Class: Other Miscellaneous Therapeutic Agents
Brands: Exondys 51
Eteplirsen is an antisense oligonucleotide designed to bind to exon 51 of dystrophin pre-mRNA.1
Uses for Eteplirsen
Eteplirsen has the following uses:
Eteplirsen is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This indication is approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with eteplirsen. A clinical benefit of eteplirsen has not been established. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.1
Eteplirsen Dosage and Administration
Eteplirsen is available in the following dosage form(s) and strength(s):
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
30 milligrams per kilogram of body weight once weekly.1
Administer as an intravenous infusion over 35 to 60 minutes.1
Dilution required prior to administration.1
Cautions for Eteplirsen
There are no human or animal data available to assess the use of eteplirsen during pregnancy. In the U.S. general population, major birth defects occur in 2 to 4% and miscarriage occurs in 15 to 20% of clinically recognized pregnancies. 1
There are no human or animal data to assess the effect of eteplirsen on milk production, the presence of eteplirsen in milk, or the effects of eteplirsen on the breastfed infant. 1
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for eteplirsen and any potential adverse effects on the breastfed infant from eteplirsen or from the underlying maternal condition. 1
Eteplirsen is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping, including pediatric patients. 1
Intravenous administration of eteplirsen (0, 100, 300, or 900 mg/kg) to juvenile male rats once weekly for 10 weeks beginning on postnatal day 14 resulted in renal tubular necrosis at the highest dose tested and decreased bone densitometry parameters (mineral density, mineral content, area) at all doses. The kidney findings were associated with clinical pathology changes (increased serum urea nitrogen and creatinine, decreased urine creatinine clearance). No effects were observed on the male reproductive system, neurobehavioral development, or immune function. An overall no-effect dose was not identified. Plasma eteplirsen exposure (AUC) at the lowest dose tested (100 mg/kg) was similar to that in humans at the recommended human dose (30 mg/kg). 1
DMD is largely a disease of children and young adults; therefore, there is no geriatric experience with eteplirsen.1
Patients with Renal or Hepatic Impairment
Eteplirsen has not been studied in patients with renal or hepatic impairment.1
Common Adverse Effects
The most common adverse reactions (incidence ≥35% and higher than placebo) were balance disorder and vomiting.1
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.
Mechanism of Action
Eteplirsen is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein, which was evaluated in clinical studies. 1
Advice to Patients
Advise patients of important precautionary information.1
AHFS First Release. 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.
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.
Sarepta Therapeutics Inc.
AHFS Drug Information. © Copyright 2016, Selected Revisions September 27, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Sarepta Therapeutics, Inc.. Exondys 51 (eteplirsen) INTRAVENOUS prescribing information. 2016 Sep.