Ozanimod

Breast Feeding; Lactation; Milk, Human; Immunosuppressive Agents; Sphingosine 1 Phosphate Receptor Modulators

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

Danger

H372 (100%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P260, P264, P270, P319, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In large controlled trials of ozanimod in patients with multiple sclerosis, serum ALT elevations were common (~5% of recipients) but were typically mild and asymptomatic, and they returned to baseline values within a few months of stopping and often even with continuation of therapy. Aminotransferase elevations above 3 times upper limit of normal (ULN) were reported in 5% of ozanimod recipients compared to less than 1% of placebo recipients and elevations above 5 times ULN in 1%. In these prelicensure clinical trials, there were no cases of acute hepatitis or clinically apparent liver injury but elevations in liver tests led to discontinuation in approximately 1% of subjects. While ozanimod is associated with lymphopenia and long term therapy is associated with risk for reactivation of herpes simplex and zoster infections, it has not been linked to cases of reactivation of hepatitis B although one such instance has been reported with fingolimod. Thus, mild-to-moderate and transient serum enzyme elevations during therapy are not uncommon, but clinically apparent liver injury with jaundice due to ozanimod has not been reported, although the clinical experience with its use has been limited.

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

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.

Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system. S1P can be expressed ubiquitously, playing an important role in regulating inflammation. S1P1R, S1P2R, and S1P3R receptors can be found in the cardiovascular, immune, and central nervous systems. S1P4R is found on lymphocytic and hematopoietic cells, while S1P5R expression is found only on the spleen (on natural killer cells) or in the central nervous system. Ozanimod is a selective modulator of S1P receptors and binds to S1P1R and S1P5R subtypes. The mechanism of action of ozanimod is not fully understood, but this drug likely reduces the migration of lymphocytes that usually aggravate the inflammation associated with MS.

Ozanimod has two major active metabolites CC112273 and CC1084037 and minor active metabolites such as RP101988, RP101075, and RP101509, which target the S1P1 and S1P5 receptors. The enzymes involved in the metabolism of ozanimod include ALDH/ADH, NAT-2, Monoamine Oxidase B, and AKR 1C1/1C2. After metabolism, ozanimod (6%), CC112273 (73%), and CC1084037 (15%) are accounted for in the circulation.