Riluzole

Riluzole tablet is indicated to extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis (ALS).

The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective.

The mode of action of Riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect:

1. an inhibitory effect on glutamate release,
2. inactivation of voltage-dependent sodium channels, and
3. ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors.

Riluzole has also been shown, in a single study, to delay median time to death in a transgenic mouse model of ALS. These mice express human superoxide dismutase bearing one of the mutations found in one of the familial forms of human ALS.

It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. In in vitro tests, riluzole protected cultured rat motor neurons from the excitotoxic effects of glutamic acid and prevented the death of cortical neurons induced by anoxia.

Due to its blockade of glutamatergic neurotransmission, riluzole also exhibits myorelaxant and sedative properties in animal models at doses of 30 mg/kg (about 20 times the recommended human daily dose) and anticonvulsant properties at a dose of 2.5 mg/kg (about 2 times the recommended human daily dose).

The recommended daily dose of Riluzole tablet in adults or older people is 100mg (50mg tablet every 12 hours). Riluzole tablet should be taken at least one hour before, or two hours after a meal, to avoid a decrease in Riluzole bioavailability.

Paediatric use: Riluzole is not recommended for use in paediatric population.

There have been no clinical studies to evaluate the interactions of riluzole with other medicinal products. In vitro studies using human liver microsomal preparations suggest that CYP 1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole. Inhibitors of CYP 1A2 (eg, caffeine, diclofenac, diazepam, nicergoline, domipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) could potentially decrease the rate of riluzole elimination, while inducers of CYP 1A2 (eg, cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Hypersensitivity to the active substance or to any of the excipients. Hepatic disease or baseline transaminases greater than 3 times the upper limit of normal.

Nausea, abnormal liver function tests, asthenia, headache, dizziness, oral paraesthesia, somnolence, tachycardia, diarrhoea, abdominal pain, vomiting, pain, anaemia, allergic reactions, angioedema, pancreatitis, interstitial lung disease.

Riluzole is contraindicated in pregnancy & breast-feeding women.

Liver impairment: Riluzole should be prescribed with care in patients with a history of abnormal liver function, or in patients with slightly elevated serum transaminases (ALT/SGPT; AST/SGOT up to 3 times the upper limit of the normal range (ULN)), bilirubin and/or gamma-glutamyl transferase (GGT) levels. Baseline elevations of several liver function tests (especially elevated bilirubin) should preclude the use of riluzole.

Because of the risk of hepatitis, serum transaminases, including ALT, should be measured before and during therapy with riluzole. ALT should be measured every month during the first 3 months of treatment, every 3 months during the remainder of the first year, and periodically thereafter. ALT levels should be measured more frequently in patients who develop elevated ALT levels. Riluzole should be discontinued if the ALT levels increase to 5 times the ULN.

Renal impairment: Riluzole is not recommended for use in patients with impaired renal function. Neutropenia: Patients should be warned to report any febrile illness to their physicians. In case of neutropenia, Riluzole should be discontinued.

Interstitial lung disease: Cases of interstitial lung disease have been reported in patients treated with Riluzole. In case of interstitial lung disease, Riluzole should be discontinued immediately.

Effects on ability to drive and use machines: Patients should be warned about the potential for dizziness or vertigo, and advised not to drive or operate machinery if these symptoms occur.

Neurodegenerative Disease Drugs / Neuromuscular Disorder Drugs

Store in a cool and dry place, protected from light, do not store above 30°C.