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Riluzole

Pronunciation

Pronunciation

(RIL yoo zole)

Index Terms

  • 2-Amino-6-Trifluoromethoxy-benzothiazole
  • RP-54274

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Rilutek: 50 mg

Generic: 50 mg

Brand Names: U.S.

  • Rilutek

Pharmacologic Category

  • Glutamate Inhibitor

Pharmacology

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

Absorption

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

Metabolism

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

Excretion

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

Half-Life Elimination

12 hours

Protein Binding

Plasma: 96%, primarily to albumin and lipoproteins

Special Populations: 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.

Special Populations: Gender

Mean Cl was found to be 30% lower in women compared with men in 1 clinical trial.

Special Populations Note

Smoking

Riluzole is eliminated 20% faster in patients who smoke.

Use: Labeled Indications

Treatment of amyotrophic lateral sclerosis (ALS); riluzole can extend survival or time to tracheostomy

Contraindications

Severe hypersensitivity reactions to riluzole or any component of the formulation

Dosing: Adult

ALS treatment: 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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling. Use with caution.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. Use with caution.

Administration

Administer at the same time each day, at least 1 hour before or 2 hours after a meal.

Dietary Considerations

Take at least 1 hour before or 2 hours after a meal.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from bright light.

Drug Interactions

Cannabis: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Osimertinib: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

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% (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

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.

Concurrent drug therapy issues:

• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Elderly: Use with caution in the elderly; clearance decreased.

• Females: Use with caution in females; clearance decreased.

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.

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.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, diarrhea, asthenia, dyspepsia, or lack of appetite. Have patient report immediately to prescriber signs of infection, severe dizziness, syncope, dyspnea, considerable headache, tachycardia, arrhythmia, polyuria, dysuria, edema of extremities, or signs of hepatic impairment (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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