Etrasimod

<p>Ulcerative Colitis</p>

<p>Oral<br /> Tablet<br /> Ulcerative Colitis<br /> Indicated for adults with moderately-to-severely active ulcerative colitis (UC)</p> <p>2 mg PO once daily<br /> &nbsp;</p>

<p>Safety and efficacy not established<br /> &nbsp;</p>

<p>Renal impairment<br /> Minimally excreted in urine; no dosage adjustment necessary</p>

<p>Hepatic impairment<br /> Mild or moderate (Child-Pugh A and B): No dosage adjustment necessary<br /> Severe (Child-Pugh C): Not recommended</p>

<p>Oral Administration<br /> May take with or without food</p>

<p>In previous 6 months, experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure</p> <p>History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block, unless patient has a functioning pacemaker<br /> &nbsp;</p>

<p>Hypertension reported; monitor blood pressure during treatment and manage appropriately</p> <p>Based on animal studies, may cause fetal harm when administered to pregnant females</p> <p>Reductions in absolute forced expiratory volume over 1 second (FEV1) were observed; perform spirometric evaluation of respiratory function during therapy if clinically indicated</p> <p>Infections: May increase the risk of infections. Obtain a complete blood count (CBC) before initiation of treatment. Monitor for infection during treatment and for 5 weeks after discontinuation. Consider interruption of treatment if a serious infection develops. Avoid use of live attenuated vaccines during and for up to 5 weeks after treatment.</p> <p>Bradyarrhythmia and Atrioventricular Conduction Delays: May result in a transient decrease in heart rate and AV conduction delays. Obtain an<br /> electrocardiogram (ECG) to assess for preexisting cardiac conduction abnormalities before starting treatment. Consider cardiology consultation for conduction abnormalities or concomitant use with other drugs that decrease heart rate.</p> <p>Liver Injury: Elevations of aminotransferases may occur. Obtain transaminase and bilirubin levels before initiating Etrasimod. Discontinue if significant liver injury is confirmed.</p>

<p>Pregnancy<br /> Based on findings from animal studies, fetal harm may occur when administered to pregnant females</p> <p>Available data from reports of pregnancies from the clinical development program are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes</p> <p>There are risks to the mother and the fetus associated with increased disease activity in women with inflammatory bowel disease during pregnancy</p> <p>Published data suggest that the risk of adverse pregnancy outcomes in females with inflammatory bowel disease is associated with increased disease activity; adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (&lt;2500 g) infants, and small for gestational age at birth</p> <p>Contraception<br /> Before initiating, counsel females of reproductive potential on the potential for a serious risk to the fetus and the need for effective contraception during treatment and for 1week following last dose</p> <p>Animal data<br /> 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)<br /> Administration to pregnant rats during organogenesis through lactation resulted in decreased pup growth and viability at maternal exposures 5x 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 24x the exposure at the MRHD</p> <p>Lactation<br /> There are no data on presence of etrasimod in human milk, effects on the breastfed infants, or effects of the drug on milk production<br /> When orally administered to female rats during pregnancy and lactation, etrasimod was detected in the plasma of offspring, suggesting excretion of etrasimod in milk<br /> &nbsp;</p>

<p>1-10%<br /> Headache (6-9%)</p> <p>Elevated liver tests (5-6%)</p> <p>Dizziness (5%)</p> <p>Arthralgia (4%)</p> <p>Nausea (3-4%)</p> <p>Hypertension (3%)</p> <p>Urinary tract infection (3%)</p> <p>Hypercholesterolemia (3%)</p> <p>Urinary tract infection (3%)</p> <p>Bradycardia (3%)</p> <p>Herpes viral infection (2%)</p> <p>Decrease in visual acuity (2.6%)</p>

<p>Sphingosine 1-phosphate (S1P) receptor 1 modulator; binds with high affinity to S1P receptors 1, 4, and 5</p> <p>Blocks capacity of lymphocytes to egress from lymphoid organs, reducing number of lymphocytes in peripheral blood to decrease inflammation</p> <p>Mechanism by which etrasimod exerts therapeutic effects in ulcerative colitis is unknown, but may involve reduction of lymphocyte migration into the intestines<br /> &nbsp;</p>