Casimersen
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Casimersen is an antisense oligonucleotide that is FDA approved for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.. Common adverse reactions include upper respiratory tract infection, cough, pyrexia, headache, arthralgia, and oropharyngeal pain..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
AMONDYS 45 is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
- Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45.
- 30 milligrams per kilogram of body weight once weekly.
- Administer as an intravenous (IV) infusion over 35 to 60 minutes via an in-line 0.2 micron filter.
- Dilution required prior to administration.
- Injection: 100 mg/2 mL in a single-dose vial
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Casimersen in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Casimersen in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
AMONDYS 45 is indicated for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Casimersen in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Casimersen in pediatric patients.
Contraindications
- AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45. Instances of hypersensitivity, including angioedema and anaphylaxis, have occurred in patients receiving AMONDYS 45.
Warnings
Hypersensitivity Reactions
- Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45. If a hypersensitivity reaction occurs, institute appropriate medical treatment, and consider slowing the infusion, interrupting, or discontinuing the AMONDYS 45 infusion and monitor until the condition resolves. AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45.
Kidney Toxicity
- Kidney toxicity was observed in animals who received casimersen. Although kidney toxicity was not observed in the clinical studies with AMONDYS 45, kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides.
- Kidney function should be monitored in patients taking AMONDYS 45. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45.
- Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting AMONDYS 45.
- During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio (UPCR) every three months.
- Only urine expected to be free of excreted AMONDYS 45 should be used for monitoring of urine protein.
- Urine obtained on the day of AMONDYS 45 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. *Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any AMONDYS 45 that is excreted in the urine and thus lead to a false positive result for urine protein.
- If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation.
Adverse Reactions
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- In the AMONDYS 45 clinical development program, 76 patients received at least one intravenous dose of AMONDYS 45 (30 mg/kg). All patients were male and had genetically confirmed Duchenne muscular dystrophy. Age at study entry was 7 to 20 years (mean 9.9 years). Most (88%) patients were White, and 9% were Asian.
- AMONDYS 45 was studied in a double-blind, placebo-controlled study (Study 1).
- Patients in ongoing Study 1 received AMONDYS 45 (n=57) 30 mg/kg or placebo (n=31) intravenously once weekly for up to 96 weeks, after which all patients received or will receive AMONDYS 45 30 mg/kg for up to 48 weeks.
- Adverse reactions observed in ≥20% of patients treated with AMONDYS 45 and 5% more frequently than in the placebo group in Study 1 are shown in Table 1.
Other adverse reactions that occurred in at least 10% of patients treated with AMONDYS 45, and that were reported at a rate at least 5% more frequently in the AMONDYS 45 group than in the placebo group, were: ear pain, nausea, ear infection, post-traumatic pain, and dizziness and light-headedness.
Postmarketing Experience
- The following adverse reactions have been identified during postapproval use of AMONDYS 45. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infusion-related reactions including rash, headache, cough, abdominal pain (including upper abdominal pain), and vomiting occurred within 24 hours from the start of an infusion of AMONDYS 45.
- Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients treated with AMONDYS 45.
Drug Interactions
There is limited information regarding Casimersen Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Casimersen in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Casimersen in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Casimersen during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Casimersen in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Casimersen in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Casimersen in geriatric settings.
Gender
There is no FDA guidance on the use of Casimersen with respect to specific gender populations.
Race
There is no FDA guidance on the use of Casimersen with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Casimersen in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Casimersen in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Casimersen in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Casimersen in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Casimersen Administration in the drug label.
Monitoring
There is limited information regarding Casimersen Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Casimersen and IV administrations.
Overdosage
There is limited information regarding Casimersen overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Casimersen Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Casimersen Mechanism of Action in the drug label.
Structure
There is limited information regarding Casimersen Structure in the drug label.
Pharmacodynamics
There is limited information regarding Casimersen Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Casimersen Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Casimersen Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Casimersen Clinical Studies in the drug label.
How Supplied
There is limited information regarding Casimersen How Supplied in the drug label.
Storage
There is limited information regarding Casimersen Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Casimersen Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Casimersen interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Casimersen Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Casimersen Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.