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Pronunciation
(RIL yoo zole)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of amyotrophic lateral sclerosis (ALS); riluzole can extend survival or time to tracheostomy
Pregnancy Risk Factor
C
Pregnancy Considerations
Impaired fertility, decreased implantation, increased intrauterine death, and adverse effects on offspring growth and viability were observed in animal studies. There are no adequate or well-controlled studies in pregnant women.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Severe hypersensitivity reactions to riluzole or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• CNS depression: May cause dizziness or somnolence; caution should be used performing tasks which require alertness (operating machinery or driving).
• Pulmonary disorders: Interstitial lung disease (primarily hypersensitivity pneumonitis) has occurred with riluzole therapy. May present as progressive dyspnea, cough, and/or chest pain; prompt evaluation and possible discontinuation of therapy may be necessary. Symptoms usually improve upon discontinuation of riluzole.
• Neutropenia: 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.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; do not administer if baseline liver function tests are elevated. May cause elevations in transaminases (usually transient) within first 3 months of therapy; discontinue if ALT levels are ≥5 times upper limit of normal or if jaundice develops.
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Elderly: Use with caution in the elderly; clearance decreased.
• Females: Use with caution in females; clearance decreased.
Adverse Reactions
>10%:
Gastrointestinal: Nausea (16%)
Neuromuscular & skeletal: Weakness (19%)
1% to 10%:
Cardiovascular: Hypertension (5%), peripheral edema (3%), tachycardia (3%)
Central nervous system: Dizziness (4%), somnolence (2%), vertigo (2%), malaise (1%)
Dermatologic: Pruritus (4%), eczema (2%), exfoliative dermatitis (1%)
Gastrointestinal: Abdominal pain (5%), vomiting (4%), flatulence (3%), oral moniliasis (1%), stomatitis (1%), tooth caries (1%)
Genitourinary: Urinary tract infection (3%), dysuria (1%)
Hepatic: Liver function tests increased (8% >3 x ULN; 2% >5 x ULN)
Neuromuscular & skeletal: Arthralgia (4%), paresthesia (circumoral; 2%), tremor (1%)
Respiratory: Lung function decreased (10%), cough increased (3%)
<1%, postmarketing, and/or case reports (Limited to important or life-threatening): Alkaline phosphatase increased, amblyopia, anaphylactoid reaction, anaphylaxis, angioedema, aplastic anemia, arthrosis, asthma, ataxia, bone necrosis, bradycardia, bundle branch block, cataract, cerebral hemorrhage, deafness, dementia, diabetes mellitus, diabetes insipidus, edema, erythema multiforme, extrapyramidal syndrome, facial paralysis, gastrointestinal hemorrhage, gastrointestinal ulcer, GGT increased, glaucoma, hallucination, heart failure, hematemesis, hematuria, hemoptysis, hepatitis, hypercalcemia, hypokalemia, hypokinesia, hyponatremia, hypotension, hypersensitivity pneumonitis, interstitial lung disease, jaundice, LDH increased, leukocytosis, leukopenia, lymphadenopathy, mania, myoclonus, neutropenia, osteoporosis, pancreatitis, peripheral neuritis, pleural effusion, pseudomembranous colitis, purpura, respiratory acidosis, seizure, subarachnoid hemorrhage, thrombosis, urinary retention, urticaria, uterine hemorrhage, ventricular fibrillation, ventricular tachycardia
Metabolism/Transport Effects
Substrate of CYP1A2 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
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.
Storage
Store at 20°C to 25°C (68°F to 77°F). Protect from bright light.
Mechanism of Action
Mechanism of action is not known. Pharmacologic properties include 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
Pharmacodynamics/Kinetics
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
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 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 renal impairment: No specific dosage adjustments recommended by manufacturer; use caution.
Dosage adjustment in hepatic impairment: No specific dosage adjustments recommended by manufacturer; use caution.
Administration: Oral
Administer at the same time each day, at least 1 hour before or 2 hours after a meal.
Monitoring Parameters
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 times ULN (upper limits of normal). Discontinue therapy if ALT levels are ≥5 times upper limit of normal or if jaundice develops.
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.
Dietary Considerations
Take at least 1 hour before or 2 hours after a meal.
Patient Education
This drug will not cure or stop disease, but it may slow progression. Take 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, sleepiness, 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.
Geriatric Considerations
In clinical trials, no difference was demonstrated between elderly and younger adults. However, renal and hepatic changes with age can be expected to result in higher serum concentrations of the parent drug and its metabolites.
Anesthesia and Critical Care Concerns/Other Considerations
Riluzole may be more effective for amyotrophic lateral sclerosis of bulbar onset.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral moniliasis and stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause agitation, depression, dizziness, insomnia, malaise, or somnolence
Mental Health: Effects on Psychiatric Treatment
May cause neutropenia; use caution with clozapine and carbamazepine. GI side effects are common; concomitant use with SSRIs, carbamazepine, valproic acid, and lithium may produce additive effects. Riluzole is a CYP1A2 substrate; cigarette smoking may increase metabolism of riluzole.
Nursing: Physical Assessment/Monitoring
Monitor for decreased liver function at beginning of therapy and periodically throughout.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Rilutek®: 50 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Rilutek)
50 mg (60): $999.94
References
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.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
Content last modified October 2011
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