viltolarsen (Rx)

>10%

Upper respiratory tract infection (63%)

Injection site reaction (25%)

Cough (19%)

Pyrexia (19%)

Contusion (13%)

Arthralgia (13%)

Diarrhea (13%)

Vomiting (13%)

Abdominal pain (13%)

Ejection fraction decreased (13%)

Urticaria (13%)

Contraindications

None

Cautions

Kidney toxicity

• Kidney toxicity observed in animals
• Clinical experience with viltolarsen is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides
• Monitor kidney function during treatment
• Only urine expected to be free of excreted drug should be used for monitoring of urine protein; urine obtained on the day of infusion, prior to infusion, or urine obtained at least 48 hr after most recent infusion, may be used; alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has potential to cross react with any drug that is excreted in urine and thus lead to a false positive result for urine protein
• Serum creatinine may not reliably measure kidney function in patients with DMD owing to reduced skeletal muscle mass
• Measure serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio before initiating
• Consider measuring GFR using an exogenous filtration marker before initiating
• During treatment, monitor urine dipstick every month and serum cystatin C and urine protein-to-creatinine ratio q3Months
• If persistent increased serum cystatin C or proteinuria detected, refer to a pediatric nephrologist for further evaluation

Pregnancy

There are no human or animal data available

Lactation

There are no human or animal data to assess effect on milk production

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

Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass

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 skipping is intended to allow for production of an internally truncated dystrophin protein

The underlying cause of DMD is a mutation or error in the gene for dystrophin, an essential protein involved in muscle fiber function

Absorption

Bioavailability: 100% (assumed)

Peak plasma time: 1 hr (end of infusion)

Distribution

Protein bound: 39-40%

Vd: 300 mL/kg

Metabolism

Metabolically stable; no metabolites detected in plasma or urine

Elimination

Half-life: 2.5 hr

Plasma clearance: 217 mL/hr/kg

Excretion: Mainly as unchanged drug in urine

Pharmacogenomics

~8% of patients with DMD have a mutation amenable to exon 53 skipping

IV Compatibilities

0.9% NaCl

IV Preparation

Inspect vial visually for particulate matter and discoloration before administration; solution should appear clear and colorless

Calculate dose and number vials required

Withdraw calculated dose from appropriate number of vials

If volume of viltolarsen dose <100 mL

• Dilution in 0.9% NaCl required
• Withdraw from 100-mL infusion bag volume of 0.9% NaCl equivalent to calculated volume of viltolarsen, THEN
• Inject viltolarsen dosage volume into infusion bag to total a volume of 100 mL

If volume of viltolarsen dose ≥100 mL

• Dilution is not required
• Inject viltolarsen dosage volume into empty infusion bag

Visually inspect infusion bag for particulates

Gently invert bag to ensure equal distribution of product; do not shake

IV Administration

Administer by IV infusion using peripheral or central venous catheter over 1 hr

Flush IV line with 0.9% NaCl after infusion

Filtration not required

Do not mix with other medications or infuse other medications concomitantly via the same IV line

Missed dose: Administer as soon as possible after the scheduled dose time

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF)
• Do not freeze

Diluted solution

• Contains no preservatives
• Room temperature: Infuse as soon as possible if stored at 20-26ºC (68-79ºF), but no more than 5 hr after preparation; complete infusion within 6 hr of preparation (allowing for 1 hr of infusion time)
• Refrigerated: If not used immediately, may refrigerate for up to 24 hr at 2-8ºC (36-46ºF)
• Do not freeze