Usual Adult Dose for Muscular Dystrophy

30 mg/kg via IV infusion weekly

Comments:

• Continued approval for this indication is contingent upon verification of clinical benefit in confirmatory trials.

Use: For the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

Usual Pediatric Dose for Muscular Dystrophy

30 mg/kg via IV infusion weekly

Comments:

• Continued approval for this indication is contingent upon verification of clinical benefit in confirmatory trials.

Use: For the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

Renal Dose Adjustments

Patients with known renal impairment should be closely monitored during treatment; no specific dose recommendations can be made based on eGFR because of the effect of reduced skeletal muscle mass on creatinine measurements in DMD patients

Liver Dose Adjustments

Data not available

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients older than 65 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer as an IV infusion over 35 to 60-minute once a week
• A topical anesthetic cream may be applied at infusion site
• Flush IV line with 0.9% Sodium Chloride Injection before and after infusion; an in-line 0.2-micron filter should be used
• If a hypersensitivity reaction occurs, consider slowing the infusion or interrupting therapy

Missed Dose: If a dose is missed administer as soon as possible after the scheduled dose

Storage requirements:

• Store refrigerated (2C to 8C; 36F to 46F) in original carton to protect from light; do not freeze

Reconstitution/preparation techniques:

• Allow vials to warm to room temperature; mix contents by gently inverting 2 or 3 times, do not shake
• Dilute to a total volume of 100 to 150 mL with 0.9% Sodium Chloride Injection prior to administration; gently invert 2 to 3 times to mix, do not shake
• Complete administration within 4 hours of dilution; if immediate use is not possible, the diluted product may be stored for up to 24 hours at 2C to 8C (36F to 46F); do not freeze, discard unused

IV compatibility: Do not mix with other medications or infuse concomitantly with other medications in same IV access line

General:

• The FDA granted accelerated approval of this drug based on surrogate endpoint data showing increased dystrophin levels in patients with DMD and a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. In clinical trials, dystrophin levels increased from 0.1% of normal at baseline to 1.02% of normal following 48 weeks or more of treatment.
• Pharmacodynamic studies have shown this increase in dystrophin protein expression positively correlated with the level of exon skipping; immunofluorescence staining has shown correct localization of truncated dystrophin to the sarcolemma in muscle fibers in treated patients.
• Trials are ongoing to assess whether this drug improves motor function in these patients.

Monitoring:

• Prior to therapy, measure serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio (UPCR); consider measuring glomerular filtration rate using an exogenous filtration marker
• Monitor for proteinuria with monthly dipstick urinalysis; if pyrogallol red is the reagent in the test, be sure to use urine obtained at least 48 hours after the most recent infusion; alternatively, use a laboratory test without this reagent to avoid receiving a false positive for urine protein
• Monitor serum cystatin C and UPCR every 3 months

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling.
• Patients/caregivers should understand that hypersensitivity reactions have occurred, and they should seek immediate medical care should signs of symptoms of hypersensitivity develop.
• Patients/caregivers should understand that nephrotoxicity has occurred with drugs similar to this drug and therefore, it will be important to monitor for kidney toxicity during treatment.

Frequently asked questions

• What are the new drugs for Duchenne muscular dystrophy?