No

Glutamate Inhibitor

Amyotrophic lateral sclerosis (ALS): Treatment of patients with ALS; riluzole can extend survival or time to tracheostomy

C

Severe hypersensitivity reactions to riluzole or any of the tablet components

Among 4000 patients given riluzole for ALS, there were 3 cases of marked neutropenia (ANC <500/mm³), all seen within the first 2 months of treatment. Use with caution in patients with concomitant renal insufficiency. Use with caution in patients with current evidence or history of abnormal liver function. Monitor liver chemistries.

>10%:

Hepatic: Increased ALT

No specific antidote or treatment information available; treatment should be supportive and directed toward alleviating symptoms

CYP1A2 enzyme substrate

Increased toxicity: Inhibitors of CYP 1A2 (eg, caffeine, theophylline, amitriptyline, quinolones) could decrease the rate of riluzole elimination

Protect from bright light

Inhibitory effect on glutamate release, inactivation of voltage-dependent sodium channels; and ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors

Absorption: Well absorbed (90%); a high fat meal decreases absorption of riluzole (decreasing AUC by 20% and peak blood levels by 45%)

Protein binding: 96% bound to plasma proteins, mainly albumin and lipoproteins

Metabolism: Extensively to 6 major and a number of minor metabolites. Metabolism is mostly hepatic and consists of cytochrome P-450 dependent hydroxylation and glucuronidation; principle isozyme is CYP 1A2

Bioavailability: Oral: Absolute (50%)

Adults: Oral: 50 mg every 12 hours; no increased benefit can be expected from higher daily doses, but adverse events are increased

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.

Monitor serum aminotransferases including ALT levels before and during therapy. Evaluate serum ALT levels every month during the first 3 months of therapy, every 3 months during the remainder of the first year and periodically thereafter. Evaluate ALT levels more frequently in patients who develop elevations. Maximum increases in serum ALT usually occurred within 3 months after the start of therapy and were usually transient when <5 x ULN (upper limits of normal).

If a decision is made to continue treatment in patients when the ALT exceeds 5 x ULN, frequent monitoring (at least weekly) of complete liver function is recommended. Discontinue treatment if ALT exceeds 10 x ULN or if clinical jaundice develops.

None reported

None reported

No information available to require special precautions

No effects or complications reported

This drug will not cure or stop disease but it may slow progression. Take as directed, at the same time each day, preferably on an empty stomach (1 hour before or 2 hours after meals). Avoid alcohol. You may experience increased spasticity, dizziness or sleepiness; use caution when driving or engaging in tasks requiring alertness until response to drug is known. Small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may reduce nausea, vomiting, or anorexia. Report fever; severe vomiting, diarrhea, or constipation; change in color of urine or stool; yellowing of skin or eyes; acute back pain or muscle pain; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Warn patients about the potential for dizziness, vertigo or somnolence and advise them not to drive or operate machinery until they have gained sufficient experience on riluzole to gauge whether or not it affects their mental or motor performance adversely. Whether alcohol increases the risk of serious hepatotoxicity with riluzole is unknown; discourage riluzole-treated patients from drinking alcohol in excess.

Tablet: 50 mg

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.