Eplontersen Sodium (Monograph)
Brand name: Wainua
Drug class:
Introduction
Antisense oligonucleotide that targets transthyretin messenger RNA (mRNA); a transthyretin (TTR) silencer.
Uses for Eplontersen Sodium
Hereditary Transthyretin-mediated Amyloidosis
Treatment of polyneuropathy in patients with hereditary transthyretin-mediated amyloidosis (designated an orphan drug by FDA for this use).
The American College of Cardiology (ACC) and American Heart Association (AHA) state that TTR silencers may be considered in patients with ATTRv polyneuropathy.
Eplontersen Sodium Dosage and Administration
General
Patient Monitoring
-
Monitor for ocular symptoms of vitamin A deficiency (e.g., night blindness, dry eyes).
Other General Considerations
-
Supplement vitamin A at the recommended daily allowance in patients taking eplontersen.
Administration
Sub-Q Administration
Administer via sub-Q injection. Patients and/or caregivers may self-administer after receiving appropriate training.
Available as single-use autoinjectors. Remove autoinjector from the refrigerator 30 minutes prior to administration and allow to reach room temperature; do not use other warming methods (e.g., microwave, hot water).
Inject sub-Q into the abdomen or upper thigh region; back of the upper arm may also be used if administered by a caregiver or healthcare provider. Avoid injecting into areas where the skin is tender, bruised, red, hard, damaged, or scarred.
If a dose is missed, administer the missed dose as soon as possible. Resume dosing at monthly intervals from the date of the most recently administered dose.
Dosage
Dosage of eplontersen sodium expressed in terms of eplontersen.
Adults
Hereditary Transthyretin-mediated Amyloidosis
Sub-Q
45 mg once monthly.
Special Populations
Hepatic Impairment
Mild hepatic impairment: No dosage adjustment necessary.
Not studied in patients with moderate or severe hepatic impairment; manufacturer makes no specific dosage recommendations for these patients.
Renal Impairment
Mild to moderate renal impairment (eGFR 30 to <90 mL/minute per 1.73 m2): No dosage adjustment necessary.
Not studied in patients with severe renal impairment or end-stage renal disease; manufacturer makes no specific dosage recommendations for these patients.
Geriatric Patients
No dosage adjustment necessary.
Cautions for Eplontersen Sodium
Contraindications
-
None.
Warnings/Precautions
Reduced Serum Vitamin A Concentrations
Eplontersen reduces serum vitamin A concentrations.
Supplement with the recommended daily allowance of vitamin A during eplontersen therapy. Manufacturer advises against administering vitamin A dosages exceeding the recommended daily allowance in an attempt to achieve normal serum vitamin A concentrations.
Refer patients who develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness, dry eyes) to an ophthalmologist.
Immunogenicity
Treatment-emergent anti-eplontersen antibodies reported. Not found to affect pharmacokinetics, pharmacodynamics, efficacy, or safety; however, data are insufficient to make any definitive conclusions.
Specific Populations
Pregnancy
No available data on eplontersen use in pregnant women to inform a drug-associated risk of adverse developmental outcomes.
No adverse developmental effects noted in animal studies.
Eplontersen treatment decreases vitamin A levels; vitamin A supplementation advised. Vitamin A is essential for normal embryofetal development, but excessive vitamin A levels are associated with adverse developmental outcomes. Effect of vitamin A supplementation on the fetus in the setting of eplontersen therapy unknown.
Lactation
Not known whether eplontersen distributes into human milk, affects the breast-fed infant, or affects milk production. Consider developmental and health benefits of breast-feeding and the woman's clinical need for the drug along with any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
Pediatric Use
Safety and efficacy not established in pediatric patients.
Geriatric Use
No overall differences in efficacy or safety observed relative to younger adults; however, greater sensitivity of some older patients cannot be ruled out.
Hepatic Impairment
Not studied in patients with moderate or severe hepatic impairment or in patients who have received a prior liver transplant. Mild hepatic impairment not expected to have a clinically meaningful effect.
Renal Impairment
Not studied in patients with severe renal impairment or end-stage renal disease. Mild or moderate renal impairment (eGFR ≥30 to <90 mL/minute per 1.73 m2) not expected to have a clinically meaningful effect.
Common Adverse Effects
Comme adverse effects (≥9%): Decreased vitamin A, vomiting.
Drug Interactions
No formal drug interaction studies conducted. Not a substrate, inhibitor, or inducer of major CYP isoenzymes. Not a substrate or inhibitor of major transporters, and does not interact with highly plasma protein bound drugs.
Eplontersen Sodium Pharmacokinetics
Absorption
Bioavailability
Time to peak plasma concentration: 2 hours.
Accumulation does not occur with repeated dosing.
Following sub-Q administration, systemic exposure increases in a slightly greater than dose-proportional manner over the dose range of 45–120 mg.
Distribution
Extent
Not known whether distributed into human milk.
Plasma Protein Binding
>98%.
Elimination
Metabolism
Metabolized by endo- and exonucleases in the liver to short oligonucleotide fragments.
Elimination Route
<1% excreted unchanged in urine.
Half-life
Mean terminal half-life is approximately 3 weeks.
Special Populations
Mild hepatic impairment (total bilirubin concentration ≤1 times the ULN and AST >1 times the ULN, or total bilirubin concentration >1 to 1.5 times the ULN and any AST): No effect on systemic exposure.
Mild or moderate renal impairment (eGFR ≥30 to <90 mL/minute per 1.73 m2): No effect on systemic exposure.
No clinically meaningful differences in pharmacokinetics observed based on age, body weight, sex, race, or Val30Met variant status.
Stability
Storage
Sub-Q
Autoinjector
2–8ºC. Store in original carton to protect from light. Do not freeze or expose to heat.
If necessary, may store prefilled syringes at room temperature (up to 30ºC) in the original carton for up to 6 weeks. Discard if not used within 6 weeks.
Actions
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Antisense oligonucleotide conjugated to a triantennary N-acetyl galactosamine ligand (GalNAc).
-
Targets and binds to transthyretin mRNA, causing degradation of both mutant and wild-type transthretin mRNA and a resultant reduction of serum transthyretin protein and transthyretin protein deposits in tissues.
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Following administration for 35 weeks, mean serum transthyretin concentrations were reduced by 81% from baseline.
Advice to Patients
-
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
-
Instruct patients to take the recommended daily allowance of vitamin A. Advise patients to notify their clinician if they experience ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness, dry eyes), and refer patients who develop such symptoms to an ophthalmologist.
-
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
-
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Advise patients of the potential risk to the fetus, including that treatment leads to a decrease in serum vitamin A levels.
-
Advise patients of other important precautionary information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
Injection, for subcutaneous use |
45 mg (of eplontersen)/0.8 mL |
Wainua (available as prefilled autoinjectors) |
AstraZeneca |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions October 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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