Dawnzera®
Donidalorsen sodium is a prekallikrein-directed antisense oligonucleotide.1
Donidalorsen has the following uses:
Donidalorsen is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.1
Donidalorsen sodium is available in the following dosage form(s) and strength(s):
Injection: 80 mg of donidalorsen in 0.8 mL solution in a single-dose autoinjector.1
Adults and Pediatric Patients 12 Years of Age
Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with donidalorsen.1 If signs and symptoms of serious hypersensitivity reactions occur, discontinue the drug and institute appropriate therapy.1
There are no available data on donidalorsen use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1 In animal reproduction studies, subcutaneous administration of donidalorsen or a pharmacologically active mouse-specific surrogate in a combined fertility and embryo-fetal development study in mice and a pre- and postnatal development study in mice with F0 parental doses up to 5 times the maximum recommended human dose (MRHD, 80 mg) on a body surface area (BSA, mg/m 2) basis did not result in any adverse effects on embryofetal development, or behavioral, fertility, and reproductive development in the F1 offspring.1 Donidalorsen does not cross the placental barrier.1 The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.1 All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.1 In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1
There are no data on the presence of donidalorsen in human milk, the effects on the breast-fed infant, or the effects on milk production.1 Donidalorsen was excreted into the milk of lactating mice; however, due to species-specific differences in lactation physiology, animal lactation data may not reliably predict levels in human milk.1 The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for donidalorsen and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1
The safety and effectiveness of donidalorsen for prophylaxis to prevent attacks of HAE have been established in pediatric patients 12 years of age and older.1 Use of donidalorsen for this indication is supported by evidence from an adequate and well-controlled trial (OASIS-HAE) that included 7 pediatric patients (12 to 17 years of age) who received donidalorsen 80 mg subcutaneously every 4 weeks (n=4) or every 8 weeks (n=3).1 The safety and effectiveness of donidalorsen in pediatric patients 12 years of age and older is extrapolated from adults from OASIS-HAE with support from pharmacokinetic analysis and pharmacodynamic response.1 No new safety signals were identified in pediatric patients 12 years of age and older who received donidalorsen.1 The safety and effectiveness of donidalorsen have not been established in pediatric patients younger than 12 years of age.1
Clinical studies of donidalorsen did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.1
No dosage adjustment of donidalorsen is required for patients with mild hepatic impairment (defined by National Cancer Institute Organ Dysfunction Working Group [NCI-ODWG] Criteria: total bilirubin ≤1 × upper limit of normal [ULN] and aspartate aminotransferase [AST] >1 × ULN, or total bilirubin >1 to 1.5 × ULN and any AST level).1 Donidalorsen has not been studied in patients with moderate or severe hepatic impairment.1 Use of donidalorsen is not recommended in patients with moderate or severe hepatic impairment (defined by NCI-ODWG Criteria: total bilirubin >1.5 x ULN regardless of AST level).1
No dosage adjustment of donidalorsen is recommended for patients with mild renal impairment (estimated glomerular filtration rate [eGFR] ≥60 to <90 mL/min/1.73 m2).1 Donidalorsen has not been studied in patients with moderate or severe renal impairment or end-stage renal disease.1
Most common adverse reactions (incidence ≥5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort.1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Donidalorsen is a prekallikrein-directed antisense oligonucleotide (ASO) covalently linked to a ligand containing three N-acetyl galactosamine (GalNAc) residues.1 The ASO-GalNAc conjugate causes ribonuclease H1 (RNase H1)-mediated degradation of prekallikrein mRNA through binding to mRNA, which results in reduced production of prekallikrein protein.1 Prekallikrein is a pro-enzyme for plasma kallikrein, which results in the release of bradykinin, a potent vasodilator causing swelling and pain in HAE.1 In patients with HAE, C1-inhibitor (C1-INH) deficiency or dysfunction leads to excessive plasma kallikrein activity, bradykinin generation, and angioedema attacks.1 Donidalorsen lowers prekallikrein concentration, preventing excessive bradykinin production in patients with HAE.1
Additional Information
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for subcutaneous use | 80 mg (of donidalorsen)/0.8 mL | Dawnzera® (available as single-dose autoinjector) | Ionis Pharmaceuticals |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions November 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.