Primary Treatment for Amyotrophic Lateral Sclerosis (ALS)
Riluzole (50 mg twice daily) is the primary treatment for Amyotrophic Lateral Sclerosis, as it is the only FDA-approved medication that has been shown to prolong survival in ALS patients. 1
Mechanism and Efficacy
- Riluzole acts as an anti-excitotoxic agent that antagonizes glutamate, which plays a key role in the neurodegeneration process of ALS 2
- Clinical trials have demonstrated that riluzole at 100 mg/day (50 mg twice daily) extends survival by approximately 2-3 months and increases the probability of surviving one year by about 9% (from 57% in placebo to 66% in the riluzole group) 2, 3
- The 100 mg daily dose (50 mg twice daily) has been established as having the best benefit-to-risk ratio compared to higher or lower doses 3, 4
Administration Guidelines
- Recommended dosage: 50 mg twice daily, taken at least 1 hour before or 2 hours after meals 1
- Serum aminotransferases should be measured before initiating treatment and monitored during therapy 1
- Interindividual variability in riluzole serum concentrations is significant (coefficient of variation=74%), which may affect individual response to treatment 5
Monitoring and Side Effects
Most common adverse reactions (incidence ≥5% and greater than placebo) include: 1, 6
- Asthenia (weakness)
- Nausea
- Dizziness
- Decreased lung function
- Abdominal pain
Liver function monitoring is essential as riluzole can cause hepatic injury: 1, 6
- Use is not recommended in patients with baseline elevations of serum aminotransferases greater than 5 times upper limit of normal
- Discontinue if there is evidence of liver dysfunction
- Increased serum transaminase levels typically occur within three months of treatment initiation and often regress after 2-6 months of continued treatment
Other important monitoring considerations: 1
- Watch for neutropenia; advise patients to report any febrile illness
- Discontinue riluzole if interstitial lung disease develops
Supportive Care and Comprehensive Management
Nutritional management is critical throughout disease progression: 7, 8
- Regular nutritional status assessment (BMI, weight loss) every 3 months
- For patients with dysphagia, adapt food texture and implement postural maneuvers
- Consider enteral nutrition via feeding tubes (preferably gastrostomy) when oral intake becomes insufficient
Physical activity recommendations: 8
- Low to moderate physical activity should be encouraged as long as it doesn't worsen the patient's condition
- Avoid excessive physical exertion that could lead to fatigue
A palliative care approach should be adopted from the time of diagnosis to address quality of life concerns 7
Important Clinical Considerations
ALS typically presents in two main forms: bulbar onset or spinal/limb onset, with bulbar onset having a shorter life expectancy 7
Drug interactions to monitor: 1
- Strong to moderate CYP1A2 inhibitors may increase riluzole-associated adverse reactions
- Strong to moderate CYP1A2 inducers may decrease efficacy
- Concomitant use with other hepatotoxic drugs may increase risk for hepatotoxicity
Riluzole should be discontinued if there is no clear benefit after a reasonable trial period, as the modest survival benefit must be weighed against potential side effects and cost 2