eteplirsen

Action and Spectrum

Mechanism of action

It is a type of antisense oligonucleotide that alters the expression of disease-causing genes. It explicitly targets exon 51 of the dystrophin gene, which is responsible for Duchenne muscular dystrophy (DMD) development. By skipping exon 51, eteplirsen enables the production of a shortened but functional dystrophin protein.

Spectrum

The spectrum of activity of eteplirsen is limited to patients with specific genetic mutations of the dystrophin gene that are amenable to exon 51 skipping. It has been shown to improve walking ability in patients with DMD and is considered a treatment option for DMD patients with certain types of mutations. However, the overall effectiveness of eteplirsen may vary among patients depending on the specific mutation and its effect on the dystrophin gene.

Drug Interaction

Adverse Reaction

Frequency defined:

>10%

Vomiting

Confusion

Balance disorder

Contact dermatitis

Frequency undefined:

Facial flushing

Transient erythema

Elevated temperatures on days of infusion

Black Box Warning

Contraindication / Caution

Contraindications

None

Caution

• It is a prescription medication and should only be used under the supervision of a healthcare provider.
• Patients should inform their doctor of allergies or pre-existing medical conditions before starting treatment with eteplirsen
• It has not been tested in pregnant women, so women who are pregnant or planning to become pregnant should inform their doctor.
• The safety and effectiveness of eteplirsen in children under the age of 6 have not been established.
• Common side effects of eteplirsen include headache, upper respiratory tract infection, and balance problems.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology

It is a morpholino antisense oligonucleotide that works by binding to exon 51 of the dystrophin pre-mRNA, which results in the exclusion of this exon during mRNA processing. This process of exon skipping allows for producing a shortened but functional dystrophin protein intended to improve muscle function in patients with DMD. DMD is a genetic disorder caused by mutations or errors in the dystrophin gene, a protein essential for muscle fiber function. Using exon-skipping technology, eteplirsen aims to address the underlying cause of DMD by restoring functional dystrophin expression.

Pharmacodynamics

It is an antisense oligonucleotide medication used to treat Duchenne muscular dystrophy (DMD) caused by specific mutations in the dystrophin gene. It works by altering the expression of dystrophin protein in muscle cells. The pharmacodynamics of eteplirsen involve skipping exon 51 of the dystrophin gene during RNA splicing, producing a shorter but functional dystrophin protein. This helps to stabilize the dystrophin-associated protein complex, leading to improved muscle function and decreased muscle damage in patients with DMD.

Pharmacokinetics

Absorption: It is administered intravenously (IV) and has a peak plasma concentration reached within 1.1-1.2 hours of the end of the infusion

Distribution: The volume of distribution (Vd) of eteplirsen is 600 mL/kg, bound to plasma proteins at a low level of 6-17%

Metabolism: It does not appear to be metabolized by hepatic microsomes of any species tested, including humans

Excretion: It has a short half-life of 3-4 hours and is rapidly cleared from the body with a total clearance of 339 mL/hr/kg. The medication is primarily excreted in the urine, and approximately 66% of the dose is eliminated within 24 hours of IV administration.

Adminstartion

Administration

Intravenous administration

The infusion site should be treated with a topical anesthetic cream before administration. The IV access line should be flushed with 0.9% sodium chloride solution before and after the infusion, and the medication should be infused for over 35-60 minutes. Eteplirsen should not be mixed with other medications or infused through the same IV access line as other medications.

Storage

Unopened vials should be stored in the refrigerator at 2-8°C, protected from light, and in their original carton. The diluted medication contains no preservatives and should be administered immediately after dilution, and the infusion should be completed within 4 hours of dilution. If the diluted solution cannot be administered immediately, it may be refrigerated for up to 24 hours. Any unused solution should be discarded.

Patient Information Leaflet

Patient information leaflet

Generic Name: eteplirsen

Pronounced: [ e-TEP-lir-sen ]

Why do we use eteplirsen?

It is an antisense oligonucleotide medication used to treat Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle weakness and loss of mobility. It treats patients with DMD caused by specific mutations in the dystrophin gene.

By altering the expression of dystrophin protein in muscle cells, eteplirsen helps to stabilize the dystrophin-associated protein complex and improve muscle function, slowing the progression of the disease.