Velsipity
(Etrasimod)Velsipity Prescribing Information
Dosage and Administration, Recommended Dosage ( 2.2 Recommended Dosage
| 06/2024 |
Warnings and Precautions, Infections ( 5.1 InfectionsRisk of Infections VELSIPITY 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 [see Clinical Pharmacology (12.2)]. VELSIPITY may, therefore, increase the susceptibility to infections. Life-threatening and rare fatal infections have been reported in association with other sphingosine 1-phosphate (S1P) receptor modulators.Before initiating treatment, obtain a recent (i.e., within 6 months or after discontinuation of prior UC therapy) CBC, including lymphocyte count. Delay initiation of VELSIPITY in patients with an active infection until the infection is resolved. In UC-1, the overall rate of infections in subjects treated with VELSIPITY was 24.9% compared to 22.2% in subjects who received placebo. In pooled data from UC-2 and UC-3, the overall rate of infections in subjects treated with VELSIPITY was 14.0% compared to 11.8% in subjects who received placebo. The most common infections were urinary tract infections and herpes viral infections in UC-1, and urinary tract infections in UC-2 and UC-3 [see Adverse Reactions (6.1)] .The proportion of subjects treated with VELSIPITY who experienced lymphocyte counts less than 0.2 x 109/L was 5.5% in UC-1 and 0.6% in UC-2 and UC-3. These events did not lead to treatment discontinuation. Peripheral blood absolute lymphocyte counts returned to the normal range in 90% of subjects within 4 to 5 weeks of stopping therapy [see Clinical Pharmacology (12.2)]. Consider interruption of treatment with VELSIPITY if a patient develops a serious infection. Because residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist up to 5 weeks after discontinuation of VELSIPITY, vigilance for infection should be continued throughout this period. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Typical symptoms associated with PML are diverse, progress over days to weeks, and 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 has been reported in multiple sclerosis (MS) patients treated with S1P receptor modulators and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants , and duration of use). Based on data from patients with MS, longer treatment duration increases the risk of PML in patients treated with S1P receptor modulators, and the majority of PML cases have occurred in patients treated with S1P receptor modulators for at least 18 months. VELSIPITY is not indicated for the treatment of MS. Physicians should 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, treatment with VELSIPITY should be suspended until PML has been excluded by an appropriate diagnostic evaluation.If PML is confirmed, discontinue treatment with VELSIPITY. Immune reconstitution inflammatory syndrome (IRIS) has been reported in MS patients treated with S1P receptor modulators who developed PML and subsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML was generally within a few months after S1P receptor modulator discontinuation. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken. Herpes Viral Infections Herpes simplex encephalitis, varicella zoster meningitis, and localized herpes viral infections have been reported with S1P receptor modulators. In UC-1, herpes zoster was reported in 0.7% of subjects treated with VELSIPITY and in none of the subjects who received placebo. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating VELSIPITY (see Vaccinations) .Cryptococcal Infection Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections have been reported with S1P receptor modulators. Physicians should be vigilant for clinical symptoms or signs of CM. Patients with symptoms or signs consistent with a cryptococcal infection should undergo prompt diagnostic evaluation and treatment. VELSIPITY treatment should be suspended until a cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated. Prior and Concomitant Treatment with Anti-neoplastic, Immune-modulating, or Non-corticosteroid Immunosuppressive Therapies VELSIPITY has not been studied in combination with anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies. Avoid concomitant administration of these therapies with VELSIPITY and in the weeks following administration because of the risk of additive immunosuppressive effects [see Warnings and Precautions (5.10)] .Vaccinations Patients without a healthcare professional-confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating VELSIPITY. A full course of VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with VELSIPITY, following which initiation of treatment with VELSIPITY should be postponed for 4 weeks to allow the full effect of vaccination to occur. No clinical data are available on the safety and efficacy of vaccinations in patients taking VELSIPITY. Vaccinations may be less effective if administered during VELSIPITY treatment. If live attenuated vaccine immunizations are required, administer at least 4 weeks prior to initiation of VELSIPITY. Avoid the use of live attenuated vaccines during and for 5 weeks after treatment with VELSIPITY.Update immunizations in agreement with current immunization guidelines prior to initiating VELSIPITY therapy. | 06/2024 |
Warnings and Precautions, Cutaneous Malignancies ( 5.7Cutaneous MalignanciesThe risk of cutaneous malignancies (including basal cell carcinoma, squamous cell carcinoma, and melanoma) is increased in patients treated with S1P receptor modulators in controlled trials. Kaposi’s sarcoma and Merkel cell carcinoma have also been reported in patients treated with S1P receptor modulators in the postmarketing setting. Skin examinations are recommended prior to or shortly after the start of treatment and periodically thereafter for all patients, particularly those with risk factors for skin cancer. Providers and patients are advised to monitor for suspicious skin lesions. If a suspicious skin lesion is observed, it should be promptly evaluated. As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a sunscreen with a high protection factor. Concomitant phototherapy with UV-B radiation or PUVA-photochemotherapy is not recommended in patients taking VELSIPITY. | 06/2024 |
VELSIPITY is indicated for the treatment of moderately to severely active ulcerative colitis (UC) in adults.
• Assessments are required prior to initiating VELSIPITY. ()2.1 Assessments, Medications, and Vaccinations Prior to First Dose of VELSIPITYBefore initiation of treatment with VELSIPITY, assess the following:
Complete Blood CountObtain a recent (i.e., within the last 6 months or after discontinuation of prior UC therapy) complete blood count (CBC), including lymphocyte count
[see Warnings and Precautions (5.1)].Cardiac EvaluationObtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist should be sought
[see Warnings and Precautions (5.2)].Liver Function TestsObtain recent (i.e., within the last 6 months) transaminase and bilirubin levels
[see Warnings and Precautions (5.3)].Ophthalmic AssessmentObtain a baseline evaluation of the fundus, including the macula, near the start of treatment with VELSIPITY
[see Warnings and Precautions (5.4)].Skin ExaminationObtain a skin examination prior to or shortly after initiation of VELSIPITY. If a suspicious skin lesion is observed, it should be promptly evaluated
[see Warnings and Precautions (5.7)].Current or Prior Medications• Determine if patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction[see Warnings and Precautions (5.2)and Drug Interactions (7)].• 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, consider possible unintended additive immunosuppressive effects before initiating treatment with VELSIPITY[seeWarnings and Precautions (5.10)and Drug Interactions (7)].
VaccinationsPatients without a healthcare professional-confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating VELSIPITY; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with VELSIPITY.
If live
attenuatedvaccine immunizations are required, administer at least 4 weeks prior to initiation of VELSIPITY.Update immunizations in agreement with current immunization guidelines prior to initiating VELSIPITY therapy
[see Warnings and Precautions (5.1)].• The recommended dosage is 2 mg orally once daily. ()2.2 Recommended Dosage• The recommended dosage of VELSIPITY is 2 mg orally once daily.• Swallow the tablet whole, with or without food[see Clinical Pharmacology (12.3)].• If a dose is missed, take the missed dose at the next scheduled time; do not double the next dose.
Tablets: 2 mg of etrasimod as a round, green, film-coated tablet, debossed with “ETR” on one side and “2” on the other side.
VELSIPITY is contraindicated in patients who:
• In the last 6 months, have experienced a myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure[see.]5.2 Bradyarrhythmia and Atrioventricular Conduction DelaysInitiation of VELSIPITY may result in a transient decrease in heart rate and AV conduction delays
[see Clinical Pharmacology (12.2)].Reduction in Heart RateInitiation of VELSIPITY may result in a transient decrease in heart rate. After the first dose of VELSIPITY 2 mg, subjects with UC experienced the greatest mean decrease from baseline in heart rate of 7.2 bpm at Hour 3 in UC-1 and Hour 2 in UC-2.
In UC-1, bradycardia was reported on the day of treatment initiation in 1% of subjects treated with VELSIPITY compared to none in subjects who received placebo. On Day 2, bradycardia was reported in 1 subject (0.3%) treated with VELSIPITY compared to none in subjects who received placebo. In UC-2 and UC-3, bradycardia was reported on the day of treatment initiation in 2.9% of subjects treated with VELSIPITY compared to none in subjects who received placebo. On Day 2, bradycardia was reported in 1 subject (0.3%) treated with VELSIPITY compared to none in subjects who received placebo. Subjects who experienced bradycardia were generally asymptomatic. Few subjects experienced symptoms, such as dizziness, and these symptoms resolved without intervention.
Atrioventricular Conduction DelaysInitiation of VELSIPITY may result in transient AV conduction delays.
On the day of treatment initiation of VELSIPITY 2 mg, first- or second-degree Mobitz type I AV blocks were observed in 0.7% of VELSIPITY-treated subjects compared to none in placebo in UC-1, and in 0.8% of VELSIPITY-treated subjects compared to none in placebo in UC-2 and UC-3. In UC-1, UC-2, and UC-3, Mobitz type II second- or third-degree AV blocks were not reported in VELSIPITY-treated subjects.
If treatment with VELSIPITY is considered, advice from a cardiologist should be sought for those individuals:
• With significant QT prolongation (QTcF ≥450 msec in males, ≥470 msec in females)• With arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs or QT prolonging drugs[see Drug Interactions (7)]• With unstable ischemic heart disease, Class I or II heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension[see Contraindications (4)]• With resting heart rate of less than 50 bpm• With history of symptomatic bradycardia, recurrent cardiogenic syncope, or severe untreated sleep apnea• With history of Mobitz type I second-degree AV block, unless the patient has a functioning pacemaker[see Contraindications (4)]
• Have a history or presence of Mobitz type II second-degree or third-degree AV block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker[see.]5.2 Bradyarrhythmia and Atrioventricular Conduction DelaysInitiation of VELSIPITY may result in a transient decrease in heart rate and AV conduction delays
[see Clinical Pharmacology (12.2)].Reduction in Heart RateInitiation of VELSIPITY may result in a transient decrease in heart rate. After the first dose of VELSIPITY 2 mg, subjects with UC experienced the greatest mean decrease from baseline in heart rate of 7.2 bpm at Hour 3 in UC-1 and Hour 2 in UC-2.
In UC-1, bradycardia was reported on the day of treatment initiation in 1% of subjects treated with VELSIPITY compared to none in subjects who received placebo. On Day 2, bradycardia was reported in 1 subject (0.3%) treated with VELSIPITY compared to none in subjects who received placebo. In UC-2 and UC-3, bradycardia was reported on the day of treatment initiation in 2.9% of subjects treated with VELSIPITY compared to none in subjects who received placebo. On Day 2, bradycardia was reported in 1 subject (0.3%) treated with VELSIPITY compared to none in subjects who received placebo. Subjects who experienced bradycardia were generally asymptomatic. Few subjects experienced symptoms, such as dizziness, and these symptoms resolved without intervention.
Atrioventricular Conduction DelaysInitiation of VELSIPITY may result in transient AV conduction delays.
On the day of treatment initiation of VELSIPITY 2 mg, first- or second-degree Mobitz type I AV blocks were observed in 0.7% of VELSIPITY-treated subjects compared to none in placebo in UC-1, and in 0.8% of VELSIPITY-treated subjects compared to none in placebo in UC-2 and UC-3. In UC-1, UC-2, and UC-3, Mobitz type II second- or third-degree AV blocks were not reported in VELSIPITY-treated subjects.
If treatment with VELSIPITY is considered, advice from a cardiologist should be sought for those individuals:
• With significant QT prolongation (QTcF ≥450 msec in males, ≥470 msec in females)• With arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs or QT prolonging drugs[see Drug Interactions (7)]• With unstable ischemic heart disease, Class I or II heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension[see Contraindications (4)]• With resting heart rate of less than 50 bpm• With history of symptomatic bradycardia, recurrent cardiogenic syncope, or severe untreated sleep apnea• With history of Mobitz type I second-degree AV block, unless the patient has a functioning pacemaker[see Contraindications (4)]