Eteplirsen (Monograph)

Brand name: Exondys 51
Drug class: Antisense Oligonucleotides
Chemical name: 5′-[P-[4-[[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]carbonyl]-1-piperazinyl]-N,N-dimethylphosphonamidate] [P-deoxy-P-(dimethylamino)](2′,3′-dideoxy-2′,3′-imino-2′,3′-seco)(2′a→ 5′)(C-m5U- C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G) RNA
Molecular formula: C₃₆₄H₅₆₉N₁₇₇O₁₂₂P₃₀
CAS number: 1173755-55-9

Medically reviewed by Drugs.com on Apr 16, 2025. Written by ASHP.

Introduction

Antisense oligonucleotide that binds to exon 51 of dystrophin premessenger RNA (pre-mRNA).

Uses for Eteplirsen

Duchenne Muscular Dystrophy

Management of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the dystrophin gene that is amenable to skipping of exon 51 (designated an orphan drug by FDA for use in this condition).

Accelerated approval based on increased dystrophin production (a surrogate marker of response). Continued approval may be contingent on verification of clinical benefit (e.g., improvement in motor function) in confirmatory studies.

Approximately 13–14% of patients with DMD have specific mutations of the dystrophin gene amenable to exon 51 skipping.

Eteplirsen Dosage and Administration

Administration

Administer by IV infusion. Use an inline 0.2-µm filter.

IV Administration

For solution compatibility information, see Compatibility under Stability.

Consider pretreatment of the infusion site with topical anesthetic cream.

Do not mix or administer simultaneously with other drugs. Flush IV line with 0.9% sodium chloride injection before and after infusion.

If a dose is missed, administer missed dose as soon as possible.

Vials are for single use only; discard unused portions since the concentrate contains no preservatives.

Dilution

Must dilute injection concentrate prior to IV infusion.

Visually inspect vials. The injection concentrate should be a clear to slightly opalescent and colorless solution that may contain trace amounts small, white to off-white amorphous particles.

Determine number of vials needed based on patient’s body weight and recommended dose. Allow vials to warm to room temperature. Mix contents by gently inverting vials 2–3 times; do not shake.

Withdraw appropriate volume of injection concentrate from appropriate number of vials using a syringe with a 21-gauge or smaller noncoring needle and dilute with 0.9% sodium chloride injection to a total volume of 100–150 mL.

Visually inspect diluted solution; do not use if it is cloudy, discolored, or contains extraneous particulate matter other than trace amounts small, white to off-white amorphous particles.

Administer immediately after dilution, completing administration within 4 hours. If immediate administration not possible, may store diluted solution at 2–8°C for up to 24 hours. Do not freeze.

Rate of Administration

Infuse IV over 35–60 minutes. If hypersensitivity reaction occurs, consider slowing infusion or interrupting therapy. (See Sensitivity Reactions under Cautions.)

Dosage

Pediatric Patients

Duchenne Muscular Dystrophy

IV

30 mg/kg once weekly.

Adults

Duchenne Muscular Dystrophy

IV

30 mg/kg once weekly.

Special Populations

No special population dosage recommendations at this time.

Cautions for Eteplirsen

Contraindications

None.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions (e.g., rash, urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, hypotension) reported.

If hypersensitivity reaction occurs, initiate appropriate medical treatment and consider slowing the eteplirsen IV infusion or interrupting therapy.

Specific Populations

Pregnancy

Not studied in female patients. Not known whether eteplirsen is associated with risk if used during pregnancy.

Lactation

Not studied in female patients. Not known whether eteplirsen is distributed into milk, affects milk production, or affects the breast-fed infant.

Consider known benefits of breast-feeding along with mother's clinical need for eteplirsen and any potential adverse effects of the drug or disease on the infant.

Pediatric Use

Eteplirsen is labeled for use in certain pediatric patients with DMD. (See Uses.)

In juvenile animal studies, renal tubular necrosis with associated clinical pathology changes and changes in bone density observed. No effects on male reproductive system, neurobehavioral development, or immune function.

Geriatric Use

No experience in geriatric patients; DMD is generally a disease of children and young adults.

Hepatic Impairment

Not studied in patients with hepatic impairment.

Renal Impairment

Not studied in patients with renal impairment.

Common Adverse Effects

Balance disorder, vomiting, contact dermatitis.

Drug Interactions

In vitro data indicate low potential for drug interactions.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Does not appear to be metabolized by hepatic microsomal enzymes.

Does not substantially inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5 in vitro.

Does not induce CYP2B6 or 3A4. Induces CYP1A2, but to a substantially lesser degree than the prototype CYP1A2 inducer (i.e., omeprazole).

Drugs Affecting or Affected by Membrane Transporters

Not a substrate or inhibitor of organic anion transporter (OAT) 1 or 3, organic cation transporter (OCT) 1 or 2, organic anion transporting protein (OATP) 1B1 or 1B3, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein (MRP) 2, or bile salt export pump (BSEP).

Eteplirsen Pharmacokinetics

Absorption

Bioavailability

Following single or multiple IV infusions at doses of 0.5 to 50 mg/kg per week, peak plasma concentrations observed near the end of infusion at 1.1–1.2 hours.

Exhibits dose proportional, linear pharmacokinetics; no substantial drug accumulation following weekly infusion.

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

6–17%.

Elimination

Metabolism

Does not appear to be metabolized by hepatic microsomal enzymes.

Elimination Route

Renal clearance accounts for approximately two-thirds of the administered dose within 24 hours of IV infusion.

Half-life

3–4 hours.

Stability

Storage

Parenteral

Injection concentrate

2–8°C; do not freeze. Protect from light; store in original carton until use.

Diluted solution: May store at 2–8°C for up to 24 hours; do not freeze.

Compatibility

Parenteral

Solution Compatibility

Compatible
Sodium chloride 0.9%

Actions

Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass.
In patients with DMD, frameshift mutations in the dystrophin gene disrupt the translational reading frame, resulting in the production of a nonfunctional dystrophin protein; approximately 63% of these mutations occur between exons 45 and 55.
Eteplirsen selectively binds to and promotes exclusion of exon 51 in dystrophin pre-mRNA, restoring the mRNA reading frame and producing an internally truncated, yet partially functional, form of dystrophin similar to that produced in Becker muscular dystrophy (a less severe type of muscular dystrophy).

Advice to Patients

Risk of hypersensitivity. Advise patients and/or their caregivers to seek immediate medical care if they experience signs or symptoms of a hypersensitivity reaction (e.g., rash, urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, hypotension).
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

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.