Zeposia Starter Pack (ozanimod hydrochloride)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Ozanimod hydrochloride, a selective sphingosine 1-phosphate (S1P) receptor modulator, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS).
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptor subtypes 1 and 5. S1P receptors are expressed in multiple organs and systems throughout the body and are involved in the regulation of a variety of physiological and cellular processes including endocytosis, cardiac function, lymphocyte/hematopoietic cell trafficking, and vascular tone. Subtype 1 of the S1P receptor (S1P1) is expressed on the surface of lymphocytes and regulates lymphocyte egress from peripheral lymphoid organs.
Activation of the S1P1 receptor causes rapid and sustained receptor internalization and degradation, blocking the capacity of lymphocytes to egress from lymph nodes. Although multiple sclerosis (MS) and ulcerative colitis are distinct autoimmune diseases with unique pathologies, both disease states are characterized by the trafficking and accumulation of autoimmune-driven B and T lymphocytes in inflamed tissue. The exact mechanism by which ozanimod exerts its therapeutic effects in MS and ulcerative colitis is unknown, but may involve reduction of lymphocyte migration into the CNS.
Findings from preclinical studies suggest that ozanimod readily crosses the blood-brain barrier and may have other effects on neuropathologic processes such as synaptic neurodegeneration and demyelination through direct modulation of neural cells (e.g., astrocytes, oligodendrocytes). Ozanimod binds to the S1P1 receptor with similar affinity as other S1P receptor modulators (e.g., fingolimod, siponimod), with 27-fold greater selectivity for the S1P1 receptor versus S1P5 receptors. Ozanimod lacks substantial activity at other S1P receptor subtypes (S1P2, S1P3, and S1P4), particularly S1P subtype 3, which is thought to mediate the cardiac conduction effects of this class of drugs.
In healthy individuals, clinically important QT-interval prolongation was not observed following administration of ozanimod titrated up to 2 times the maximum recommended dosage over 4 days.
In controlled trials in patients with MS and ulcerative colitis, mean lymphocyte counts decreased to approximately 45% of baseline at 3 months following initiation of ozanimod and remained low with continued treatment. Following discontinuance of ozanimod, the median time to recovery of peripheral lymphocyte counts was 30 days; lymphocytes returned to the normal range within 3 months in 90% of patients.
Following oral administration of ozanimod hydrochloride, peak plasma concentrations of the drug are achieved in approximately 6-8 hours. Administration with a high-fat, high-calorie meal does not affect peak plasma concentration or systemic exposure of the drug. Peak plasma concentrations and AUC of ozanimod are dose proportional over the dose range of 0.46-0.92 mg.
Steady-state plasma concentrations of ozanimod are attained after approximately 102 hours. For the major CC112273 metabolite, steady-state plasma concentrations are attained after approximately 45 days with an accumulation ratio of 16-fold. Ozanimod and its metabolites are 98.2-99.8% bound to plasma proteins.
Animal data indicate that ozanimod readily crosses the blood-brain barrier. Ozanimod is metabolized via multiple pathways to form major active metabolites (CC112273 and CC1084037) and minor active metabolites (RP101988, RP101075, and RP112509), all of which possess similar activity and selectivity for S1P receptor subtypes 1 and 5. Ozanimod is metabolized by alcohol/aldehyde dehydrogenase; one of the byproducts of this pathway is metabolized by monoamine oxidase-B (MAO-B).
Following a single oral dose of radiolabeled ozanimod 0.92 mg, approximately 26% of radioactivity was recovered in urine and 37% in feces, primarily in the form of inactive metabolites. The mean plasma half-life is approximately 21 hours for ozanimod and approximately 11 days for its major metabolites CC112273 and CC1084037. Approximately 94% of circulating active drug is represented by ozanimod (6%), CC112273 (73%), and CC1084037 (15%) in humans.
Age, sex, renal impairment, race/ethnicity, body weight, and smoking status do not have clinically important effects on the pharmacokinetics of ozanimod.
USES: This medication is used to treat multiple sclerosis (MS). Ozanimod is not a cure for MS but it is thought to help by preventing immune system cells (lymphocytes) from attacking the nerves in your brain and spinal cord. It helps decrease the number of episodes of disease worsening (relapses) and may prevent or delay disability.
Ozanimod is also used to treat a certain bowel disease (ulcerative colitis). It helps to reduce symptoms of ulcerative colitis such as diarrhea, rectal bleeding, and stomach pain.
Generic name: ozanimod hydrochloride
Pronunciation: (oh-ZAN-i-mod)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Zeposia Starter Pack:
- Relapsing Form Of Multiple Sclerosis
- Secondary Progressive Multiple Sclerosis
- Ulcerative Colitis
Also known as: Colitis Ulcerativa, Multiple Sclerosis, Relapsing Form.
Dosing
Dosage of ozanimod hydrochloride is expressed in terms of ozanimod.
When initiating ozanimod therapy, dosage must be titrated to minimize the risk of adverse cardiac effects. The manufacturer recommends the following dosage titration schedule over the first 7 days of treatment (see Table 1).
Table 1: Ozanimod Dosage Titration Regimen
Days Dosage Days 1-4 0.23 mg once daily Days 5-7 0.46 mg once daily Day 8 and after 0.92 mg once daily
If a dose is missed during the first 2 weeks of treatment, reinitiate the dosage titration regimen. If a dose is missed after the first 2 weeks of treatment, retitration of the dosage is not necessary; skip the missed dose and resume the regular dosing schedule the following day.
Administer orally once daily without regard to food. Swallow capsules whole.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Ozanimod and its metabolites do not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C19, 2C8, 2C9, 2D6, or 3A, and do not induce CYP isoenzymes 1A2, 2B6, and 3A.
Major metabolites (CC112273 and CC1084037) inhibit monoamine oxidase-B (MAO-B) with over 1000-fold selectivity over MAO-A.
Ozanimod and its metabolites do not inhibit P-glycoprotein (P-gp), organic anion transport protein (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, multidrug and toxin extrusion transporter (MATE) 1, or MATE2K. The major ozanimod metabolites do not inhibit breast cancer resistance protein (BCRP) at clinically relevant concentrations.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Patients with any of the following conditions within the previous 6 months: myocardial infarction (MI), unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or class III or IV heart failure.
*Presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block unless patient has a functioning pacemaker.
*Severe untreated sleep apnea.
*Concomitant treatment with a monoamine oxidase (MAO) inhibitor.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse reactions reported with ozanimod in MS trials (occurring in >=4% of patients) were upper respiratory infection, liver enzyme elevations, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
The most common adverse reactions reported with ozanimod in ulcerative colitis trials (occurring in >=4% of patients) were liver enzyme elevations, upper respiratory infection, and headache.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of ozanimod have not been established in pediatric patients.
There are insufficient data on the developmental risk associated with ozanimod during pregnancy. However, the S1P receptor targeted by ozanimod has been demonstrated to have an important role in embryogenesis, including neural and vascular development. In animal studies, administration of ozanimod during pregnancy had adverse effects on fetal development, including embryolethality, increased fetal malformation, and neurobehavioral changes in the absence of maternal toxicity.
A pregnancy exposure registry that monitors pregnancy outcomes in women with MS exposed to ozanimod during pregnancy is available. Healthcare providers are encouraged to register patients, or pregnant women may register themselves at https://www.zeposiapregnancyregistry.com/ or by calling 1-877-301-9314.
It is not known whether ozanimod is distributed into human milk; however, the drug is distributed into milk in rats at concentrations higher than those in maternal plasma. The effects of ozanimod on the nursing infant or on milk production are not known.
Consider the developmental and health benefits of breast-feeding along with the importance of ozanimod to the female and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
Clinical studies of ozanimod did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently than younger patients. No clinically significant differences in the metabolism of ozanimod and its major metabolite CC112273 were observed in clinical studies based on age. Because of the greater frequency of decreased hepatic and cardiac function in geriatric patients, monitor such patients for cardiac and hepatic adverse reactions during ozanimod therapy.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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