Donidalorsen (DAWNZERA®) Side Effects and Safety Management Guide

Donidalorsen (brand name DAWNZERA®) is a prescription prekallikrein-directed antisense oligonucleotide indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years of age and older. It is administered subcutaneously at 80 mg every 4 weeks (an every-8-weeks regimen may be considered). Beyond the intended therapeutic effect, adverse reactions may occur. Most are mild, but serious hypersensitivity requires immediate discontinuation and medical attention.

1. Most Common Adverse Reactions (incidence ≥5%)

• Injection site reactions: The most frequent, occurring in ~24% of patients on the q4week regimen. Manifestations include erythema, discoloration, pain, pruritus, induration, bruising, hematoma, swelling, local reaction, and urticaria. All injection site reactions were mild, non-serious, and the majority resolved without any treatment, with erythema being the most common.

• Upper respiratory tract infection: ~9% incidence, typically mild.

• Urinary tract infection: ~9% incidence, mild, resolves with symptomatic care.

• Abdominal discomfort: ~7% incidence, brief and mild, generally does not interrupt therapy.

2. Other System-Level Reactions

• Genitourinary (1%–10%): urinary tract infection.

• Gastrointestinal (1%–10%): abdominal discomfort.

• Hematologic: decreased platelet count (frequency not reported).

• Hepatic: elevated liver enzymes—ALT, AST, GGT (frequency not reported).

• Hypersensitivity / anaphylaxis​ (frequency not reported): symptoms include generalized rash, dyspnea, chest pain, peri-oral swelling.

• Contraindication: history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any excipient.

3. Patient Guidance

• Remove the autoinjector from refrigeration 30 minutes before injection and allow to reach room temperature naturally—do not​ use microwaves, hot water, or other artificial heating.

• Self-injection sites: abdomen or anterior thigh. The posterior upper arm is reserved for trained caregivers or clinicians. Avoid the 2-inch periumbilical area, bruised, reddened, indurated, or scarred skin.

• Not recommended in patients with moderate-to-severe hepatic impairment; inform your physician of any low platelet counts or liver disease history.

• Seek emergency care immediately for generalized rash, difficulty breathing, chest pain, or facial/peri-oral swelling.