Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Rilutek (Aventis Pharma)
50 mg tablets
Approved indication: amyotrophic lateral sclerosis
Australian Medicines Handbook Section 16.8
Amyotrophic lateral sclerosis is one of the motor neurone diseases. The degeneration of neurones progressively leads to bulbar palsy. Most patients die of respiratory failure or choking within three years of diagnosis.
The cause of the disease is unknown, but one theory is that there is an accumulation of glutamate in the affected neurones. One of the actions of riluzole is inhibiting the release of glutamate so it has been studied to see if it has neuroprotective effects.
In a placebo-controlled trial the deterioration in muscle strength was significantly slower in patients who had been treated with riluzole. After one year 57 of the 77 patients given riluzole were alive while only 45 of the 78 patients given placebo had survived.1 This difference (74% versus 58%) was statistically significant.
A dose-ranging study established 100 mg daily as the best balance between benefit and harm.2 Patients take 50 mg twice a day. The tablets are well absorbed, but their bioavailability is reduced by food. There is extensive hepatic metabolism, mainly involving cytochrome P450 1A2. This means there is a potential for interactions with drugs such as amitriptyline, quinolones and caffeine (CYP1A2 inhibitors), and rifampicin (CYP1A2 inducer). Most of the metabolites are excreted in the urine, so riluzole should be used with caution in patients with renal or hepatic impairment.
Patients need regular monitoring of their liver function particularly in the first few months of treatment. A fever should prompt a check of the white blood cell count as neutropenia has been reported. The most common adverse effects of riluzole are asthenia, nausea and decreased lung function. Approximately 14% of the patients in clinical trials withdrew because of adverse events.
Although riluzole offers hope to patients with amyotrophic lateral sclerosis, it is not a cure. In the dose-ranging study the unadjusted outcome did not show a significant benefit. After 18 months 134 of the 236 patients given 100 mg riluzole had survived without a tracheostomy but so had 122 of the 242 patients given a placebo.2 In the double-blind trial, the reduction in mortality declined after the first year of therapy. Treatment appeared to be of most benefit to patients whose disease began with bulbar involvement. When the onset involved the limbs, riluzole had no significant survival advantage over placebo1, however this finding was not confirmed in the second study.2 Overall riluzole probably increases survival, without a tracheostomy, by two to four months.
- The ALS/Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994;330:585-91.
- Lacomblez L, Bensimon G, Leigh NP, Guillet P, Meininger V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet 1996;347:1425-31.