GOE-loe-DIR-sen

Therapeutic Classification: n/a

Pharmacologic Classification: antisense oligonucleotides

• Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

• Binds to exon 51 of dystrophin pre-messenger RNA (mRNA), resulting in exclusion of this exon during mRNA processing. Exon skipping allows for production of an internally truncated dystrophin protein.

• Increased dystrophin production.

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to extravascular tissues.

Metabolism/Excretion: Not hepatically metabolized. Primarily excreted unchanged in urine.

Half-life: 3.4 hr.

(plasma concentrations)

Contraindicated in:

• None reported.

Use Cautiously in:

• Renal impairment
• OB: Safety not established in pregnancy
• Lactation: Safety not established in breastfeeding.

CV: tachycardia.

EENT: nasopharyngitis.

GI: abdominal pain, nausea, vomiting, constipation, diarrhea.

GU: nephrotoxicity.

Local: injection site pain.

MS: back pain.

Neuro: headache, dizziness.

Resp: cough.

Misc: falls, fever, hypersensitivity reactions.

Drug-Drug:

• None reported.

• IV (Adults and Children): 30 mg/kg once weekly.

• Solution for injection: 50 mg/mL;

• Monitor for signs and symptoms of hypersensitivity reactions (rash, fever, pruritus, urticaria, dermatitis, skin exfoliation) during infusion. If hypersensitivity reaction occurs, consider slowing infusion rate or interrupting therapy. Treat symptomatically.

• Assess serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio before starting therapy. Monitor glomerular filtration rate (GFR) by 24-hr urine collection before starting and periodically during therapy; serum creatinine may not be a reliable measure due to reduced muscle mass. Monitor for proteinuria by dipstick urinalysis monthly. Monitor serum cystatin C and urine protein-to-creatinine ratio every 3 mo. Use urine obtained on the day of infusion prior to infusion or urine obtained at least 48 hr after most recent infusion. If proteinuria or persistent elevated serum cystatin C occurs, refer to pediatric nephrologist for further evaluation.

• May apply topical anesthetic cream to infusion site before infusion.
• Intermittent Infusion: Allow vials to warm to room temperature. Mix contents of each vial by inverting gently 2–3 times; do not shake. Solution is clear to slightly opalescent, colorless, and may contain trace amounts of small, white to off-white amorphous particles; do not administer solutions that are cloudy, discolored, or contain additional particulate matter. Withdraw volume required from each vial with 21–gauge or smaller needle.
  Diluent: 0.9% NaCl for total volume of 100–150 mL. Gently invert 2–3 times to mix; do not shake. Solution is stable for 4 hr at room temperature including infusion time or 24 hr if refrigerated. Do not freeze. Discard unused solution.
• Rate: Infuse over 35–60 min via an in-line 0.2 micron filter. Flush line with 0.9% NaCl before and after infusion.
• Y-Site Incompatibility: Do not administer with or mix with other medications.

• Explain purpose of medication to patient.
• Advise patient to notify health care professional immediately if signs and symptoms of hypersensitivity reactions occur.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize importance of regular lab tests to monitor for renal toxicity.

• Increased dystrophin production.

Vyondys 53