VELSIPITY™ (etrasimod) 7 DRUG INTERACTIONS

(etrasimod)

Prescribing Information

7 DRUG INTERACTIONS

Etrasimod is primarily metabolized by CYP2C8, CYP2C9, and CYP3A4. Table 3 includes drugs with clinically important drug interactions when administered concomitantly with VELSIPITY and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information.

The effect of concomitant use of VELSIPITY with a combination of separate drugs that are moderate to strong inhibitors or inducers of either CYP2C8, CYP2C9, or CYP3A4 is unknown. However, based on the information below, a similar clinically significant change in exposure cannot be ruled out when two or more metabolic pathways are affected.

Table 3: Drugs That Affect VELSIPITY CYP-Mediated Metabolic Pathways
Anti-Arrhythmic Drugs and QT Prolonging Drugs
Clinical Impact	A transient decrease in heart rate and AV conduction delays may occur when initiating VELSIPITY [see Warnings and Precautions (5.2)]. Because of the potential additive effect on heart rate, VELSIPITY may increase the risk of QT prolongation and Torsades de Pointes with concomitant use of Class Ia and Class III anti-arrhythmic drugs and QT prolonging drugs.
Prevention or Management	Seek the advice of a cardiologist before initiating VELSIPITY treatment with Class Ia (e.g., quinidine, procainamide), Class III anti-arrhythmic drugs (e.g., amiodarone, sotalol), or other drugs that prolong the QT interval.
Beta-Blockers or Calcium Channel Blockers
Clinical Impact	A transient decrease in heart rate and AV conduction delays may occur when initiating VELSIPITY [see Warnings and Precautions (5.2)]. Concomitant use of VELSIPITY in patients receiving stable beta blocker treatment did not result in additive effects on heart rate reduction [see Clinical Pharmacology (12.2)]. However, the risk of additive heart rate reduction following initiation of beta blocker therapy with stable VELSIPITY treatment or concomitant use with other drugs that may decrease heart rate is unknown.
Prevention or Management	VELSIPITY can be initiated in patients receiving stable doses of beta blocker treatment. Seek the advice of a cardiologist before initiating a beta blocker in a patient receiving stable VELSIPITY treatment or concomitant use with other drugs that may decrease heart rate (e.g., calcium channel blockers).
Anti-Neoplastic, Immune-Modulating, or Non-Corticosteroid Immunosuppressive Therapies
Clinical Impact	Risk of additive immune system effects with VELSIPITY VELSIPITY has not been studied in combination with anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies.
Prevention or Management	Avoid concomitant administration during and in the weeks following administration of VELSIPITY. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects [see Warnings and Precautions (5.10)].
Moderate to Strong Inhibitors of CYP2C9 and CYP3A4
Clinical Impact	Increased exposure of etrasimod was observed with concomitant use with a drug that is a moderate inhibitor of CYP2C9 and a moderate inhibitor of CYP3A4 (i.e., fluconazole) [see Clinical Pharmacology (12.3)].
Prevention or Management	Concomitant use with a drug that is a moderate to strong inhibitor of CYP2C9 and a moderate to strong inhibitor of CYP3A4 is not recommended.
CYP2C9 Poor Metabolizers Using Moderate to Strong Inhibitors of CYP2C8 or CYP3A4
Clinical Impact	Increased exposure of etrasimod in patients who are CYP2C9 poor metabolizers is expected with concomitant use of moderate to strong inhibitors of CYP2C8 or CYP3A4 [see Clinical Pharmacology (12.3, 12.5)].
Prevention or Management	Concomitant use not recommended.
Rifampin
Clinical Impact	Concomitant use with a drug that is a combined CYP3A4 (strong), CYP2C8 (moderate) and CYP2C9 (moderate) inducer (i.e., rifampin) decreases exposure to etrasimod [see Clinical Pharmacology (12.3)].
Prevention or Management	Concomitant use not recommended.

Medication Guide

MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 06/2024
MEDICATION GUIDE VELSIPITY™ (Vel-sip-itee) (etrasimod) tablets, for oral use
Read this Medication Guide before you start taking VELSIPITY and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or treatment.
What is the most important information I should know about VELSIPITY? VELSIPITY can cause serious side effects, including:
1. Infections. VELSIPITY can increase your risk of serious infections. These infections can be life-threatening and cause death. VELSIPITY lowers the number of white blood cells (lymphocytes) in your blood. This usually returns to normal within 4 to 5 weeks after you stop taking VELSIPITY. Your healthcare provider will test your blood before you start taking VELSIPITY. Call your healthcare provider right away if you have any of these symptoms of an infection during treatment with VELSIPITY, and for 5 weeks after you stop taking VELSIPITY:
	• fever or high temperature • tiredness • flu-like symptoms	• pain when peeing or peeing more often than usual. These can be signs of a urinary tract infection. • headache with fever, neck stiffness, sensitivity to light, nausea, or confusion. These may be symptoms of meningitis, an infection of the lining around your brain and spine.
Your healthcare provider may delay or stop your VELSIPITY treatment if you have an infection. 2. Slow heart rate (also known as bradyarrhythmia) when you start taking VELSIPITY. VELSIPITY may cause your heart rate to temporarily slow down especially after you take your first dose. You will have a test called an electrocardiogram (ECG) to check the electrical activity of your heart before you take your first dose of VELSIPITY. Call your healthcare provider if you experience these symptoms of slow heart rate:
	• feeling dizzy • feeling lightheaded • feeling like your heart is beating slowly or skipping beats • feeling short of breath			• feeling confused • feeling tired • chest pain
See "What are the possible side effects of VELSIPITY?" for more information about side effects.
What is VELSIPITY? • VELSIPITY is a prescription medicine used to treat adults with moderately to severely active ulcerative colitis. It is not known if VELSIPITY is safe and effective in children.
Do not take VELSIPITY if you: • have had a heart attack, chest pain (unstable angina), stroke or mini stroke (transient ischemic attack or TIA), and certain types of heart failure requiring hospitalization in the last 6 months. • have or have had a history of unusual heartbeats (arrhythmia) that is not corrected by a pacemaker. Talk to your healthcare provider before taking VELSIPITY if you have any of these conditions or do not know if you have any of these conditions.
Before taking VELSIPITY, tell your healthcare provider about all of your medical conditions, including if you: • have a serious infection or an infection that does not go away or that keeps coming back (chronic). • are unable to fight infections due to a disease. • have received a vaccine in the past 4 weeks or are scheduled to receive a vaccine. You should be brought up to date with all age required vaccines before starting treatment with VELSIPITY. VELSIPITY may affect how well a vaccine works. Tell your healthcare provider that you are receiving treatment with VELSIPITY before receiving a vaccine. • have chickenpox or received the vaccine for chickenpox. Your healthcare provider may do a blood test for the chickenpox virus. You may need to get the full course of the chickenpox vaccine and then wait 4 weeks before you start taking VELSIPITY. • have a slow heart rate. • have an irregular or abnormal heartbeat (arrhythmia). • have heart disease, Class I or II heart failure, history of a heart attack, high blood pressure or uncontrolled high blood pressure. • have cerebrovascular disease or history of a stroke or ministroke. • history of repeated fainting. • have or have had liver problems. • have or have had skin cancer. • have breathing problems, including untreated sleep apnea. • are pregnant or plan to become pregnant. VELSIPITY may harm your unborn baby. Talk with your healthcare provider if you are pregnant or plan to become pregnant. If you are a female who can become pregnant, you should use effective birth control during your treatment with VELSIPITY and for 7 days after you stop taking VELSIPITY. Talk to your healthcare provider about what birth control method is right for you during this time. Tell your healthcare provider right away if you become pregnant while taking VELSIPITY or within 7 days after you stop taking VELSIPITY. Pregnancy Registry: There is a registry for women who become pregnant during treatment with VELSIPITY. If you become pregnant while taking VELSIPITY, talk to your healthcare provider about registering with the VELSIPITY Pregnancy Registry. The purpose of this registry is to collect information about your health and your baby’s health. Either you or your healthcare provider can contact this registry by calling 1-800-616-3791. • are breastfeeding or plan to breastfeed. It is not known if VELSIPITY passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take VELSIPITY. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using VELSIPITY with other medicines can cause serious side effects. Especially tell your healthcare provider if you take or have taken: • medicines to control your heart rhythm (antiarrhythmics), heartbeat, or blood pressure. These may be called beta blockers or calcium channel blockers. • medicines that affect your immune system. • certain medicines known as moderate to strong inhibitors of both CYP2C9 and CYP3A4, medicines such as fluconazole. If you are taking fluconazole, you should not take VELSIPITY. • Rifampin. If you are taking rifampin, you should not take VELSIPITY. You should not receive live vaccines at least 4 weeks before starting VELSIPITY, during treatment with VELSIPITY and for 5 weeks after you stop taking VELSIPITY. Talk to your healthcare provider before you receive a vaccine during treatment and for 5 weeks after treatment with VELSIPITY. If you receive a live vaccine, you may get the infection the vaccine was meant to prevent. Vaccines may not work as well when given during treatment with VELSIPITY. Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of your medicines to show the list to your healthcare provider and pharmacist when you get a new medicine.
How should I take VELSIPITY? • Take VELSIPITY exactly as your healthcare provider tells you to take it. • Take VELSIPITY 1 time each day. • Swallow VELSIPITY tablets whole. • Take VELSIPITY with or without food. • If a dose is missed, take the missed dose at the next scheduled time; do not double the next dose.
What are the possible side effects of VELSIPITY? VELSIPITY can cause serious side effects, including: • See "What is the most important information I should know about VELSIPITY?" • Liver problems. VELSIPITY may cause liver problems. Your healthcare provider will do blood tests to check your liver before you start taking VELSIPITY. Call your healthcare provider right away if you have any of the following symptoms:
	• unexplained nausea • vomiting • stomach area (abdominal pain) • tiredness		• loss of appetite • yellowing of the whites of your eyes or skin • dark colored urine
If you develop any of these symptoms, your healthcare provider will do blood tests to check your liver and may stop your treatment with VELSIPITY. • Increased blood pressure. Your healthcare provider should check your blood pressure during treatment with VELSIPITY and treat you as needed. • A problem with your vision called macular edema. Your healthcare provider should test your vision around the time you start taking VELSIPITY or at any time you notice vision changes during your treatment with VELSIPITY. Call your healthcare provider right away if you have any of the following symptoms:
	• blurriness or shadows in the center of your vision • sensitivity to light				• a blind spot in the center of your vision • unusually colored vision
• Types of skin cancer. Certain types of skin cancer have happened with medicines in the same class as VELSIPITY. Limit the amount of time you spend in sunlight and ultraviolet (UV) light while taking VELSIPITY. Wear protective clothing and use a sunscreen with a high sun protection factor. Tell your healthcare provider if you have any changes in the appearance of your skin. • Swelling and narrowing of the blood vessels in your brain. A condition called Posterior Reversible Encephalopathy Syndrome (PRES) has happened with drugs in the same class. Symptoms of PRES usually get better when you discontinue treatment. If not treated, PRES may cause a stroke. Call your healthcare provider right away if you have any of the following symptoms: o sudden severe headache o sudden confusion o sudden loss of vision or other changes in your vision o seizure o If you develop any of these symptoms, your healthcare provider will stop treatment with VELSIPITY. • Breathing problems. Some people who take medicines in the same class as VELSIPITY may experience shortness of breath. Your healthcare provider may do tests to check your breathing during treatment with VELSIPITY. Call your healthcare provider right away if you have new or worsening breathing problems. The most common side effects of VELSIPITY include headache, elevated liver tests, and dizziness. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of VELSIPITY. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Pfizer at 1-800-438-1985.
How should I store VELSIPITY? • Store VELSIPITY at room temperature between 68°F to 77°F (20°C to 25°C). Keep VELSIPITY and all medicines out of the reach of children.
General information about the safe and effective use of VELSIPITY. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VELSIPITY for a condition for which it was not prescribed. Do not give VELSIPITY to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about VELSIPITY that is written for health professionals.
What are the ingredients in VELSIPITY? Active ingredient: etrasimod arginine. Inactive ingredients: Tablet core: magnesium stearate, mannitol, microcrystalline cellulose, and sodium starch glycolate. Tablet coating: FD&C blue #1/brilliant blue FCF aluminum lake, FD&C blue #2/indigo carmine aluminum lake, FD&C yellow #5/tartrazine aluminum lake, macrogol 4000 JP/PEG 3350, polyvinyl alcohol (partially hydrolyzed), talc, and titanium dioxide. LAB-1541-2.0

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