Ozanimod

Ozanimod is a prescription medication used for the treatment of multiple sclerosis and ulcerative colitis.

• Ozanimod is available under various brand names: Zeposia

Common side effects of Ozanimod 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

Serious side effects of Ozanimod include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• unexplained nausea
• loss of appetite
• vomiting
• yellowing of the whites of the eyes or skin
• stomach area (abdominal) pain
• dark colored urine
• tiredness
• increased blood pressure
• breathing problems
• blurriness or shadows in the center of your vision
• a blind spot in the center of your vision
• sensitivity to light
• unusually colored vision
• sudden severe headache
• sudden loss of vision or other changes in your vision
• seizure
• sudden confusion
• severe worsening of multiple sclerosis

Rare side effects of Ozanimod include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 0.23 mg
• 0.46 mg
• 0.92 mg

Multiple Sclerosis

Adult dosage

Initial dose titration and maintenance

• Days 1-4: 0.23 mg orally every day
• Days 5-7: 0.46 mg orally every day
• Day 8 and thereafter: 0.92 mg orally every day

Ulcerative Colitis

Adult dosage

Initial dose titration and maintenance

• Days 1-4: 0.23 mg orally every day
• Days 5-7: 0.46 mg orally every day
• Day 8 and thereafter: 0.92 mg orally every day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ozanimod has severe interactions with the following drugs:
• isocarboxazid
  • linezolid
  • phenelzine
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
  • selegiline transdermal
  • tranylcypromine
  • upadacitinib
• Ozanimod has serious interactions with at least 175 other drugs.
• Ozanimod has moderate interactions with at least 167 other drugs.
• Ozanimod has no noted minor interactions with at least 31 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• MI, unstable angina, stroke, TIA, decompensated heart failure (HF) requiring hospitalization, or Class III or IV HF within the last 6 months
• Mobitz type II second- or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker
• Severe untreated sleep apnea
• MAOIs

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ozanimod?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ozanimod?”

Cautions

• Based on animal studies, may cause fetal harm
• Clinical trials reported increased systolic blood pressure; monitoring blood pressure during treatment and managing appropriately
• Dose-dependent reductions in FEV1 and FVC were reported; perform a spirometric evaluation of respiratory function during therapy, if clinically indicated
• Rare cases of posterior reversible encephalopathy syndrome were reported in patients receiving an S1P receptor modulator
• Liver injury
  • Use in patients with hepatic impairment is not recommended; obtain transaminase and bilirubin levels, if not recently available (i.e., within 6 months), before initiation of therapy
  • Check hepatic enzymes 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 therapy if significant liver injury confirmed
  • Progressive multifocal leukoencephalopathy (PML)
  • 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 and other multiple sclerosis (MS) and UC therapies and has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants)
  • Physicians should be vigilant for clinical symptoms or MRI findings that may be suggestive of PML; MRI findings may be apparent before clinical signs or symptoms
  • If PML is suspected, treatment should be suspended until PML has been excluded by an appropriate diagnostic evaluation; if PML is confirmed, treatment should be discontinued
  • In MS, severe exacerbation of the disease, including disease rebound, is rarely reported after discontinuation of an S1P receptor modulator; the possibility of severe exacerbation of the disease should be considered after stopping treatment
  • Patients should be observed for a severe increase in disability upon therapy discontinuation; appropriate treatment should be instituted, as required
• Macular edema
  • An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients at any time if there is any change in vision while taking medication
  • Continuation of therapy in patients with macular edema not evaluated; a decision on whether or not therapy should be discontinued needs to take into account potential benefits and risks for an individual patient
  • Patients with a history of uveitis and patients with a history of diabetes mellitus are at increased risk of macular edema during therapy; the incidence of macular edema is also increased in patients with a history of uveitis
  • In addition to examination of the fundus, including the macula, before treatment, patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations
• Infections
  • May cause a mean reduction in peripheral blood lymphocyte count to 45% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissue
  • Increased risk of susceptibility to infections (eg, viral upper respiratory tract infections, urinary tract infections, herpes infections)
  • Life-threatening and rare fatal infections have occurred
  • Delay initiation in patients with an active infection until it is resolved
  • Consider interrupting treatment if a serious infection develops
  • Owing to the drug’s long half-life, continue monitoring for infections for 3 months
• Bradyarrhythmias and AV conduction delays
  • Dose initiation may result in a transient decrease in HR and AV conduction delays; follow the titration schedule to reach the maintenance dose
  • Obtain cardiology consultation for patients with
  • Significant QT prolongation (QTcF above 450 msec in males, above 470 msec in females)
  • Arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic drugs
  • Ischemic heart disease, HF, history of cardiac arrest or MI, CV disease, and uncontrolled hypertension
  • History of second-degree Mobitz type II or higher AV block, sick sinus syndrome, or sinoatrial heart block
• Drug interaction overview
  • Immunosuppressants, immunomodulators, or antineoplastics
  • After discontinuing ozanimod, the median time for peripheral blood lymphocytes to return to the normal range was 30 days, with approximately 90% of patients in the normal range within 3 months
  • Use of immunosuppressants within this period may lead to an additive effect on the immune system, and, therefore, caution should be applied when initiating other drugs 4 weeks after the last ozanimod dose
  • Conversely, when switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing the risk of disease reactivation, when initiating ozanimod
  • Initiating ozanimod after treatment with alemtuzumab is not recommended
  • Antiarrhythmic drugs, QT-prolonging drugs, or drugs that decrease HR
  • Has not been studied in patients taking QT-prolonging drugs
  • Obtain cardiology consultation to assess risk
  • Class Ia (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia
  • Because of the potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT-prolonging drugs
• Vaccination
  • Vaccinations may be less effective during and up to 3 months after discontinuing ozanimod
  • Owing to the risk of infection, avoid live attenuated vaccines during treatment and for up to 3 months after discontinuation
• CYP2C8 inhibitors and inducers
  • Active metabolites are metabolized by CYP2C8
  • Strong CYP2C8 inhibitors: Coadministration is not recommended owing to increased systemic exposure of active metabolites and risk of adverse effects
  • Strong CYP2C8 inducers: Avoid coadministration; may decrease systemic exposure and efficacy
• BCRP inhibitors
  • Coadministration is not recommended owing to increased systemic exposure to active metabolites and the risk of adverse effects
• MAOIs
  • Coadministration with MAO-B inhibitors may decrease the exposure of the active metabolites of ozanimod
  • Additionally, metabolites of ozanimod may inhibit MAO
  • The potential for a clinical interaction with MAOIs has not been studied; however, the increased risk of nonselective MAOI may lead to hypertensive crisis
  • Therefore, coadministration with MAOI (eg, selegiline, phenelzine, linezolid) is contraindicated
  • At least 14 days should elapse between discontinuation and initiation of treatment with MAO inhibitors
• Adrenergic and serotonergic drugs
  • Because an active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis
  • Coadministration with drugs or OTC medications that can increase norepinephrine or serotonin (eg, opioid drugs, SSRIs, SNRIs, tricyclics, tyramine) is not recommended
  • Monitor patients for hypertension with concomitant sympathomimetic use
• Tyramine
  • MAO in the GI tract and liver (primarily type A) protects exogenous amines (eg. 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 (eg, aged cheese, pickled herring) may cause the release of norepinephrine, resulting in a rise in blood pressure (tyramine reaction)
  • Avoid foods containing a large amount of tyramine while taking recommended ozanimod doses

Pregnancy & Lactation

• Data are not available regarding use in pregnant women
• Based on animal studies, may cause fetal harm
  • Contraception
• Before initiating treatment, counsel females of childbearing potential regarding the potential for serious fetal risks and the need for contraception during treatment and for 3 months after stopping ozanimod
• Lactation
  • Data are not available on the presence of human milk, effects on breastfed infants, or effects on milk production