Section 08 · Monograph
Riluzole
Reviewed Nov 2026FDA label
Rilutek / Tiglutik / ExservanGlutamate release inhibitor
- Forms
- Tab: 50mg | Susp: 5mg/mL | Film: 50mg
- Dose
- 50mg BID
- MOA
- ↓Presynaptic glutamate release
Indications
- Treatment of amyotrophic lateral sclerosis (ALS) to extend survival or time to tracheostomyFDA-labeled
- Approved across multiple formulations: Rilutek (tablet), Tiglutik (thickened oral suspension), Exservan (orally disintegrating film), and generic riluzole tablets/suspensionFDA-labeled
Off-Label Uses
- Investigated (not FDA-approved) for treatment-resistant OCD and anxiety spectrum disorders as a glutamate-modulating augmentation agentOff-label
- Studied in spinocerebellar ataxia and other neurodegenerative disordersOff-label
- Explored in bipolar depression as adjunctive glutamatergic therapyOff-label
Mechanism of Action
- Exact mechanism of therapeutic benefit in ALS is unknown
- Proposed to inhibit presynaptic glutamate release, reducing excitotoxic motor neuron injury
- Inactivates voltage-dependent sodium channels on glutamatergic nerve terminals
- May interfere with intracellular events following excitatory amino acid receptor stimulation
- Weak inhibitory activity at some GABA-uptake and NMDA/kainate receptor sites described in vitro
Full Dosing
Adult / usual
- Tablets (Rilutek/generic): 50 mg orally every 12 hours, taken at least 1 hour before or 2 hours after meals
- Oral suspension (Tiglutik): 50 mg (10 mL) orally every 12 hours; shake gently before each dose
- Oral film (Exservan): 50 mg orally disintegrating film placed on the tongue every 12 hours without water; do not cut or split
- Do not use if baseline serum aminotransferases exceed 5x the upper limit of normal
Renal
- No dose adjustment tables established for renal impairment; use with caution and avoid in severe hepatic impairment
Contraindications
- Known hypersensitivity to riluzole or any component of the formulation (including anaphylaxis reported)
Drug Interactions
- Strong/moderate CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) increase riluzole exposure and adverse reaction risk
- CYP1A2 inducers (cigarette smoking, omeprazole, rifampin, charbroiled foods) may lower riluzole plasma levels and reduce efficacy
- Concomitant hepatotoxic drugs may increase hepatotoxicity risk
- Theophylline and other CYP1A2 substrates may have altered clearance with concurrent riluzole
Adverse Effects
- Asthenia/fatigue
- Nausea and abdominal pain
- Decreased pulmonary function (FVC decline)
- Hypertension
- Elevated liver transaminases (dose-related)
- Oral hypoesthesia (notably more frequent with oral suspension)
- Dizziness and somnolence
- Neutropenia (may be severe)
- Interstitial lung disease (rare, can be serious)
Monitoring Parameters
- Serum aminotransferases at baseline, then monthly for the first 3 months, every 3 months for the remainder of the first year, and periodically thereafter
- Discontinue if ALT exceeds 5x ULN or if signs/symptoms of liver dysfunction occur
- CBC/neutrophil count if febrile illness develops
- Pulmonary status/symptoms — discontinue promptly if interstitial lung disease is suspected
- Body weight and nutritional/respiratory status per routine ALS multidisciplinary care
Pregnancy & Lactation
- Animal studies showed developmental toxicity at clinically relevant exposures; no adequate human data — use only if potential benefit justifies potential fetal risk
- No human pregnancy registry data establish a drug-associated risk of major birth defects or miscarriage
- Unknown whether riluzole is present in human milk; effects on the breastfed infant and on milk production are unknown