Eteplirsen- Exondys 51-@- (Sep 2016)- Musculo-skeletal
Drug Name:Eteplirsen- Exondys 51-@- (Sep 2016)- Musculo-skeletal
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
17. Exondys Eteplirsen 9/19/2016
To treat patients with Duschenne muscular dystrophy
Press Release
Approved by FDA on 9/19/2016 (Ref- FDA approved List- 2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use EXONDYS
safely and effectively. See full prescribing information for EXONDYS
.
EXONDYS (eteplirsen) injection, for intravenous use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
EXONDYS 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 51skipping.
This indication is approved under accelerated approval based on an
increase in dystrophin in skeletal muscle observed in some patients
treated with EXONDYS.
A clinical benefit of EXONDYS has not been established.
Continued approval for this indication may be contingent upon verification
of a clinical benefit in confirmatory trials.
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reactions (incidence .35% and higher than
placebo) were balance disorder and vomiting
Contra-Indications:
CONTRAINDICATIONS
None
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
EXONDYS 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 51skipping.
This indication is approved under accelerated approval based on an
increase in dystrophin in skeletal muscle observed in some patients
treated with EXONDYS.
A clinical benefit of EXONDYS has not been established.
Continued approval for this indication may be contingent upon verification
of a clinical benefit in confirmatory trials.
DOSAGE AND ADMINISTRATION
30 milligrams per kilogram of body weight once weekly
Administer as an intravenous infusion over 35 to 60 minutes
.Dilution required prior to administration
DOSAGE FORMS AND STRENGTHS
Injection:
100 mg/2 mL (50 mg/mL) in single-dose vial
500 mg/10 mL (50 mg/mL) in single-dose vial
OVERDOSAGE
There is no experience with overdose of EXONDYS
Patient Information:
HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
EXONDYS 51 injection is supplied in single-dose vials. The solution is clear and
colorless, and may have some opalescence.
Single-dose vials containing 100 mg/2 mL (50 mg/mL) eteplirsen NDC 60923-363-02
Single-dose vials containing 500 mg/10 mL (50 mg/mL) eteplirsen NDC 60923-284-10
Storage and Handling
Store EXONDYS 51 at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light and store
EXONDYS in the original carton until ready for use.
Manufactured for:
Sarepta Therapeutics, Inc.
Cambridge, MA 02142 USA
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. 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.
2. Pharmacokinetics
Following single or multiple intravenous infusions of EXONDYS 51 in male
pediatric DMD patients, plasma concentration-time profiles of eteplirsen were
generally similar and showed multi-phasic decline.
The majority of drug elimination occurred within 24 hours. Approximate
dose-proportionality and linearity in PK properties were observed following
multiple-dose studies (0.5 mg/kg/week [0.017 times the recommended dosage]
to 50 mg/kg/week [1.7 times the recommended dosage]).
There was no significant drug accumulation following weekly dosing
across this dose range. The inter-subject variability for eteplirsen Cmax and
AUC range from 20 to 55%.
Following single or multiple intravenous infusions of EXONDYS ,
the peak plasma concentrations (Cmax) of eteplirsen occurred near the end
of infusion (i.e., 1.1 to 1.2 hours across a dose range of 0.5 mg/kg/week to
50 mg/kg/week).
Distribution
In vitro investigation suggested that plasma protein binding of eteplirsen
in human ranges between 6 to 17%. The mean apparent volume of distribution
(Vss) of eteplirsen was 600 mL/kg following weekly intravenous infusion of
EXONDYS at 30 mg/kg.
Twenty-four hours after the end of the infusion, mean concentrations of eteplirsen
were 0.07% of Cmax. Accumulation of eteplirsen during once weekly dosing has
not been observed.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
There are no human or animal data available to assess the use of
EXONDYS 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.
2 Lactation
Risk Summary
There are no human or animal data to assess the effect of EXONDYS
on milk production, the presence of eteplirsen in milk, or the effects of EXONDYS
on the breastfed infant.
3.Pediatric Use
EXONDYS 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 skipping, including pediatric patients .
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).
4. Geriatric Use
DMD is largely a disease of children and young adults; therefore, there is no
geriatric experience with EXONDYS .
5. Patients with Renal or Hepatic Impairment
EXONDYS has not been studied in patients with renal or hepatic impairment.
6. OVERDOSAGE
There is no experience with overdose of EXONDYS
