Brand name: Tiglutik
Drug class: Amyotrophic Lateral Sclerosis (ALS) Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Antiglutamate agent that acts in the CNS.

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.

The American Academy of Neurology published an evidence-based review of treatments for ALS in 2009; however, the only disease-modifying drug available at that time was riluzole. Additional agents (e.g., edaravone, tofersen) are currently available; however, these drugs have not been shown to provide much, if any, improvement in survival. Referral to a specialized multidisciplinary clinic should be considered for patients with ALS.

Riluzole Dosage and Administration

General

Patient Monitoring

• Monitor serum aminotransferases, including ALT levels, before and during riluzole therapy.

• Monitor for signs and symptoms of hepatic injury (monthly for the first 3 months of treatment, then periodically thereafter).

Administration

Oral Administration

Administer orally twice daily, 1 hour before or 2 hours after a meal.

Available as tablets or oral suspension.

Oral Suspension

Gently shake bottle for at least 30 seconds prior to administration.

May administer by mouth or via percutaneous endoscopic gastrostomy tubes (i.e., silicone or polyurethane PEG tubes).

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.

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

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.

Females and Males of Reproductive Potential

Riluzole use in rats resulted in decreased fertility indices and increases in embryolethality.

Pediatric Use

Safety and efficacy not established.

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 baseline elevations of serum aminotransferases >5 times the ULN or evidence of liver dysfunction (e.g., elevated bilirubin).

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.

Common Adverse Effects

Most common adverse effects (≥5%) with riluzole tablets: asthenia, nausea, dizziness, decreased lung function, abdominal pain.

Most common adverse effects (≥5%) with riluzole oral suspension: oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, abdominal pain.

Drug Interactions

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

Riluzole Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability approximately 60%.

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

Similar pharmacokinetics observed following intragastric administration (via feeding tube) and oral administration of the oral suspension under fasting conditions.

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

Oral Suspension

Store oral suspension upright at 20–25°C (excursions permitted to 15–30°C); protect from bright light and do not freeze. Use within 15 days of initially opening the bottle.

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 CSF 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

• Advise patients to read the FDA-approved patient labeling (Instructions for Use).

• Instruct patients on how to administer the specific dosage form of riluzole prescribed.

• Advise patients to inform their clinician of any manifestations of possible liver injury (e.g., yellowing of the whites of the eyes).

• Risk of neutropenia; advise patients to inform their clinician of any febrile illness.

• Risk of interstitial lung disease; advise patients to inform their clinician of any respiratory symptoms (e.g., dry cough, difficult or labored breathing).

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Advise patients to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Reload page with references included

Frequently asked questions

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

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