|Other names||A77 1726|
|Drug class||Pyrimidine synthesis inhibitor|
|Main uses||Multiple sclerosis (MS)|
|Side effects||Headache, diarrhea, liver problems, nausea, hair loss|
|Typical dose||14 mg per day|
|Elimination half-life||2 weeks|
|Excretion||Bile duct/fecal, kidney|
|Chemical and physical data|
|Molar mass||270.211 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Teriflunomide, sold under the brand name Aubagio, is a medication used to treat multiple sclerosis (MS); specifically relapsing-remitting MS. In Scotland it is used as a second line treatment to interferon beta and glatiramer. It is taken by mouth.
Common side effects include headache, diarrhea, liver problems, nausea, and hair loss. Other side effects may include liver failure, peripheral neuropathy, and interstitial lung disease. Use in the two years before or during pregnancy may harm the baby. It is a pyrimidine synthesis inhibitor. While how it works is not entirely clear, it is believed to decrease the number of lymphocytes. It is the active metabolite of leflunomide.
Teriflunomide was approved for medical use in the United States in 2012 and and Europe 2013. In the United Kingdom it costs the NHS about 1,100 pounds per month. This amount in the United States costs about 8,400 USD as of 2021.
Teriflunomide was investigated in the phase III clinical trial TEMSO as a medication for multiple sclerosis (MS). However, a subsequent comparison trial reported that although permanent discontinuations were less common among people with MS who received teriflunomide compared with interferon beta-1a, relapses were more common with teriflunomide.
It is taken at a dose of 14 mg once per day.
Mechanisms of action
Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase. It is uncertain whether this explains its effect on MS lesions.
Teriflunomide inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. Teriflunomide may decrease the risk of infections compared to chemotherapy-like drugs because of its more-limited effects on the immune system.
Activation of leflunomide
Teriflunomide is the main active in vivo metabolite of the generically available leflunomide. Upon administration of leflunomide, 70% of the drug administered converts into teriflunomide. The only difference between the molecules is the opening of the isoxazole ring. This is considered a simple structural modification and a technically simple one-step synthetic transformation. Upon oral administration of leflunomide in vivo, the isoxazole ring of leflunomide is opened and teriflunomide is formed.
"Regardless of the substance administered (leflunomide or teriflunomide), it is the same molecule (teriflunomide)—the one exerting the pharmacological, immunological or metabolic action in view of restoring, correcting or modifying physiological functions, and does not present, in clinical use, a new chemical entity to patients." Because of this, EMA initially had not considered teriflunomide being a new active substance.
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- ClinicalTrials.gov Phase III Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO)
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