RILUZOLE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Riluzole is a benzothiazole that reduces glutamate release, inhibits voltage-gated sodium channels, and modulates glutamatergic neurotransmission, potentially via antagonism of NMDA receptors and inhibition of presynaptic glutamate release. Its neuroprotective effects in ALS are thought to involve reduction of excitotoxicity.

What the body does with it

Metabolism	Primarily hepatic via CYP1A2 (major), with minor contributions from CYP2B6, CYP2C9, CYP2E1, CYP3A4, and UGTs (UGT1A1, UGT1A9, UGT1A10). Also undergoes glucuronidation and oxidation to a N-hydroxyriluzole glucuronide.
Excretion	Primarily renal (approximately 90% of absorbed dose excreted in urine, with 2% unchanged; remainder as glucuronide conjugates and other metabolites). Fecal excretion accounts for <5%.
Half-life	Terminal elimination half-life is 12-14 hours (mean 12.9 h) in healthy adults; no significant accumulation at steady state with twice-daily dosing.
Protein binding	Approximately 96% bound to plasma proteins, primarily albumin and lipoproteins.
Volume of Distribution	Approximately 3.4 L/kg (indicating extensive tissue distribution, likely due to lipophilicity and binding to tissues).
Bioavailability	Oral bioavailability is approximately 60% (range 36-76% under fasting conditions); high-fat meal reduces AUC by 20% and delays Tmax.
Onset of Action	Oral: Slowing of disease progression typically observed after 3-6 months of continuous therapy; no immediate clinical effect.
Duration of Action	Sustained effect with chronic dosing; benefit on survival or tracheostomy-free survival persists as long as therapy continues (median treatment duration 12-18 months in trials).

Classification & Brands

Dosing & administration

50 mg orally every 12 hours.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥30 mL/min; insufficient data for GFR <30 mL/min, but use with caution.
Liver impairment	Contraindicated in patients with baseline elevation of serum aminotransferases >5× ULN or Child-Pugh class C. For Child-Pugh class A or B, caution advised; no specific dose adjustment established, monitor transaminases.
Pediatric use	Not established; safety and efficacy in pediatric patients (<18 years) have not been studied.
Geriatric use	No specific dose adjustment recommended based on age alone; consider renal and hepatic function, and monitor for adverse effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP1A2 inhibitors may increase levels Can cause elevated liver enzymes and neutropenia.

Breastfeeding	No data on excretion in human milk. M/P ratio unknown. Because of potential adverse effects (respiratory depression, hepatic injury), caution advised; consider alternative or discontinue breastfeeding.
Teratogenic Risk	FDA Pregnancy Category C. Animal studies show fetal toxicity (reduced fetal weights, skeletal variations) at maternal toxic doses. No adequate human studies. First trimester: potential risk unknown; avoid unless benefit justifies risk. Second/third trimester: limited data; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Nausea
Serious Effects

Absolute Contraindications

Absolute: Hypersensitivity to riluzole or any excipient, significant hepatic impairment (baseline ALT >5x ULN, jaundice, or cirrhosis with Child-Pugh class B/C), concurrent use of tizanidine or other CYP1A2 inhibitors that significantly increase riluzole exposure, breastfeeding, pregnancy (relative, due to potential fetal harm; weight benefit-risk).

Clinical Precautions

Precautions

Hepatotoxicity (elevated aminotransferases; discontinue if ALT >5x ULN or clinical jaundice), neutropenia (severe, absolute neutrophil count <500/mm3; discontinue if infection suspected), interstitial lung disease (discontinue if respiratory symptoms develop), risk of hypersensitivity reactions, renal impairment (not recommended if CrCl <60 mL/min), pregnancy (may cause fetal harm based on animal data; advise effective contraception), lactation (avoid breastfeeding), elderly patients (monitor for adverse effects due to age-related renal/hepatic decline)

Drug interactions

Loading safety data…

RILUZOLE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP1A2 (major), with minor contributions from CYP2B6, CYP2C9, CYP2E1, CYP3A4, and UGTs (UGT1A1, UGT1A9, UGT1A10). Also undergoes glucuronidation and oxidation to a N-hydroxyriluzole glucuronide.
Excretion	Primarily renal (approximately 90% of absorbed dose excreted in urine, with 2% unchanged; remainder as glucuronide conjugates and other metabolites). Fecal excretion accounts for <5%.
Half-life	Terminal elimination half-life is 12-14 hours (mean 12.9 h) in healthy adults; no significant accumulation at steady state with twice-daily dosing.
Protein binding	Approximately 96% bound to plasma proteins, primarily albumin and lipoproteins.
Volume of Distribution	Approximately 3.4 L/kg (indicating extensive tissue distribution, likely due to lipophilicity and binding to tissues).
Bioavailability	Oral bioavailability is approximately 60% (range 36-76% under fasting conditions); high-fat meal reduces AUC by 20% and delays Tmax.
Onset of Action	Oral: Slowing of disease progression typically observed after 3-6 months of continuous therapy; no immediate clinical effect.
Duration of Action	Sustained effect with chronic dosing; benefit on survival or tracheostomy-free survival persists as long as therapy continues (median treatment duration 12-18 months in trials).

Classification & Brands

Dosing & administration

50 mg orally every 12 hours.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥30 mL/min; insufficient data for GFR <30 mL/min, but use with caution.
Liver impairment	Contraindicated in patients with baseline elevation of serum aminotransferases >5× ULN or Child-Pugh class C. For Child-Pugh class A or B, caution advised; no specific dose adjustment established, monitor transaminases.
Pediatric use	Not established; safety and efficacy in pediatric patients (<18 years) have not been studied.
Geriatric use	No specific dose adjustment recommended based on age alone; consider renal and hepatic function, and monitor for adverse effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP1A2 inhibitors may increase levels Can cause elevated liver enzymes and neutropenia.

Breastfeeding	No data on excretion in human milk. M/P ratio unknown. Because of potential adverse effects (respiratory depression, hepatic injury), caution advised; consider alternative or discontinue breastfeeding.
Teratogenic Risk	FDA Pregnancy Category C. Animal studies show fetal toxicity (reduced fetal weights, skeletal variations) at maternal toxic doses. No adequate human studies. First trimester: potential risk unknown; avoid unless benefit justifies risk. Second/third trimester: limited data; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Nausea
Serious Effects

RILUZOLE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

RILUZOLE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

Clinical Tips & Counseling