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Riluzole

Class: Central Nervous System Agents, Miscellaneous
VA Class: CN900
Chemical Name: 6-(Trifluoromethoxy)-2-benzothiazolamine
Molecular Formula: C8H5F3N2OS
CAS Number: 1744-22-5
Brands: Rilutek; also available generically

Medically reviewed by Drugs.com on May 25, 2021. Written by ASHP.

Introduction

Antiglutamate agent that acts in the CNS; a synthetic aryl-substituted benzothiazolamine.

Uses for Riluzole

Amyotrophic Lateral Sclerosis

Management of amyotrophic lateral sclerosis (ALS, Lou Gehrig disease, Charcot sclerosis); designated an orphan drug by FDA for this use.

Has been shown to slow disease progression and prolong survival to a modest degree (e.g., by about 2–3 months); because of this possible benefit, experts recommend that the drug should be offered to patients with ALS.

Riluzole Dosage and Administration

General

  • Measure serum aminotransferases, including ALT levels, before and during riluzole therapy. (See Hepatic Effects under Cautions.)

Administration

Oral Administration

Administer orally twice daily, 1 hour before or 2 hours after meals. (See Food under Pharmacokinetics.)

Dosage

Adults

Amyotrophic Lateral Sclerosis
Oral

50 mg twice daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations; however, use not recommended in patients with aminotransferase concentrations >5 times ULN or evidence of liver dysfunction. (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Riluzole

Contraindications

History of severe hypersensitivity reactions to riluzole or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis reported.

Hepatic Effects

Liver injury, including fatalities, reported. Asymptomatic elevations of aminotransferase concentrations (e.g., ALT) also reported and have recurred following rechallenge with the drug. Maximum increases in ALT occurred within the first 3 months of therapy.

Monitor serum aminotransferase concentrations prior to and during therapy; also monitor for signs and symptoms of hepatic injury (monthly for the first 3 months of treatment, then periodically thereafter). Use not recommended in patients with aminotransferase concentrations >5 times ULN. Discontinue therapy if there is evidence of liver dysfunction (e.g., elevated bilirubin concentrations).

Neutropenia

Severe neutropenia (ANC <500/mm3) reported within first 2 months of therapy. Advise patients to report febrile illness.

Interstitial Lung Disease

Interstitial lung disease, including hypersensitivity pneumonitis, reported. Discontinue immediately if interstitial lung disease develops.

Specific Populations

Pregnancy

No adequate data on use of riluzole in pregnant women. In animal studies, adverse developmental effects (e.g., decreased embryofetal/offspring viability, growth, and functional development) observed at clinically relevant doses.

If used during pregnancy, advise patient of potential risk to the fetus

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Advise patients that the potential for serious adverse effects in nursing infants from riluzole is not known.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No overall differences in safety or efficacy between patients ≥65 years of age and younger adults. However, greater sensitivity in some older individuals cannot be ruled out.

Hepatic Impairment

Increased exposure to riluzole observed in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment; such patients may be at increased risk of adverse effects. Pharmacokinetics not studied in patients with severe hepatic impairment.

Use not recommended in patients with preexisting signs or symptoms of liver dysfunction. (See Hepatic Effects under Cautions.)

Renal Impairment

Clinically important pharmacokinetic changes not observed in patients with moderate or severe renal impairment. Pharmacokinetics not studied in patients undergoing hemodialysis.

Race

Japanese patients more likely to have increased riluzole concentrations; risk of riluzole-associated adverse effects may be greater in such patients. (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Asthenia, nausea, decreased lung function, hypertension, abdominal pain, vomiting, arthralgia, dizziness, dry mouth, insomnia, pruritus, tachycardia, flatulence, increased cough, peripheral edema, urinary tract infection, circumoral paresthesia, somnolence, vertigo, eczema.

Interactions for Riluzole

Substrate of CYP1A2.

Drugs Affecting Hepatic Microsomal Enzymes

Moderate or potent inhibitors of CYP1A2: In vitro findings suggest increased riluzole exposure likely; may increase risk of riluzole-associated adverse effects.

Inducers of CYP1A2: In vitro findings suggest decreased riluzole exposure likely; may reduce efficacy of riluzole.

Specific Drugs

Drug

Interaction

Allopurinol

Possible increased risk of hepatotoxicity

Ciprofloxacin

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Digoxin

No effect on riluzole protein binding in vitro

Fluvoxamine

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Imipramine

No effect on riluzole protein binding in vitro

Methoxsalen

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Methyldopa

Possible increased risk of hepatotoxicity

Mexiletine

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Oral contraceptives

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Quinine

No effect on riluzole protein binding in vitro

Sulfasalazine

Possible increased risk of hepatotoxicity

Vemurafenib

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Warfarin

No effect on riluzole or warfarin protein binding in vitro

Zileuton

Increased riluzole exposure likely; possible increased risk of riluzole-associated adverse effects

Riluzole Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability approximately 60%.

With multiple-dose administration, riluzole accumulates in plasma by about twofold.

Food

Food reduces AUC by 20% and peak plasma concentrations by 45%.

Special Populations

Mild or moderate hepatic impairment (Child-Pugh class A or B): AUC increased by 1.7- or 3-fold, respectively.

Severe hepatic impairment: Pharmacokinetics not studied.

Moderate or severe renal impairment: No clinically important effect on pharmacokinetics.

Patients undergoing hemodialysis: Pharmacokinetics not studied.

Age ≥65 years: No clinically important effect on pharmacokinetics.

Gender: Mean AUC approximately 45% higher in females compared with males.

Race: Clearance 50% lower in Japanese patients compared with Caucasian patients after normalizing for body weight.

Smokers: Clearance approximately 20% higher in smokers compared with nonsmokers.

Distribution

Plasma Protein Binding

96% (mainly to albumin and lipoproteins).

Elimination

Metabolism

Metabolized by CYP1A2 and by direct and sequential glucuronidation.

Elimination Route

Excreted in urine (90%) mainly as metabolites and in feces (5%).

Half-life

12 hours.

Stability

Storage

Oral

Tablets

20°–25°C; protect from bright light.

Actions and Spectrum

  • Precise mechanism of action has not been fully elucidated but appears to involve interference with the effects mediated by excitatory amino acids (EAAs) in the CNS, possibly through inhibition of glutamic acid release, blockade or inactivation of voltage-dependent sodium channels, and/or activation of a G-protein-dependent signal transduction pathway.

  • May act via noncompetitive blockade of EAA receptors; however, does not appear to bind to any known glutamate receptor.

  • Exhibits neuroprotective properties in vitro and in vivo in animals, including inhibition of neuronal toxicity associated with exposure to EAAs or cerebrospinal fluid from ALS patients, and inhibits neuronal toxicity associated with anoxia or focal or global ischemia.

  • Prolonged survival in a study in a transgenic mouse model of ALS but did not delay onset of the disease.

Advice to Patients

  • Importance of patients informing clinician of any manifestations of possible liver injury (e.g., yellowing of the whites of the eyes).

  • Importance of patients informing clinician of any febrile illness.

  • Importance of patients informing clinician of any respiratory symptoms (e.g., dry cough, difficult or labored breathing).

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Riluzole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

50 mg*

Rilutek

Covis

Riluzole Tablets

AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 4, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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