Overview
11 DESCRIPTION Donidalorsen is a prekallikrein-directed antisense oligonucleotide (ASO) covalently linked to a ligand containing three N ‑acetyl galactosamine (GalNAc) residues to facilitate delivery of the ASO to hepatocytes. DAWNZERA contains donidalorsen sodium as the active ingredient.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Donidalorsen is an ASO‑GalNAc conjugate that causes ribonuclease H1 (RNase H1)‑mediated degradation of PKK mRNA through binding to PKK mRNA, which results in reduced production of PKK protein. PKK is a pro‑enzyme for plasma kallikrein, which results in the release of bradykinin, a potent vasodilator causing swelling and pain in HAE. In patients with HAE, C1‑inhibitor (C1‑INH) deficiency or dysfunction leads to excessive plasma kallikrein activity, bradykinin generation, and angioedema attacks. Donidalorsen lowers PKK concentration, preventing excessive bradykinin production in patients with HAE. 12.
Indications
- 1 INDICATIONS AND USAGE DAWNZERA™ is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. DAWNZERA is a prekallikrein directed antisense oligonucleotide indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. ( 1 )
Common Doses
- 80 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of DAWNZERA is 80 mg administered subcutaneously every 4 weeks. A dosage of 80 mg every 8 weeks may also be considered. ( 2.1 ) See full prescribing information for administration instructions. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of DAWNZERA is 80 mg administered subcutaneously every 4 weeks. A dosage of 80 mg administered subcutaneously every 8 weeks may be considered. Missed Dose(s) If a dose of DAWNZERA is missed, administer DAWNZERA as soon as possible.
Contraindications
- 4 CONTRAINDICATIONS DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA [see Warnings and Precautions (5.1) and Adverse Reactions (6) ] . History of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA.
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Risk of Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence ≥ 5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ionis Pharmaceuticals at 1-833-644-6647 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.