Velsipity
(Etrasimod)Dosage & Administration
Velsipity Prescribing Information
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.
Etrasimod undergoes extensive hepatic metabolism
Use of VELSIPITY in patients with severe hepatic impairment is not recommended. No dosage adjustment is needed in patients with mild to moderate hepatic impairment.
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)]
• 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 liveattenuatedvaccines during and for up to 5 weeks after treatment. ()5.1 InfectionsRisk of InfectionsVELSIPITY 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 LeukoencephalopathyProgressive 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 InfectionsHerpes 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 InfectionCases 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 TherapiesVELSIPITY 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)].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. 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
attenuatedvaccine 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.
• 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. (,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)].,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)]
)7 DRUG INTERACTIONSEtrasimod 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.
Table 3: Drugs That Affect VELSIPITY CYP-Mediated Metabolic Pathways Anti-Arrhythmic Drugs and QT Prolonging DrugsClinical ImpactA transient decrease in heart rate and AV conduction delays may occur when initiating VELSIPITY
[see Warnings and Precautions (5.2)].Because of the potential additive effect on heart rate, VELSIPITY may increase the risk of QT prolongation and Torsades de Pointes with concomitant use of Class Ia and Class III anti-arrhythmic drugs and QT prolonging drugs.
Prevention orManagementSeek the advice of a cardiologist before initiating VELSIPITY treatment with Class Ia (e.g., quinidine, procainamide), Class III anti-arrhythmic drugs (e.g., amiodarone, sotalol), or other drugs that prolong the QT interval.
Beta-Blockers or Calcium Channel BlockersClinical ImpactA transient decrease in heart rate and AV conduction delays may occur when initiating VELSIPITY
[see Warnings and Precautions (5.2)].Concomitant use of VELSIPITY in patients receiving stable beta blocker treatment did not result in additive effects on heart rate reduction
[see Clinical Pharmacology (12.2)]. However, the risk of additive heart rate reduction following initiation of beta blocker therapy with stable VELSIPITY treatment or concomitant use with other drugs that may decrease heart rate is unknown.Prevention orManagementVELSIPITY can be initiated in patients receiving stable doses of beta blocker treatment.
Seek the advice of a cardiologist before initiating a beta blocker in a patient receiving stable VELSIPITY treatment or concomitant use with other drugs that may decrease heart rate (e.g., calcium channel blockers).
Anti-Neoplastic, Immune-Modulating, or Non-Corticosteroid Immunosuppressive TherapiesClinical ImpactRisk of additive immune system effects with VELSIPITY
VELSIPITY has not been studied in combination with anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies.
Prevention orManagementAvoid concomitant administration during and in the weeks following administration of VELSIPITY. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects
[seeWarnings and Precautions (5.10)].Moderate to Strong Inhibitors of CYP2C9andCYP3A4Clinical ImpactIncreased exposure of etrasimod was observed with concomitant use with a drug that is a moderate inhibitor of CYP2C9
anda moderate inhibitor of CYP3A4 (i.e., fluconazole)[see Clinical Pharmacology (12.3)].Prevention orManagementConcomitant use with a drug that is a moderate to strong inhibitor of CYP2C9
anda moderate to strong inhibitor of CYP3A4 is not recommended.CYP2C9 Poor Metabolizers Using Moderate to Strong Inhibitors of CYP2C8orCYP3A4Clinical ImpactIncreased exposure of etrasimod in patients who are CYP2C9 poor metabolizers is expected with concomitant use of moderate to strong inhibitors of CYP2C8
orCYP3A4[see Clinical Pharmacology (12.3, 12.5)].Prevention orManagementConcomitant use not recommended.
RifampinClinical ImpactConcomitant use with a drug that is a combined CYP3A4 (strong), CYP2C8 (moderate) and CYP2C9 (moderate) inducer (i.e., rifampin) decreases exposure to etrasimod
[see Clinical Pharmacology (12.3)].Prevention orManagementConcomitant use not recommended.
See full prescribing information for a list of clinically important drug interactions.
• Liver Injury: Elevations of aminotransferases may occur. Obtain transaminase and bilirubin levels before initiating VELSIPITY. Discontinue if significant liver injury is confirmed. (,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)].)5.3 Liver InjuryElevations of aminotransferases may occur in patients receiving VELSIPITY. In UC-1, elevations of alanine transaminase (ALT) greater than 3-fold the upper limit of normal (ULN) occurred in 4.5% of subjects who received VELSIPITY and 2.1% of subjects who received placebo. In UC-2 and UC-3, elevations of ALT greater than 3-fold the ULN occurred in 2.5% of subjects who received VELSIPITY and 0.5% of subjects who received placebo.
Obtain transaminase and bilirubin levels, if not recently available (i.e., within last 6 months), before initiation of VELSIPITY.
Obtain transaminases and bilirubin in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. Discontinue VELSIPITY 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 VELSIPITY. Periodically conduct an evaluation of the fundus, including the macula, while on therapy and any time there is a change in vision. Consider discontinuing VELSIPITY if macular edema develops. (,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)].)5.4 Macular EdemaS1P receptor modulators, including VELSIPITY, have been associated with an increased risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with VELSIPITY. 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 of time (i.e., 6 months) can lead to permanent visual loss. Consider discontinuing VELSIPITY if macular edema develops.
• Increased Blood Pressure: Monitor blood pressure during treatment. ()5.5 Increased Blood PressureIn UC-1 and UC-2 and UC-3, subjects treated with VELSIPITY had an average increase of approximately 1 to 4 mm Hg in systolic blood pressure and approximately 1 to 2 mm Hg in diastolic blood pressure compared to <1.5 mm Hg and <1 mm Hg in subjects receiving placebo, respectively. The increase was first detected after 2 weeks of treatment and remained within the specified average range of BP increases throughout treatment. Hypertension was reported as an adverse reaction in UC-1
[see Adverse Reactions (6.1)].Monitor blood pressure during treatment with VELSIPITY and manage appropriately.
• 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 VELSIPITY. (,5.6 Fetal RiskBased on animal studies, VELSIPITY may cause fetal harm when administered to a pregnant woman. In animal reproduction studies conducted in rats and rabbits, embryofetal toxicity was observed with administration of etrasimod at clinically relevant doses. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception to avoid pregnancy during and for one week after stopping VELSIPITY
[see Use in Specific Populations (8.1, 8.3)].)8.3 Females and Males of Reproductive PotentialBased on animal data, VELSIPITY may cause fetal harm when administered to pregnant women
[see Use in Specific Populations (8.1)].ContraceptionFemalesBefore initiation of VELSIPITY treatment, females of reproductive potential should be counseled on the potential for a serious risk to the fetus and the need for effective contraception during treatment with VELSIPITY and for one week following the last dose
[see Warnings and Precautions (5.6)and Use in Specific Populations (8.1)].• 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. (,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)].)5.7 Cutaneous 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.
• Posterior Reversible Encephalopathy Syndrome (PRES): If symptoms develop, obtain a physical and neurological exam, and consider MRI. ()5.8 Posterior Reversible Encephalopathy SyndromeRare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving S1P receptor modulators. If a patient develops any neurological or psychiatric symptoms/signs (e.g., 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, the physician should promptly schedule a complete physical and neurological examination and should consider an MRI. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, discontinue treatment with VELSIPITY.
• Respiratory Effects: May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated. ()5.9 Respiratory EffectsReductions in absolute forced expiratory volume over 1 second (FEV1) were observed in subjects treated with VELSIPITY as early as 3 months after treatment initiation. In UC-1, the decline in absolute FEV1from baseline in subjects treated with VELSIPITY compared to placebo was 79 mL (95% CI: -152, -5) at 3 months. In UC-2, reductions in absolute FEV1were not observed. There is insufficient information to determine the reversibility of the decrease in FEV1after drug discontinuation. In UC-1 and UC-2, subjects with UC and asthma and/or chronic obstructive pulmonary disease were treated with VELSIPITY; however, interpretation of changes in pulmonary function test measures in this population are limited due to small sample sizes. Spirometric evaluation of respiratory function should be performed during therapy with VELSIPITY 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. ()5.10 Unintended Additive Immune System Effects from Prior Treatment with Immunosuppressive or Immune-Modulating DrugsWhen switching to VELSIPITY from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects
[see Drug Interactions (7)].• Immune System Effects After Stopping VELSIPITY: If using concomitant immunosuppressants, monitor patients for infectious complications for up to 5 weeks after the last dose of VELSIPITY. ()5.11 Immune System Effects After Stopping VELSIPITYAfter stopping VELSIPITY, lymphocyte counts returned to the normal range in 90% of subjects within 4 to 5 weeks of stopping VELSIPITY
[see Clinical Pharmacology (12.2)]. 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 of VELSIPITY[see Drug Interactions (7)].