casimersen (Rx)

Brand and Other Names:Amondys 45
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, solution

  • 50mg/mL (2-mL single-dose vial)

Duchenne Muscular Dystrophy

Indicated for Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping

30 mg/kg IV once weekly

Dosage Modifications

Renal impairment

  • Non-DMD patients with renal impairment: Renal clearance decreased; pharmacokinetics not studied in patients with Stage 4 or 5 CKD (eGFR <30 mL/min/1.73 m2)
  • DMD patients with renal impairment: Owing to effects of reduced skeletal muscle mass on creatinine measurements, no specific dosage adjustment can be recommended

Hepatic impairment

  • Not studied
  • Drug does not undergo hepatic metabolism, and systemic clearance is not expected to be affected by hepatic impairment

Dosing Considerations

Monitoring parameters

  • Note: Obtain urine sample on day of infusion before starting or at least 48 hr after infusion to retrieve drug-free urine
  • Alternatively, avoid using a laboratory test that uses reagent pyrogallol red; reagent may cross react with drug excreted in urine leading to a false positive result for urine protein
  • Before initiation
    • Serum cystatin C
    • Urine dipstick
    • Urine protein-to-creatinine ratio (UPCR)
    • Consider glomerular filtration rate (GFR)
  • During treatment
    • Serum cystatin C every 3 months
    • Urine dipstick every month
    • UPCR every 3 months
    • Consider GFR

Dosage Forms & Strengths

injection, solution

  • 50mg/mL (2-mL single-dose vials)

Duchenne Muscular Dystrophy

Indicated for Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping

30 mg/kg IV once weekly

Dosage Modifications

Renal impairment

  • Non-DMD patients with renal impairment: Renal clearance decreased; pharmacokinetics not studied in patients with Stage 4 or 5 CKD (eGFR <30 mL/min/1.73 m2)
  • DMD patients with renal impairment: Owing to effects of reduced skeletal muscle mass on creatinine measurements, no specific dosage adjustment can be recommended

Hepatic impairment

  • Not studied
  • Drug does not undergo hepatic metabolism, and systemic clearance is not expected to be affected by hepatic impairment

Dosing Considerations

Monitoring parameters

  • Note: Obtain urine sample on day of infusion before starting or at least 48 hr after infusion to retrieve drug-free urine
  • Alternatively, avoid using a laboratory test that uses reagent pyrogallol red; reagent may cross react with drug excreted in urine leading to a false positive result for urine protein
Before initiation
  • Serum cystatin C
  • Urine dipstick
  • Urine protein-to-creatinine ratio (UPCR)
  • Consider GFR
During treatment
  • Serum cystatin C every 3 months
  • Urine dipstick every month
  • UPCR every 3 months
  • Consider GFR
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Adverse Effects

>10%

Upper respiratory tract infections (65%)

Cough (33%)

Pyrexia (33%)

Headache (32%)

Arthralgia (21%)

Oropharyngeal pain (21%)

>10%

  • Reported at a rate at least 5% more frequent than placebo
    • Ear pain
    • Nausea
    • Ear infection
    • Post-traumatic pain
    • Dizziness
    • Lightheadedness
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Warnings

Contraindications

None

Cautions

Nephrotoxicity

  • Based on animal data, may cause nephrotoxicity
  • Although not observed in clinical studies with casimersen, nephrotoxicity (eg, potentially fatal glomerulonephritis) observed in some antisense oligonucleotides
  • Monitor serum cystatin C, urine dipstick, urine protein-to-creatinine ratio, and consider GFR
  • If persistent increased serum cystatin C or proteinuria detected, refer patient to pediatric nephrologist for further evaluation
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Pregnancy & Lactation

Pregnancy

No data are available to assess use during pregnancy

Lactation

There are no human or animal data to assess effects on milk production, drug presence in milk, or effects on breastfed infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass

PMO binds to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping

Exon 45 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping

Absorption

Peak plasma time: Reached at end of infusion

Accumulation: Not observed in plasma following once-weekly dosing

Distribution

Vd (steady-state): 367 mL/kg

Metabolism

Metabolically stable in human hepatic microsomal incubations

No metabolites were detected in plasma or urine

Elimination

Clearance: 180 mL/hr/kg

Half-life: 3.5 hr

Excretion: Urine (>90% unchanged); feces (negligible)

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Administration

IV Compatibilities

0.9% NaCl

IV Preparation

Calculate total dose, drug volume, and number of vials needed

Allow vials to reach to room temperature; gently invert each vial 2-3 times to mix; do NOT shake

Visually inspect each vial; solution is clear to slightly opalescent, colorless liquid, and may contain trace amounts of small, white to off-white amorphous particles; discard if cloudy, discolored or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles

Withdraw calculated volume with a 21-gauge or smaller bore non-coring needle; replace needle periodically during preparation

Dilute withdrawn drug in 0.9% NaCl to make a total volume of 100-150 mL; gently invert 2-3 times to mix; do NOT shake

Visually inspect diluted solution; discard if cloudy, discolored or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles

Administer immediately after dilution; complete infusion within 4 hr of dilution; if unable to administer immediately refrigerate

IV Administration

Consider applying topical anesthetic cream to infusion site before administering

Infuse over 35-60 min via in-line 0.2-micron filter

Flush IV access line with 0.9% NaCl before and after infusion

Do not mix or infuse other medications concomitantly via the same IV access

Missed dose: Administer as soon as possible after scheduled dose

Storage

Contains no preservatives

Unopened vials

  • Refrigerate at 2-8ºC (36-46ºF); do not freeze
  • Store in original carton until ready for use to protect from light

Diluted solutions

  • If unable to use immediately, refrigerate at 2-8ºC (36-46ºF) for up to 24 hr; do NOT freeze; discard any unused drug
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Images

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.