Riluzole/Tiglutik

Background

Riluzole is a drug used to treat people with Amyotrophic Lateral Sclerosis (ALS) or Motor Neuron Disease (MND). Riluzole is not a cure for ALS/MND, but it may extend survival or time until tracheostomy. It is available in three dosage forms: tablet, oral suspension, and thin film.

The tablet form, Rilutek, was approved by the Food and Drug Administration (FDA) in USA in 1995 and by the European Medicine Agency (EMA) in Europe in 1996.

The oral suspension form, Tiglutik or Teglutik, which is designed for people living with ALS/MND who have difficulty swallowing tablets, is currently approved in many countries including USA, Canada, Europe, Israel, Australia, Brazil, Japan, and China.

The thin film form is available in the US (with the commercial name of Exservan), and in the UK and the EU (with the commercial name of Emylif).

Proposed Mechanism of Action

Neurons have a finely regulated system that allows chemical signals (neurotransmitters) to be translated into electrical signals, which travel much faster and allow efficient communications among neurons. This mechanism is essential for the correct functioning of the human brain, and it is particularly important for motor neurons, which are among the largest neurons in the central nervous system.

ALS/MND is characterized by a progressive and selective death of motor neurons, the causes of which are mostly unknown. One of the mechanisms thought to be involved in this process is excitotoxicity, which occurs when neurons are exposed to excessive levels of a neurotransmitter called glutamate, causing a dysregulated neuronal activation. This may lead to neuronal damage and eventual death.

Riluzole was the first compound ever approved for the treatment of ALS/MND. Riluzole’s mechanism of action is not fully understood; however, it is thought to interfere with the excessive glutamate release that leads to excitotoxicity in ALS/MND.

Of note, other clinical trials in people living with ALS/MND with compounds that have a similar mechanism of action have failed. Therefore, riluzole’s action has been hypothesized to expand to other aspects of neurotransmission or even other molecular mechanisms linked to ALS/MND. These hypotheses are currently under investigation.

Clinical Trials

Riluzole was approved based on two international clinical trials that included a total of 1,114 people living with ALS/MND (PALS).

In the first study, 155 PALS were treated with 100 mg of riluzole or placebo daily for 12 months. By the end of the study, the treatment extended survival or time until tracheostomy (where a breathing tube is inserted directly into the throat) by roughly three months compared to placebo.

In the second study, 959 PALS were treated with three different concentrations of riluzole (50 mg, 100 mg, 200 mg) or placebo daily for 18 months. Both the 100 mg and 200 mg treatments extended survival or showed significant delay in the need for tracheostomy when compared to placebo. However, the 200 mg dose resulted in more side effects.

Dose and Administration

Riluzole comes in three forms and has several brand names:

Tablet form: Rilutek contain 50 mg of the active compound (riluzole). The recommended dose is 50 mg twice daily (every 12 hours) taken orally.
Oral suspension form: Tiglutik or Teglutik is recommended for patients who have difficulty in swallowing or receive nutrition via feeding tube. The dosage recommendation is the same as Rilutek. The FDA approved Tiglutik in 2018, whereas Teglutik has been available in the UK since 2015.
Thin film form: Exservan/Emylif dissolves on the tongue. It is applied one to two hours prior to a meal.

Riluzole is recommended for all patients diagnosed with ALS/MND. However, due to lack of studies, it is unclear whether it is equally effective after five years from symptom onset.

Reported Side Effects

Riluzole is safe and generally well tolerated at a dose of 100 mg daily for up to seven years. The most common side effects are numbness around the mouth, nausea, dizziness, diarrhea, lack of energy, high blood pressure, decreased lung function, and abdominal pain. Rare cases have reported liver injury.

In 2020, a study showed that out 15 peer-reviewed studies in PALS treated with riluzole in real-world settings, eight found that survival was a median of 6 to 19 months longer on riluzole than on placebo. Riluzole’s effects and safety continue to be investigated in people living with ALS/MND.

Riluzole should be administered and monitored under the care of a physician.

Disclaimer: Consult with your doctor to determine if riluzole is an option for you. Always disclose your medical history, including any drugs, natural supplements, or herbal medicines you are currently using. Your doctor will determine the right plan for your needs.

SOURCES

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