길레니아

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

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P270, P273, P280, P301+P317, P302+P352, P318, P319, P321, P330, P332+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In large randomized controlled trials of fingolimod in patients with multiple sclerosis, serum ALT elevations above 3 times ULN were reported in 8% to 14% of fingolimod compared to 2% to 3% of placebo recipients. ALT elevations above 5 times ULN occurred in 4.5% with fingolimod vs 1% with placebo. The enzyme elevations were usually transient and not associated with symptoms or jaundice and required drug discontinuation in less than 1% of cases. No instances of acute hepatitis or clinically apparent liver injury were reported in the preregistration trials of fingolimod. Subsequent to its approval and more wide scale use, however, instances of clinically apparent liver injury attributed to fingolimod were reported including cases of acute liver failure requiring emergency liver transplantation. The onset of liver injury was often within days or weeks of starting treatment and the pattern of liver enzyme elevations was usually hepatocellular. For these reasons, patients should be evaluated for liver disease and monitored for liver test abnormalities before starting treatment and regularly during and for two months after discontinuing therapy. In addition, at least one instance of reactivation of hepatitis B in an inactive HBsAg carrier has been reported and pre-screening for markers of HBV infection is also recommended. Thus, mild-to-moderate and transient serum enzyme elevations during therapy are not uncommon, and clinically apparent liver injury with jaundice due to fingolimod can occur.

L04AA27

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

In multiple sclerosis, fingolimod binds to sphingosine receptors, reducing its associated neuroinflammation.In COVID-19, it may reduce lung inflammation and improve the clinical outcomes of patients with this disease. Fingolimod causes a transient reduction in heart rate and AV conduction during treatment initiation. It has the potential to prolong the QT interval.

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 systems. 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. The active form of the drug, fingolimod phosphate, is a sphingosine 1-phosphate receptor modulator that exerts its mechanism of action in MS by binding to various sphingosine 1-phosphate receptors (1, 3, 4, and 5). It suppresses the exit of lymphocytes from lymph nodes, leading to a lower level of lymphocytes circulating in the peripheral circulation. This reduces the inflammation that is associated with MS. The mechanism of action of fingolimod is not fully understood but may be related to reduced lymphocyte circulation into the central nervous system. Immune modulating treatment such as fingolimod is not typically employed for SARS-CoV-2 pneumonia. Despite this, with the tissue findings of pulmonary edema and hyaline membrane formation, the timely use of immune modulators such as fingolimod can be considered to prevent acute respiratory distress syndrome (ARDS) associated with COVID-19.