RILUTEK Film-coated tablet Ref.[8613] Active ingredients: Riluzole

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 (see section 4.8).

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. There is no experience with dose reduction or rechallenge in patients who have developed an increase of ALT to 5 times ULN. Readministration of riluzole to patients in this situation cannot be recommended.

Neutropenia

Patients should be warned to report any febrile illness to their physicians. The report of a febrile illness should prompt physicians to check white blood cell counts and to discontinue riluzole in case of neutropenia (see section 4.8).

Interstitial lung disease

Cases of interstitial lung disease have been reported in patients treated with riluzole, some of them were severe (see section 4.8). If respiratory symptoms develop such as dry cough and/or dyspnoea, chest radiography should be performed, and in case of findings suggestive of interstitial lung disease (e.g. bilateral diffuse lung opacities), riluzole should be discontinued immediately. In the majority of the reported cases, symptoms resolved after medicinal product discontinuation and symptomatic treatment.

Renal impairment

Studies at repeated doses have not been conducted in patients with impaired renal function (see section 4.2).

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium free”.

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 (e.g. caffeine, diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) could potentially decrease the rate of riluzole elimination, while inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Pregnancy

RILUTEK is contraindicated in pregnancy (see sections 4.3 and 5.3). Clinical experience with riluzole in pregnant women is lacking

Breast-feeding

RILUTEK is contraindicated in breast-feeding women (see sections 4.3 and 5.3). It is not known whether riluzole is excreted in human milk.

Fertility

Fertility studies in rats revealed slight impairment of reproductive performance and fertility at doses of 15 mg/kg/day (which is higher than the therapeutic dose), probably due to sedation and lethargy.

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

No studies on the effects on the ability to drive and use machines have been performed.

Summary of safety profile

In phase III clinical studies conducted in ALS patients treated with riluzole, the most commonly reported adverse reactions were asthenia, nausea and abnormal liver function tests.

Tabulated summary of adverse reactions

Undesirable effects ranked under headings of frequency are listed below, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Description of selected adverse reactions

Hepato-biliary disorders

Increased alanine aminotransferase usually appeared within 3 months after the start of therapy with riluzole; they were usually transient and levels returned to below twice the ULN after 2 to 6 months while treatment was continued. These increases could be associated with jaundice. In patients (n=20) from clinical studies with increases in ALT to more than 5 times the ULN, treatment was discontinued and the levels returned to less than 2 times the ULN within 2 to 4 months in most cases (see section 4.4).

Study data indicate that Asian patients may be more susceptible to liver function test abnormalities – 3.2% (194/5995) of Asian patients and 1.8% (100/5641) of Caucasian patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.