Teriflunomide

270.2072696

270.21

1308068-626-2

1C058IKG3B

L04AA31|L - Antineoplastic and immunomodulating agents

2942000000

73.1

3.3

white to beige

1.424±0.06 g/cm3(Predicted)

229-232°C

410.8±45.0 °C(Predicted)

202.3±28.7 °C

1.552

soluble in DMSO (practically insoluble in water).DMSO: soluble 5mg/mL, clear (warmed)

Hygroscopic, -20°C Freezer, Under Inert Atmosphere

NONH for all modes of transport

3

22

Xn

P264, P270, P301+P312, P330, P501

H302

|Warning|H302 (95.74%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 48 companies from 6 notifications to the ECHA C&L Inventory.

Teriflunomide is contraindicated in pregnant women or women of childbearing age due to the risk of teratogenicity. Teriflunomide is also contraindicated in severe hepatic impairment due to reports of hepatotoxicity, hepatic failure, and death.

In large randomized controlled trials of teriflunomide, serum ALT elevations occurred in 13% to 15% of teriflunomide compared to 9% of placebo recipients. Elevations above 3 times the upper limit of normal occurred in 6% of teriflunomide versus 4% of placebo recipients, usually within the first 6 months of therapy. The enzyme elevations were usually transient and not associated with symptoms or jaundice, but led to drug discontinuation in 2% to 3% of patients. The abnormalities resolved rapidly with drug discontinuation and resolved spontaneously in at least half of patients without drug modification. During preregistration trials, a single case of severe liver injury with jaundice was described, ALT elevations appearing 5 months after starting teriflunomide. Because of this and the known hepatotoxic potential of leflunomide, teriflunomide was given a "black box" warning regarding hepatotoxicity, and routine monitoring of liver tests is recommended monthly for the first 6 months and intermittently thereafter. Since approval and more wide scale usage, there have been no cases of clinical apparent liver injury published in the medical literature, although the package label mentions hepatitis and hepatic failure as possible adverse events. Clinically apparent liver injury has been reported with leflunomide, generally presenting with a hepatocellular or mixed pattern of serum enzyme elevations within 1 to 6 months of starting therapy. Immunoallergic and autoimmune features have not been prominent in these cases. Some cases, however, have been severe leading to acute liver failure and death. Whether similar cases occur with teriflunomide is not known.

Teriflunomide is extensively plasma protein bound(>99%).

Used in the treatment of relapsing forms of multiple sclerosis (MS).|FDA Label|AUBAGIO is indicated for the treatment of adult patients and paediatric patients aged 10 years and older with relapsing remitting multiple sclerosis (MS) (please refer to section 5.1 for important information on the population for which efficacy has been established).|Treatment of multiple sclerosis

Teriflunomide is an orally available immunomodulatory agent used to treat relapsing multiple sclerosis. Teriflunomide is associated with transient serum enzyme elevations during therapy and with rare instances of acute liver injury.

Multiple Sclerosis Agents

Teriflunomide is an immunomodulatory agent that decreases the amount of activated CNS lymphocytes, which results in anti-inflammatory and antiproliferative effects.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)

After oral administration of teriflunomide, maximum plasma concentrations are reached, on average, in 1-4 hours.|Teriflunomide is eliminated unchanged and mainly through bile. Specifically 37.5% is eliminated in the feces and 22.6% in urine.|After a single intravenous dose, the volume of distribution is 11 L.|After a single IV dose, teriflunomide has a total body clearance of 30.5 mL/h.

Teriflunomide mainly undergoes hydrolyis to minor metabolites. Other minor metabolic pathways include oxidation, N-acetylation and sulfate conjugation. Teriflunomide is not metabolized by CYP450 or flavin monoamine oxidase.

The median half-life is 18 to 19 days.

The exact mechanism by which teriflunomide acts in MS is not known. What is known is that teriflunomide prevents pyrimidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase, and this may be involved in its immunomodulatory effect in MS.

(2Z)-2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-butenamide

Human drugs -> Aubagio -> EMA Drug Category|Selective immunosuppressants -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients