RILUZOLE — riluzole tablet, film coated
Rising Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
RILUZOLE is indicated for the treatment of amyotrophic lateral sclerosis (ALS)
2 DOSAGE AND ADMINISTRATION
The recommended dosage for RILUZOLE is 50 mg taken orally twice daily. RILUZOLE should be taken at least 1 hour before or 2 hours after a meal [see Clinical Pharmacology (12.3)].
Measure serum aminotransferases before and during treatment with RILUZOLE [see Warnings and Precautions (5.1)].
3 DOSAGE FORMS AND STRENGTHS
Tablets: 50 mg film-coated, capsule-shaped, white, with “RPR 202” on one side.
RILUZOLE is contraindicated in patients with a history of severe hypersensitivity reactions to riluzole or to any of its components (anaphylaxis has occurred) [see Adverse Reactions (6.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Hepatic Injury
Cases of drug-induced liver injury, some of which were fatal, have been reported in patients taking RILUZOLE tablets. Asymptomatic elevations of hepatic transaminases have also been reported, and in some patients have recurred upon rechallenge with RILUZOLE.
In clinical studies, the incidence of elevations in hepatic transaminases was greater in RILUZOLE treated patients than placebo-treated patients. The incidence of elevations of ALT above 5 times the upper limit of normal (ULN) was 2% in RILUZOLE-treated patients. Maximum increases in ALT occurred within 3 months after starting RILUZOLE. About 50% and 8% of RILUZOLE-treated patients in pooled Studies 1 and 2, had at least one elevated ALT level above ULN and above 3 times ULN, respectively [see Clinical Studies (14)].
Monitor patients for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. The use of RILUZOLE is not recommended if patients develop hepatic transaminases levels greater than 5 times the ULN. Discontinue RILUZOLE if there is evidence of liver dysfunction (e.g., elevated bilirubin).
Cases of severe neutropenia (absolute neutrophil count less than 500 per mm3) within the first 2 months of RILUZOLE treatment have been reported. Advise patients to report febrile illnesses.
5.3 Interstitial Lung Disease
Interstitial lung disease, including hypersensitivity pneumonitis, has occurred in patients taking RILUZOLE. Discontinue RILUZOLE immediately if interstitial lung disease develops.
6 ADVERSE REACTIONS
The following adverse reactions are described below and elsewhere in the labeling:
- Hepatic Injury [see Warnings and Precautions (5.1)]
- Neutropenia [see Warnings and Precautions (5.2)]
- Interstitial lung disease [see Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Controlled Clinical TrialsIn the placebo-controlled clinical trials in patients with ALS (Study 1 and 2), a total of 313 patients received RILUZOLE 50 mg twice daily [see Clinical Studies (14)]. The most common adverse reactions in the RILUZOLE group (in at least 5% of patients and more frequently than in the placebo group) were asthenia, nausea, dizziness, decreased lung function, and abdominal pain. The most common adverse reactions leading to discontinuation in the RILUZOLE group were nausea, abdominal pain, constipation, and elevated ALT.
There was no difference in rates of adverse reactions leading to discontinuation in females and males. However, the incidence of dizziness was higher in females (11%) than in males (4%). The adverse reaction profile was similar in older and younger patients. There were insufficient data to determine if there were differences in the adverse reaction profile in different races.
Table 1 lists adverse reactions that occurred in at least 2% of RILUZOLE-treated patients (50 mg twice daily) in pooled Study 1 and 2, and at a higher rate than placebo.
Table 1. Adverse Reactions in Pooled Placebo-Controlled Trials (Studies 1 and 2) in Patients with ALS
|RILUZOLE 50 mg twice daily (N=313)||Placebo (N=320)|
|Decreased lung function||10%||9%|
|Urinary Tract Infection||3%||2%|
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of RILUZOLE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Acute hepatitis and icteric toxic hepatitis [see Warnings and Precautions (5.1)]
- Renal tubular impairment
7 DRUG INTERACTIONS
7.1 Agents that may Increase Riluzole Blood Concentrations
Co-administration of RILUZOLE (a CYP1A substrate) with CYP1A2 inhibitors was not evaluated in a clinical trial; however, in vitro findings suggest an increase in riluzole exposure is likely. The concomitant use of strong or moderate CYP1A2 inhibitors (e.g., ciprofloxacin, enoxacin, fluvoxamine, methoxsalen, mexiletine, oral contraceptives, thiabendazole, vemurafenib, zileuton) with RILUZOLE may increase the risk of RILUZOLE-associated adverse reactions [see Clinical Pharmacology (12.3)].
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