Rilutek · 4.1 Therapeutic indications · 1

HOS-083225 · has-adverse-reaction-information · PDF-Seite 4

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). 4  Very common Common Uncommon Not known Blood and Anaemia Severe lymphatic neutropenia (see system disorders section 4.4) Immune system Anaphylactoid disorders reaction, angioedema Nervous system Headache, disorders dizziness, oral paraesthesia, somnolence Cardiac Tachycardia disorders Respiratory, Interstitial lung thoracic and disease (see mediastinal section 4.4) disorders Gastrointestinal Nausea Diarrhoea, Pancreatitis disorders abdominal pain, vomiting Skin and Rash subcutaneous tissue disorders Hepato-biliary Abnormal liver Hepatitis disorders function tests General Asthenia Pain disorders and administration site conditions 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

Auszug; vollständigen Abschnitt im Original lesen.

HOS-083221 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Hepatic disease or baseline transaminases greater than 3 times the upper limit of normal. Patients who are pregnant or breast-feeding.

HOS-083220 · has-indication-information · PDF-Seite 2

RILUTEK is indicated to extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis (ALS). Clinical trials have demonstrated that RILUTEK extends survival for patients with ALS (see section 5.1). Survival was defined as patients who were alive, not intubated for mechanical ventilation and tracheotomy-free. There is no evidence that RILUTEK exerts a therapeutic effect on motor function, lung function, fasciculations, muscle strength and motor symptoms. RILUTEK has not been shown to be effective in the late stages of ALS. Safety and efficacy of RILUTEK has only been studied in ALS. Therefore, RILUTEK should not be used in patients with any other form of motor neurone disease.

HOS-083223 · has-interaction-information · PDF-Seite 4

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.

HOS-083224 · has-pregnancy-information · PDF-Seite 4

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.

HOS-083222 · has-warning-information · PDF-Seite 3

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”. 3