Riluzole

Riluzole is a glutamate release inhibitor used in amyotrophic lateral sclerosis, where it prolongs survival by about 2 to 3 months, or delays ventilation or tracheostomy. Benefit is modest, and it is started early and continued under specialist care.

Mechanism. Reduces presynaptic glutamate release by stabilising voltage-gated sodium channels, and may interfere with postsynaptic excitatory signals.

Pharmacokinetics. Bioavailability about 60% and protein binding about 96%. Half-life is about 12 hours. It is metabolised by cytochrome P450 1A2. Smoking induces it, and ciprofloxacin and fluvoxamine inhibit it.

First-line use. Amyotrophic lateral sclerosis (including bulbar onset), to be started as early as practical.

• Oral riluzole: 50 mg twice daily, taken at least 1 hour before or 2 hours after meals. No titration is needed. Maximum 100 mg daily.

• For people with swallowing difficulty, the oral suspension 5 mg/mL or orodispersible film can be used at the same dose.

• Treatment continues until the disease is advanced, commonly until tracheostomy or ventilator dependence.

Kidney, liver, weight and age.

• Kidney: no adjustment in mild to moderate impairment; use caution in severe impairment.

• Liver: contraindicated in liver disease or transaminases over three times the upper limit of normal.

• Older adults: no adjustment.

Contraindications. Hypersensitivity, liver disease or transaminases over three times the upper limit of normal, and pregnancy and breastfeeding.

Serious adverse effects. Hepatotoxicity, neutropenia (report any febrile illness), interstitial lung disease, and anaphylaxis (rare).

Common adverse effects. Asthenia, nausea, raised liver enzymes, dizziness, vertigo, somnolence, abdominal pain and oral paraesthesia.

Interactions. Cytochrome P450 1A2 inhibitors (ciprofloxacin, fluvoxamine) raise levels, and inducers (smoking, rifampicin, omeprazole) lower levels. Other hepatotoxic drugs add risk.

Common prescribing errors. Missing baseline and scheduled liver tests. Taking with a large meal. Starting in liver disease.

Special groups.

• Pregnancy: contraindicated.

• Breastfeeding: contraindicated.

• Smokers: levels are lower, and cessation may raise levels.

Formulations. Tablets 50 mg. Oral suspension 5 mg/mL. Orodispersible film 50 mg in some markets.

Monitoring.

• Baseline liver function and full blood count.

• Liver function every month for 3 months, then every 3 months for the rest of the first year, and periodically after that. Stop if alanine aminotransferase exceeds five times the upper limit, or for neutropenia or interstitial lung disease.

• Function (for example the ALS functional rating scale), weight, respiratory function and swallow at each specialist review.

Stopping. No taper is needed.

Referral and escalation. Refer every person with suspected amyotrophic lateral sclerosis to a specialist multidisciplinary clinic.