Zeposia

What Is Zeposia?

Zeposia (ozanimod) is a sphingosine 1- phosphate receptor modulator used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing- remitting disease, and active secondary progressive disease, in adults.

What Are Side Effects of Zeposia?

Common side effects of Zeposia include:

• upper respiratory infection,
• liver transaminase elevation,
• dizziness on standing (orthostatic hypotension),
• urinary tract infection (UTI),
• back pain,
• high blood pressure (hypertension), and
• upper abdominal pain

Tell your doctor all medications and supplements you use.

Dosage for Zeposia

The recommended maintenance dosage of Zeposia is 0.92 mg orally once daily.

Zeposia in Children

Safety and effectiveness of Zeposia in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Zeposia?

Zeposia may interact with:

• anti-neoplastic medications,
• immune-modulating drugs,
• immunosuppressive therapies,
• anti-arrhythmics,
• live attenuated vaccines,
• strong CYP2C8 inhibitors (e.g., gemfibrozil),
• BCRP inhibitors (e.g., cyclosporine, eltrombopag),
• strong CYP2C8 inducers (e.g., rifampin),
• monoamine oxidase inhibitors (MAOIs), and
• drugs or over-the-counter medications that can increase norepinephrine or serotonin [e.g., opioids, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclics, tyramine]

Tell your doctor all medications and supplements you use.

Zeposia During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Zeposia; it may harm a fetus. Women of childbearing potential should be counseled on the potential for a serious risk to the fetus and the need for contraception during treatment with Zeposia. Because of the time it takes to eliminate the drug from the body after stopping treatment, the potential risk to the fetus may persist and women of childbearing age should use effective contraception for 3 months after stopping Zeposia. It is unknown if Zeposia passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Zeposia (ozanimod) Capsules, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Zeposia Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, rash; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• slow heartbeats, chest pain, shortness of breath, feeling like your heart is skipping beats;
• a light-headed feeling, like you might pass out;
• cough, new or worsening shortness of breath;
• sudden confusion, severe headache, or vision loss;
• a seizure;
• pounding in your neck or ears;
• liver problems--nausea, vomiting, upper stomach pain, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes);
• changes in vision--blurred vision, increased sensitivity to light, seeing an unusual color in your vision, or having a blind spot or shadows in the center of your vision; or
• symptoms of infection--fever, tiredness, cough, rash, increased urination, pain or burning when you urinate, neck stiffness, increased sensitivity to light.

Common side effects may include:

• back pain;
• urination problems;
• high or low blood pressure;
• abnormal liver function tests; or
• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zeposia (Ozanimod Capsules)

 

Zeposia Professional Information

SIDE EFFECTS

The following serious adverse reactions are described elsewhere in the labeling:

• Infections [see WARNINGS AND PRECAUTIONS]
• Bradyarrhythmia and Atrioventricular Conduction Delays [see WARNINGS AND PRECAUTIONS]
• Liver Injury [see WARNINGS AND PRECAUTIONS]
• Fetal Risk [see WARNINGS AND PRECAUTIONS]
• Increased Blood Pressure [see WARNINGS AND PRECAUTIONS]
• Respiratory Effects [see WARNINGS AND PRECAUTIONS]
• Macular Edema [see WARNINGS AND PRECAUTIONS]
• Posterior Reversible Encephalopathy Syndrome [see WARNINGS AND PRECAUTIONS]
• Unintended Additive Immunosuppressive Effects from Prior Treatment with Immunosuppressive or Immune-Modulating Drugs [see WARNINGS AND PRECAUTIONS]
• Severe Increase in Multiple Sclerosis Disability after Stopping ZEPOSIA [see WARNINGS AND PRECAUTIONS]
• Immune System Effects after Stopping ZEPOSIA [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Common Adverse Reactions

Multiple Sclerosis

The safety of ZEPOSIA was evaluated in two randomized, double-blind, active comparator-controlled clinical studies in which 882 patients received ZEPOSIA 0.92 mg [see Clinical Studies].

Table 2 lists adverse reactions that occurred in at least 2% of ZEPOSIA-treated patients and greater than comparator. The most common adverse reactions that occurred in at least 4% of ZEPOSIA-treated patients and greater than in patients who received IFN beta-1a were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.

Table 2: Adverse Reactions with an Incidence of at Least 2% in ZEPOSIA-Treated Patients and at Least 1% Greater than IFN beta-1aPPin Patients with Multiple Sclerosis (Pooled MS Study 1 and Study 2)^a

Adverse Reactions	MS Studies 1 and 2
	ZEPOSIA 0.92 mg Once Dailye (n=882) %	IFN beta-1a 30 mcg Intramuscularly Once Weekly (n=885) %
Upper respiratory infection b	26	23
Hepatic transaminase elevation c	10	5
Orthostatic hypotension	4	3
Urinary tract infection	4	3
Back pain	4	3
Hypertension d	4	2
Upper abdominal pain	2	1
a Data are not an adequate basis for comparison of rates between ZEPOSIA and the active control. b Includes the following terms:nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, rhinitis, viral respiratory tract infection, viral upper respiratory tract infection, rhinorrhea, tracheitis, and laryngitis. c Includes the following terms: alanine aminotransferase increased, gamma-glutamyl transferase increased, aspartate aminotransferase increased, hepatic enzyme increased, abnormal liver function test, and increased transaminases. d Includes hypertension, essential hypertension, and orthostatic hypertension. e ZEPOSIA was initiated with a 7-day titration [see DOSAGE AND ADMINISTRATION].

Ulcerative Colitis

The safety of ZEPOSIA was evaluated in two randomized, double-blind, placebo-controlled clinical studies [UC Study 1 (induction), n=429; and UC Study 2 (maintenance), n=230] in adult patients with moderately to severely active ulcerative colitis [see Clinical Studies]. Additional data from the induction period of a randomized, double-blind, placebo-controlled study (UC Study 3, NCT01647516) included 67 patients who received ZEPOSIA 0.92 mg once daily.

Common adverse reactions in UC Study 1 and Study 3 and in UC Study 2 are listed in Tables 3 and 4, respectively. The most common adverse reactions that occurred in at least 4% of ZEPOSIA-treated patients and greater than in patients who received placebo were liver test increased, upper respiratory infection, and headache.

Table 3: Adverse Reactions with an Incidence of at Least 2% in ZEPOSIA-Treated Patients and at Least 1% Greater than Placebo in Patients with Ulcerative Colitis (Pooled UC Study 1 and Study 3)

Adverse Reactions	Induction Periods (UC Study 1 and Study 3)
	ZEPOSIA 0.92 mg Once Daily (n=496)c,d %	Placebo (n=281) %d
Upper respiratory infectiona	5	4
Liver test increased b	5	0
Headache	4	3
Pyrexia	3	2
Nausea	3	2
Arthralgia	3	1
a PIncludes the following terms: streptococcal pharyngitis, pharyngotonsillitis, bacterial pharyngitis, nasopharyngitis, upper respiratory tract infection, pharyngitis, sinusitis, tonsillitis, viral upper respiratory tract infection, laryngitis, acute sinusitis, catarrh, chronic sinusitis, upper respiratory tract inflammation, chronic tonsillitis, viral pharyngitis, viral sinusitis, bacterial sinusitis, bacterial upper respiratory tract infection, viral labyrinthitis, laryngeal inflammation, and pharyngeal inflammation. b PIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, liver function test increased, blood alkaline phosphatase increased, and increased transaminases. c PZEPOSIA was initiated with a 7-day titration [see DOSAGE AND ADMINISTRATION]. d Percentages were calculated as the sum of each individual study percentage multiplied by its Cochran-Mantel-Haenszel weight.

Table 4: Adverse Reactions with an Incidence of at Least 4% in ZEPOSIA-Treated Patients and at Least 1% Greater than Placebo in Patients with Ulcerative Colitis (UC Study 2)

Adverse Reactions	Maintenance Period (UC Study 2)
	ZEPOSIA 0.92 mg Once Daily (n=230) %	Placebo (n=227) %
Liver test increaseda	11	2
Headache	5	<1
a PIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, blood bilirubin increased, liver function test increased, and blood alkaline phosphatase increased.

Other Adverse Reactions

Reduction in Heart Rate

Initiation of ZEPOSIA may result in transient decrease in heart rate in MS and UC patients [see WARNINGS AND PRECAUTIONS].

Respiratory Effects

Dose-dependent reductions in absolute FEVR1R and FVC were observed in MS and UC patients treated with ZEPOSIA [see WARNINGS AND PRECAUTIONS].

Malignancies

Malignancies, such as melanoma, basal cell carcinoma, breast cancer, seminoma, cervical carcinoma, and adenocarcinomas, including rectal adenocarcinoma, were reported with ZEPOSIA in controlled trials of MS and UC. An increased risk of cutaneous malignancies has been reported with another S1P receptor modulator.

Hypersensitivity

Hypersensitivity, including rash and urticaria, has been reported with ZEPOSIA in active-controlled MS clinical trials.

Peripheral Edema

Peripheral edema was observed in 3% of ZEPOSIA-treated patients and in 0.4% of patients who received placebo in UC Study 2.

DRUG INTERACTIONS

Tables 5 and 6 include drugs with clinically important drug, tyramine, and vaccine interactions when administered concomitantly with ZEPOSIA and instructions for preventing or managing them.

Table 5: Clinically Relevant Interactions Affecting Drugs, Tyramine, and Vaccines Co-administered with ZEPOSIA

Anti-Neoplastic, Immune-Modulating, or Non-Corticosteroid Immunosuppressive Therapies
Clinical 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].
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]. 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 [see WARNINGS AND PRECAUTIONS]. 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 Rate
Clinical 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]. 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]. If treatment initiation with ZEPOSIA is considered in patients on QT prolonging drugs, advice from a cardiologist should be sought.
Adrenergic and Serotonergic Drugs
Clinical Impact:	Because an active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis with co-administration of ZEPOSIA with drugs or over-the-counter medications that can increase norepinephrine or serotonin [e.g., opioid drugs, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclics, tyramine]. Opioid Drugs Serious, sometimes fatal reactions have been precipitated with concomitant use of opioid drugs (e.g., meperidine and its derivatives, methadone, or tramadol) and MAOIs, including selective MAO-B inhibitors. Although a small number of patients treated with ZEPOSIA were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from co-administration. Serotonergic Drugs Although a small number of patients treated with ZEPOSIA were concomitantly exposed to serotonergic medications, this exposure was not adequate to rule out the possibility of an adverse reaction from co-administration. Sympathomimetic Medications Concomitant use of ZEPOSIA with pseudoephedrine did not potentiate the effects on blood pressure [see CLINICAL PHARMACOLOGY]. However, hypertensive crisis has occurred with administration of ZEPOSIA alone [see WARNINGS AND PRECAUTIONS] and hypertensive crisis has been reported with co-administration of other selective and nonselective MAO inhibitors (e.g., rasagiline) with sympathomimetic medications.
Prevention or Management:	Co-administration of ZEPOSIA with drugs or over-the-counter medications that can increase norepinephrine or serotonin (e.g., opioid drugs, SSRIs, SNRIs, tricyclics, tyramine) is not recommended. Monitor patients for hypertension with concomitant use.
Combination Beta Blocker and Calcium Channel Blocker
Clinical 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]. 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.
Tyramine
Clinical Impact:	MAO in the gastrointestinal tract and liver (primarily type A) provides protection from exogenous amines (e.g., tyramine). If tyramine were absorbed intact, it could lead to severe hypertension, including hypertensive crisis. Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines (e.g., aged cheese, pickled herring) may cause release of norepinephrine resulting in a rise in blood pressure (tyramine reaction).
Prevention or Management:	Patients should be advised to avoid foods containing a large amount of tyramine while taking recommended doses of ZEPOSIA [see WARNINGS AND PRECAUTIONS].
Vaccination
Clinical Impact:	During, and for up to three months after, discontinuation of treatment with ZEPOSIA, vaccinations may be less effective. The use of live attenuated vaccines may carry the risk of infection.
Prevention or Management:	Live attenuated vaccines should be avoided during ZEPOSIA treatment and for up to 3 months after discontinuation of treatment with ZEPOSIA [see WARNINGS AND PRECAUTIONS].

Table 6: Clinically Relevant Interactions Affecting ZEPOSIA When Co-administered with Other Drugs

Monoamine Oxidase (MAO) Inhibitors
Clinical Impact:	Co-administration of ZEPOSIA with MAO-B inhibitors may decrease exposure of the active metabolites of ozanimod. In addition, metabolites of ozanimod may inhibit MAO [see CLINICAL PHARMACOLOGY]. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
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 Inhibitors
Clinical Impact:	Co-administration of ZEPOSIA with strong CYP2C8 inhibitors increases the exposure of the active metabolites of ozanimod [see CLINICAL PHARMACOLOGY], 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 Inducers
Clinical 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], which may decrease the efficacy of ZEPOSIA.
Prevention or Management:	Co-administration of ZEPOSIA with strong CYP2C8 inducers should be avoided.

Read the entire FDA prescribing information for Zeposia (Ozanimod Capsules)