Riluzole is a neuroprotective agent used for therapy of amyotrophic lateral sclerosis. Riluzole is associated with a low rate of serum aminotransferase elevations during therapy and has been linked to rare instances of clinically apparent, acute liver injury.
Riluzole (ril' ue zole) is a benzothiazole that is neuroprotective in vitro and in vivo. The mechanism by which it protects neurons from toxic injury is unknown, but it appears to inhibit glutamate release, to block post-synaptic glutamate receptors and to inactivate voltage dependent sodium channels. Studies in patients with amyotrophic lateral sclerosis suggest that riluzole may slow disease progression and neurologic deterioration. Riluzole was approved for use in the United States in 1995 and is commonly used in management of amyotrophic lateral sclerosis. Riluzole is available in tablets of 50 mg under the brand name Rilutek. The typical maintenance dosage is 50 mg every 12 hours. Common side effects include fatigue, weakness, dizziness, nausea, diarrhea, and cough.
Serum aminotransferase elevations occur in approximately up to 12% of patients on long term riluzole therapy, but elevations above 3 times the upper limit of normal (ULN) occur in less than 3% of patients. These elevations are usually mild-to-moderate in severity and are rarely associated with symptoms. Most elevations resolve spontaneously, but persistent or marked elevations require drug discontinuation or dose modification. Routine monitoring of serum aminotransferase levels is recommended for the first 6 months of therapy. Clinically apparent liver injury due to riluzole is rare, but several cases have been reported, arising after 1 to 12 months of therapy and characterized by a hepatocellular or mixed pattern of serum enzyme elevations. Immunoallergic and autoimmune features were uncommon. Most cases were mild to moderate in severity and recovery was rapid upon drug discontinuation, but evidently fatal cases have been reported to the sponsor.
Mechanism of Injury
Riluzole is extensively metabolized by the liver by the cytochrome P450 system into multiple intermediates, not all of which have been characterized. The hepatotoxicity of riluzole may be related to production of a toxic or immunogenic intermediate.
Outcome and Management
The severity of liver injury from riluzole ranges from minor, transient elevations in serum aminotransferase levels to acute hepatic injury with jaundice and possible to acute liver failure. Routine monitoring of serum aminotransferase levels is recommended during the first 6 months of riluzole therapy and therapy discontinued for elevations greater than 5 times ULN. Riluzole has not been linked to cases of chronic hepatitis or vanishing bile duct syndrome. Restarting riluzole can result in recurrence of liver injury and should be avoided.
REPRESENTATIVE TRADE NAMES
Riluzole – Rilutek®
Product labeling at DailyMed, National Library of Medicine, NIH
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References Last Updated: 10 January 2014
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