AMONDYS 45
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMONDYS 45 (AMONDYS 45).
Amondys 45 (casimersen) is a phosphorodiamidate morpholino oligomer that binds to exon 45 of dystrophin pre-mRNA, excluding it during splicing to restore the mRNA reading frame in Duchenne muscular dystrophy (DMD) patients with amenable mutations. This enables production of internally truncated but functional dystrophin protein.
| Metabolism | Casimersen is not metabolized by cytochrome P450 enzymes; it is primarily eliminated by renal excretion as unchanged drug via glomerular filtration with some tubular reabsorption. |
| Excretion | Primarily renal, with 100% of the dose excreted as unchanged drug in urine. |
| Half-life | Terminal elimination half-life is approximately 3.6 hours, necessitating frequent dosing (weekly) to maintain therapeutic levels. |
| Protein binding | Low to moderate protein binding, approximately 35–40%, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.15 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Subcutaneous administration: 100% bioavailability; not administered orally. |
| Onset of Action | Subcutaneous injection: time to peak plasma concentration is 2.5 hours; clinical effects on dystrophin production are observed after 48 weeks of weekly dosing. |
| Duration of Action | Weekly dosing regimen maintains plasma concentrations above therapeutic threshold; clinical benefit requires continued administration. |
Intravenous infusion over 35-60 minutes: 30 mg/kg once every 7 days.
| Dosage form | SOLUTION |
| Renal impairment | No specific renal adjustment guidelines; use caution in patients with renal impairment. |
| Liver impairment | No specific hepatic adjustment guidelines; use caution in patients with hepatic impairment. |
| Pediatric use | Same as adults: 30 mg/kg intravenously once every 7 days. |
| Geriatric use | No specific geriatric dose adjustment; monitor renal function and fluid balance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMONDYS 45 (AMONDYS 45).
| Breastfeeding | It is unknown if AMONDYS 45 is excreted in human milk. No M/P ratio data available. Because many drugs are excreted in human milk, caution should be exercised when administered to a nursing woman. |
| Teratogenic Risk | There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have not been conducted. The risk of fetal harm cannot be ruled out; use during pregnancy only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Hypersensitivity reactions (including fever, flushing, rash, and urticaria) have occurred during administration.","Renal toxicity: In animal studies, renal tubular vacuolation and degeneration were observed; monitor renal function during treatment."] |
| Food/Dietary | No known food interactions. No dietary restrictions required. Grapefruit and other CYP450 inhibitors are not expected to interact as casimersen is not metabolized by CYP enzymes. |
| Clinical Pearls |
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| No specific monitoring requirements beyond standard prenatal care. Monitor for maternal adverse reactions and assess fetal growth as clinically indicated. |
| Fertility Effects | No studies on fertility effects in humans have been performed. Animal studies have not been conducted to evaluate the impact on fertility. |
| AMONDYS 45 (casimersen) is an antisense oligonucleotide indicated for Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. Administer as IV infusion over 35-60 minutes once weekly. Premedicate with NSAIDs or corticosteroids if infusion reactions occur. Monitor renal function (serum cystatin C, urine protein) due to potential nephrotoxicity. Do not use in patients with a mutation not amenable to exon 45 skipping. |
| Patient Advice | AMONDYS 45 is not a cure for DMD but may slow disease progression. · You will receive this medication as a weekly intravenous infusion lasting 35-60 minutes. · Serious allergic reactions may occur during or after infusion; report chest pain, shortness of breath, fever, chills, or rash immediately. · Kidney function will be monitored regularly; you may need blood and urine tests. · Do not stop or change the dose without consulting your doctor. |