RyR1 Structural Alterations Explain Statin-Associated Muscle Dysfunction
December 16, 2025
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Brand Name :
Dawnzera
Synonyms :
donidalorsen
Class :
Kallikrein Inhibitors
Brand Name :
Dawnzera
Synonyms :
donidalorsen
Class :
Kallikrein Inhibitors
ADULT DOSING
Dosage Forms & Strengths
SC solution, injection
single-dose autoinjector
0.8 ml/80 mg
Hereditary Angioedema (HAE)
Indicated for the prevention of hereditary angioedema (HAE) attacks
The suggested dose is 80 mg subcutaneously every four weeks
Administration every eight weeks may be considered
Indicated for the prevention of hereditary angioedema (HAE) attacks
The suggested dose is 80 mg subcutaneously every four weeks
Administration every eight weeks may be considered
PEDIATRIC DOSING
Dosage Forms & Strengths
Indicated for the prevention of hereditary angioedema (HAE) attacks ≥12 years
The suggested dose is 80 mg subcutaneously every four weeks
Administration every eight weeks may be considered
GERIATRIC DOSING
Refer to adult dosin
Action
A prekallikrein (PKK)–targeted antisense oligonucleotide (ASO) is chemically linked to a ligand containing three N-acetylgalactosamine (GalNAc) units, which enhances uptake of the ASO by hepatocytes.
Once inside the cell, the conjugate binds to PKK mRNA and triggers ribonuclease H1 (RNase H1)–mediated cleavage, leading to decreased synthesis of PKK protein.
Since PKK is a key activator of inflammatory pathways, its reduction helps limit the mediators responsible for acute episodes of hereditary angioedema.
Frequency Not Defined
Decreased platelet count
Hypersensitivity reactions
Anaphylaxis
Generalized rash
Dyspnea
Chest pain
Peri-oral swelling
Increased liver function tests
1-10%
Abdominal discomfort (7%)
Urinary tract infection (9%)
Upper respiratory tract infection (9%)
>10%
Injection site reactions (24%)
Black Box Warning
None
Contraindication/Caution:
Contraindication:
Hypersensitivity reaction
Caution:
Hypersensitivity
Pregnancy Warnings:
Pregnancy category: N/A
Lactation: Excretion in human breastmilk is unknown
Pregnancy categories:
Category A: Satisfactory and well-controlled studies show no evidence of risk to the fetus in the first trimester or in the later trimester.
Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.
Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.
Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.
Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.
Category N: There is no data available for the drug under this category.
Pharmacology:
A prekallikrein (PKK)–targeted antisense oligonucleotide (ASO) is chemically linked to a ligand containing three N-acetylgalactosamine (GalNAc) units, which enhances uptake of the ASO by hepatocytes.
Once inside the cell, the conjugate binds to PKK mRNA and triggers ribonuclease H1 (RNase H1)–mediated cleavage, leading to decreased synthesis of PKK protein.
Since PKK is a key activator of inflammatory pathways, its reduction helps limit the mediators responsible for acute episodes of hereditary angioedema.
Pharmacokinetics:
Absorption
The drug is absorbed with a peak plasma time of approximately 2 hours (range 0.25-8 hours). The peak plasma concentration is about 417 ng/mL with every 4-week dosing and 416 ng/mL with every 8-week dosing.
Distribution
The drug is highly protein bound (>98%). Its volume of distribution is 69.8 L in the central compartment and 1840 L in the peripheral compartment.
Metabolism
The drug is expected to be metabolized by endo- and exonucleases in the liver into short oligonucleotide fragments of varying sizes.
Elimination and excretion
Its elimination is characterized by a biphasic half-life, with an initial phase of approximately 5 hours reflecting tissue distribution and a terminal phase of about 1 month. Less than 1% of the administered dose is excreted in the urine.
Administration:
Subcutaneous injections should be given in the abdomen or upper thigh. A caregiver or healthcare professional may alternatively administer the injection in the back or upper arm. If a dose is missed, it should be taken as soon as possible, after which the treatment schedule should be continued based on the timing of the most recent dose.
Patient information leaflet
Generic Name: donidalorsen
Why do we use donidalorsen ?
Donidalorsen is a novel, RNA-targeted preventative therapy for hereditary angioedema.
Donidalorsen is approved for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older.
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