Zeposia
(Ozanimod Hydrochloride)Dosage & Administration
Zeposia Prescribing Information
Dosage and Administration (
Before initiation of treatment with ZEPOSIA, assess the following:
Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist should be sought
Obtain a recent (i.e., within the last 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC), including lymphocyte count
Obtain recent (i.e., within the last 6 months) transaminase and bilirubin levels
• If patients are taking anti-neoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with ZEPOSIA[see Warnings and Precautions (5.1)and Drug Interactions (7)].• Determine if patients are taking drugs that could slow heart rate or atrioventricular conduction[see Warnings and Precautions (5.3)and Drug Interactions (7)].
Patients without a healthcare professional-confirmed history of chickenpox or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating ZEPOSIA; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with ZEPOSIA
If live
Warnings and Precautions (
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 patients treated with S1P receptor modulators, including ZEPOSIA, and other multiple sclerosis (MS) and UC therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants,
If PML is confirmed, treatment with ZEPOSIA should be discontinued.
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.
Warnings and Precautions (
In MS Study 1 and Study 2, elevations of ALT to 5-fold the upper limit of normal (ULN) or greater occurred in 1.6% of patients treated with ZEPOSIA 0.92 mg and 1.3% of patients who received IFN beta-1a. Elevations of 3-fold the ULN or greater occurred in 5.5% of patients treated with ZEPOSIA and 3.1% of patients who received IFN beta-1a. The median time to an elevation of 3-fold the ULN was 6 months. The majority (79%) of patients continued treatment with ZEPOSIA with values returning to less than 3-fold the ULN within approximately 2-4 weeks. ZEPOSIA was discontinued for a confirmed elevation greater than 5-fold the ULN. Overall, the discontinuation rate because of elevations in hepatic enzymes was 1.1% of patients with MS treated with ZEPOSIA 0.92 mg and 0.8% of patients who received IFN beta-1a.
In UC Study 1, elevations of ALT to 5-fold the ULN or greater occurred in 0.9% of patients treated with ZEPOSIA 0.92 mg and 0.5% of patients who received placebo, and in UC Study 2 elevations occurred in 0.9% of patients and no patients, respectively. In UC Study 1, elevations of ALT to 3-fold the ULN or greater occurred in 2.6% of UC patients treated with ZEPOSIA 0.92 mg and 0.5% of patients who received placebo, and in UC Study 2 elevations occurred in 2.3% of patients and no patients, respectively. In controlled and uncontrolled UC studies, the majority (96%) of patients with ALT greater than 3-fold the ULN continued treatment with ZEPOSIA with values returning to less than 3-fold the ULN within approximately 2 to 4 weeks. Overall, the discontinuation rate because of elevations in hepatic enzymes was 0.4% in patients treated with ZEPOSIA 0.92 mg, and none in patients who received placebo in the controlled UC studies.
Individuals with an AST or ALT greater than 1.5-fold ULN were excluded from MS Study 1 and Study 2 and greater than 2 times the ULN for UC Study 1 and Study 3. There are no data to establish that patients with preexisting liver disease are at increased risk to develop elevated liver function test values when taking ZEPOSIA. Dosage adjustment in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) is required
In MS Study 1 and Study 2, patients treated with ZEPOSIA had an average increase of approximately 1 to 2 mm Hg in systolic pressure over patients who received IFN beta-1a, and no effect on diastolic pressure. The increase in systolic pressure was first detected after approximately 3 months of treatment and persisted throughout treatment. Hypertension was reported as an adverse reaction in 3.9% of patients treated with ZEPOSIA 0.92 mg and in 2.1% of patients who received IFN beta-1a. Two patients treated with ZEPOSIA in MS Study 1 and one patient treated with interferon (IFN) beta-1a in Study 2 experienced a hypertensive crisis that was not clearly influenced by a concomitant medication.
The mean increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in UC patients treated with ZEPOSIA is similar to patients with MS. In UC Study 1 and Study 3, the average increase from baseline in SBP was 3.7 mm Hg in patients treated with ZEPOSIA and 2.3 mm Hg in patients treated with placebo. In UC Study 2, the average increase from baseline in SBP was 5.1 mm Hg in patients treated with ZEPOSIA and 1.5 mm Hg in patients treated with placebo. There was no effect on DBP.
Hypertension was reported as an adverse reaction in 1.2% of patients treated with ZEPOSIA 0.92 mg and none in patients treated with placebo in UC Study 1 and Study 3, and in 2.2% and 2.2% of patients in UC Study 2, respectively. Hypertensive crisis was reported in two patients receiving ZEPOSIA and one patient receiving placebo.
Blood pressure should be monitored during treatment with ZEPOSIA and managed appropriately.
ZEPOSIA is indicated for the treatment of:
• relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.• moderately to severely active ulcerative colitis (UC) in adults.
• Assessments are required prior to initiating ZEPOSIA. ()2.1 Assessments Prior to First Dose of ZEPOSIABefore initiation of treatment with ZEPOSIA, assess the following:
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 (5.3)].Complete Blood CountObtain a recent (i.e., within the last 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC), including lymphocyte count
[see Warnings and Precautions (5.1)].Liver Function TestsObtain recent (i.e., within the last 6 months) transaminase and bilirubin levels
[see Warnings and Precautions (5.4)].Ophthalmic AssessmentObtain a baseline evaluation of the fundus, including the macula, near the start of treatment with ZEPOSIA[see Warnings and Precautions (5.8)].Skin ExaminationObtain a baseline skin examination prior to or shortly after initiation of ZEPOSIA. If a suspicious skin lesion is observed, it should be promptly evaluated[see Warnings and Precautions (5.9)].Current or Prior Medications• If patients are taking anti-neoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with ZEPOSIA[see Warnings and Precautions (5.1)and Drug Interactions (7)].• Determine if patients are taking drugs that could slow heart rate or atrioventricular conduction[see Warnings and Precautions (5.3)and Drug Interactions (7)].
VaccinationsPatients without a healthcare professional-confirmed history of chickenpox or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating ZEPOSIA; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with ZEPOSIA
[see Warnings and Precautions (5.1)and Drug Interactions (7)].If live
attenuatedvaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA.• Titration is required for treatment initiation. ()2.2 Recommended Dosage for Multiple Sclerosis and Ulcerative ColitisInitiate ZEPOSIA with a 7-day titration, as shown in Table 1
[seeWarnings and Precautions (5.3)].After initial titration, the recommended dosage of ZEPOSIA is 0.92 mg taken orally once daily starting on Day 8.Swallow ZEPOSIA capsules whole, with or without food
[see Clinical Pharmacology (12.3)].Table 1: Dose Titration Regimen Days 1-4
0.23 mg once daily
Days 5-7
0.46 mg once daily
Day 8 and thereafter
0.92 mg once daily*
*Patients with mild to moderate hepatic impairment (Child-Pugh class A or B) should take 0.92 mg once every other day
[see Recommended Dosage in Patients with Hepatic Impairment (2.3).]• The recommended maintenance dosage is 0.92 mg orally once daily. ()2.2 Recommended Dosage for Multiple Sclerosis and Ulcerative ColitisInitiate ZEPOSIA with a 7-day titration, as shown in Table 1
[seeWarnings and Precautions (5.3)].After initial titration, the recommended dosage of ZEPOSIA is 0.92 mg taken orally once daily starting on Day 8.Swallow ZEPOSIA capsules whole, with or without food
[see Clinical Pharmacology (12.3)].Table 1: Dose Titration Regimen Days 1-4
0.23 mg once daily
Days 5-7
0.46 mg once daily
Day 8 and thereafter
0.92 mg once daily*
*Patients with mild to moderate hepatic impairment (Child-Pugh class A or B) should take 0.92 mg once every other day
[see Recommended Dosage in Patients with Hepatic Impairment (2.3).]• The recommended maintenance dosage in patients with mild or moderate chronic hepatic impairment (Child-Pugh class A or B) is 0.92 mg once every other day. ()2.3 Recommended Dosage in Patients with Hepatic ImpairmentIn patients with mild or moderate hepatic impairment (Child-Pugh class A or B), initiate ZEPOSIA with a 7-day titration, as shown in Table 1. After initial titration, the recommended dosage of ZEPOSIA in these patients is 0.92 mg taken orally once every other day, starting on Day 8
[see Use in Specific Populations (8.6)andClinical Pharmacology (12.3)].• If a dose is missed within the first 2 weeks of treatment, reinitiate with the titration regimen. If a dose is missed after the first 2 weeks of treatment, continue treatment as planned. ()2.4 Reinitiation of ZEPOSIA after Treatment InterruptionIf a dose of ZEPOSIA is missed during the first 2 weeks of treatment, reinitiate treatment using the titration regimen
[see Dosage and Administration (2.2)].If a dose of ZEPOSIA is missed after the first 2 weeks of treatment, continue with the treatment as planned
.
Capsules:
• 0.23 mg ozanimod: light grey opaque body/light grey opaque cap imprinted with black ink "OZA" on the cap and "0.23 mg" on the body• 0.46 mg ozanimod: light grey opaque body/orange opaque cap imprinted with black ink "OZA" on the cap and "0.46 mg" on the body• 0.92 mg ozanimod: orange opaque body/orange opaque cap imprinted with black ink "OZA" on the cap and "0.92 mg" on the body
In patients with mild or moderate hepatic impairment (Child-Pugh class A or B), initiate ZEPOSIA with a 7-day titration, as shown in Table 1. After initial titration, the recommended dosage of ZEPOSIA in these patients is 0.92 mg taken orally once every other day, starting on Day 8
In patients with mild (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B), the exposures of ozanimod and its active metabolites are higher than those in healthy controls
The pharmacokinetics of ozanimod and its active metabolites were not evaluated in patients with severe hepatic impairment (Child-Pugh class C). Therefore, use of ZEPOSIA in patients with severe hepatic impairment is not recommended.
ZEPOSIA is contraindicated in patients who:
• In the last 6 months, have experienced a myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure[see5.3 Bradyarrhythmia and Atrioventricular Conduction DelaysSince initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays
,an up-titration scheme should be used to reach the maintenance dosage of ZEPOSIA[see Dosage and Administration (2.2)and Clinical Pharmacology (12.2)].ZEPOSIA was not studied in patients who had:
• A myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization within the last 6 months• New York Heart Association Class III / IV heart failure• Cardiac conduction or rhythm disorders, including sick sinus syndrome, significant QT prolongation (QTcF > 450 msec in males, > 470 msec in females), risk factors for QT prolongation, or other conduction abnormalities or cardiac condition that in the opinion of the treating investigator could jeopardize the patient's health• Other pre-existing stable cardiac conditions without clearance from a cardiologist• Severe untreated sleep apnea• A resting heart rate less than 55 beats per minute (bpm) at baseline
Reduction in Heart RateInitiation of ZEPOSIA may result in a transient decrease in heart rate. After the initial dose of ZEPOSIA 0.23 mg, the greatest mean decrease from baseline in heart rate occurred at Hour 5 on Day 1 (decrease of 1.2 bpm in MS Study 1 and Study 2, and 0.7 bpm in UC Study 1 and Study 3), returning to near baseline at Hour 6. With continued up-titration, the maximal heart rate effect of ozanimod occurred on Day 8. The utility of performing first-dose cardiac monitoring when initiating ZEPOSIA in patients with characteristics similar to those studied in the clinical trials of ZEPOSIA is unclear. Heart rates below 40 bpm were not observed. Initiation of ZEPOSIA without titration may result in greater decreases in heart rate
[see Dosage and Administration (2.2)].In MS Study 1 and Study 2, bradycardia was reported on the day of treatment initiation in 0.6% of patients treated with ZEPOSIA compared to no patients who received IFN beta-1a. After Day 1, the incidence of bradycardia was 0.8% in patients treated with ZEPOSIA compared to 0.7% of patients who received IFN beta-1a. In UC Study 1 and Study 3, bradycardia was reported on the day of treatment initiation in 1 patient (0.2%) treated with ZEPOSIA compared to none in patients who received placebo. After Day 1, bradycardia was reported in 1 patient (0.2%) treated with ZEPOSIA. In UC Study 2, bradycardia was not reported.
Atrioventricular Conduction DelaysInitiation of ZEPOSIA may result in transient atrioventricular conduction delays. At ZEPOSIA exposures higher than the recommended dosage without dose titration, first- and second-degree type 1 atrioventricular blocks were observed in healthy volunteers; however, in MS Study 1 and Study 2 and UC Study 1 and Study 3 with dose titration, Mobitz type 2 second- or third-degree atrioventricular blocks were not reported in patients treated with ZEPOSIA.
If treatment with ZEPOSIA 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• With ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension• With a history of with second-degree Mobitz type II or higher AV block, sick-sinus syndrome, or sinoatrial heart block[see Contraindications (4)]
]• Have the 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[see]5.3 Bradyarrhythmia and Atrioventricular Conduction DelaysSince initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays
,an up-titration scheme should be used to reach the maintenance dosage of ZEPOSIA[see Dosage and Administration (2.2)and Clinical Pharmacology (12.2)].ZEPOSIA was not studied in patients who had:
• A myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization within the last 6 months• New York Heart Association Class III / IV heart failure• Cardiac conduction or rhythm disorders, including sick sinus syndrome, significant QT prolongation (QTcF > 450 msec in males, > 470 msec in females), risk factors for QT prolongation, or other conduction abnormalities or cardiac condition that in the opinion of the treating investigator could jeopardize the patient's health• Other pre-existing stable cardiac conditions without clearance from a cardiologist• Severe untreated sleep apnea• A resting heart rate less than 55 beats per minute (bpm) at baseline
Reduction in Heart RateInitiation of ZEPOSIA may result in a transient decrease in heart rate. After the initial dose of ZEPOSIA 0.23 mg, the greatest mean decrease from baseline in heart rate occurred at Hour 5 on Day 1 (decrease of 1.2 bpm in MS Study 1 and Study 2, and 0.7 bpm in UC Study 1 and Study 3), returning to near baseline at Hour 6. With continued up-titration, the maximal heart rate effect of ozanimod occurred on Day 8. The utility of performing first-dose cardiac monitoring when initiating ZEPOSIA in patients with characteristics similar to those studied in the clinical trials of ZEPOSIA is unclear. Heart rates below 40 bpm were not observed. Initiation of ZEPOSIA without titration may result in greater decreases in heart rate
[see Dosage and Administration (2.2)].In MS Study 1 and Study 2, bradycardia was reported on the day of treatment initiation in 0.6% of patients treated with ZEPOSIA compared to no patients who received IFN beta-1a. After Day 1, the incidence of bradycardia was 0.8% in patients treated with ZEPOSIA compared to 0.7% of patients who received IFN beta-1a. In UC Study 1 and Study 3, bradycardia was reported on the day of treatment initiation in 1 patient (0.2%) treated with ZEPOSIA compared to none in patients who received placebo. After Day 1, bradycardia was reported in 1 patient (0.2%) treated with ZEPOSIA. In UC Study 2, bradycardia was not reported.
Atrioventricular Conduction DelaysInitiation of ZEPOSIA may result in transient atrioventricular conduction delays. At ZEPOSIA exposures higher than the recommended dosage without dose titration, first- and second-degree type 1 atrioventricular blocks were observed in healthy volunteers; however, in MS Study 1 and Study 2 and UC Study 1 and Study 3 with dose titration, Mobitz type 2 second- or third-degree atrioventricular blocks were not reported in patients treated with ZEPOSIA.
If treatment with ZEPOSIA 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• With ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension• With a history of with second-degree Mobitz type II or higher AV block, sick-sinus syndrome, or sinoatrial heart block[see Contraindications (4)]
• Have severe untreated sleep apnea[see]5.3 Bradyarrhythmia and Atrioventricular Conduction DelaysSince initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays
,an up-titration scheme should be used to reach the maintenance dosage of ZEPOSIA[see Dosage and Administration (2.2)and Clinical Pharmacology (12.2)].ZEPOSIA was not studied in patients who had:
• A myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization within the last 6 months• New York Heart Association Class III / IV heart failure• Cardiac conduction or rhythm disorders, including sick sinus syndrome, significant QT prolongation (QTcF > 450 msec in males, > 470 msec in females), risk factors for QT prolongation, or other conduction abnormalities or cardiac condition that in the opinion of the treating investigator could jeopardize the patient's health• Other pre-existing stable cardiac conditions without clearance from a cardiologist• Severe untreated sleep apnea• A resting heart rate less than 55 beats per minute (bpm) at baseline
Reduction in Heart RateInitiation of ZEPOSIA may result in a transient decrease in heart rate. After the initial dose of ZEPOSIA 0.23 mg, the greatest mean decrease from baseline in heart rate occurred at Hour 5 on Day 1 (decrease of 1.2 bpm in MS Study 1 and Study 2, and 0.7 bpm in UC Study 1 and Study 3), returning to near baseline at Hour 6. With continued up-titration, the maximal heart rate effect of ozanimod occurred on Day 8. The utility of performing first-dose cardiac monitoring when initiating ZEPOSIA in patients with characteristics similar to those studied in the clinical trials of ZEPOSIA is unclear. Heart rates below 40 bpm were not observed. Initiation of ZEPOSIA without titration may result in greater decreases in heart rate
[see Dosage and Administration (2.2)].In MS Study 1 and Study 2, bradycardia was reported on the day of treatment initiation in 0.6% of patients treated with ZEPOSIA compared to no patients who received IFN beta-1a. After Day 1, the incidence of bradycardia was 0.8% in patients treated with ZEPOSIA compared to 0.7% of patients who received IFN beta-1a. In UC Study 1 and Study 3, bradycardia was reported on the day of treatment initiation in 1 patient (0.2%) treated with ZEPOSIA compared to none in patients who received placebo. After Day 1, bradycardia was reported in 1 patient (0.2%) treated with ZEPOSIA. In UC Study 2, bradycardia was not reported.
Atrioventricular Conduction DelaysInitiation of ZEPOSIA may result in transient atrioventricular conduction delays. At ZEPOSIA exposures higher than the recommended dosage without dose titration, first- and second-degree type 1 atrioventricular blocks were observed in healthy volunteers; however, in MS Study 1 and Study 2 and UC Study 1 and Study 3 with dose titration, Mobitz type 2 second- or third-degree atrioventricular blocks were not reported in patients treated with ZEPOSIA.
If treatment with ZEPOSIA 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• With ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension• With a history of with second-degree Mobitz type II or higher AV block, sick-sinus syndrome, or sinoatrial heart block[see Contraindications (4)]
• Are taking a monoamine oxidase (MAO) inhibitor[see]7 DRUG INTERACTIONSTables 5 and 6 include drugs with clinically important drug and vaccine interactions when administered concomitantly with ZEPOSIA and instructions for preventing or managing them.
Table 5: Clinically Relevant Interactions Affecting Drugs and Vaccines Co-administered with ZEPOSIA Anti-Neoplastic, Immune-Modulating, or Non-Corticosteroid Immunosuppressive TherapiesClinical Impact:ZEPOSIA has not been studied in combination with anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies with the exception of cyclosporine, which had no pharmacokinetic interaction
[see Clinical Pharmacology (12.3)].Prevention or Management:Caution should be used during concomitant administration because of the risk of additive immune effects during such therapy and in the weeks following administration
[see Warnings and Precautions (5.1)].
When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects[seeWarnings and Precautions (5.11)].Alemtuzumab: Initiating treatment with ZEPOSIA after alemtuzumab is not recommended because of the characteristics and duration of alemtuzumab immune suppressive effects.Beta interferon or glatiramer acetate: ZEPOSIA can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.Anti-Arrhythmic Drugs, QT Prolonging Drugs, Drugs That May Decrease Heart RateClinical Impact:ZEPOSIA has not been studied in patients taking QT prolonging drugs.
Class Ia (e.g., quinidine, procainamide) and Class III (e.g., amiodarone, sotalol) anti-arrhythmic drugs have been associated with cases of Torsades de Pointes in patients with bradycardia.Prevention or Management:If treatment with ZEPOSIA is considered in patients on Class Ia or Class III anti-arrhythmic drugs, advice from a cardiologist should be sought
[see Warnings and Precautions (5.3)].
Because of the potential additive effects on heart rate, treatment with ZEPOSIA should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties[see Warnings and Precautions (5.3)].If treatment initiation with ZEPOSIA is considered in patients on QT prolonging drugs, advice from a cardiologist should be sought.Combination Beta Blocker and Calcium Channel BlockerClinical Impact:The co-administration of ZEPOSIA with both a beta blocker and a calcium channel blocker has not been studied. However, there is a potential of additive effects on heart rate.
Prevention or Management:Treatment with ZEPOSIA should generally not be initiated in patients who are concurrently treated with both a heart rate lowering calcium channel blocker (e.g., verapamil, diltiazem) and beta blocker
[see Warnings and Precautions (5.3)].If treatment initiation with ZEPOSIA is considered in patients on both a heart rate lowering calcium channel blocker and beta blocker, advice from a cardiologist should be sought.VaccinationClinical Impact:During, and for up to three months after, discontinuation of treatment with ZEPOSIA, vaccinations may be less effective. The use of live
attenuatedvaccines may carry the risk of infection.Prevention or Management:Live
attenuatedvaccines should be avoided during ZEPOSIA treatment and for up to 3 months after discontinuation of treatment with ZEPOSIA[see Warnings and Precautions (5.1)].Table 6: Clinically Relevant Interactions Affecting ZEPOSIA When Co-administered with Other Drugs Monoamine Oxidase (MAO) InhibitorsClinical Impact:The effect of MAO inhibition on ozanimod and/or its metabolites has not been studied clinically. Potential effects on efficacy or safety with co-administration of MAO inhibitors because of altered exposures of ozanimod and/or its metabolites cannot be ruled out.
Prevention or Management:Co-administration of ZEPOSIA with MAO inhibitors (e.g., selegiline, phenelzine, linezolid) is contraindicated. At least 14 days should elapse between discontinuation of ZEPOSIA and initiation of treatment with MAO inhibitors.
Strong CYP2C8 InhibitorsClinical Impact:Co-administration of ZEPOSIA with strong CYP2C8 inhibitors increases the exposure of the active metabolites of ozanimod
[see Clinical Pharmacology (12.3)], which may increase the risk of ZEPOSIA adverse reactions.Prevention or Management:Co-administration of ZEPOSIA with strong CYP2C8 inhibitors (e.g., gemfibrozil) is not recommended.
Strong CYP2C8 InducersClinical Impact:Co-administration of ZEPOSIA with strong CYP2C8 inducers (e.g., rifampin) reduces the exposure of the major active metabolites of ozanimod
[see Clinical Pharmacology (12.3)], which may decrease the efficacy of ZEPOSIA.Prevention or Management:Co-administration of ZEPOSIA with strong CYP2C8 inducers should be avoided.
• Vaccination: Avoid use of live attenuated vaccines during and for up to 3 months after treatment with ZEPOSIA.• See full prescribing information for a list of clinically important drug interactions.