Dosing and uses of Exondys 51 (eteplirsen)
Adult dosage forms and strengths
IV solution
- 50mg/mL (as 100mg/2mL or 500mg/10mL single-dose vials)
Duchenne Muscular Dystrophy
Indicated for Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping
30 mg/kg IV once weekly
Also see Administration
Dosing Considerations
Approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients
Clinical benefit has not been established
Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials
Pediatric dosage forms and strengths
IV solution
- 50mg/mL (as 100mg/2mL or 500mg/10mL single-dose vials)
Duchenne Muscular Dystrophy
Indicated for Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping
30 mg/kg IV once weekly
Also see Administration
Dosing Considerations
Approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients
Clinical benefit has not been established
Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials
Exondys 51 (eteplirsen) adverse (side) effects
>10%
Balance disorder (38%)
Vomiting (38%)
Contact dermatitis (25%)
Confusion (>10%)
Frequency not defined
Transient erythema
Facial flushing
Elevated temperature on days of infusion
Warnings
Contraindications
None
Cautions
Approved under accelerated approval; clinical benefit has not been established
Pregnancy
Pregnancy
There are no human data available to assess the use during pregnancy
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Exondys 51 (eteplirsen)
Mechanism of action
Morpholino antisense oligonucleotide 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
The underlying cause of Duchenne muscular dystrophy (DMD) is a mutation or error in the gene for dystrophin, an essential protein involved in muscle fiber function
Absorption
Peak plasma time: 1.1-1.2 hr (near end of infusion across dose range of 0.5-50 mg/kg/wk)
Distribution
Protein bound: 6-17% (in vitro data)
Vd: 600 mL/kg
Metabolism
Does not appear to be metabolized by hepatic microsomes of any species tested, including humans
Elimination
Half-life: 3-4 hr
Total clearance: 339 mL/hr/kg (at 12 week of therapy with 30 mg/kg/wk)
Excretion: ~66% urine within 24 hr of IV administration
Pharmacogenomics
Indicated processing in patients with genetic mutations that are amenable to exon 51 skipping
Administration
IV Preparation
Allow vials to warm to room temperature
Mix vial contents by gently inverting 2-3 times; DO NOT SHAKe
Inspected visually for particulate matter and discoloration prior to administration; should appear as a clear, colorless solution that may have some opalescence
Do not use if solution is discolored or particulate matter is present
With a syringe fitted with a ≤21-ga noncoring needle, withdraw the calculated volume from the appropriate number of vials
Dilute withdrawn dose in 0.9% NaCl to a total volume of 100-150 mL; again, visually inspect for particulates
IV Administration
Consider applying a topical anesthetic cream to infusion site prior to administration
Flush IV access line with 0.9% NaCl before and after infusion
Infuse IV over 35-60 min
Do not mix with other medications or infuse other medications concomitantly via the same IV access
Storage
Unopened vials
- Refrigerate at 2-8°C (36-46°F)
- Do not freeze
- Protect from light and store in original carton until ready for use
Diluted drug
- Contains no preservatives; should be administered immediately after dilution
- Complete infusion of diluted solution within 4 hr of dilution
- If unable to administer immediately, diluted solution may be refrigerated for up to 24 hr at 2-8°C (36-46°F)
- Do not freeze
- Discard unused solution
