Class: CNS agent
- Tablets 50 mg
Unknown; however, the following properties may be related to its effect: inhibition of glutamate release; inactivation of voltage-dependent sodium channels; interference with intracellular events that follow transmitter binding at excitatory amino acid receptors. These effects may protect neural tissues against degenerative changes.
Well absorbed (approximately 90%). Oral bioavailability is approximately 60%. High-fat meals decrease absorption, decreasing AUC approximately 20% and peak blood levels by approximately 45%. Steady state is less than 5 days.
Protein binding is 96%, mainly to albumin and lipoproteins.
Extensively metabolized to 6 major and a number of minor metabolites via CYP-450 dependent hydroxylation and glucuronidation. CYP1A2 is the main isoenzyme involved in N-hydroxylation.
Eliminated in urine (more than 85% glucuronide metabolites; 2% unchanged) and small amount in feces. Half-life is 12 h (after multiple dosing).
Special PopulationsRenal Function Impairment
There is no significant difference in pharmacokinetic parameters between patients with moderate and severe renal insufficiency and healthy patients.Hepatic Function Impairment
AUC increased by about 1.7- and 3-fold in patients with mild and moderate chronic hepatic insufficiency, respectively. The pharmacokinetics have not been studied in patients with severe hepatic impairment.Elderly
The pharmacokinetic parameters after multiple-dose administration are not affected in the elderly.Gender
Mean Cl was found to be 30% lower in women compared with men in 1 clinical trial.Race
No significant racial differences in pharmacokinetic parameters were found between Japanese and white patients.Smoking
Riluzole is eliminated 20% faster in patients who smoke.
Indications and Usage
Treatment of patients with amyotrophic lateral sclerosis (ALS; Lou Gehrig disease).
Dosage and AdministrationAdults
PO 50 mg every 12 h.
Because it is unknown whether alcohol increases the risk of serious hepatotoxicity with riluzole administration, discourage patients from drinking excessive amounts of alcohol.Carbamazepine plus phenobarbital
Epileptic patients receiving concomitant carbamazepine and phenobarbital experienced marked, rapid elevations of liver enzymes with jaundice and bilirubin 4 mo after starting riluzole. Values returned to normal 7 wk after discontinuation of treatment. Use with caution and carefully monitor liver function.CYP1A2 inducers (eg, cigarette smoke, omeprazole, rifampin)
May enhance riluzole elimination. Monitor the response of the patient. If an interaction is suspected, increase the riluzole dose as needed.CYP1A2 inhibitors (eg, amitriptyline, caffeine, quinolones, theophylline)
May reduce riluzole elimination. Monitor the response of the patient. If an interaction is suspected, decrease the riluzole dose as needed.Food
A high-fat meal reduces riluzole absorption. Riluzole should be taken 1 h before or 2 h after a meal to avoid food-related decreases in bioavailability. Charcoal-broiled food may increase the rate of riluzole elimination.Hepatotoxic drugs (eg, allopurinol, methyldopa, sulfasalazine)
The clinical trials in ALS excluded patients on concomitant medications that were potentially hepatotoxic. Accordingly, there is no information about the safety of administering riluzole in conjunction with such medications. If such a combination is administered, exercise caution.
Hypertension (7%); tachycardia (3%); postural hypotension (2%); palpitations (1%).
Asthenia (20%); dizziness (13%); headache (8%); depression, hypertonia (6%); vertigo (5%); insomnia, somnolence (4%); circumoral paresthesia (3%); aggravation reaction (2%); agitation, hostility, tremor (at least 1%); malaise (1%).
Pruritus (4%); eczema (2%); alopecia, exfoliative dermatitis (1%).
Nausea (21%); anorexia, diarrhea (9%); abdominal pain (8%); dyspepsia (6%); vomiting (5%); dry mouth (4%); flatulence (3%); oral moniliasis, stomatitis, tooth disorder (1%).
Urinary tract infection (5%); dysuria (1%).
Weight loss (5%); peripheral edema (4%).
Decreased lung function (16%); rhinitis (9%); increased cough (4%); sinusitis (2%).
Arthralgia (5%); back pain (4%); phlebitis (1%).
Measure serum aminotransferases before and during therapy. Evaluate serum ALT levels every month during the first 3 mo of treatment, every 3 mo during the remainder of the first year, and periodically thereafter.
Category C .
Safety and efficacy not established.
Use with caution in elderly patients whose hepatic function may be compromised because of age.
Use with caution in patients with current evidence or history of abnormal liver function indicated by significant elevations of liver enzymes, bilirubin, or GGT levels. Baseline elevations of several LFTs (especially elevated bilirubin) should preclude use of riluzole.
Special Risk Patients
Women may possess a lower metabolic capacity to eliminate riluzole as compared with men.
Cases of marked neutropenia (absolute neutrophil count [ANC] less than 500/mm 3 ) have been reported within the first 2 mo of treatment. Hgb, Hct, and erythrocytes counts were reported to fall below the lower limit of normal during treatment.
Interstitial lung disease
Cases have been reported, some of them severe, and many of these cases were hypersensitivity pneumonitis.
Neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma, and methemoglobinemia.
- Instruct patient to take medication at least 1 h before or 2 h after a meal.
- Instruct patient to take with a full glass of water.
- Instruct patient to take medicine at same time each day and, if a dose is missed, to take the next dose as originally planned.
- Instruct patient not to change dose or discontinue medication without consulting health care provider. Larger than prescribed doses do not increase effectiveness, but do increase the adverse effects.
- Have patient report any serious adverse effects to health care provider, including asthenia, decreased level of consciousness, diarrhea, dizziness, nausea, and respiratory distress.
- Inform patient of need for frequent laboratory tests while taking medication. Be sure to keep appointments.
- Instruct patient to report fever to health care provider.
- Instruct patient to avoid drinking alcohol in excess while taking this medication.
- Advise patient that drug may cause dizziness, somnolence, or vertigo, and not to drive or operate machinery until patient has gained enough experience to gauge whether it affects mental or motor performance adversely.
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