Riluzole

Approved Indications:

• Amyotrophic Lateral Sclerosis (ALS): Riluzole is indicated to slow the progression of ALS, specifically by delaying the need for tracheostomy or mechanical ventilation. It does not cure ALS or reverse existing damage but may modestly prolong survival or delay disease progression.

Off-label / Clinically Accepted Uses:

• Spinal Muscular Atrophy (SMA) – Investigational
• Huntington's Disease – Experimental studies
• Other motor neuron diseases (MNDs): Limited evidence suggests neuroprotective benefits, though not formally approved.

Adults:

• Recommended Dose: 50 mg orally every 12 hours.
• Route: Oral administration.
• Duration: Continuous long-term use is standard, unless disease progression or intolerance occurs.
• Food Consideration: Should be taken at least 1 hour before or 2 hours after meals, as high-fat meals reduce absorption.

Pediatrics:

• Safety and efficacy not established. Not recommended.

Elderly:

• Use with caution; no specific dose adjustment unless hepatic impairment is present.

Renal Impairment:

• No specific dosage adjustment recommended, but use with caution in severe impairment.

Hepatic Impairment:

• Mild to Moderate (Child-Pugh A/B): Use with caution and monitor liver enzymes regularly.
• Severe (Child-Pugh C): Contraindicated due to risk of significant accumulation and hepatotoxicity.

Riluzole exerts its neuroprotective effects by reducing glutamate-induced excitotoxicity, a key factor in the progression of ALS. It inhibits presynaptic glutamate release and enhances its reuptake, thus lowering extracellular glutamate concentrations. Additionally, it blocks voltage-gated sodium channels on neurons, reducing neuronal firing and calcium influx, thereby limiting the cascade of excitotoxic neuronal injury and delaying motor neuron degeneration.

• Absorption: Rapid oral absorption; peak plasma levels occur within 1 to 1.5 hours.
• Bioavailability: ~60% (reduced with high-fat meals).
• Distribution: Widely distributed; ~97% bound to plasma proteins, primarily albumin.
• Metabolism: Extensively hepatic; primarily metabolized via cytochrome P450 enzyme CYP1A2 into inactive metabolites.
• Half-life: Approximately 12 hours.
• Elimination: Excreted mainly via the urine (as metabolites); <1% excreted unchanged.

• Pregnancy: Not assigned a specific FDA category (per updated labeling). Animal studies show fetal harm at high doses. Use only if potential benefit justifies potential risk to the fetus.
• Lactation: Unknown whether Riluzole is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended while using Riluzole.

• Primary Class: Neuroprotective Agent
• Subclass: Glutamate Release Inhibitor

• Known hypersensitivity to Riluzole or any component of the formulation
• Severe hepatic impairment (e.g., baseline ALT >5x ULN)
• Active liver disease
• Concomitant use with other hepatotoxic drugs (relative contraindication)

• Hepatotoxicity: Monitor liver function before and during treatment. Discontinue if ALT levels exceed 5x ULN.
• Neutropenia: Rare but serious neutropenia may occur; monitor blood counts if infection signs appear.
• Interstitial Lung Disease (ILD): Discontinue if unexplained respiratory symptoms or pulmonary infiltrates occur.
• High-risk populations: Use cautiously in elderly, those with liver dysfunction, and polypharmacy patients.

Common Side Effects:

• Neurological: Dizziness, headache, somnolence
• Gastrointestinal: Nausea, abdominal pain, diarrhea
• General: Fatigue, asthenia

Serious Adverse Effects:

• Hepatic: Elevated ALT/AST, hepatitis, liver failure
• Hematologic: Neutropenia
• Pulmonary: Interstitial lung disease, dyspnea

Onset & Severity:

• Hepatic enzyme elevations typically occur within 3 months.
• Many common side effects are mild to moderate and transient.

• CYP1A2 Inhibitors (e.g., fluvoxamine, ciprofloxacin): May increase Riluzole levels and toxicity.
• CYP1A2 Inducers (e.g., smoking, omeprazole): May reduce efficacy by decreasing drug concentration.
• Hepatotoxic agents (e.g., methotrexate, isoniazid): Additive risk of liver damage.
• Alcohol: Increases risk of hepatotoxicity—avoid concurrent use.

• No recent changes in approved indications.
• Updated guidelines emphasize:
• Liver enzyme monitoring every month during the first 3 months of therapy, then quarterly.
• Not recommended for pediatric ALS patients due to lack of safety data.
• Riluzole remains a first-line therapy in ALS per ALS Association and NICE guidelines.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C (59°F–86°F).
• Humidity: Protect from excessive moisture.
• Light: Store in original packaging to protect from light.
• Handling: Tablets should be kept in a tightly closed container. Do not use crushed or split tablets unless instructed.