anti-multiple sclerosis agents
- Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
- Moderately to severely active ulcerative colitis.
Acts as a sphingosine 1–phosphate (S1P) receptor modulator that binds to SIP receptors 1 and 5, resulting in ↓ migration of lymphocytes from lymph nodes into peripheral blood, the CNS, and the intestine.
- ↓ frequency of relapses/delayed accumulation of disability in MS.
- Achievement of clinical remission in ulcerative colitis.
Distribution: Extensively distributed to tissues.
Protein Binding: Ozanimod– 98%; CC112273– 99.8%; CC1084037– 99%.
Metabolism and Excretion: Metabolized by several enzymes into 2 major active metabolites (CC112273 and CC1084037) and 3 minor active metabolites. These metabolites are further converted by multiple enzymes systems. Excreted in feces (37%) and urine (26%), primarily as inactive metabolites.
Half-life: Ozanimod– 21 hr; CC112273 and CC1084037– 11 days.
TIME/ACTION PROFILE (plasma concentrations)
|PO||unknown||6–8 hr||24 hr|
- MI, unstable angina, stroke, TIA, decompensated HF requiring hospitalization, or class III or IV HF within previous 6 mo;
- 2nd- or 3rd-degree heart block, sick sinus syndrome, or sinoatrial block (in the absence of a pacemaker);
- Severe untreated sleep apnea
- Use of MAO inhibitor concurrently or within 14 days of last dose of ozanimod
- Active acute/chronic untreated infection;
- Hepatic impairment
- OB: Pregnancy (may cause fetal harm).
Use Cautiously in:
- QT interval prolongation (>450 msec in males, >470 msec females), hypokalemia, hypomagnesemia, congenital long QT syndrome, or concurrent use of QT interval prolonging medications;
- Heart rate <55 bpm
- Cardiac arrhythmias requiring use of class Ia or III antiarrhythmics;
- Ischemic heart disease, MI, HF, cardiac arrest, cerebrovascular disease, or uncontrolled hypertension;
- Uveitis or diabetes mellitus (↑ risk of macular edema)
- Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
- Rep: Women of reproductive potential
- Pedi: Safety and effectiveness not established in children;
- Geri: Risk of adverse reactions may be ↑ in older adults; consider age-related ↓ in cardiac/renal/hepatic function, chronic illnesses, and concurrent drug therapy.
Adverse Reactions/Side Effects
CV: bradycardia, heart block, hypertension, orthostatic hypotension
EENT: macular edema
GI: ↑ liver enzymes, abdominal pain
Neuro: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
Resp: ↓ pulmonary function
Misc: INFECTION (including bacterial, viral and fungal), MALIGNANCY, hypersensitivity reactions
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- ↑ risk of immunosuppression with antineoplastics, immunosuppressants, or immune modulating therapies ; avoid initiating therapy with ozanimod after alemtuzumab therapy is discontinued.
- Concurrent use of QT-interval prolonging medications may ↑ risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
- Class Ia antiarrhythmics and class III antiarrhythmics may ↑ risk of torsade de pointes in presence of bradycardia; use concurrently with caution.
- Strong CYP2C8 inhibitors, including gemfibrozil, may ↑ levels of active metabolite and risk of toxicity.
- Opioids, SSRIs, SNRIs, TCAs or sympathomimetic drugs may ↑ risk of hypertensive crises.
- Live-attenuated vaccines ↑ risk of infection; avoid concurrent use and for 3 mo following last dose.
Foods containing high amounts of tyramine (>150 mg) may lead to severe hypertension; avoid concurrent use.
PO (Adults): 0.23 mg once daily on Days 1–4, then 0.46 mg once daily on Days 5–7, then 0.92 mg once daily thereafter starting on Day 8.
Capsules: 0.23 mg, 0.46 mg, 0.92 mg
- Assess ECG for preexisting conduction abnormalities before starting therapy. May cause transient decrease in HR and atrioventricular conduction delays.
- Monitor BP during therapy. May cause hypertension requiring treatment.
- Perform ophthalmic exam to assess fundus, including the macula, before starting therapy in patients with a history of uveitis or macular edema.
Monitor for signs and symptoms of infection (fever, tiredness, body aches, chills, nausea, vomiting, headache, sore throat) before starting, periodically during and for 3 mo after therapy. Delay start of therapy until infection resolved. Interrupt therapy if serious infection occurs.
Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the Jakob Cruzfeldt (JC) virus, that may be fatal; hold dose and notify health care professional promptly. PML symptoms may begin gradually (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) and may include deteriorating renal function. Monitoring MRI every 6 mo may identify PML before clinical signs and symptoms occur. If PML confirmed, discontinue ozanimod.
- Monitor for respiratory effects (reductions in forced expiratory volume [FEV1 ] and forced vital capacity [FVC]) with spirometry periodically during therapy.
Monitor for signs and symptoms of posterior reversible encephalopathy syndrome (PRES) (impaired consciousness, convulsions, visual disturbances including blindness, loss of motor function, movement disorders, psychiatric disturbances, papilledema, visual impairment). Discontinue therapy if PRES develops. Usually reversible with discontinuation of ozanimod.
- Assess for signs and symptoms of severe increased disability and disease exacerbation after stopping therapy with ozanimod.
Lab Test Considerations:
Obtain CBC with lymphocyte count before starting therapy. Peripheral blood lymphocytes return to normal range within 30 days to 3 mo.
- Obtain AST, ALT, and bilirubin levels before starting therapy.
- Test for antibodies to varicella zoster virus (VZV) before starting therapy.
- Administer varicella zoster virus vaccination of antibody-negative patients before starting therapy. If live attenuated vaccine immunizations are required, administer at least 1 mo before start of therapy. Avoid use of live attenuated vaccines during and for 3 mo after therapy.
- PO Administer once daily without regard to food. DNC: Swallow capsules whole; do not crush, open, or chew.
- If a dose is missed during first 2 wk of therapy, restart using initial dosing regimen.
- Instruct patient to take ozanimod as directed. If a dose is missed during first 14 days of therapy, contact health care professional. Starting doses will need to be repeated. Do not discontinue therapy without consulting health care professional, may cause severe increase in disability. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Advise patient to avoid foods or beverages containing tyramine (see food sources for specific nutrients); may cause a hypertensive crisis.
- Instruct patient not to receive live-attenuated vaccines during and for 3 mo after therapy due to risk of infection.
Advise patient to notify health care professional immediately if signs and symptoms of infection (fever, cough, feeling very tired, painful and frequent urination, flu-like symptoms, rash, headache with fever, neck stiffness, sensitivity to light, nausea or confusion), PRES (sudden severe headache, sudden loss of vision or visual changes, sudden confusion, seizure), PML, or allergic reaction (rash, itchy hives, swelling of lips, tongue or face) occur.
- Advise patient to notify health care professional if signs and symptoms of slow HR (dizziness, shortness of breath, lightheadedness, confusion, feeling like heart is beating slowly or skipping beats, chest pain, tiredness), liver injury (unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, dark urine), respiratory effects (new or worsening shortness of breath), or changes in vision (blurriness or shadows in the center of vision, a blind spot in center of vision, sensitivity to light, unusually colored vision) occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 3 mo after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- ↓ frequency of relapses/delayed accumulation of disability with MS.
- Achievement of clinical remission in ulcerative colitis.