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RILUTEK is a brand name for Riluzole, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE ..................................................................................... 3 CONTRAINDICATIONS .......................................................................................................... 5 WARNINGS AND PRECAUTIONS…
Verbatim from this product's HC label. Tap a section to expand.
, Recommended Dose and Dosage Adjustment, Special Populations, Hepatic Insufficiency).
Renal Insufficiency:
After a single oral dose of riluzole 50 mg, no significant difference in mean pharmacokinetic parameters between n = 12 subjects with moderate or severe chronic renal insufficiency (10 to 50 mL/min) and n = 12 healthy volunteers were observed.
(See WARNINGS AND PRECAUTIONS, Special Populations, Renal Insufficiency, DOSAGE AND ADMINISTRATION, Recommended Dose and Dosage Adjustment, Special Populations, Renal Insufficiency). 5 days of treatment at 50 mg riluzole BID) in n = 18 elderly and n = 18 young subjects are not affected in the elderly (> 70 years) (See WARNINGS AND PRECAUTIONS, Special Populations, Geriatrics).
Gender:
In one placebo-controlled clinical trial with population pharmacokinetics, RILUTEK mean clearance was found to be 30% lower in female patients (corresponding to an approximate increase in AUC of 45%). CYP 1A2 activity has been reported to be lower in women than in men.
Therefore, a gender effect on riluzole kinetics may be expected in women, resulting in higher blood concentrations of riluzole and its metabolites. However, regarding benefits or adverse events of riluzole, no gender effect was seen in controlled trials.
Smoking:
Cigarette smoking is known to induce CYP 1A2. Patients who smoke cigarettes would be expected to eliminate riluzole faster. There is no information, however on the effect of, or need for, dosage adjustment in these patients.
Race:
A clinical study was conducted in Germany to evaluate the pharmacokinetics of riluzole and its metabolite N-hydroxyriluzole following repeated oral administration twice daily for 8 days in n = 16 healthy Japanese and n = 16 Caucasian adult males, with the former having Japanese citizenship, and resident in North America or Europe for < 10 years.
Results showed no difference in mean pharmacokinetic parameters between the two groups, either for RILUTEK or the major metabolite. STORAGE AND STABILITY RILUTEK should be stored at room temperature (15 to 30°C) and protected from bright light.
Adverse Drug Reaction Overview The most commonly observed adverse events associated with the use of RILUTEK, more frequently than with placebo treatment were: asthenia, nausea, elevations in liver function tests, dizziness, decreased lung function, diarrhea, abdominal pain, pneumonia, vomiting, vertigo, circumoral paresthesia, anorexia and somnolence.
Approximately 14% (n = 199) of the 1396 individuals with ALS who received RILUTEK in clinical trials discontinued treatment because of an adverse event. Of those patients who discontinued due to adverse events, the most commonly reported associated adverse events were nausea, abdominal pain, constipation and ALT elevations.
Hepatitis, anaphylactoid reaction, angioedema and pancreatitis have been reported in isolated cases. Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse drug reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The events cited in the table below reflect all adverse experiences of ALS patients in placebo- controlled trials, treated with either RILUTEK at the recommended daily dosage of 100 mg/day or placebo, where the incidence with RILUTEK was numerically greater than placebo by at least 1%.
Page 10 of 37 Table 1 -Adverse Events Occurring in Placebo-Controlled Clinical Trials, for which the incidence with RILUTEK was ≥ 1% than placebo SYSTEM ORGAN CLASS Preferred Term Rilutek (100 mg/day) Studies 216, 301, 302 (N=395) % Placebo Studies 216, 301, 302 (N=406) % Asthenia 17 11General disorders and administration site conditions Pain 5 2 Nausea 14 9 Abdominal pain 5 4 Vomiting 4 2 Gastrointestinal disorders Paraesthesia oral 1 0 Headache 7 6 Dizziness 3 2Nervous system disorder Somnolence 2 1 Cardiac disorders Tachycardia 3 2 Alanine aminotransferase (ALT/SGPT) abnormal 29 14 Aspartate aminotransferase (AST/SGOT) abnormal 23 19 Gamma-glutamyltransferase (GGT) abnormal 15 11 Hepatobiliary Disorders Blood bilirubin abnormal 12 8 Confirmatory Phase IV trial (study 401) Study 401 is an open-label Phase IV confirmatory trial conducted in Canada, consisting of a prospective treatment arm of n = 414 ALS patients treated with RILUTEK at the recommended daily dosage of 100 mg/day and a historical control arm for which there are no safety data.
RILUTEK is contraindicated in: - Patients who have a history of hypersensitivity reactions to riluzole or any of the tablet components. For a complete listing of the tablet components, see the DOSAGE FORMS, COMPOSITION AND PACKAGING section of the product monograph.
- Patients who have hepatic disease or who have baseline transaminases greater than 3 times the ULN (upper limit of normal) (See WARNINGS AND PRECAUTIONS, General, Liver Injury / Monitoring Liver Chemistries; ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions, Hepatic Insufficiency; DOSAGE AND ADMINISTRATION, Special Population, Hepatic Insufficiency).
- Patients who are pregnant or breast-feeding WARNINGS AND PRECAUTIONS General Liver Injury / Monitoring Liver Chemistries RILUTEK is contraindicated in Patients who have hepatic disease or who have baseline transaminases greater than 3 times the ULN (upper limit of normal) (See CONTRAINDICATIONS).
RILUTEK should be used with caution in patients with a history of abnormal liver function, with known concomitant liver insufficiency or in patients with elevations in any of serum transaminase (ALT/SGPT; AST/SGOT), bilirubin, or gamma-glutamyl transferase (GGT) levels.
Baseline elevations of several liver function tests (especially including elevated bilirubin) should preclude the use of RILUTEK® (See CONTRAINDICATIONS; DOSAGE AND ADMINISTRATION, Special Populations, Hepatic Insufficiency; ADVERSE REACTIONS, Abnormal Hematologic and Clinical Chemistry Findings).
Liver chemistries should be monitored in all patients on RILUTEK as the drug can increase serum aminotransferase, even in patients without a prior history of liver abnormality. Serum ALT levels 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 (See WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Riluzole in Canada.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Keep in a safe place out of the reach of children. Page 23 of
Patients treated with RILUTEK were instructed to report any events that occurred during the study. However, the investigators had to report only a) any events which required discontinuation of study drug and b) all serious adverse events, with the exception of events due to the progression of ALS, hospitalization for permanently assisted ventilation or tracheostomy (primary efficacy endpoints).
In addition, the investigators were to assess causality as either possibly related, or not related, to RILUTEK. 5%) of the patients. Within this subset, there were only two patients with serious adverse reactions: one patient presented with vomiting and Page 11 of 37 diarrhea of moderate intensity and another patient presented with increased alanine aminotransferase rated as severe in intensity.
Table 2 shows the most common treatment-emergent adverse reactions (TEAR) considered possibly related to study medication and for which the incidence was ≥ 1%. Table 2 -The most common treatment-emergent adverse reactions (TEAR) considered possibly related to study medication occurring in study 401 and for which the incidence was ≥ 1% System Organ Class Preferred Term Studies 401 (N=414) % Nausea 6 Stomach discomfort 3 Diarrhea 2 Dyspepsia 1 Constipation 1 Gastrointestinal Disorders Hypoaesthesia oral 1 General Disorders and Administration Site Conditions Fatigue 4 Dizziness 4 Headache 1 Nervous System Disorder Dysgeusia 1 Psychiatric Disorders Insomnia 1 Rash 1Skin and Subcutaneous Tissue Disorders Pruritus 1 Hepatobiliary Disorders* Alanine aminotransferase (ALT/SGPT) abnormal 1 * Alert terms (ALT and/or AST values >10 times the upper limit of normal) or abnormal values that led to study drug termination Page 12 of 37 Other Events Observed During the Clinical Development of RILUTEK RILUTEK has been administered to 1713 individuals during all clinical trials, some of which were placebo-controlled (safety data from Study 401 are not included due to differences in data collection process).
All reported adverse events are included below except those already listed in the previous tables, those too general to be informative, and those events where a drug cause was remote. For the placebo-controlled trials, events are included if the incidence rate for RILUTEK is numerically greater than the rate for placebo.
It is important to emphasize that although the events reported occurred during treatment with RILUTEK, they were not necessarily caused by it. 01%). Blood and Lymphatic System Disorders Uncommon: leucocytosis, leucopenia Rare: aplastic anemia, hypochromic anemia, iron deficiency anemia, lymphadenopathy, neutropenia.
Cardiac Disorders Uncommon: bundle branch block, congestive heart failure, heart failure, pericarditis, ventricular extrasystoles Rare: bradycardia, cyanosis, ventricular fibrillation, ventricular tachycardia Endocrine Disorders Rare: diabetes insipidus, parathyroid disorder Ear and Labyrinth Disorders: Rare: deafness, ear pain, hyperacusis, vestibular disorder Eye Disorders: Uncommon: amblyopia, ophthalmitis Rare: […]
There were uncommon instances of jaundice and hepatitis. RILUTEK should be discontinued if the ALT levels increase to 5 X the ULN. There is no experience with dose reduction or rechallenge in patients who have developed an increase of Page 6 of 37 ALT to 5 X ULN.
Readministration of RILUTEK to patients in this situation cannot be recommended. In cases of RILUTEK-induced hepatic injury manifested by elevated liver enzymes, the effect of the hepatic injury on RILUTEK metabolism is unknown (See ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions, Hepatic Insufficiency).
Findings from Clinical Trials Experience in almost 800 ALS patients indicates that about 50% of RILUTEK-treated patients will experience at least one ALT/SGPT level above the ULN, about 8% will have elevations >3 X ULN, and about 2% of patients will have elevations >5 X ULN.
A single non-ALS patient with epilepsy treated with concomitant carbamazepine and phenobarbital experienced marked, rapid elevations of liver enzymes with jaundice (ALT 26 X ULN, AST 17 X ULN, and bilirubin 11 X ULN) four months after starting RILUTEK; these returned to normal 7 weeks after treatment discontinuation.
Maximum increases in serum ALT usually occurred within 3 months after the start of RILUTEK therapy and were usually transient when < 5 X ULN. In trials, if ALT levels were < 5 X ULN, treatment continued and ALT levels usually returned to below 2 X ULN within 2 to 6 months.
However, treatment in studies was discontinued if ALT levels exceeded 5 X ULN; in these cases, the levels generally returned to less than 2 X ULN within 2 to 6 months. Carcinogenesis and Mutagenesis See the TOXICOLOGY, Mutagenicity section for the animal data.
Hematologic Patients should be warned to report any febrile illness to their physicians. The report of a febrile illness should prompt treating physicians to check white blood cell counts and to discontinue RILUTEK in case of neutropenia (See ADVERSE REACTIONS, Abnormal Hematologic and Clinical Findings).
Among approximately 5000 patients given RILUTEK for ALS, there were three cases of marked neutropenia (absolute neutrophil count less than 500/mm3), all seen within the first 2 months of RILUTEK treatment. In one case, neutrophil counts rose on continued treatment.
In a second case, counts rose after therapy was stopped. A third case was more complex, with marked anemia as well as neutropenia and the etiology of both is uncertain.
Respiratory, Thoracic and Mediastinal Disorders Interstitial lung disease:
Cases of interstitial lung disease have been reported in patients treated with RILUTEK, some of them were severe (See ADVERSE REACTIONS). g. bilateral diffuse lung Page 7 of 37 opacities), RILUTEK should be discontinued immediately. In the majority of the reported cases, symptoms resolved after drug discontinuation and symptomatic treatment.
Hepatic/Biliary/Pancreatic See CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, General, Liver Injury / Monitoring Liver Chemistries and Special Population, Hepatic Insufficiency, ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions, Hepatic Insufficiency; DOSAGE AND ADMINISTRATION, Special Population, Hepatic Insufficiency.
Special Populations Pregnant Women:
There are no adequate and well-controlled studies in pregnant women and RILUTEK is known to cross the placental barrier in rats. RILUTEK must not be used in pregnant women (See CONTRAINDICATIONS). In the pregnant rat, the transfer of 14C-riluzole across the placenta to the foetus has been detected.
5 times, respectively, the recommended maximum human daily dose on a mg/m2 basis. Evidence of maternal toxicity was also observed at these doses. When […]