Acoramidis Hydrochloride (Monograph)

Brand name: Attruby
Drug class: Cardiac Drugs, Miscellaneous

Introduction

Acoramidis hydrochloride is a transthyretin stabilizer.

Uses for Acoramidis Hydrochloride

Acoramidis hydrochloride has the following uses:

Acoramidis hydrochloride 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.

Acoramidis Hydrochloride Dosage and Administration

General

Acoramidis hydrochloride is available in the following dosage form(s) and strength(s):

Tablets: 356 mg of acoramidis

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosage of acoramidis hydrochloride is 712 mg orally twice daily.

Swallow tablets whole; do not cut, crush, or chew.

Cautions for Acoramidis Hydrochloride

Contraindications

None.

Warnings/Precautions

Specific Populations

Pregnancy

Available data with acoramidis use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproductive studies in rats and rabbits, no embryofetal abnormalities were observed at exposures up to 34 times and 13 times the clinical exposure at the maximum recommended human dose, respectively.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Report pregnancies to the BridgeBio reporting line at 1-844-550-2246.

Lactation

There are no available data on the presence of acoramidis in either human or animal milk or the effects of the drug on the breastfed infant or maternal milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for acoramidis and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of acoramidis have not been established in pediatric patients.

Geriatric Use

No dosage adjustment is required for elderly patients (≥65 years). Of the total number of participants randomized in the clinical study (n=632), 97% were 65 years of age and over, with a median age of 78 years.

Common Adverse Effects

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 acoramidis 712 mg (two 356 mg tablets) administered orally twice daily in a randomized, double-blind, placebo-controlled trial of 30 months fixed treatment duration. The median duration of exposure to acoramidis in the safety population was 29 months. There was a higher frequency of GI adverse reactions such as diarrhea (11.6% versus 7.6%) and upper abdominal pain (5.5% versus 1.4%) in the acoramidis versus placebo group, respectively. The majority of these GI adverse reactions were categorized as mild and resolved without drug discontinuation.

A similar proportion of acoramidis-treated and placebo-treated participants discontinued study drug because of an adverse event (9.3% and 8.5%, respectively).

Initiation of acoramidis causes an increase in serum creatinine and decrease in eGFR which generally occurs within 4 weeks of starting therapy and stabilizes. In a trial of adults with ATTR-CM, a mean increase in serum creatinine of 0.2 and 0.0 mg/dL and a mean decrease in eGFR of 8.2 and 0.7 mL/min/1.73 m² was observed in the acoramidis and placebo groups, respectively, at Day 28. The changes in serum creatinine and eGFR were reversible after treatment discontinuation.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

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.

Advice to Patients

Advise patients to read the FDA-approved patient labeling (Patient Information).
Advise patients who are exposed to acoramidis during pregnancy to contact the BridgeBio reporting line at 1-844-550-2246. Advise patients to inform their healthcare provider of a known or suspected pregnancy.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.