Ozanimod

Ozanimod is a medication that belongs to the sphingosine 1-phosphate receptor modulator class. It is prescribed for adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, or active secondary progressive disease. Additionally, it is used to treat ulcerative colitis in adults. Ozanimod works by reducing the activity of immune cells that can lead to nerve damage. The USFDA approved Ozanimod capsules in March 2020.

BRAND NAME:

Zeposia – Zeposia are available in the form of hard capsules with strengths 0.46mg, 0.23mg, and 0.92mg containing ozanimod as the active ingredient.

MECHANISM OF ACTION:

The pathogenesis of IBD involves the migration of lymphocytes from lymphoid tissues to the intestines, where they promote inflammation. S1P signaling is involved in lymphocyte trafficking and plays a role in inflammation. S1P binds to S1P1 receptors on lymphocytes, enabling them to migrate from lymphoid tissues into the circulation and to sites of inflammation. At sites of inflammation, S1P is involved in the recruitment of immune cells, which further exacerbates the inflammatory process. The enzymatic pathways that control S1P levels are dysregulated in the intestinal tissue with IBD. Ozanimod is an S1P receptor modulator that binds with high affinity to the S1P1 and S1P5 receptor subtypes, leading to S1P1 receptor internalization and thus reducing the capacity of lymphocytes to grow from lymphoid tissue. Ozanimod and its major active metabolites do not bind to the S1P2-4 receptors in vitro, limiting some of the off-target effects that are associated with non-selective S1P receptor modulators.

PHARMACOKINETICS:

Absorption: Ozanimod is absorbed in the gastrointestinal tract after oral administration. It takes 6 to 8 hours after administration to achieve 0.244 ng/mL. It takes 102 hours after administration to reach a steady state.

Distribution: The average volume of distribution of ozanimod is 5590L.

Metabolism: Ozanimod has two major active metabolites, CC112273 and CC1084037, and other minor metabolites similar to S1P1 and S1P5.

Excretion: About 26% of the labeled drug was accounted for in the urine and 37% in the feces, mainly in the form of inactive metabolites.

PHARMACODYNAMICS:

Ozanimod reduces circulating lymphocytes that cause the neuroinflammation associated with MS, reducing debilitating symptoms and, possibly, disease progression. During clinical trials, ozanimod reduced MS- associated brain volume loss in several regions. Ozanimod causes the sequestration of peripheral lymphocytes, reducing circulating lymphocytes in the gastrointestinal tract.

DOSAGE AND ADMINISTRATION:

Ozanimods are available in the form of capsules. Based on the patient's health condition the dosage will be recommended.

For multiple sclerosis and ulcerative colitis, in adults, the dosage recommended on days 1 to 4, is 0.23mg once a day. Next 5 to 7 days, 0.46mg once a day is recommended. And on the day and after 0.92mg once a day is recommended.

For children, the dosage must be determined by the doctor.

DRUG INTERACTIONS:

Before taking ozanimod it is required to discuss with the doctor if the patient is undergoing any other treatment. Some medications might interact with ozanimod and cause adverse effects. Below are the medications that are to be avoided while taking ozanimod by informing the doctor, they may change the dosage form.

Class 1A and class III anti-arrhythmias and known QT-prolonging drugs should not be used in combination with ozanimod.
CYP2C8 inhibitors, such as gemfibrozil, and CYP2C8 inducers, like rifampin, can influence the metabolism of ozanimod and should be avoided.
Inhibitors of the breast cancer resistance protein, such as cyclosporine and eltrombopag, should be avoided as they can interfere with the metabolism of ozanimod.
Monoamine oxidase inhibitors, including selegiline, phenelzine, and linezolid, should not be taken with ozanimod due to the potential for severe hypertension.
Opioids, selective serotonin reuptake inhibitors, and selective norepinephrine reuptake inhibitors may cause hypertension when used in combination with ozanimod.

FOOD INTERACTIONS:

Avoid tyramine-containing foods and supplements as they can increase the risk of hypertension.

CONTRAINDICATIONS:

It is contraindicated in patients suffering from myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure, sick sinus syndrome, sinoatrial block, severe untreated sleep apnea, and persons taking monoamine oxidase inhibitors.

ADVERSE EFFECTS: