Riluzoleside effects

The following adverse reactions are described below and elsewhere in the labeling: Hepatic Injury Neutropenia Interstitial lung disease Most common adverse reactions (incidence greater than or equal to 5% and greater than placebo) were asthenia, nausea, dizziness, decreased lung function, and abdominal pain To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 Trials In the placebo-controlled clinical trials in patients with ALS (Study 1 and 2), a total of 313 patients received riluzole 50 mg twice daily. 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 Tablets 50 mg twice daily (N=313) Placebo (N=320) Asthenia 19% 12% Nausea 16% 11% Decreased lung function 10% 9% Hypertension 5% 4% Abdominal pain 5% 4% Vomiting 4% 2% Arthralgia 4% 3% Dizziness 4% 3% Dry mouth 4% 3% Insomnia 4% 3% Pruritus 4% 3% Tachycardia 3% 1% Flatulence 3% 2% Increased cough 3% 2% Peripheral edema 3% 2% Urinary Tract Infection 3% 2% Circumoral paresthesia 2% 0% Somnolence 2% 1% Vertigo 2% 1% Eczema 2% 1%

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 Renal tubular impairment Pancreatitis