Section 08 · Monograph
Sodium phenylbutyrate-taurursodiol
Reviewed Nov 2026FDA label
Relyvrio (WITHDRAWN Apr 2024)Neuroprotective combination
- Forms
- Oral packet: 3g/1g
- Dose
- No longer marketed (PHOENIX trial negative); legacy patients only
- MOA
- ↓ER stress + mitochondrial dysfunction
Indications
- MARKET STATUS NOTE: RELYVRIO (sold as ALBRIOZA in Canada) was voluntarily withdrawn from the US market by Amylyx Pharmaceuticals in April 2024 after the confirmatory Phase 3 PHOENIX trial failed to meet its primary endpoint; it is no longer commercially available in the US, and FDA formally withdrew approval of the NDA in 2025. Content below is retained for historical/educational reference only and should not be used to guide current prescribingFDA-labeled
- Formerly indicated for treatment of amyotrophic lateral sclerosis (ALS) in adults (accelerated approval pathway based on the CENTAUR trial, granted September 2022)FDA-labeled
Mechanism of Action
- Mechanism by which the combination exerted a therapeutic effect in ALS was not established
- Sodium phenylbutyrate: a chemical chaperone believed to reduce endoplasmic reticulum stress and may act as a histone deacetylase (HDAC) inhibitor
- Taurursodiol (ursodoxicoltaurine): believed to reduce mitochondrial-associated cell death by stabilizing mitochondrial and endoplasmic reticulum membranes
- Proposed complementary/synergistic action against neuronal proteotoxic and mitochondrial stress pathways implicated in motor neuron death
Full Dosing
Adult / usual
- Historical regimen: one packet (3 g sodium phenylbutyrate / 1 g taurursodiol) once daily for the first 3 weeks
- Maintenance (after week 3): one packet twice daily, approximately 12 hours apart
- Each packet mixed with 8 ounces of room-temperature water; must be consumed within 1 hour of mixing
- Administered at least 1 hour before or after consuming a meal
Renal
- Dose adjustment (once daily) recommended for patients with moderate hepatic or renal impairment; not studied in severe impairment
Contraindications
- None listed in the original FDA label
Drug Interactions
- Bile acid sequestrants (cholestyramine, colestipol, colesevelam) may reduce taurursodiol absorption — avoid coadministration
- Aluminum-containing antacids may reduce taurursodiol absorption
- Strong bile salt export pump (BSEP) inhibitors (e.g., cyclosporine) may increase taurursodiol/bile acid levels — monitor liver enzymes and bilirubin if coadministered
- Additive risk with other HDAC-inhibiting agents given phenylbutyrate's HDAC-inhibitory activity
Adverse Effects
- Diarrhea (~25% vs ~19% placebo)
- Abdominal pain (~21% vs ~13% placebo)
- Nausea (~18% vs ~13% placebo)
- Upper respiratory tract infection (~18% vs ~10% placebo)
- Salivary hypersecretion
- Fatigue
- GI effects most prominent during the initial 3-week once-daily titration phase
Monitoring Parameters
- GI tolerability, particularly diarrhea severity, especially in patients with disorders of enterohepatic or pancreatic circulation
- Sodium intake/fluid status in patients with heart failure, hypertension, or renal impairment (each packet contributes substantial sodium load)
- Liver function tests if coadministered with strong BSEP inhibitors
- Given the 2024 withdrawal, monitoring is now primarily relevant to historical/educational context
Pregnancy & Lactation
- Based on animal data (increased stillbirth and pup mortality in rat studies at all doses tested), may cause fetal harm; no adequate human data were available
- No data on presence of either component in human milk or effects on the breastfed infant or milk production
- These considerations are of historical/educational relevance only given the 2024 market withdrawal