.
Overdose
If you take more Velsipity than prescribed, contact your doctor immediately or go to the nearest hospital emergency department. Bring the medication package and this information with you. In clinical studies, no specific overdose cases with etrasimod have been reported, but based on its pharmacological action, an overdose could potentially cause pronounced bradycardia and increased immunosuppression.
Stopping or Restarting Treatment
Do not stop taking Velsipity or change your dose without first consulting your doctor. If your treatment is interrupted for 7 or more consecutive days, the following precautions apply when restarting:
- Take the tablet with food for the first 3 days of re-initiation
- Your doctor may perform an ECG before restarting, as the first-dose heart rate effects can recur
- Depending on your heart condition, you may need at least 4 hours of monitoring after the re-initiation dose
After stopping Velsipity, the drug and its effects remain in the body for up to approximately 14 days. During this period, your lymphocyte count may remain low, and side effects may still occur.
What Are the Side Effects of Velsipity?
Like all medicines, Velsipity can cause side effects, although not everyone experiences them. Many of the side effects are related to the drug's mechanism of action on the immune system and its transient effects on heart function. Your doctor will monitor you for the most important potential complications through regular blood tests, heart monitoring, and eye examinations.
Below is a classification of side effects by frequency, based on clinical trial data and post-marketing surveillance:
Very Common
May affect more than 1 in 10 people
- Lymphopenia – low levels of lymphocytes (a type of white blood cell). This is an expected effect of the drug's mechanism but increases infection susceptibility.
Common
May affect up to 1 in 10 people
- Bradycardia – slow heart rate, usually transient at treatment start
- Hypertension – elevated blood pressure
- Urinary tract infection
- Lower respiratory tract infection (e.g., bronchitis, pneumonia)
- Hypercholesterolemia – elevated blood cholesterol levels
- Headache
- Dizziness
- Elevated liver enzymes – may indicate liver stress
- Neutropenia – low levels of neutrophils (another type of white blood cell)
- Visual impairment
Uncommon
May affect up to 1 in 100 people
- Atrioventricular (AV) block – a type of heart rhythm disturbance where the electrical signal between the upper and lower chambers of the heart is delayed or blocked
- Macular edema – swelling in the central part of the retina, which can cause visual changes including blurred vision and blind spots
- Signs of serious infection: high fever, severe flu-like symptoms, shingles, stiff neck with headache and light sensitivity
- Visual changes: blurred vision, shadows or blind spots in the center of your vision, light sensitivity, or unusually tinted vision
- Signs of PML: progressive weakness, clumsiness, visual problems, memory loss, confusion
- Signs of liver damage: yellowing of skin or eyes, dark urine, unexplained right-sided abdominal pain
- Signs of PRES: sudden severe headache, vision changes, confusion, seizures
The risk of infections continues for approximately 2 weeks after stopping Velsipity, as the drug takes this long to clear from the body and for lymphocyte counts to recover. Be vigilant for signs of infection during this washout period.
If you experience any side effects not listed here, or if any side effects become serious, inform your doctor or pharmacist. Reporting suspected adverse reactions helps ensure ongoing monitoring of the medicine's benefit-risk balance.
How Should You Store Velsipity?
Proper storage of Velsipity ensures the medication remains effective and safe throughout its shelf life. The following storage guidelines should be observed:
- Keep out of the sight and reach of children
- No special temperature storage requirements – store at room temperature
- Keep in the original packaging to protect from moisture
- Do not use after the expiry date (EXP) printed on the bottle, blister, or carton. The expiry date refers to the last day of that month.
- Do not use if the packaging appears damaged or shows signs of tampering
- Do not dispose of medicines via wastewater or household waste. Ask your pharmacist about safe disposal of unused medicines to help protect the environment.
Velsipity is available in bottles of 30 film-coated tablets and in blister packs of 28 or 98 film-coated tablets. Not all pack sizes may be available in your country.
What Does Velsipity Contain?
Understanding the full composition of your medication is important, particularly if you have known allergies to specific excipients (inactive ingredients). Below is the complete list of ingredients in Velsipity 2 mg film-coated tablets.
Active substance: Etrasimod arginine, equivalent to 2 mg etrasimod per tablet.
Tablet core (inactive ingredients):
- Magnesium stearate (E470b)
- Mannitol (E421)
- Microcrystalline cellulose (E460i)
- Sodium starch glycolate (type A)
Film coating:
- Brilliant blue FCF aluminium lake (E133)
- Indigo carmine aluminium lake (E132)
- Tartrazine aluminium lake (E102)
- Macrogol 4000 (E1521)
- Poly(vinyl alcohol) (E1203)
- Talc (E553b)
- Titanium dioxide (E171)
The coating of Velsipity contains tartrazine (E102), which may cause allergic reactions in some individuals, particularly those with aspirin sensitivity. Inform your doctor if you have a known sensitivity to tartrazine or azo dyes.
Sodium content: This medicine contains less than 1 mmol (23 mg) sodium per tablet and is essentially sodium-free.
Appearance: Velsipity 2 mg is a green, round, film-coated tablet approximately 6 mm in diameter, debossed with "ETR" on one side and "2" on the other side.
Marketing authorization holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.
Manufacturers: Almac Pharma Services (Ireland) Limited, Dundalk, Ireland; and Almac Pharma Services Limited, Portadown, Craigavon, United Kingdom.
Can You Drive While Taking Velsipity?
Based on clinical trial data, etrasimod has little or no influence on the ability to drive and use machines under normal circumstances. However, because dizziness is a common side effect and heart rate changes can occur particularly in the early days of treatment, caution is warranted during this period. If you experience dizziness or feel unwell after taking Velsipity, refrain from driving or operating machinery until the symptoms pass. Individual responses to the medication may vary, so use your own judgment regarding activities that require alertness and coordination.
Frequently Asked Questions About Velsipity
Velsipity (etrasimod) is used for the treatment of moderate to severe active ulcerative colitis (UC) in adults and adolescents aged 16 years and older. It is prescribed for patients who have had an inadequate response to, lost response to, or were intolerant of conventional therapy or a biologic agent. It is not approved for Crohn's disease or other forms of inflammatory bowel disease.
Velsipity is an oral, once-daily S1P receptor modulator, which distinguishes it from biologic therapies (like anti-TNF agents or integrin inhibitors) that require infusions or injections. Compared to ozanimod (another oral S1P modulator approved for UC), etrasimod has a different selectivity profile for S1P receptors. Unlike JAK inhibitors (such as tofacitinib or upadacitinib), which broadly inhibit intracellular signaling, etrasimod acts by sequestering lymphocytes in lymph nodes, offering a distinct mechanism and side effect profile.
An ECG is required because Velsipity can temporarily slow the heart rate and affect heart rhythm when treatment is first started. The ECG helps your doctor ensure that you do not have an underlying heart rhythm disorder that could be worsened by the medication. If you have certain pre-existing heart conditions, your doctor may also monitor you for at least 4 hours after your first dose. This precaution helps identify any clinically significant cardiac effects early.
No. Velsipity is contraindicated during pregnancy due to the risk of harm to the unborn baby. Based on findings in animal studies, etrasimod may cause birth defects. Women of childbearing potential must use effective contraception while taking Velsipity and for at least 14 days after stopping treatment. A negative pregnancy test is required before starting therapy. If you become pregnant while taking Velsipity, stop the medication immediately and contact your doctor.
If you forget to take a dose, simply skip it and take your next scheduled dose at the usual time. Do not take a double dose. If you miss doses for 7 or more consecutive days, contact your doctor before restarting, as additional precautions such as taking the tablet with food for the first 3 days and possibly an ECG may be necessary.
In clinical trials, some patients began to experience symptom improvements within the first few weeks of treatment. However, the full therapeutic benefit of Velsipity may take several months to develop. In the ELEVATE UC 52 trial, significant improvements were seen at week 12 and were maintained through week 52. Your doctor will assess your response and determine whether to continue treatment based on your individual progress.
References
- European Medicines Agency (EMA). Velsipity (etrasimod) – Summary of Product Characteristics. European Public Assessment Report. 2023. Available at: ema.europa.eu
- Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. The Lancet. 2023;401(10383):1159-1171. doi:10.1016/S0140-6736(23)00061-2
- U.S. Food and Drug Administration (FDA). FDA approves new treatment for moderately to severely active ulcerative colitis. FDA News Release. October 2023.
- Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: Ulcerative Colitis in Adults. American Journal of Gastroenterology. 2019;114(3):384-413.
- Raine T, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. Journal of Crohn's and Colitis. 2022;16(1):2-17.
- World Health Organization (WHO). Inflammatory bowel disease – factsheet. Available at: who.int
- British National Formulary (BNF). Etrasimod. NICE Evidence. 2024. Available at: bnf.nice.org.uk
Editorial Team
This article was written by the iMedic Medical Editorial Team, which includes specialists in gastroenterology, clinical pharmacology, and inflammatory bowel disease. All content is reviewed according to international medical guidelines and follows the iMedic Editorial Standards.
Reviewed by board-certified gastroenterologists with expertise in inflammatory bowel disease and immunomodulatory therapy.
Based on EMA SmPC, FDA prescribing information, ACG and ECCO clinical guidelines, and peer-reviewed clinical trial data (ELEVATE UC program).
Conflict of interest: The iMedic editorial team receives no funding from pharmaceutical companies. This content is entirely independent and is not sponsored, endorsed, or influenced by the manufacturer of Velsipity.