Etrasimod

Etrasimod is a prescription medication used for the treatment of adults with moderately to severely active ulcerative colitis (UC).

• Etrasimod is available under the following different brand names: Velsipity.

Common side effects of Etrasimod include:

• headache
• elevated values on liver tests 
• worsening of UC
• SARS-CoV-2 infection 
• dizziness 
• pyrexia
• arthralgia
• abdominal pain
• nausea

Serious side effects of Etrasimod include:

• liver problems
• increased blood pressure
• swelling and narrowing of the blood vessels in your brain
• breathing problems
• slow heart rate

Rare side effects of Etrasimod include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 2 mg

UC

Adult dosage

• 2 mg orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Etrasimod has severe interactions with no other drugs
• Etrasimod has serious interactions with no 221 other drugs
• Etrasimod has moderate interactions with 73 other drugs
• Etrasimod has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• In the 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
• History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Etrasimod?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Etrasimod?”

Cautions

• Hypertension reported; monitor blood pressure during treatment and manage appropriately
• Based on animal studies, may cause fetal harm when administered to pregnant women
• Reductions in absolute forced expiratory volume over 1 second were observed; perform the spirometric evaluation of respiratory function during therapy if clinically indicated
• Malignancies
  • Cases of malignancies (including skin malignancies) reported; recommend skin examinations before or shortly after the start of treatment and periodically thereafter for all patients, particularly those with risk factors for skin cancer
  • Monitor for suspicious skin lesions
  • If a suspicious skin lesion is observed, promptly evaluate
  • Advise to limit exposure to sunlight and ultraviolet light by wearing protective clothing and using a sunscreen with a high protection factor
• Posterior reversible encephalopathy syndrome (PRES)
  • Rare cases of PRES reported
  • If any neurological or psychiatric symptoms/signs (eg, cognitive deficits, behavioral changes, cortical visual disturbances, or any other neurological cortical symptoms/signs), any symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological deterioration develop, promptly schedule a complete physical and neurological examination and consider an MRI
  • Symptoms of PRES are usually reversible but may evolve into an ischemic stroke or cerebral hemorrhage
  • Delay in diagnosis and treatment may lead to permanent neurological sequelae
  • If PRES is suspected, discontinue treatment
• Immune system effects with immunosuppressive or immune-modulating drugs
  • When switching to etrasimod from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects
  • Use of immunosuppressants within this period may lead to an additive effect on the immune system, and therefore, monitor patients receiving concomitant immunosuppressants for infectious complications up to 5 weeks after the last dose
• Increased risk for infections
  • Causes a mean reduction in peripheral blood lymphocyte count to approximately 45% of baseline values at week 52 because of reversible sequestration of lymphocytes in lymphoid tissues, therefore, may increase the susceptibility to infections
  • Life-threatening and rare fatal infections reported in association with other sphingosine 1-phosphate (S1P) receptor modulators
  • Before initiating, obtain a recent (ie, within 6 months or after discontinuation of prior UC therapy) CBC, including lymphocyte count
  • Delay initiation in patients with an active infection until the infection is resolved
  • Consider interrupting therapy if a serious infection develops
  • Owing to residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist up to 5 weeks after discontinuation
• Progressive multifocal leukoencephalopathy (PML)
  • PML is an opportunistic viral infection of the brain caused by the John Cunningham virus that typically occurs in patients who are immunocompromised and that usually leads to death or severe disability
  • Typical PML symptoms include progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; and changes in thinking, memory, and orientation leading to confusion and personality changes
  • PML reported in patients with multiple sclerosis (MS) treated with S1P receptor modulators and has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants)
  • Be vigilant for clinical symptoms or unexplained neurologic findings that may be suggestive of PML
  • MRI findings may be apparent before clinical signs or symptoms
  • If PML is suspected, suspend treatment until PML is ruled out
  • If PML is confirmed, discontinue treatment
• Immune reconstitution inflammatory syndrome (IRIS)
  • IRIS reported in patients with MS treated with S1P receptor modulators who developed PML and subsequently discontinued treatment
  • IRIS presents as a clinical decline in a patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI
  • Onset time of IRIS was generally within a few months after S1P receptor modulator discontinuation
  • Monitor for developing IRIS and appropriately treat associated inflammation
• Herpes viral infections
  • Herpes simplex encephalitis, varicella zoster meningitis, and localized herpes viral infections reported
  • Confirm history of varicella (chickenpox)
  • Test patients without documentation of a full course of vaccination against varicella zoster virus (VZV) for antibodies to VZV before initiating
• Cryptococcal infection
  • Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections reported
  • Closely monitor for clinical symptoms or signs of CM
  • Promptly evaluate patients with symptoms or signs consistent with a cryptococcal infection and treat them appropriately
  • Suspend treatment until a cryptococcal infection has been excluded
  • If CM is diagnosed, initiate appropriate treatment
• Bradyarrhythmia and AV conduction delays
  • May cause a transient decrease in heart rate and AV conduction delays
  • Subjects who experienced bradycardia were generally asymptomatic.
  • Few subjects experienced symptoms (eg, dizziness), which resolved without intervention
  • If treatment is considered, consult a cardiologist for the following individuals
  • With significant QT prolongation (QTcF greater than 450 msec in men, greater than 470 msec in women)
  • With arrhythmias requiring treatment with class Ia or class III anti-arrhythmic drugs or QT-prolonging drugs
  • With unstable ischemic heart disease, class I or II heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension
  • With a resting heart rate below 50 bpm
  • With a history of symptomatic bradycardia, recurrent cardiogenic syncope, or severe untreated sleep apnea
  • With a history of Mobitz type I second-degree AV block, unless the patient has a functioning pacemaker
• Liver injury
  • Elevations of aminotransferases may occur
  • Obtain transaminase and bilirubin levels, if not recently available (ie, within the last 6 months), before initiating
  • Obtain transaminases and bilirubin if symptoms develop suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, dark urine)
  • Discontinue if significant liver injury confirmed
• Macular edema
  • S1P receptor modulators have been associated with an increased risk for macular edema
  • Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment
  • Periodically conduct an evaluation of the fundus, including the macula, while on therapy and any time there is a change in vision
  • Macular edema over an extended period (ie, 6 months) can lead to permanent visual loss
  • Consider discontinuing if macular edema develops
• Drug interaction overview
  • Antiarrhythmic and QT-prolonging drugs
    • Consult a cardiologist before initiating class Ia (eg, quinidine, procainamide), class III anti-arrhythmic drugs (eg, amiodarone, sotalol), or other drugs that prolong the QT interval
    • A transient decrease in heart rate and AV conduction delays may occur when initiating
    • Owing to the potential additive effect on heart rate, etrasimod may increase the risk for QT prolongation and torsades de pointes with concomitant use of class Ia and class III antiarrhythmic and QT-prolonging drugs
  • Beta-blockers and calcium channel blockers
    • May initiate etrasimod in patients receiving stable doses of beta-blocker treatment
    • Consult a cardiologist before initiating a beta-blocker in a patient receiving stable etrasimod treatment or concomitant use with other drugs that may decrease heart rate (eg, calcium channel blockers)
  • Antineoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies
  • Avoid coadministration
    • Not studied in combination with antineoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies
    • These therapies may potentiate the risk for additive immunosuppressive effects
  • Moderate or strong CYP2C9 and CYP3A4 inhibitor
    • Not recommended
    • Moderate inhibitor of CYP2C9 and a moderate inhibitor of CYP3A4 (ie, fluconazole) may increase the exposure to etrasimod
  • CYP2C9 poor metabolizers using moderate to strong inhibitors of CYP2C8 or CYP3A4
    • Not recommended
    • 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
  • Vaccinations
    • Patients without a healthcare professional–confirmed history of varicella (chickenpox) or documentation of a full course of vaccination against VZV should be tested for antibodies to VZV before initiating
    • A full course of VZV vaccination of antibody-negative patients is recommended before initiating, and initiation of treatment should be postponed for 4 weeks to allow the full
    • Vaccinations may be less effective if administered during treatment
    • If live attenuated vaccine immunizations are required, administer at least 4 weeks before initiating
    • Avoid use of live attenuated vaccines during and for 5 weeks after treatment
    • Update immunizations in agreement with current immunization guidelines before initiating therapy

Pregnancy and Lactation

• Based on findings from animal studies, fetal harm may occur when administered to pregnant women
• Available data from reports of pregnancies from the clinical development program are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• There are risks to the mother and fetus associated with increased disease activity in women with inflammatory bowel disease during pregnancy
• Published data suggest that the risk for 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 (below 2500 g) infants, and small for gestational age at birth
• Pregnancy exposure registry
  • Registry monitors pregnancy outcomes in women exposed to etrasimod during pregnancy
  • Encourage pregnant women exposed to etrasimod to contact the pregnancy registry by calling 1-800-616-3791
  • Contraception
  • Before initiating, counsel females of reproductive potential on the potential for serious risk to the fetus and the need for effective contraception during treatment and for 1 week following the last dose
• Lactation
  • There are no data on the presence of etrasimod in human milk, its effects on breastfed infants, or milk production
  • When orally administered to women rats during pregnancy and lactation, etrasimod was detected in the plasma of offspring, suggesting excretion of etrasimod in milk