Overview
11 DESCRIPTION ATTRUBY contains 356 mg acoramidis equivalent to 400 mg acoramidis HCl. Acoramidis HCl is a transthyretin stabilizer. The chemical name of acoramidis HCl is 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid hydrochloride. The molecular formula is C 15 H 18 FN 2 O 3 Cl, and the molecular weight is 328.77 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Acoramidis is a selective stabilizer of transthyretin (TTR). Acoramidis binds TTR at thyroxine binding sites and slows dissociation of the TTR tetramer into its constituent monomers, the rate-limiting step in amyloidogenesis. 12.2 Pharmacodynamics TTR Stabilization Changes in serum TTR level or in vitro TTR stabilization assays were utilized as pharmacodynamic markers of TTR stabilization. Increases in mean serum TTR levels were observed by Day 28 in ATTR-CM patients treated with ATTRUBY. Near-complete in vitro TTR stabilization was observed as early as Day 28 and through completion of a 30-month study of patients with ATTR-CM (wild-type and variant) treated with the recommended dosage [see Clinical Studies ( 14 )] .
Indications
- 1 INDICATIONS AND USAGE ATTRUBY is indicated for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization. ATTRUBY is a transthyretin stabilizer indicated for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization. ( 1 , 2.1 )
Common Doses
- 712 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of ATTRUBY is 712 mg orally twice daily. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of ATTRUBY is 712 mg orally twice daily (with or without food). Swallow tablets whole; do not cut, crush, or chew.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 ) To report SUSPECTED ADVERSE REACTIONS, contact BridgeBio Pharma Inc. at 1-844-550-2246 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Side Effects
- 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data reflect the exposure of 421 participants with ATTR-CM to ATTRUBY 712 mg (administered as two 356 mg tablets) administered orally twice daily in a randomized, double-blind, placebo-controlled trial of 30 months fixed treatment duration.
Interactions
- 7 DRUG INTERACTIONS UDP-glucuronosyltransferases (UGT) Inducers and Strong CYP3A Inducers Acoramidis is metabolized by UGT enzyme-mediated glucuronidation. Concomitant use of UGT inducers can potentially decrease acoramidis exposure. While acoramidis is not metabolized by CYP3A, strong CYP3A inducers can also induce UGT enzymes. Avoid concomitant use of ATTRUBY with UGT inducers and strong CYP3A inducers. Sensitive Cytochrome P450 2C9 (CYP2C9) substrates Acoramidis inhibits CYP2C9 and may result in an increase in CYP2C9 substrate concentrations when these drugs are co administered.