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Exondys 51

Generic Name: Eteplirsen
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


Antisense oligonucleotide that binds to exon 51 of dystrophin premessenger RNA (pre-mRNA).1 3 5 17

Uses for Exondys 51

Duchenne Muscular Dystrophy

Management of Duchenne muscular dystrophy 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).1 2 3 4

Accelerated approval based on increased dystrophin production (a surrogate marker of response).1 15 Continued approval may be contingent on verification of clinical benefit (e.g., improvement in motor function) in confirmatory studies.1

Approximately 13–14% of patients with Duchenne muscular dystrophy have specific mutations of the dystrophin gene amenable to exon 51 skipping.3 5 6 9 11

Exondys 51 Dosage and Administration


Administer by IV infusion.1

IV Administration

For solution compatibility information, see Compatibility under Stability.

Consider pretreatment of the infusion site with topical anesthetic cream.1

Do not mix or administer simultaneously with other drugs.1 Flush IV line with 0.9% sodium chloride injection before and after infusion.1

If a dose is missed, administer missed dose as soon as possible.1

Vials are for single use only; discard unused portions since the concentrate contains no preservatives.1


Must dilute injection concentrate prior to IV infusion.1

Determine number of vials needed based on patient’s body weight and recommended dose.1 Allow vials to warm to room temperature.1 Mix contents by gently inverting vials 2–3 times; do not shake.1

Withdraw appropriate volume of injection concentrate 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.1

Administer immediately after dilution, completing administration within 4 hours.1 If immediate administration not possible, may store diluted solution at 2–8°C for up to 24 hours.1 Do not freeze.1

Rate of Administration

Infuse over 35–60 minutes.1


Pediatric Patients

Duchenne Muscular Dystrophy

30 mg/kg once weekly.1


Duchenne Muscular Dystrophy

30 mg/kg once weekly.1

Special Populations

No special population dosage recommendations at this time.1

Cautions for Exondys 51


  • None.1


Warnings and Precautions

Manufacturer states there are no warnings or precautions associated with eteplirsen therapy.1

Specific Populations


Not studied in female patients.1 Not known whether eteplirsen is associated with risk if used during pregnancy.1


Not studied in female patients.1 Not known whether eteplirsen is distributed into milk, affects milk production, or affects the breast-fed infant.1

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.1

Pediatric Use

Eteplirsen is labeled for use in certain pediatric patients with Duchenne muscular dystrophy.1 (See Uses.)

In juvenile animal studies, renal tubular necrosis with associated clinical pathology changes and changes in bone density observed.1 No effects on male reproductive system, neurobehavioral development, or immune function.1

Geriatric Use

No experience in geriatric patients; Duchenne muscular dystrophy is generally a disease of children and young adults.1

Hepatic Impairment

Not studied in patients with hepatic impairment.1

Renal Impairment

Not studied in patients with renal impairment.1

Common Adverse Effects

Balance disorder,1 vomiting,1 contact dermatitis.1

Interactions for Exondys 51

In vitro data indicate low potential for drug interactions.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Does not appear to be metabolized by hepatic microsomal enzymes.1

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

Does not induce CYP2B6 or 3A4.1 Induces CYP1A2, but to a substantially lesser degree than the prototype CYP1A2 inducer (i.e., omeprazole).1

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).1

Exondys 51 Pharmacokinetics



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.1

Exhibits dose proportional, linear pharmacokinetics; no substantial drug accumulation following weekly infusion.1 3



Not known whether distributed into human milk.1

Plasma Protein Binding




Does not appear to be metabolized by hepatic microsomal enzymes.1

Elimination Route

Renal clearance accounts for approximately two-thirds of the administered dose within 24 hours of IV infusion.1 3


3–4 hours.1 3




Injection concentrate

2–8°C; do not freeze.1 Protect from light; store in original carton until use.1

Diluted solution: may store at 2–8°C for up to 24 hours; do not freeze.1


For information on systemic interactions resulting from concomitant use, see Interactions.


Solution Compatibility


Sodium chloride 0.9%1


  • Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass.1 3 4 17

  • In patients with Duchenne muscular dystrophy, 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 55.4 5 6

  • 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.1 3 4 5

Advice to Patients

  • 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.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


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.



Dosage Forms


Brand Names



For injection concentrate, for IV infusion

50 mg/mL

Exondys 51

Sarepta Therapeutics

AHFS DI Essentials. © Copyright 2018, Selected Revisions January 29, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Sarepta Therapeutics, Inc. Exondys 51 (eteplirsen) concentrate for injection prescribing information. Cambridge, MA; 2016 Sep.

2. Food and Drug Administration. Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2017 Jan 18.

3. Mendell JR, Rodino-Klapac LR, Sahenk Z et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013; 74:637-47. [PubMed 23907995]

4. Mendell JR, Goemans N, Lowes LP et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016; 79:257-71. [PubMed 26573217]

5. Kole R, Krieg AM. Exon skipping therapy for Duchenne muscular dystrophy. Adv Drug Deliv Rev. 2015; 87:104-7. [PubMed 25980936]

6. Guncay A, Yokota T. Antisense oligonucleotide drugs for Duchenne muscular dystrophy: how far have we come and what does the future hold?. Future Med Chem. 2015; 7:1631-5. [PubMed 26423833]

7. Gloss D, Moxley RT, Ashwal S et al. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016; 86:465-72. [PubMed 26833937]

8. Matthews E, Brassington R, Kuntzer T et al. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016; :CD003725. [PubMed 27149418]

9. Shieh PB. Duchenne muscular dystrophy: clinical trials and emerging tribulations. Curr Opin Neurol. 2015; 28:542-6. [PubMed 26280938]

10. Miceli MC, Nelson SF et al. Letter to Billy Dunn, MD, Director, Division of Neurology Products, Office of Drug Evaluation I, Center for Drug Evaluation and Research. Letter. 2016 Feb 24. Accessed 2017 Jan 19.

11. Miceli MC, Nelson SF. The case for eteplirsen: Paving the way for precision medicine. Mol Genet Metab. 2016; 118:70-1. [PubMed 27102846]

12. Kesselheim AS, Avorn J. Approving a Problematic Muscular Dystrophy Drug: Implications for FDA Policy. JAMA. 2016; 316:2357-2358. [PubMed 27775756]

13. Food and Drug Administration. Briefing document from the peripheral and central nervous system drugs advisory committee meeting. Jan 22, 2016. NDA 206488 eteplirsen. From FDA website.

14. Sarepta Therapeutics, Inc. Peripheral and central nervous system drugs advisory committee eteplirsen briefing document addendum. Jan 22, 2016. NDA 206488. From FDA website.

15. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 206488Orig1s000: Summary review. From FDA website.

16. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 206488Orig1s000: Medical Review. From FDA website.

17. Cirak S, Arechavala-Gomeza V, Guglieri M et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet. 2011; 378:595-605. [PubMed 21784508]

18. Reinig AM, Mirzaei S, Berlau DJ. Advances in the Treatment of Duchenne Muscular Dystrophy: New and Emerging Pharmacotherapies. Pharmacotherapy. 2017; 37:492-499. [PubMed 28152217]

19. Irwin AN, Herink MC. Eteplirsen for the Treatment of Duchenne Muscular Dystrophy: Quality of Evidence Concerns-an Alternative Viewpoint. Pharmacotherapy. 2017; [PubMed 28741800]

20. Confirmatory study of eteplirsen in DMD patients (PROMOVI). From registry. Accessed 2017 Sept 15.