EXONDYS 51
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXONDYS 51 (EXONDYS 51).
Antisense oligonucleotide that binds to exon 51 of dystrophin pre-mRNA, inducing skipping of exon 51 during splicing to restore the reading frame and produce a truncated but functional dystrophin protein in patients with Duchenne muscular dystrophy (DMD) who have confirmed mutations amenable to exon 51 skipping.
| Metabolism | Metabolized via exonuclease-mediated hydrolysis to shorter oligonucleotides. |
| Excretion | Primarily eliminated via renal excretion as intact oligonucleotide. Approximately 30-40% of administered dose is excreted unchanged in urine within 24 hours. No significant biliary or fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 28-32 days. This long half-life supports weekly dosing intervals. |
| Protein binding | Not extensively bound to plasma proteins; less than 10% bound. Primary binding proteins: albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Approximately 0.5-1.0 L/kg. Indicates distribution primarily into extracellular fluid and tissues, with limited penetration into CNS. |
| Bioavailability | Not administered orally; intravenous infusion only. Bioavailability via IV is 100%. |
| Onset of Action | Intravenous infusion: Clinical effect (increase in dystrophin production) observed after approximately 12 weeks of weekly dosing, as measured by muscle biopsy. |
| Duration of Action | Duration of pharmacodynamic effect (dystrophin expression) persists for at least 12 weeks after discontinuation, based on biopsy data. Clinical benefit may wane over several months without continued dosing. |
30 mg/kg intravenously over 35-60 minutes once weekly
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. Not studied in patients with end-stage renal disease. |
| Liver impairment | No dose adjustment required for hepatic impairment. Not studied in patients with significant hepatic impairment. |
| Pediatric use | Same as adult dosing: 30 mg/kg intravenously over 35-60 minutes once weekly, approved for patients aged 6 months and older with Duchenne muscular dystrophy and confirmed exon 51 skipping. |
| Geriatric use | No specific geriatric studies; dose selection should be cautious due to higher frequency of renal and hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EXONDYS 51 (EXONDYS 51).
| Breastfeeding | It is unknown whether eteplirsen is excreted in human milk. No data available on M/P ratio. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Exondys 51 (eteplirsen) is an antisense oligonucleotide indicated for Duchenne muscular dystrophy. No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no adverse developmental outcomes were observed in mice at doses up to 10 times the human clinical dose. Risk cannot be ruled out; use only if clearly needed. First trimester: insufficient data. Second/third trimester: insufficient data. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have occurred; monitor for signs and symptoms during infusion.","Thrombocytopenia and coagulation abnormalities: Platelet count should be monitored before and during treatment.","Renal toxicity: Renal function should be monitored; cases of glomerulonephritis and nephrotic syndrome have been reported."] |
| Food/Dietary | No known food or dietary interactions. Follow a balanced diet as recommended for DMD management. |
| Clinical Pearls |
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| Fetal Monitoring | No specific maternal or fetal monitoring requirements established. Standard obstetric monitoring is recommended. Monitor for infusion reactions (hypotension, chest pain, urticaria) during administration. Renal function monitoring recommended due to potential for renal toxicity. |
| Fertility Effects | No human data on fertility effects. In animal studies, no effects on male or female fertility were observed in mice at doses up to 10 times the human dose. |
| Administer via intravenous infusion over 35-60 minutes; premedicate with corticosteroids and antihistamines if infusion reactions occur. Monitor for hypersensitivity reactions, including anaphylaxis, during and after infusion. Efficacy is limited to DMD patients with a confirmed mutation amenable to exon 51 skipping; genetic testing is mandatory before initiation. Assess renal function prior to therapy; avoid use in patients with significant renal impairment. Infusion-related reactions may be mitigated by slowing infusion rate or interrupting therapy. Not a cure; continue supportive care. May cause thrombocytopenia; monitor platelet counts periodically. |
| Patient Advice | This medication is for patients with Duchenne muscular dystrophy who have a specific genetic mutation that can be treated with exon 51 skipping. · You will receive this drug as an intravenous infusion given over 35-60 minutes every week. · Common side effects include headache, fever, cough, vomiting, nausea, and infusion-related reactions. Seek medical help if you experience hives, difficulty breathing, swelling, or chest pain. · You may need pre-medication to reduce infusion reactions. Follow your doctor's instructions. · Do not stop treatment without consulting your doctor, as this drug does not cure DMD but may slow disease progression. · Inform your doctor if you have kidney problems, as dose adjustment may be needed. |