sodium phenylbutyrate/taurursodiol

Therapeutic Classification: agents for amyotrophic lateral sclerosis, none assigned

Pharmacologic Classification: histone deacetylase inhibitors, bile acid replacements

Indications ⬆ ⬇

REMS

Amyotrophic lateral sclerosis (ALS).

Action ⬆ ⬇

Sodium phenylbutyrate: Acts as a histone deacetylase inhibitor. Its mechanism of benefit in ALS is unknown. Taurursodiol: A bile acid. Its mechanism of benefit in ALS is unknown.

Therapeutic effects:

Slowed decline in motor, bulbar, and respiratory function.

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption following oral administration unknown. High-fat meal decreases absorption of sodium phenylbutyrate.

Distribution: Unknown.

Protein Binding: Sodium phenylbutyrate: 82%; Taurursodiol: 98%.

Metabolism/Excretion: Sodium phenylbutyrate is metabolized in the liver and kidney. Taurursodiol undergoes enterohepatic recirculation. Sodium phenylbutyrate primarily (80–100%) excreted in urine as a metabolite. Excretion pathway of taurursodiol unknown.

Half-Life: Sodium phenylbutyrate: 0.46 hr; Taurursodiol: 4.3 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
Sodium phenylbutyrate (PO)	unknown	30 min	unknown
Taurursodiol (PO)	unknown	4.5 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Moderate or severe renal impairment;
Moderate or severe hepatic impairment.

Use Cautiously in:

Biliary disorders (↑ risk of diarrhea);
Pancreatic disorders, intestinal malabsorption, or intestinal disorders (may cause ↓ absorption);
HF, renal disease, or hypertension (↑ sodium content);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

GI: ↑salivation, abdominal pain, diarrhea, nausea

Neuro: dizziness, fatigue

Resp: upper respiratory tract infection

Interactions ⬆ ⬇

Drug-drug:

Absorption may be ↓ by bile acid sequestrants, including cholestyramine, colesevelam, and colestipol, as well as aluminum-based antacids; avoid concurrent use.
Bile salt export pump inhibitors, including cyclosporine may ↑ levels and risk of toxicity; avoid concurrent use.
Probenecid may ↑ levels of active metabolite and risk of toxicity; avoid concurrent use.
Histone deacetylase inhibitors, including belinostat, romidepsin, and vorinostat may ↑ risk of toxicity; avoid concurrent use.
OATP1B3 inhibitors may ↑ risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 1 packet once daily for 3 wks, then 1 packet twice daily thereafter.

Availability ⬆ ⬇

Powder for oral suspension: sodium phenylbutyrate 3 g and taurursodiol 1 g/packet

Assessment ⬆ ⬇

Assess symptoms of ALS before starting and periodically during therapy.

Implementation ⬆ ⬇

PO: Administer Relyvrio before a snack or meal. Empty contents of packet in a cup containing 8 oz of room temperature water and stir vigorously. Take orally or administer via feeding tube within 1 hr of preparation. Reconstituted suspension may be stored for up to 1 hr at room temperature. Discard any unused suspension after 1 hr.

Patient/Family Teaching ⬆ ⬇

Instruct patient and caregiver to take Relyvrio as directed. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify their health care professional if they have new or worsening diarrhea.
Inform patient that 2 packets of Relyvrio contain 928 mg sodium. Advise patient to limit sodium intake if they are sensitive to sodium (HF, severe renal insufficiency, or other conditions associated with sodium retention) should limit their sodium intake
Inform patient to avoid aluminum-based antacids during therapy; may interfere with the absorption of Relyvrio.
Advise patient to monitor for diarrhea; notify health care professional if diarrhea becomes severe.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇