Riluzole

Riluzole is indicated for the treatment of amyotrophic lateral sclerosis (ALS).

The mode of action of riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect:

• An inhibitory effect on glutamate release (activation of glutamate reuptake),
• Inactivation of voltage-dependent sodium channels, 
• Ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors.

The recommended dosage for Riluzole is 50 mg taken orally twice daily. Riluzole should be taken at least 1 hour before or 2 hours after a meal. Measure serum aminotransferases before and during treatment with Riluzole.

Strong to moderate CYP1A2 inhibitors: Coadministration may increase Riluzole-associated adverse reactions

Strong to moderate CYP1A2 inducers: Coadministration may result in decreased efficacy 

Hepatotoxic drugs: Riluzole-treated patients that take other hepatotoxic drugs may be at increased risk for hepatotoxicity.

Riluzole is contraindicated in patients with a history of severe hypersensitivity reactions to riluzole or to any of its components (anaphylaxis has occurred).

The following adverse reactions are described below and elsewhere in the labeling: Hepatic Injury, Neutropenia, Interstitial lung disease.

Pregnancy: Based on animal data, may cause fetal harm

Lactation: It is not known if riluzole is excreted in human milk. Riluzole or its metabolites have been detected in milk of lactating rat. Women should be advised that many drugs are excreted in human milk and that the potential for serious adverse reactions in nursing infants from Riluzole is unknown.

Hepatic Injury: Cases of drug-induced liver injury, some of which were fatal, have been reported in patients taking Riluzole. Asymptomatic elevations of hepatic transaminases have also been reported, and in some patients have recurred upon rechallenge with Riluzole.

In clinical studies, the incidence of elevations in hepatic transaminases was greater in Riluzoletreated patients than placebo-treated patients. The incidence of elevations of ALT above 5 times the upper limit of normal (ULN) was 2% in Riluzole-treated patients. Maximum increases in ALT occurred within 3 months after starting Riluzole. About 50% and 8% of Riluzoletreated patients in pooled Studies 1 and 2, had at least one elevated ALT level above ULN and above 3 times ULN, respectively 

Monitor patients for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. The use of Riluzole is not recommended if patients develop hepatic transaminases levels greater than 5 times the ULN. Discontinue Riluzole if there is evidence of liver dysfunction (e.g., elevated bilirubin).

Neutropenia: Cases of severe neutropenia (absolute neutrophil count less than 500 per mm3) within the first 2 months of Riluzole treatment have been reported. Advise patients to report febrile illnesses.

Interstitial Lung Disease: Interstitial lung disease, including hypersensitivity pneumonitis, has occurred in patients taking Riluzole. Discontinue Riluzole immediately if interstitial lung disease develops.

Reported symptoms of overdose following ingestion of Riluzole ranging from 1.5 to 3 grams (30 to 60 times the recommended dose) included acute toxic encephalopathy, coma, drowsiness, memory loss, and methemoglobinemia. No specific antidote for the treatment of Riluzole overdose is available.

Neurodegenerative Disease Drugs / Neuromuscular Disorder Drugs.

Store at controlled room temperature, 20°C to 25°C, and protect from bright light.