ozanimod

Contraindicated in:

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;
Severe hepatic impairment.

Use Cautiously in:

QT interval prolongation (>450 msec [males], >470 msec [females]), hypokalemia, hypomagnesemia, congenital long QT syndrome, or concurrent use of QT interval prolonging medications;
HR <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);
Immunocompromised or taking other immunosuppressant medications (↑ risk of progressive multifocal leukoencephalopathy [PML]);
Mild or moderate hepatic impairment (↓ dose);
OB: Other agents preferred for MS or ulcerative colitis;
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.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, heart block, hypertension, orthostatic hypotension

Derm: BASAL/SQUAMOUS CELL CARCINOMA, MELANOMA

EENT: macular edema

GI: ↑liver enzymes, abdominal pain, HEPATOTOXICITY

Hemat: lymphopenia

Neuro: pml, posterior reversible encephalopathy syndrome (pres)

Resp: ↓pulmonary function

Misc: IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS), infection (including bacterial, viral and fungal), hypersensitivity reactions, MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors, including phenelzine, selegiline, and linezolid, may ↑ risk of hypertensive crises; concurrent use or use within 14 days of last dose of ozanimod contraindicated.
↑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 torsades de pointes in presence of bradycardia; use concurrently with caution.
Strong CYP2C8 inhibitors, including gemfibrozil, may ↑ levels of active metabolite and risk of toxicity.
Strong CYP2C8 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
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.
Beta blockers, diltiazem, verapamil, digoxin, or ivabradine may ↑ risk of bradycardia.

Drug-Food:

Foods containing high amounts of tyramine (>150 mg) may lead to severe hypertension; avoid concurrent use.

Availability ⬆ ⬇

Capsules: 0.23 mg; 0.46 mg; 0.92 mg

Route/Dosage ⬆ ⬇

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.

Hepatic Impairment

PO (Adults ): Mild or moderate hepatic impairment: 0.23 mg once daily on Days 1–4, then 0.46 mg once daily on Days 5–7, then 0.92 mg every other day thereafter starting on Day 8.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Therapeutic effects:

↓frequency of relapses/delayed accumulation of disability in MS.
Achievement of clinical remission in ulcerative colitis.

Classifications ⬆ ⬇

Therapeutic Classification: anti-multiple sclerosis agents

Pharmacologic Classification: receptor modulators

Pharmacokinetics ⬆ ⬇

Absorption: Unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: Ozanimod: 98%; CC112273: 99.8%; CC1084037: 99%.

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	6–8 hr	24 hr

Patient/Family Teaching ⬆ ⬇

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 ↑ 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.
Advise patient to notify health care professional if they develop signs and symptoms of liver dysfunction, infection, PML, new onset dyspnea, PRES (sudden headache, confusion, seizures, loss of vision, weakness), hypersensitivity reactions (rash or itchy hives; swelling of lips, tongue, or face), skin lesions, nodules (shiny pearly nodules), patches or open sores that do not heal within wks, or changes in vision.
Advise patient to notify health care professional if they develop signs and symptoms of slow HR (dizziness, shortness of breath, confusion, feeling of skipped heartbeats, chest pain).
Instruct patient not to receive live-attenuated vaccines during and for 3 mo after treatment due to risk of life-threatening infection. Advise patients who have not had a health care professional–confirmed history of chickenpox or a full course vaccination to be tested for antibodies to VZV before starting therapy.
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.
Caution patient to avoid exposure to sunlight and ultraviolet light, wear protective clothing, and use sunscreen with a high protection factor to minimize risk of cutaneous malignancies.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 3 mo after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patients of registry that monitors outcomes in women exposed to ozanimod. To enroll patient in the pregnancy registry, call 1-877-301-9314 or visit www.zeposiapregnancyregistry.com.

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Indications ⬇

Contraind./Precautions ⬆ ⬇