6 ADVERSE REACTIONS

The following clinically significant 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 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 tablets 50 mg twice daily [see Clinical Studies (14)]. The most common adverse reactions in the 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‑ treated patients 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

Additional Adverse Reaction with EXSERVAN

In an open-label pharmacokinetic study in healthy subjects (n=32), oral hypoesthesia was observed in 38% of subjects taking EXSERVAN, compared to no subjects taking riluzole tablets, under fasting conditions.

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
•: Pancreatitis