VELSIPITY™ (etrasimod) 8 USE IN SPECIFIC POPULATIONS

(etrasimod)

Prescribing Information

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to VELSIPITY during pregnancy. Pregnant females exposed to VELSIPITY and healthcare providers are encouraged to contact the pregnancy registry by calling 1-800-616-3791.

Risk Summary

Based on findings from animal studies, VELSIPITY may cause fetal harm when administered to a pregnant woman. Available data from reports of pregnancies from the clinical development program with VELSIPITY are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with increased disease activity in women with inflammatory bowel disease during pregnancy (see Clinical Considerations).

In animal reproduction studies, administration of etrasimod during organogenesis produced adverse effects on development, including embryolethality and fetal malformations, in both rats and rabbits at maternal exposures 5 and 6 times, respectively, the exposure at the maximum recommended human dose (MRHD). Administration of VELSIPITY to pregnant rats during organogenesis through lactation resulted in decreased pup growth and viability at maternal exposures 5 times the exposure at the MRHD, as well as impaired reproductive performance in first generation offspring, including decreased implantations and increased pre-implantation loss at maternal exposures 24 times the exposure at the MRHD (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

Data

Animal Data

In an embryo-fetal development study in pregnant rats, etrasimod was orally administered at 1, 2, or 4 mg/kg/day (5, 11, and 21 times the exposure at the MRHD of 2 mg, based on AUC comparison) during the period of organogenesis, from gestation day 6 to 17. No maternal toxicity was observed up to 21 times the exposure at the MRHD. Increased post-implantation loss with a corresponding decrease in the number of viable fetuses was observed at 4 mg/kg/day (21 times the exposure at the MRHD). Etrasimod-related fetal external and/or visceral malformations were noted at all dose levels (≥5 times the exposure at the MRHD).

In an embryo-fetal development study in pregnant rabbits, etrasimod was orally administered at 2, 10, or 20 mg/kg/day (0.8, 6, and 11 times the exposure at the MRHD of 2 mg, based on AUC comparison) during the period of organogenesis, from gestation day 7 to 20. Increased post-implantation loss with a corresponding decrease in the number of viable fetuses was observed at 10 and 20 mg/kg/day (6 and 11 times the exposure at the MRHD). Etrasimod-related fetal malformations including aortic arch defects and fused sternebrae were noted at 10 and/or 20 mg/kg/day (6 and 11 times the exposure at the MRHD). There were no adverse effects on embryofetal development at 2 mg/kg/day (less than the exposure at the MRHD).

In a pre- and post-natal development study in rats, etrasimod was orally administered at 0.4, 2, or 4 mg/kg/day (2, 10, and 24 times the exposure at the MRHD of 2 mg, based on AUC comparison) throughout pregnancy and lactation, from gestation day 6 through lactation day 20. Mortality during delivery and impaired maternal performance including increased post-implantation loss, increased number of females with stillborn pups, increased number of stillborn pups per litter, decreased viability index, and/or decreased lactation index was observed at 2 and 4 mg/kg/day (10 and 24 times the exposure at the MRHD). Etrasimod was detected in the plasma of F1 offspring, indicating exposure from the milk of the lactating dam. Decreased pup body weights were observed during the preweaning period at all dose levels (maternal exposures ≥2 times the exposure at the MRHD), and decreased pup viability was observed at 2 and 4 mg/kg/day (maternal exposures 10 and 24 times the exposure at the MRHD). Reduced fertility and reproductive performance including reduction in implantations and increased preimplantation loss in F1 offspring occurred at the highest dose tested (maternal exposures 24 times the exposure at the MRHD).

8.2 Lactation

Risk Summary

There are no data on the presence of etrasimod in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. When etrasimod was orally administered to female rats during pregnancy and lactation, etrasimod was detected in the plasma of the offspring, suggesting excretion of etrasimod in milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VELSIPITY and any potential adverse effects on the breastfed infant from VELSIPITY or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

Based on animal data, VELSIPITY may cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)].

Contraception

Females

Before initiation of VELSIPITY treatment, females of reproductive potential should be counseled on the potential for a serious risk to the fetus and the need for effective contraception during treatment with VELSIPITY and for one week following the last dose [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1)].

8.4 Pediatric Use

The safety and effectiveness of VELSIPITY in pediatric patients have not been established.

8.5 Geriatric Use

Of the 577 VELSIPITY-treated subjects in the three clinical trials (UC-1, UC-2, and UC-3), 30 subjects (5%) were 65 years of age and older, while 3 subjects (<1%) were 75 years of age and older. Clinical studies of VELSIPITY did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger adult subjects. The pharmacokinetics of etrasimod are similar in subjects 65 years of age and older compared to younger adult subjects [see Clinical Pharmacology (12.3)].

8.6 Hepatic Impairment

Etrasimod undergoes extensive hepatic metabolism. Exposure to etrasimod was similar in subjects with mild and moderate hepatic impairment (Child-Pugh A and B) compared to subjects with normal hepatic function; however, etrasimod exposure was increased in subjects with severe hepatic impairment (Child‑Pugh C) compared to subjects with normal hepatic function [see Clinical Pharmacology (12.3)].

Use of VELSIPITY in patients with severe hepatic impairment is not recommended. No dosage adjustment is needed in patients with mild to moderate hepatic impairment.

8.7 CYP2C9 Poor Metabolizers

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. Concomitant use of VELSIPITY is not recommended in these patients [see Clinical Pharmacology (12.3, 12.5)].

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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