Dosing & Uses
Dosage Forms & Strengths
injection, solution
- 50mg/mL (2-mL single-dose vial)
Duchenne Muscular Dystrophy
Indicated for Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping
30 mg/kg IV once weekly
Dosage Modifications
Renal impairment
- Non-DMD patients with renal impairment: Renal clearance decreased; pharmacokinetics not studied in patients with Stage 4 or 5 chronic kidney disease (eGFR <30 mL/min/1.73 m2)
- DMD patients with renal impairment: Owing to effects of reduced skeletal muscle mass on creatinine measurements, no specific dosage adjustment can be recommended
Hepatic impairment
- Not studied
- Drug does not undergo hepatic metabolism, and systemic clearance is not expected to be affected by hepatic impairment
Dosing Considerations
Monitoring parameters
- Note: Obtain urine sample on day of infusion before starting or at least 48 hr after infusion to retrieve drug-free urine
- Alternatively, avoid using a laboratory test that uses reagent pyrogallol red; reagent may cross-react with drug excreted in urine, leading to a false-positive result for urine protein
-
Before initiation
- Serum cystatin C
- Urine dipstick
- Urine protein-to-creatinine ratio (UPCR)
- Consider GFR
-
During treatment
- Serum cystatin C every 3 months
- Urine dipstick every month
- UPCR every 3 months
- Consider GFR
Dosage Forms & Strengths
injection, solution
- 50mg/mL (2-mL single-dose vials)
Duchenne Muscular Dystrophy
Indicated for Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping
30 mg/kg IV once weekly
Dosage Modifications
Renal impairment
- Non-DMD patients with renal impairment: Renal clearance decreased; pharmacokinetics not studied in patients with Stage 4 or 5 chronic kidney disease (eGFR <30 mL/min/1.73 m2)
- DMD patients with renal impairment: Owing to effects of reduced skeletal muscle mass on creatinine measurements, no specific dosage adjustment can be recommended
Hepatic impairment
- Not studied
- Drug does not undergo hepatic metabolism, and systemic clearance is not expected to be affected by hepatic impairment
Dosing Considerations
Monitoring parameters
- Note: Obtain urine sample on day of infusion before starting or at least 48 hr after infusion to retrieve drug-free urine
- Alternatively, avoid using a laboratory test that uses reagent pyrogallol red; reagent may cross-react with drug excreted in urine, leading to a false-positive result for urine protein
Before initiation
- Serum cystatin C
- Urine dipstick
- Urine protein-to-creatinine ratio (UPCR)
- Consider GFR
During treatment
- Serum cystatin C every 3 months
- Urine dipstick every month
- UPCR every 3 months
- Consider GFR
Adverse Effects
>10%
Upper respiratory tract infections (65%)
Cough (33%)
Pyrexia (33%)
Headache (32%)
Arthralgia (21%)
Oropharyngeal pain (21%)
>10%
-
Reported at a rate at least 5% more frequent than placebo
- Ear pain
- Nausea
- Ear infection
- Posttraumatic pain
- Dizziness
- Lightheadedness
Postmarketing Reports
Hypersensitivity reactions, including angioedema and anaphylaxis
Warnings
Contraindications
Hypersensitivity to drug or components
Cautions
Hypersensitivity reactions, including angioedema and anaphylaxis, reported; if hypersensitivity reaction occurs, institute appropriate medical treatment, and consider slowing infusion, interrupting, or discontinuing the infusion and monitor until condition resolves
Nephrotoxicity
- Based on animal data, may cause nephrotoxicity
- Although not observed in clinical studies with casimersen, nephrotoxicity (eg, potentially fatal glomerulonephritis) observed in some antisense oligonucleotides
- Monitor serum cystatin C, urine dipstick, UPCR, and consider GFR
- If persistent increased serum cystatin C or proteinuria detected, refer patient to pediatric nephrologist for further evaluation
Pregnancy & Lactation
Pregnancy
No data are available to assess use during pregnancy
Lactation
There are no human or animal data to assess effects on milk production, drug presence in milk, or effects on breastfed infants
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.Pharmacology
Mechanism of Action
Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass
PMO binds to exon 45 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 45 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
Peak plasma time: Reached at end of infusion
Accumulation: Not observed in plasma following once-weekly dosing
Distribution
Vd (steady-state): 367 mL/kg
Metabolism
Metabolically stable in human hepatic microsomal incubations
No metabolites were detected in plasma or urine
Elimination
Clearance: 180 mL/hr/kg
Half-life: 3.5 hr
Excretion: Urine (>90% unchanged); feces (negligible)
Administration
IV Compatibilities
0.9% NaCl
IV Preparation
Calculate total dose, drug volume, and number of vials needed
Allow vials to reach to room temperature; gently invert each vial 2-3 times to mix; do NOT shake
Visually inspect each vial; solution is clear to slightly opalescent, colorless liquid, and may contain trace amounts of small, white to off-white amorphous particles; discard if cloudy, discolored, or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles
Withdraw calculated volume with a 21-gauge or smaller-bore non-coring needle; replace needle periodically during preparation
Dilute withdrawn drug in 0.9% NaCl to make a total volume of 100-150 mL; gently invert 2-3 times to mix; do NOT shake
Visually inspect diluted solution; discard if cloudy, discolored, or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles
Administer immediately after dilution; complete infusion within 4 hr of dilution; if unable to administer immediately, refrigerate
IV Administration
Consider applying topical anesthetic cream to infusion site before administering
Infuse over 35-60 min via in-line 0.2-micron filter
Flush IV access line with 0.9% NaCl before and after infusion
Do not mix or infuse other medications concomitantly via the same IV access
Missed dose: Administer as soon as possible after scheduled dose
Storage
Contains no preservatives
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF); do not freeze
- Store in original carton until ready for use to protect from light
Diluted solutions
- If unable to use immediately, refrigerate at 2-8ºC (36-46ºF) for up to 24 hr; do NOT freeze; discard any unused drug
Images
Formulary
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