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New FDA Drug Approvals - January 2023


sodium phenylbutyrate and taurursodiol

Albrioza (Canadian), Relyvrio

Pharmaceutical company: Amylyx

Pharmacologic classification:Histone deacetylase inhibitor, hydrophilic bile acid

Therapeutic classification:Miscellaneous CNS drug

AVAILABLE FORMS

Oral suspension: 3 g sodium phenylbutyrate and 1 g taurursodiol in single-dose packet

INDICATIONS AND DOSAGES

Amyotrophic lateral sclerosis

Adults: Initially, one packet PO daily for 3 weeks. Then, increase to the maintenance dose of one packet b.i.d.

CONTRAINDICATIONS AND CAUTIONS

  • Avoid use in those with moderate or severe hepatic impairment and abnormal kidney function.
  • Use cautiously in those with disorders that interfere with bile acid circulation, disorders of enterohepatic circulation (biliary infection, active cholecystitis), severe pancreatic disorders (pancreatitis), and intestinal disorders that may alter concentrations of bile acids (ileal resection, regional ileitis).
  • Use cautiously in patient’s sensitive to salt intake such as those with HF, abnormal kidney function, or other conditions associated with sodium retention because of the high sodium content of this drug.
  • Safety and effectiveness in children haven’t been established.
  • Dialyzable drug: Unknown.

PREGNANCY-LACTATION-REPRODUCTION

  • There are no data on the use in pregnant patients.
  • It’s unknown if this drug is present in human milk. The risks and benefits should be considered.

INTERACTIONS

Drug-drug. Aluminum-based antacids: May interfere with taurursodiol absorption. Avoid use together; consider other acid-lowering agents.
Bile acid sequestering agents (cholestyramine, colestipol, colesevelam): May decrease taurursodiol absorption. Avoid use together. Consider alternative cholesterol-lowering agents.
CYP1A2, CYP2B6, CYP3A4 substrates (ramelteon, bupropion, aminophylline): May decrease level of these isoenzymes. Avoid use to together when a small change in substrate plasma level may lead to serious toxicities or loss of efficacy.

CYP2C8 and CYP2B6 substrates (repaglinide): May increase level of these substrates. Avoid use together when a small change in substrate plasma level may lead to serious toxicities or loss of efficacy.

Histone deacetylace (HDAC) inhibitor (phenylbutyrate): May increase risk of adverse effects as this drug contains phenylbutyrate. Avoid use of other HDAC inhibitors, because of additive effects.
Inhibitors of bile acid transporters (cyclosporine): May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. Avoid use together; if concomitant use with strong inhibitor is necessary, use caution and monitor serum transaminases and bilirubin.

OATP1B3 inhibitors (rifampicin, pioglitazone): May increase level of taurursodiol. Avoid use together.
OAT1 substrates (adefovir, tenofovir, statins): May increase levels of OAT1 substrates. Avoid use of together.

P-glycoprotein and BCRP substrates (digoxin, methotrexate, rosuvastatin): May increase levels of these substrates. Avoid use together when a small change in substrate levels may lead to serious toxicities or loss of efficacy with this drug.

Probenecid: May affect kidney excretion of sodium phenylbutyrate metabolites. Avoid use together.
Strong CYP3A4 inducers (phenytoin, rifampin): May decrease taurursodiol level. Monitor use together.

ADVERSE REACTIONS

CNS: Fatigue, dizziness.
EENT: Salivary hypersecretion.

GI: Diarrhea, abdominal pain, nausea.

Respiratory: URI.

Reactions in bold italics are life-threatening.

Released: January 2023

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