Attruby (acoramidis HCl)
Amyloidosis Agents - Protein Stabilizers Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Acoramidis hydrocholoride is a transthyretin (TTR) stabilizer.
Acoramidis selectively stabilizes transthyretin (TTR) by binding to thyroxine-binding sites, reducing tetramer dissociation, which is the rate-limiting step in amyloid formation. Increased serum TTR levels and near-complete in vitro stabilization were observed by day 28 and maintained through 30 months in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
Acoramidis reduces free thyroxine serum levels without affecting thyroid-stimulating hormone (TSH), likely due to reduced binding or displacement from TTR. In a clinical study, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and troponin I increases at 30 months were lower in acoramidis-treated patients compared to placebo, with NT-proBNP rising at approximately half the rate observed with placebo. At 1.2 times peak plasma concentration, acoramidis does not cause clinically significant QTc prolongation.
Systemic exposure of acoramidis increases in a less than dose-proportional manner, with AUC rising by only 130% over the dosage range of 89-712 mg twice daily. Steady-state concentrations are reached within 4 days. Peak plasma concentrations of acoramidis occur about 1 hour after oral administration, and pharmacokinetics remain unaffected by a high-fat meal.
Plasma protein binding is 96%, primarily to transthyretin. Acoramidis has an effective half-life of approximately 6 hours and undergoes metabolism through glucuronidation via uridine diphosphate-glucuronosyltransferase (UGT) 1A9, UGT1A1, and UGT2B7, forming a major metabolite, acoramidis-beta-D-glucuronide (Acoramidis-AG), which accounts for 8% of total circulating drug. Acoramidis-AG is about one-third as pharmacologically active as acoramidis and has low covalent binding potential.
Following a single oral 712 mg radiolabeled dose of acoramidis, 32% is recovered in feces (15% unchanged), 68% is recovered in urine (<10% unchanged).
USES: This medication is used to treat a certain type of heart failure (transthyretin-mediated amyloidosis). It is used to help prevent the heart failure from getting worse and needing treatment in a hospital. Acoramidis works by slowing the buildup of a certain protein (amyloid fibrils) that causes heart problems.
Generic name: acoramidis HCl
Drug class: Amyloidosis Agents - Protein Stabilizers
Therapeutic class: Endocrine
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Attruby
Indications
The following indications are listed for Attruby:
- Transthyretin-Related Amyloid Cardiomyopathy
Also known as: Cardiomyopathy Due To Attr, Transthyretin Amyloid Cardiomyopathy.
Dosing
Acoramidis is commercially available as the hydrochloride salt; dosage is expressed in terms of acoramidis.
Administer acoramidis orally with or without food.
Swallow the tablets whole; do not cut, crush, or chew.
Store acoramidis at 20-25degreesC with permitted excursions between 15-30degreesC. Keep in the original blister card until use to protect from moisture.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Attruby 356 Mg Tablet | Maintenance | Take 2 tablets (712 mg) by oral route 2 times per day. |
No dosing information is available for this tab.
Drug interactions
Acoramidis is a substrate of uridine diphosphate-glucuronosyltransferase (UGT) 1A9, UGT1A1, and UGT2B7.
Acoramidis is a time-dependent inhibitor of CYP2C9 and does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2D6, CYP3A4, or CYP3A5. Acoramidis does not induce CYP1A2, CYP2B6, or CYP3A4.
Acoramidis is a substrate for organic anion transporter 1 (OAT1) and breast cancer resistance protein (BCRP). Acoramidis inhibits OAT1 and OAT3 but does not inhibit multidrug and toxin extrusion protein 1 (MATE1), organic cation transporter 1 (OCT1), OCT2, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, MATE2-K, BCRP, P-glycoprotein (P-gp), or bile salt export pump (BSEP).
There are no contraindication interactions for this drug.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Acoramidis/Ugt And Selected Cyp3a4 Inducers
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: UGT and selected CYP3A4 inducers may induce the metabolism of acoramidis, which is glucuronidated by UGT1A9, UGT1A1, and UGT2B7.(1)
CLINICAL EFFECTS: Concurrent use of UGT and selected CYP3A4 inducers may result in decreased levels and effectiveness of acoramidis.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of acoramidis states to avoid concomitant use of acoramidis with UGT inducers and strong CYP3A inducers.(1)
DISCUSSION: UGT and selected CYP3A4 inducers linked to this monograph include: carbamazepine, efavirenz, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and ritonavir.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
- No disease contraindications
Adverse reactions
In a clinical trial, adverse effects reported more often in patients receiving acoramidis than placebo were diarrhea and upper abdominal pain.
There are no severe adverse reactions for this drug.
More Frequent
- Diarrhea
Less Frequent
- Upper abdominal pain
Precautions
No enhanced messaging available.
The safety and efficacy in pediatric patients have not been studied.
Data on acoramidis use in pregnancy are insufficient to assess risks of birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal studies, no embryofetal abnormalities were observed at exposures up to 34 times the human dose in rats and 13 times the human dose in rabbits.
Report pregnancies to the BridgeBio reporting line at 1-844-550-2246.
Data on acoramidis in human milk or whether the drug has any effects on a breastfed child or on milk production are unavailable. The benefits of breastfeeding should be weighed against the mother's need for acoramidis and potential risks to the infant.
The manufacturer states that no dosage adjustment is needed for patients >=65 years of age.
No dosage adjustment is needed for patients >=65 years of age. In the principal clinical study, 97% of patients were >=65 years of age, with a median of 78 years of age.
ICD codes
| Code | Type | Description |
|---|---|---|
| Transthyretin-related amyloid cardiomyopathy | ||
| E85.4 | ICD10CM | Organ-limited amyloidosis |
| E85.82 | ICD10CM | Wild-type transthyretin-related (ATTr) amyloidosis |
| I43 | ICD10CM | Cardiomyopathy in diseases classified elsewhere |
ICD code information from First Databank (FDB).
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.