golodirsen (Rx)

>10%

Headache (41%)

Pyrexia (41%)

Fall (29%)

Abdominal pain (27%)

Nasopharyngitis (27%)

Cough (27%)

Vomiting (27%)

Nausea (20%)

1-10%

>5%

• Administration site pain
• Back pain
• Pain
• Diarrhea
• Dizziness
• Ligament sprain
• Contusion
• Influenza
• Oropharyngeal pain
• Rhinitis
• Skin abrasion
• Ear infection
• Seasonal allergy
• Tachycardia
• Catheter site-related reaction
• Constipation
• Fracture

Frequency Not Defined

Hypersensitivity

Contraindications

None

Cautions

Hypersensitivity

• Hypersensitivity reactions, including rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation, reported, some requiring treatment
• If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting therapy

Renal toxicity

• Renal toxicity was observed in animals
• Although renal toxicity was not observed in the clinical studies, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides
• Monitor renal function during therapy
• Because of the effect of reduced skeletal muscle mass on creatinine measurements, serum creatinine may not be a reliable measure of renal function in patients with DMD
• Measure GFR by 24-hr urine collection before initiating therapy
• Monthly monitoring for proteinuria by dipstick urinalysis and monitoring of serum cystatin C and urine protein-to-creatinine ratio q3Months is recommended
• If confirmed dipstick proteinuria of 2+ or greater or elevated serum cystatin C, a 24-hr urine collection to quantify proteinuria and assess GFR should be performed
• Only urine expected to be free of excreted drug should be used for monitoring of urine protein; urine obtained on day of infusion prior to infusion, or urine obtained at least 48 hours after most recent infusion, may be used; alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross-react with drug excreted in the urine and thus lead to a false-positive result for urine protein
• If a persistent increase in serum cystatin C or proteinuria detected, refer to a pediatric nephrologist for further evaluation

Pregnancy

No human or animal data are available to assess use during pregnancy

Lactation

No human or animal data are available to assess effects on milk production, presence in milk, or effects on the breastfed infant

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.

Mechanism of Action

Binds to exon 53 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping

Exon 53 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping

Absorption

Systemic exposure increases proportionally with dose, with minimal accumulation

Distribution

Protein bound:33-39%

Vd: 668 mL/kg

Metabolism

Metabolically stable; no metabolites detected in plasma or urine

Elimination

Half-life: 3.4 hr

Plasma clearance: 346 mL/hr/kg

Mostly excreted unchanged in urine

IV Preparation

Preservative-free concentrated solution that requires dilution before administration

Inspect vials visually for particulate matter and discoloration; solution should appear as a clear to slightly opalescent, colorless liquid

Use aseptic technique

Allow vials to warm to room temperature

Gently invert vials to mix contents; do not shake

Withdraw calculated dose from vial(s) and dilute in 0.9% NaCl for a total volume of 100-150 mL; gently invert 2-3 times to mix; do not shake

Visually inspect diluted solution for particulates

Administer immediately after dilution; complete infusion within 4 hr of dilution

IV Administration

Consider topical anesthetic cream application to the infusion site before administration

Flush IV access line with 0.9% NaCl before and after infusion

Infuse IV over 35-60 minutes

Do not mix with other medication or infuse other medication concomitantly vial same IV access line

Missed dose: May be administered as soon as possible after the scheduled dose

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF)
• Do not freeze
• Store in original carton until ready for use to protect from light

Diluted solution

• If immediate use is not possible, may store for up to 24 hr at 2-8ºC (36-46ºF)
• Do not freeze