Version May 2024
Duchenne muscular dystrophy: IV: 30 mg/kg once weekly.
There are no dosage adjustments provided in the manufacturer's labeling; monitor closely.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Casimersen: Pediatric drug information")
Duchenne muscular dystrophy (DMD): Children and Adolescents: IV: 30 mg/kg/dose once weekly. Note: Dosing based on clinical trials in pediatric patients aged 7 to 13 years at study entry.
There are no dosage adjustments provided in the manufacturer's labeling. Renal clearance of casimersen is reduced in non-Duchenne muscular dystrophy (DMD) adult patients with renal impairment; patients with known kidney impairment should be closely monitored; however, creatinine is not a reliable measurement of kidney function due to the reduced skeletal muscle mass in patients with DMD.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Although not observed in clinical trials with casimersen, kidney toxicity was observed in animal studies (mice and rats) at higher than recommended doses. The concern for a potential for renal toxicity with casimersen stems from cases of glomerulonephritis, including potentially fatal cases, observed with some antisense oligonucleotides (ASOs), specifically inotersen. These cases of inotersen-induced glomerulonephritis were accompanied by nephrotic syndrome.
Mechanism: Oligonucleotide agents are distributed primarily to the kidney, accounting for 20% of an administered dose. ASOs are filtered through the glomerulus and rapidly reabsorbed by the proximal tubule epithelium. Any potential ASO “class toxicities” may slightly vary by agent and preclinical animal data may overpredict renal effects of these agents (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in male children, adolescents, and young adults.
>10%:
Gastrointestinal: Nausea
Nervous system: Dizziness, headache, pain (post-traumatic)
Neuromuscular & skeletal: Arthralgia
Respiratory: Cough, oropharyngeal pain, upper respiratory tract infection
Miscellaneous: Fever
Postmarketing: Hypersensitivity: Hypersensitivity reaction (including anaphylaxis and angioedema)
Known hypersensitivity (eg, anaphylaxis, angioedema) to casimersen or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity reactions: Hypersensitivity reactions (eg, anaphylaxis, angioedema) have occurred with treatment.
Disease-related concerns:
• Renal impairment: Renal clearance is reduced in non-Duchenne muscular dystrophy (DMD) patients with renal impairment; however, creatinine is not a reliable measurement of kidney function in patients with DMD due to the reduced muscle mass.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Amondys 45: 100 mg/2 mL (2 mL)
Yes
IV: Dilution required prior to administration. Administer by IV infusion over 35 to 60 minutes immediately after dilution through a 0.2-micron, in-line filter attached to the primary IV tubing; complete infusion within 4 hours (stable for 4 hours at room temperature). If hypersensitivity occurs, consider slowing, interrupting, or discontinuing the infusion. Use of a topical anesthetic cream on the infusion site may be considered prior to administration. Flush IV access line with NS before and after infusion. Do not mix with other medications or infuse other medications concomitantly via the same IV access line. Discard unused portion.
Parenteral: IV: Must be diluted prior to administration. May consider application of a topical anesthetic cream at the infusion site prior to administration. Administer by IV infusion over 35 to 60 minutes through an in-line 0.2 micron filter; infusion must be completed within 4 hours of preparation (stable for 4 hours at room temperature). If hypersensitivity occurs, consider slowing, interrupting, or discontinuing the infusion; monitor until resolution. Flush IV access line with NS before and after infusion.
Duchenne muscular dystrophy: Treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.
None known.
There are no known significant interactions.
Casimersen is approved for the treatment of Duchenne muscular dystrophy, a condition that primarily affects males. Animal reproduction studies have not been conducted and females were not included in the original studies.
It is not known if casimersen is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Proteinuria by dipstick urinalysis (baseline and monthly); serum cystatin C and urine protein-to-creatinine ratio (baseline and every 3 months); GFR using an exogenous filtration marker (baseline); hypersensitivity reactions during infusion.
Binds to exon 45 of dystrophin premessenger RNA (mRNA), resulting in exclusion of this exon during mRNA processing. Exon 45 skipping allows for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 45 skipping.
Distribution: Vdss: 367 mL/kg.
Protein binding: 8.4% to 31.6%.
Half-life elimination: 3.5 hours.
Excretion: Urine: >90% as unchanged drug.
Renal function: In non-Duchenne muscular dystrophy adults with chronic kidney disease (CKD), AUC increased ~1.2-fold and 1.8-fold in stage 2 CKD and stage 3 CKD, respectively. Cmax increased 1.2-fold in stage 3 CKD.
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