RELYVRIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RELYVRIO (RELYVRIO).
Sodium phenylbutyrate and taurursodiol are hypothesized to reduce endoplasmic reticulum stress and mitochondrial dysfunction, thereby attenuating neuronal cell death in amyotrophic lateral sclerosis (ALS). Sodium phenylbutyrate is a histone deacetylase inhibitor that may improve protein chaperone function, while taurursodiol is a bile acid that inhibits apoptosis and may reduce mitochondrial dysfunction.
| Metabolism | Sodium phenylbutyrate: Primarily metabolized by beta-oxidation and conjugation with glutamine to form phenylacetylglutamine, which is excreted renally. Taurursodiol: Not significantly metabolized; undergoes limited hepatic metabolism and is excreted primarily in feces. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 70-80% of administered dose), with minor fecal elimination (<10%) and negligible biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 120-140 hours (5-6 days), allowing for once-weekly dosing. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 10-15 L (0.14-0.21 L/kg), indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 60-80%. |
| Onset of Action | Oral administration: clinical effect (reduction in plasma neurofilament light chain levels) observed within 4 weeks; maximum effect by 12 weeks. |
| Duration of Action | Duration of therapeutic effect persists for the dosing interval (1 week) with sustained suppression of disease biomarkers; drug accumulation occurs over first 12 weeks. |
Oral, 3 g (6 capsules) once daily.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dose adjustment recommended based on renal function. Clinical data limited in severe renal impairment (eGFR <30 mL/min/1.73 m²); use caution. |
| Liver impairment | Contraindicated in Child-Pugh Class B and C hepatic impairment. No dose adjustment in Child-Pugh Class A; however, clinical data limited. |
| Pediatric use | Safety and efficacy not established in pediatric patients. No approved dosing. |
| Geriatric use | No specific dose adjustment in elderly. Clinical studies included limited numbers of patients ≥65 years; no differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RELYVRIO (RELYVRIO).
| Breastfeeding | No human data; M/P ratio unknown. Excretion into human milk is unknown. Caution advised; consider developmental benefits of breastfeeding versus potential drug exposure. |
| Teratogenic Risk | No human data; animal studies show no teratogenic effects at clinically relevant doses. Risk cannot be excluded; avoid use in first trimester unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["None."]
| Precautions | ["Sodium phenylbutyrate can lead to elevated ammonia levels; monitor blood ammonia during treatment.","Taurursodiol may cause constipation.","Patients with hepatic impairment may have increased exposure to sodium phenylbutyrate; use with caution.","Diarrhea and abdominal pain have been reported."] |
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| Monitor maternal liver function tests (ALT, AST, bilirubin) at baseline and periodically. Fetal ultrasound for growth and anatomy if exposure occurs during pregnancy. |
| Fertility Effects | No human fertility studies; animal studies show no impairment of fertility at clinically relevant doses. |