Eplontersen Sodium (Monograph)

Brand name: Wainua
Drug class: Antisense Oligonucleotides

Introduction

Eplontersen sodium is an antisense oligonucleotide that targets transthyretin (TTR) mRNA.

Uses for Eplontersen Sodium

Eplontersen has the following uses:

Eplontersen is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Eplontersen Sodium Dosage and Administration

General

Eplontersen sodium is available in the following dosage form(s) and strength(s):

Injection: 45 mg (of eplontersen)/0.8 mL in a single-dose autoinjector.

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 eplontersen is 45 mg administered by subcutaneous injection once monthly.

• Administer eplontersen into the abdomen or upper thigh region; the back of the upper arm can be used if a healthcare provider or caregiver administers the injection.

Related/similar drugs

Vyndamax, tafamidis, eplontersen, Wainua, Amvuttra, Vyndaqel, Onpattro

Cautions for Eplontersen Sodium

Contraindications

None.

Warnings/Precautions

Reduced Serum Vitamin A Levels and Recommended Supplementation

Eplontersen treatment leads to a decrease in serum vitamin A levels.

Supplementation at the recommended daily allowance of vitamin A is advised for patients taking eplontersen. Higher doses than the recommended daily allowance of vitamin A should not be given to try to achieve normal serum vitamin A levels during treatment with eplontersen, as serum vitamin A levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness, dry eyes).

Specific Populations

Pregnancy

There are no available data on eplontersen use in pregnant women to inform drug-associated risk of adverse developmental outcomes. Eplontersen treatment leads to a decrease in serum vitamin A levels, and vitamin A supplementation is advised for patients taking eplontersen. Vitamin A is essential for normal embryofetal development; however, excessive levels of vitamin A are associated with adverse developmental effects. The effect of vitamin A supplementation on the fetus in the setting of a reduction in maternal serum TTR caused by eplontersen administration is unknown.

No adverse developmental effects were observed when eplontersen or a mouse-specific surrogate was administered to mice prior to mating and continuing throughout organogenesis.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Lactation

There is no information regarding the presence of eplontersen in human milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for eplontersen and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No dose adjustment is required in patients ≥65 years of age. In the principal efficacy study, 44 (31%) patients were 65 to 74 years of age, and 8 (5.6%) patients were ≥75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR]≥30 to <90 mL/min/1.73 m².

Eplontersen has not been studied in patients with severe renal impairment or end-stage renal disease.

Hepatic Impairment

No dose adjustment is necessary in patients with mild hepatic impairment (total bilirubin ≤1 x ULN and AST >1 x ULN, or total bilirubin >1.0 to 1.5 x ULN and any AST).

Eplontersen has not been studied in patients with moderate or severe hepatic impairment.

Common Adverse Effects

Most common adverse reactions (that occurred in at least 9% of patients treated with eplontersen) were decreased vitamin A and vomiting.

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

Eplontersen is an antisense oligonucleotide covalently linked to a ligand containing three N-acetyl galactosamine (GalNAc) residues. The drug causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

• Inform patients that eplontersen treatment leads to a decrease in vitamin A levels measured in the serum. Instruct patients to take the recommended daily allowance of vitamin A. Advise patients to contact their healthcare provider if they experience ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness, dry eyes) and refer them to an ophthalmologist if they develop these symptoms.

• Instruct patients that if they are pregnant or plan to become pregnant while taking eplontersen they should inform their healthcare provider. Advise patients of the potential risk to the fetus, including that eplontersen treatment leads to a decrease in serum vitamin A levels.

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.

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