Etragut

Etragut is a sphingosine 1-phosphate receptor modulator indicated for the treatment of moderately to severely active ulcerative colitis in adults.

The recommended dosage of Etrasimod is 2 mg orally once daily. Swallow the tablet whole, with or without food. If a dose is missed, take the missed dose at the next scheduled time; do not double the next dose.

Etrasimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1, 4, and 5 (S1P

• 1,4,5
• ). Etrasimod has minimal activity on S1P
• 3
• (25-fold lower than C
• max
• at the recommended dose) and no activity on S1P
• 2

. Etrasimod partially and reversibly blocks the capacity of lymphocytes to egress from lymphoid organs, reducing the number of lymphocytes in peripheral blood. The mechanism by which etrasimod exerts therapeutic effects in UC is unknown but may involve the reduction of lymphocyte migration into the intestines.

Most common adverse reactions (incidence ≥5%) are: headache, elevated liver tests, and dizziness.

In the last 6 months, experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker.

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.

Bradyarrhythmia and Atrioventricular Conduction Delays

: May result in a transient decrease in heart rate and AV conduction delays. Obtain an

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.

Liver Injury

: Elevations of aminotransferases may occur. Obtain transaminase and bilirubin levels before initiating Etragut. Discontinue if significant liver injury is confirmed.

Macular Edema

: May increase the risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with Etragut. Periodically conduct an evaluation of the fundus, including the macula, while on therapy and any time there is a change in vision. Consider discontinuing Etragut if macular edema develops.

Increased Blood Pressure

: Monitor blood pressure during treatment.

Fetal Risk

: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for one week after stopping Etragut.

Cutaneous Malignancies

: Obtain a skin examination prior to or shortly after the start of treatment and periodically during treatment, especially if risk factors. Promptly evaluate suspicious skin lesions.

Posterior Reversible Encephalopathy Syndrome (PRES)

: If symptoms develop, obtain a physical and neurological exam, and consider MRI.

Respiratory Effects

: May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated.

Unintended Additive Immune System Effects from Prior Treatment with Immunosuppressive or Immune-Modulating Drugs

: Consider the half-life and mode of action of prior therapies.

Immune System Effects After Stopping Etragut

: If using concomitant immunosuppressants, monitor patients for infectious complications for up to 5 weeks after the last dose of Etragut

There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to Etrasimod during pregnancy. 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.

Etragut 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.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.