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 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).
(For additional information see "Casimersen: Drug information")
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).
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
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). Flush IV access line with NS before and after infusion.
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). 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.
Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Diluted solution may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F).
Treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping (FDA approved in pediatric patients [age not specified] and adults).
Note: Indication received accelerated approval based on an increase in skeletal muscle dystrophin production observed in clinical trial interim analysis; continued approval may be contingent upon confirmatory trials.
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. As reported in male patients.
>10%:
Gastrointestinal: Nausea
Nervous system: Dizziness, headache, pain (post-traumatic)
Neuromuscular & skeletal: Arthralgia
Otic: Otalgia, otitis media
Respiratory: Cough, oropharyngeal pain, upper respiratory tract infection
Miscellaneous: Fever
There are no contraindications listed in the manufacturer's labeling.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
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.
Baseline: Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio; consider measuring GFR.
During therapy: Urine dipstick (monthly), serum cystatin C and urine protein-to-creatinine ratio (every 3 months).
Note: Urine samples should be obtained before or ≥48 hours after the infusion to ensure that urine does not contain excreted casimersen; casimersen excreted in the urine may cross react with pyrogallol red and lead to a false positive urine protein finding.
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.
