1 INDICATIONS AND USAGE TIGLUTIK is indicated for the treatment of amyotrophic lateral sclerosis (ALS).

TIGLUTIK is indicated for the treatment of amyotrophic lateral sclerosis (ALS) ( 1 )

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) ] Most common adverse reactions (incidence greater than or equal to 5% and greater than placebo) were oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ITF Pharma Inc.

at 1-800-664-1490 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 of Riluzole Tablets 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 [see Clinical Studies (14) ].

The most common adverse reactions in riluzole-treated patients (in at least 5% of patients and more frequently than on placebo) were asthenia, nausea, decreased lung function, hypertension, 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 the rate of adverse reactions leading to discontinuation between 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 are insufficient data to assess racial differences in the adverse reaction profile.

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 on placebo.

Table 1.

Adverse Reactions in Pooled Placebo-Controlled Trials (Studies 1 and 2) in Patients with ALS Adverse Reaction 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 Additional Adverse Reactions with TIGLUTIK In an open-label pharmacokinetic study in healthy subjects (n=36), oral hypoesthesia was observed in 29% of subjects taking TIGLUTIK, compared to 6% in patients taking riluzole tablets, under fasting conditions.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval 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 Pancreatitis