riluzole
Brand: Rilutek, Tiglutik (oral suspension), Exservan (oral film)
Prototype Drug
Drug Class: neuroprotective agent / glutamate antagonist
Drug Family: antiparkinsonian
Subclass: benzothiazole antiglutamatergic agent
Organ Systems: cns
Mechanism of Action
Reduces glutamatergic neurotransmission by inhibiting glutamate release, blocking sodium channels, and partially antagonizing NMDA receptors. Motor neurons in ALS are selectively vulnerable to glutamate excitotoxicity; riluzole reduces this excitotoxic neurodegeneration, modestly slowing disease progression. It was the first FDA-approved treatment for ALS.
glutamate release inhibitor (presynaptic)voltage-gated sodium channelsNMDA receptor
Indications
- amyotrophic lateral sclerosis (ALS) — delays disease progression and extends tracheostomy-free survival
Contraindications
- severe hepatic impairment (ALT >5x ULN)
Adverse Effects
Common
- asthenia
- nausea
- diarrhea
- dizziness
- decreased respiratory function
Serious
- hepatotoxicity (elevated ALT/AST — monitor LFTs)
- neutropenia (rare)
- interstitial lung disease (rare)
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~60%; high-fat meals decrease absorption by 20% |
| Distribution | protein binding ~96% |
| Metabolism | primarily CYP1A2; active metabolite OHRILUZOLE; smoking induces CYP1A2 and reduces riluzole levels |
| Excretion | renal (approximately 90% as metabolites) |
| Half-life | 12 hours |
| Onset | weeks to months for clinical effect |
| Peak | 1-1.5 hours |
| Duration | 12 hours |
| Protein Binding | 96% |
| Vd | 245 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) | increase riluzole levels; liver toxicity risk | major |
| tobacco smoking (CYP1A2 inducer) | decreases riluzole levels significantly; reduced efficacy | major |
| hepatotoxic drugs | additive liver injury risk | moderate |
Nursing Considerations
- Liver function tests must be monitored at baseline, monthly for first 3 months, then quarterly for first year, then periodically — discontinue if ALT exceeds 5x ULN.
- Administer on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption; high-fat meals reduce riluzole absorption.
- Smoking induces CYP1A2 and significantly reduces riluzole plasma levels — document smoking status and counsel patients about the interaction with their ALS medication.
- Provide clear expectations: riluzole extends tracheostomy-free survival by approximately 2-3 months on average and delays time to mechanical ventilation; it does not reverse or dramatically slow functional decline.
Clinical Pearls
- Riluzole is the longest-established ALS treatment (FDA-approved 1995) with an effect size of approximately 2-3 months extension in tracheostomy-free survival — modest but statistically significant, and clinically meaningful to patients and families.
- CYP1A2 induction by tobacco smoking is clinically significant; ALS patients who smoke have substantially lower riluzole plasma levels than non-smokers, potentially nullifying the modest survival benefit.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.