>10%:

Gastrointestinal: Nausea (12% to 21%)

Neuromuscular & skeletal: Weakness (15% to 20%)

Respiratory: Lung function decreased (10% to 16%)

1% to 10%:

Cardiovascular: Edema, hypertension, tachycardia

Central nervous system: Agitation, circumoral paresthesia, depression, dizziness, headache, insomnia, malaise, somnolence, tremor, vertigo

Dermatologic: Alopecia, eczema, pruritus

Gastrointestinal: Abdominal pain, anorexia, diarrhea, dyspepsia, flatulence, oral moniliasis, stomatitis, vomiting

Hepatic: Liver function tests increased

Neuromuscular & skeletal: Arthralgia, back pain

Respiratory: Cough increased, rhinitis, sinusitis

Miscellaneous: Aggravation reaction

<1% (Limited to important or life-threatening): Exfoliative dermatitis, neutropenia, postural hypertension, seizure

CYP1A2 inducers: May decrease the levels/effects of riluzole. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.

CYP1A2 inhibitors: May increase the levels/effects of riluzole. Example inhibitors include amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.

Ethanol: Avoid ethanol (due to CNS depression and possible risk of liver toxicity).

Food: A high-fat meal decreases absorption of riluzole (decreasing AUC by 20% and peak blood levels by 45%). Charbroiled food may increase riluzole elimination.

Absorption: 90%; high-fat meal decreases AUC by 20% and peak blood levels by 45%

Protein binding, plasma: 96%, primarily to albumin and lipoproteins

Metabolism: Extensively hepatic to six major and a number of minor metabolites via CYP1A2 dependent hydroxylation and glucuronidation

Bioavailability: Oral: Absolute: 60%

Half-life elimination: 12 hours

Excretion: Urine (90%; 85% as metabolites, 2% as unchanged drug) and feces (5%) within 7 days

Dosage adjustment in smoking: Cigarette smoking is known to induce CYP1A2; 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.

Dosage adjustment in special populations: Females and Japanese patients may possess a lower metabolic capacity to eliminate riluzole compared with male and Caucasian subjects, respectively

Dosage adjustment in renal impairment: Use with caution in patients with concomitant renal insufficiency

Dosage adjustment in hepatic impairment: Use with caution in patients with current evidence or history of abnormal liver function indicated by significant abnormalities in serum transaminase, bilirubin or GGT levels. Baseline elevations of several LFTs (especially elevated bilirubin) should preclude use of riluzole.

In trials, if ALT levels were <5 times ULN, treatment continued and ALT levels usually returned to below 2 times ULN within 2-6 months. There is no experience with continued treatment of ALS patients once ALT values exceed 5 times ULN.

If a decision is made to continue treatment in patients when the ALT exceeds 5 times ULN, frequent monitoring (at least weekly) of complete liver function is recommended. Discontinue treatment if ALT exceeds 10 times ULN or if clinical jaundice develops. Monitor temperature, especially during first 2 months of therapy.

Bensimon G, Lacomblez L, Meininger V, et al, "A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis. ALS/Riluzole Study Group,"N Engl J Med, 1994, 330(9):585-91

Wokke J, "Riluzole,"Lancet, 1996, 348(9030):795-9.