Riluzole

Riluzole is a Neuroprotective agent belonging to the Glutamate antagonist class.

Riluzole is a glutamate antagonist used to treat amyotrophic lateral sclerosis.

Riluzole is Rapidly absorbed from the gastrointestinal tract. High-fat meals decrease the rate and extent of absorption. It has Absolute bioavailability of Approximately 60%. Time to peak plasma concentration: 1 to 1.5 hours. Riluzole is Widely distributed throughout the body. It crosses the blood-brain barrier. It is having Volume of distribution of Approximately 3.4 L/kg. Plasma protein binding is Approximately 97%, mainly to albumin and lipoproteins. Riluzole is Extensively metabolized in the liver mainly via oxidation by CYP1A2 isoenzyme to the major active metabolite, N-hydroxy-riluzole; undergoes subsequent glucuronidation. It is excreted Via urine in (90%, >85% as glucuronides and 2% as unchanged drug) and via faeces in (5%).

Riluzole shows side effects like Weakness, dizziness, dry mouth, mouth numbness, difficulty falling asleep or staying asleep, drowsiness, etc.

Riluzole is available in the form of oral tablet, oral film, oral suspension.

Riluzole is available in India, US, Canada, Belgium, France, Germany, Spain, and Australia.

Riluzole belongs to Glutamate antagonist class and acts as Neuroprotective agent.

Riluzole is a glutamate inhibitor used to slow disease progression and prolong survival rate in patients with amyotrophic lateral sclerosis. The exact mechanism of its action is not fully elucidated but is shown to inhibit the release of glutamate, inactivate voltage-dependent Na channels, and interfere with intracellular events following binding of transmitter at excitatory amino acid receptors.

The Onset and Duration of action of Riluzole is not clinically established.

The Time to peak plasma concentration of Riluzole is approximately 1-1.5 hours.

Riluzole is available in the form of oral tablet, oral film, oral suspension.

Riluzole tablet, film and suspension are taken orally usually twice daily.

Riluzole is a benzothiazole drug indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS).

Riluzole is a Neuroprotective agent belonging to the Glutamate antagonist class.

Riluzole is a glutamate inhibitor used to slow disease progression and prolong survival rate in patients with amyotrophic lateral sclerosis. The exact mechanism of its action is not fully elucidated but is shown to inhibit the release of glutamate, inactivate voltage-dependent Na channels, and interfere with intracellular events following binding of transmitter at excitatory amino acid receptors.

Riluzole is approved for use in the following clinical indications:

Riluzole is a glutamate antagonist used to treat amyotrophic lateral sclerosis.

• Amyotrophic lateral sclerosis

Adult oral Dose: 50 mg twice a day. Discontinue if ALT levels increase to 5 times the upper limit of normal (ULN).

Riluzole is available in various strengths as 50 mg; 50 mg/10 mL.

Riluzole is available in the form of oral tablet, oral film, oral suspension.

Riluzole is contraindicated in patients with

• Riluzole is contraindicated in patients who have a history of severe hypersensitivity reactions to riluzole or any of the tablet components.

• Neutropenia

Among approximately 4000 patients given riluzole for ALS, there were three cases of marked neutropenia (absolute neutrophil count less than 500/mm3), all seen within the first 2 months of riluzole treatment. In one case, neutrophil count rose on continued treatment. In a second case, counts rose after therapy was stopped. A third case was more complex, with marked anemia as well as neutropenia and the etiology of both is uncertain. Patients should be warned to report any febrile illness to their physicians. The report of febrile illness should prompt treating physicians to check white blood cell counts.

• Liver Injury / Monitoring Liver Chemistries

Riluzole should be prescribed with care in patients with current evidence or history of abnormal liver function indicated by significant abnormalities in serum transaminase (ALT/SGPT; AST/SGOT), bilirubin, and/or gamma-glutamate transferase (GGT) levels. Baseline elevations of several LFTs (especially elevated bilirubin) should preclude the use of Riluzole. Riluzole, even in patients without a prior history of liver disease, causes serum aminotransferase elevations. Treatment should be discontinued if ALT levels are ≥ 5 X ULN or if clinical jaundice develops.

It is not known whether riluzole is excreted in human breast milk. Because many drugs are excreted in human milk, and because the potential for serious adverse reactions in nursing infants from Riluzole is unknown, women should be advised not to breast-feed during treatment with Riluzole.

There are no adequate and well-controlled studies in pregnant women. Riluzole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Common

Neutropenia, dizziness, drowsiness, vertigo, interstitial lung disease, Tachycardia, Oral paranesthesia, diarrhea, abdominal pain, nausea, vomiting, Asthenia, pain, Angioedema, anaphylactoid reaction, Abnormal LFT, Headache.

Rare

Hepatic injury.

Hepatotoxic Drugs

The clinical trials in ALS excluded patients on concomitant medications which were potentially hepatotoxic, (e.g., allopurinol, methyldopa, sulfasalazine). Accordingly, there is no information about the safety of administering Riluzole in conjunction with such medications. If the practitioner chooses to prescribe such a combination, caution should be exercised.

Drugs Highly Bound to Plasma Proteins:

Riluzole is highly bound (96%) to plasma proteins, binding mainly to serum albumin and to lipoproteins. The effect of riluzole (up to 5 mcg/mL) on warfarin (5 mcg/mL) binding did not show any displacement of warfarin. Conversely, riluzole binding was unaffected by the addition of warfarin, digoxin, imipramine and quinine at high therapeutic concentrations.

Effect of Other Drugs on Riluzole Metabolism:

In vitro studies using human liver microsomal preparations suggest that CYP 1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole and, therefore, potential interactions may occur when riluzole is given concurrently with agents that affect CYP 1A2 activity. Potential inhibitors of CYP 1A2 (e.g., caffeine, phenacetin, theophylline, amitriptyline, and quinolones) could decrease the rate of riluzole elimination, while inducers of CYP 1A2 (e.g., cigarette smoke, charcoal-broiled food, rifampicin, and omeprazole) could increase the rate of riluzole elimination.

Effect of Riluzole on the Metabolism of Other Drugs:

CYP 1A2 is the principal isoenzyme involved in the initial oxidative metabolism of riluzole; potential interactions may occur when riluzole is given concurrently with other agents which are also metabolized primarily by CYP 1A2 (e.g., theophylline, caffeine, and tacrine). Currently, it is not known whether riluzole has any potential for enzyme induction in humans.

The common side effects of Riluzole include the following

Common side effects

Weakness, dizziness, dry mouth, mouth numbness, difficulty falling asleep or staying asleep, drowsiness, swelling of the hands, feet, ankles, or lower legs, fast heart rate.

Rare side effects

Hives, rash, itching, difficulty breathing or swallowing, dry cough, nausea, stomach pain, vomiting, extreme tiredness, unusual bleeding or bruising loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, dark urine, fever, chills, cough, or other signs of infection, muscle or joint pain, headache.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Riluzole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known whether riluzole is excreted in human breast milk. Because many drugs are excreted in human milk, and because the potential for serious adverse reactions in nursing infants from Riluzole is unknown, women should be advised not to breast-feed during treatment with Riluzole.

• Pediatric Use

The safety and the effectiveness of Riluzole in pediatric patients have not been established.

• Geriatric Use

Age-related compromised renal and hepatic function may cause a decrease in clearance of riluzole. In controlled clinical trials, about 30% of patients were over 65. There were no differences in adverse effects between younger and older patients.

Symptoms: Methemoglobinemia, memory loss, acute toxic encephalopathy with stupor and coma.

Management: Symptomatic and supportive treatment.

• Pharmacodynamic

Riluzole is a glutamate inhibitor used to slow disease progression and prolong survival rate in patients with amyotrophic lateral sclerosis. The exact mechanism of its action is not fully elucidated but is shown to inhibit the release of glutamate, inactivate voltage-dependent Na channels, and interfere with intracellular events following binding of transmitter at excitatory amino acid receptors.

• Pharmacokinetics

Absorption

Riluzole is Rapidly absorbed from the gastrointestinal tract. High-fat meal decreases the rate and extent of absorption. It is having Absolute bioavailability of Approximately 60%. Time to peak plasma concentration: 1 to 1.5 hours.

Distribution

Riluzole is Widely distributed throughout the body. It crosses the blood-brain barrier. It is having Volume of distribution of Approximately 3.4 L/kg. Plasma protein binding is Approximately 97%, mainly to albumin and lipoproteins.

Metabolism and Excretion

Riluzole is Extensively metabolized in the liver mainly via oxidation by CYP1A2 isoenzyme to the major active metabolite, N-hydroxy-riluzole; undergoes subsequent glucuronidation. It is excreted Via urine in (90%, >85% as glucuronides and 2% as unchanged drug) and via faeces in (5%).

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020599s011s012lbl.pdf
• https://go.drugbank.com/drugs/DB00740
• https://medlineplus.gov/druginfo/meds/a696013.html#:~:text=Riluzole is used to treat,that affect nerves and muscles.
• https://www.drugs.com/dosage/riluzole.html