Brand name: Rilutek; also available generically
Drug class: Central Nervous System Agents, Miscellaneous
VA class: CN900
Chemical name: 6-(Trifluoromethoxy)-2-benzothiazolamine
Molecular formula: C₈H₅F₃N₂OS
CAS number: 1744-22-5

Medically reviewed by Drugs.com on May 25, 2023. Written by ASHP.

Introduction

Antiglutamate agent that acts in the CNS;^{2 3 4 5 6 7 10 11 12 13 27} a synthetic aryl-substituted benzothiazolamine.^{1 2 3 4 5 6 7 9 27}

Uses for Riluzole

Amyotrophic Lateral Sclerosis

Management of amyotrophic lateral sclerosis (ALS, Lou Gehrig disease, Charcot sclerosis);^{1 7 11 15 22 24 27} designated an orphan drug by FDA for this use.²⁶

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.^{1 24 27 34 35}

Riluzole Dosage and Administration

General

• Measure serum aminotransferases, including ALT levels, before and during riluzole therapy.¹ (See Hepatic Effects under Cautions.)

Administration

Oral Administration

Administer orally twice daily, 1 hour before or 2 hours after meals.^{1 22 24 27} (See Food under Pharmacokinetics.)

Dosage

Adults

Amyotrophic Lateral Sclerosis

Oral

50 mg twice daily.¹

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.¹ (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations.¹

Geriatric Patients

No specific dosage recommendations.¹

Cautions for Riluzole

Contraindications

History of severe hypersensitivity reactions to riluzole or any ingredient in the formulation.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis reported.¹

Hepatic Effects

Liver injury, including fatalities, reported.¹ Asymptomatic elevations of aminotransferase concentrations (e.g., ALT) also reported and have recurred following rechallenge with the drug.¹ Maximum increases in ALT occurred within the first 3 months of therapy.¹

Monitor serum aminotransferase concentrations prior to and during therapy;¹ also monitor for signs and symptoms of hepatic injury (monthly for the first 3 months of treatment, then periodically thereafter).¹ Use not recommended in patients with aminotransferase concentrations >5 times ULN.¹ Discontinue therapy if there is evidence of liver dysfunction (e.g., elevated bilirubin concentrations).¹

Neutropenia

Severe neutropenia (ANC <500/mm³) reported within first 2 months of therapy.¹ Advise patients to report febrile illness.¹

Interstitial Lung Disease

Interstitial lung disease, including hypersensitivity pneumonitis, reported.¹ Discontinue immediately if interstitial lung disease develops.¹

Specific Populations

Pregnancy

No adequate data on use of riluzole in pregnant women.¹ In animal studies, adverse developmental effects (e.g., decreased embryofetal/offspring viability, growth, and functional development) observed at clinically relevant doses.¹

If used during pregnancy, advise patient of potential risk to the fetus¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Advise patients that the potential for serious adverse effects in nursing infants from riluzole is not known.¹

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

No overall differences in safety or efficacy between patients ≥65 years of age and younger adults.¹ However, greater sensitivity in some older individuals cannot be ruled out.¹

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.¹ Pharmacokinetics not studied in patients with severe hepatic impairment.¹

Use not recommended in patients with preexisting signs or symptoms of liver dysfunction.¹ (See Hepatic Effects under Cautions.)

Renal Impairment

Clinically important pharmacokinetic changes not observed in patients with moderate or severe renal impairment.¹ Pharmacokinetics not studied in patients undergoing hemodialysis.¹

Race

Japanese patients more likely to have increased riluzole concentrations; risk of riluzole-associated adverse effects may be greater in such patients.¹ (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Asthenia,¹ nausea,¹ decreased lung function,¹ hypertension,¹ abdominal pain,¹ vomiting,¹ arthralgia,¹ dizziness,¹ dry mouth,¹ insomnia,¹ pruritus,¹ tachycardia,¹ flatulence,¹ increased cough,¹ peripheral edema,¹ urinary tract infection,¹ circumoral paresthesia,¹ somnolence,¹ vertigo,¹ eczema.¹

Drug Interactions

Substrate of CYP1A2.¹

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.¹

Inducers of CYP1A2: In vitro findings suggest decreased riluzole exposure likely; may reduce efficacy of riluzole.¹

Specific Drugs

Riluzole Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability approximately 60%.¹

With multiple-dose administration, riluzole accumulates in plasma by about twofold.¹

Food

Food reduces AUC by 20% and peak plasma concentrations by 45%.¹

Special Populations

Mild or moderate hepatic impairment (Child-Pugh class A or B): AUC increased by 1.7- or 3-fold, respectively.¹

Severe hepatic impairment: Pharmacokinetics not studied.¹

Moderate or severe renal impairment: No clinically important effect on pharmacokinetics.¹

Patients undergoing hemodialysis: Pharmacokinetics not studied.¹

Age ≥65 years: No clinically important effect on pharmacokinetics.¹

Gender: Mean AUC approximately 45% higher in females compared with males.¹

Race: Clearance 50% lower in Japanese patients compared with Caucasian patients after normalizing for body weight.¹

Smokers: Clearance approximately 20% higher in smokers compared with nonsmokers.¹

Distribution

Plasma Protein Binding

96% (mainly to albumin and lipoproteins).¹

Elimination

Metabolism

Metabolized by CYP1A2 and by direct and sequential glucuronidation.¹

Elimination Route

Excreted in urine (90%) mainly as metabolites and in feces (5%).¹

Half-life

12 hours.¹

Stability

Storage

Oral

Tablets

20°–25°C; protect from bright light.¹

Actions and Spectrum

• Precise mechanism of action has not been fully elucidated¹ but appears to involve interference with the effects mediated by excitatory amino acids (EAAs) in the CNS, possibly through inhibition of glutamic acid release,^{2 3 4 5 6 9 11 12 15 17 18 27} blockade or inactivation of voltage-dependent sodium channels,^{4 5 6 7 15 17 18 19 27} and/or activation of a G-protein-dependent signal transduction pathway.^{6 17 27}

• May act via noncompetitive blockade of EAA receptors;^{5 14} however, does not appear to bind to any known glutamate receptor.^{2 4 6}

• Exhibits neuroprotective properties in vitro and in vivo in animals, including inhibition of neuronal toxicity associated with exposure to EAAs ⁷ or cerebrospinal fluid from ALS patients,^{6 7} and inhibits neuronal toxicity associated with anoxia^{4 7 9} or focal or global ischemia.^{2 3 4 6 7 9}

• Prolonged survival in a study in a transgenic mouse model of ALS but did not delay onset of the disease.^{21 22}

• Importance of patients informing clinician of any manifestations of possible liver injury (e.g., yellowing of the whites of the eyes).¹

• Importance of patients informing clinician of any febrile illness.¹

• Importance of patients informing clinician of any respiratory symptoms (e.g., dry cough, difficult or labored breathing).¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information.¹ (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.

Frequently asked questions

• What is the difference between Rilutek, Tiglutik and Exservan?

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