VELSIPITY Dosage & Rx Info | Uses, Side Effects

Velsipity Generic Name & Formulations

Legal Class

General Description

Etrasimod 2mg; tabs.

Pharmacological Class

Sphingosine 1-phosphate receptor modulator.

How Supplied

Tabs—30

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Manufacturer

Pfizer Inc.

Generic Availability

Mechanism of Action

The mechanism by which etrasimod exerts therapeutic effects in ulcerative colitis is unknown, but may involve reduction of lymphocyte migration into the intestines. Etrasimod binds with high affinity to S1P receptors 1, 4, and 5 (S1P_1,4,5), blocking the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.

Velsipity Indications

Indications

Moderately to severely active ulcerative colitis (UC) in adults.

Velsipity Dosage and Administration

Prior to Treatment Evaluations

Complete Blood Count: Obtain a recent (eg, within the last 6 months or after discontinuation of prior UC therapy) CBC, including lymphocyte count.

Cardiac Evaluation: Obtain an ECG to determine whether preexisting conduction abnormalities are present. Seek advice from a cardiologist for patients with certain preexisting conditions.

Liver Function Tests: Obtain recent (eg, within the last 6 months) transaminase and bilirubin levels.

Ophthalmic Assessment: Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with Velsipity.

Current or Prior Medications: Assess if patients are taking drugs that could slow HR or AV conduction. Consider possible unintended additive immunosuppressive effects prior to initiation treatment if patients are taking anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies, or if there is a history of prior use of these drugs.

Vaccinations: Test for antibodies to varicella zoster virus (VZV) prior to initiating treatment in patients without a healthcare professional-confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against VZV. If live attenuated vaccine immunizations are required, give at least 4 weeks prior to initiating. Update immunizations according to current guidelines prior to initiating.

Skin Examination: Obtain a skin exam prior to or shortly after initiating. Promptly evaluate if a suspicious skin lesion is observed.

Adult

Swallow whole. 2mg once daily.

Children

Not established.

Velsipity Contraindications

Contraindications

Recent (within last 6 months) occurrence of: MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV heart failure. Presence of Mobitz Type II 2^nd- or 3^rd-degree AV block, sick sinus syndrome, or sino-atrial block, unless paced.

Velsipity Boxed Warnings

Not Applicable

Velsipity Warnings/Precautions

Warnings/Precautions

Increased risk of infections (may be fatal). Obtain recent CBC (within last 6 months or after discontinuation of prior UC therapy) prior to initiation. Monitor for infections during and for up to 5 weeks after discontinuation. Consider treatment interruption if serious infection develops. Active infection: do not start until infection resolved. Test for antibodies to varicella zoster virus prior to initiation; if negative, consider immunization before starting etrasimod. Withhold and evaluate if progressive multifocal leukoencephalopathy (PML) is suspected; discontinue if confirmed and monitor for immune reconstitution inflammatory syndrome (IRIS). Immunosuppressed. Risk of bradyarrhythmia, AV conduction delays upon initiation of etrasimod. Obtain ECG prior to initiation to determine if preexisting conduction abnormalities are present. Significant QT prolongation, arrhythmias, unstable ischemic heart disease, Class I or II HF, history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, symptomatic bradycardia, recurrent cardiogenic syncope, severe untreated sleep apnea, history of Mobitz type I 2^nd-degree AV block (unless paced): refer to cardiologist if treatment is considered. Monitor BP during treatment. Obtain recent LFTs (within 6 months) prior to initiation. Monitor for hepatic dysfunction; discontinue if significant liver injury is confirmed. Respiratory function: perform spirometric evaluation as needed. Increased risk of macular edema; consider discontinuing if develops. Obtain ophthalmic exam at baseline, and if any change in vision during therapy. Increased risk for skin cancer. Perform baseline skin exam prior to or after initiation and periodically thereafter (esp. with risk factors); monitor for suspicious skin lesions and evaluate if observed. Limit exposure to sun, UV light. CYP2C9 poor metabolizers, severe hepatic impairment: not recommended. Elderly. Pregnancy. Advise females of reproductive potential to use effective contraception during and for 1 week after discontinuation. Nursing mothers.

Pregnancy Considerations

Pregnancy Exposure Registry

Pregnant females exposed to Velsipity and healthcare providers are encouraged to contact the pregnancy registry by calling 1-800-616-3791.

Risk Summary

May cause fetal harm. Available data are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

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, low birth weight infants, and small for gestational age at birth.

Nursing Mother Considerations

Risk Summary

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.
Consider the developmental and health benefits of breastfeeding 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.

Pediatric Considerations

Safety and efficacy have not been established.

Hepatic Impairment Considerations

Severe hepatic impairment: not recommended.

Other Considerations for Specific Populations

Females and Males of Reproductive Potential

May cause fetal harm.
Contraception: Counsel females of reproductive potential on the potential serious risk to the fetus and the need for effective contraception during treatment and for 1 week following the last dose.

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 is not recommended in these patients.

Velsipity Pharmacokinetics

Absorption

Median time to reach C_max: ~4 hours (range: 2–8 hours) after administration.

Distribution

Mean apparent volume of distribution: 66 L. Plasma protein bound: 97.9%.

Metabolism

Oxidation and dehydrogenation mediated primarily by CYP2C8, CYP2C9, and CYP3A4; minor contributions by CYP2C19 and CYP2J2. Also undergoes conjugation primarily by UGTs; minor contribution by sulfotransferases.

Elimination

Fecal (~82%), renal (5%). Half-life: ~30 hours. Apparent steady state oral clearance: ~1 L/h.

Velsipity Interactions

Interactions

Avoid concomitant antineoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies; when switching from drugs with prolonged immune effects, consider the half-life and mode of action to avoid additive immunosuppression. Increased risk of QT prolongation and torsades de pointes with antiarrhythmic and QT prolonging drugs (eg, quinidine, procainamide, amiodarone, sotalol); refer to cardiologist prior to initiation. Avoid live attenuated vaccines during and for up to 5 weeks after discontinuing etrasimod; may have suboptimal response; if live vaccines are required, administer at least 4 weeks prior to initiating etrasimod. Potential additive effects on HR when concomitant with both a beta blocker and a calcium channel blocker; refer to cardiologist prior to initiation. Concomitant a moderate to strong CYP2C9 inhibitor and a moderate to strong CYP3A4 inhibitor: not recommended. Concomitant a combined CYP3A4 (strong), CYP2C8 (moderate), and CYP2C9 (moderate) inducer (eg, rifampin): not recommended. Concomitant moderate to strong CYP2C8 or CYP3A4 inhibitors in CYP2C9 poor metabolizers: not recommended.

Velsipity Adverse Reactions

Adverse Reactions

Headache, elevated liver tests, dizziness, arthralgia, hypertension, UTI, nausea, hypercholesterolemia, herpes infection; bradycardia, malignancies, macular edema, respiratory effects, PML, IRIS; rare: posterior reversible encephalopathy syndrome (discontinue if suspected).

Velsipity Clinical Trials

Clinical Trials

The approval was based on data from 2 randomized, double-blind, placebo-controlled phase 3 trials, ELEVATE UC 52 (ClinicalTrials.gov Identifier: NCT03945188) and ELEVATE UC 12 (ClinicalTrials.gov Identifier: NCT03996369). Both trials evaluated the efficacy and safety of etrasimod vs placebo in patients with UC who had previously failed or were intolerant to at least 1 conventional, biologic, or Janus kinase (JAK) inhibitor therapy.

In ELEVATE UC 52 (N=408), the coprimary endpoints were clinical remission at week 12 and week 52. Clinical remission (based on the modified Mayo score) was defined as a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopic score of no more than 1 (excluding friability).

At week 12, 27% of patients in the etrasimod arm (n=274) and 7% of patients in the placebo arm (n=134) had achieved clinical remission (treatment difference, 20% [95% CI, 13-27]; P <.001). At week 52, 32% of patients treated with etrasimod achieved clinical remission vs 7% of the placebo group (treatment difference, 26% [95% CI, 19-33]; P <.001). Significant improvements were also observed with etrasimod vs placebo on secondary endpoints including endoscopic improvement, histologic-endoscopic mucosal improvement, corticosteroid-free clinical remission, and maintenance of clinical remission (all P <.001).

In ELEVATE UC 12 (N=333), the primary endpoint was clinical remission at week 12. Results showed a significantly greater proportion of patients treated with etrasimod achieved the primary endpoint compared with placebo (26% vs 15%; treatment difference, 11% [95% CI, 3-20]; P <.001). Significant improvements were also seen in endoscopic improvement and histologic-endoscopic mucosal improvement (secondary endpoints) with etrasimod compared with placebo (all P <.001).

Velsipity Note