DAWNZERA donidalorsen 80 mg/.8mL Injection, Solution, 1 syringe
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Drugs used in hereditary angioedema class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Donidalorsen injection is used to prevent attacks of hereditary angioedema (HAE; genetic condition causing recurrent episodes of severe swelling). Donidalorsen is in a class of medications called prekallikrein-directed antisense oligonucleotides. It works by blocking the production of the protein that causes the swelling in patients with HAE.
Read the full MedlinePlus article ↗Patient education
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 22ADO53M6F
A mineral salt derived from phosphoric acid, used as a buffer to maintain the pH balance of the medication and help stabilize the active ingredients.
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UNII 3980JIH2SW
A salt form of phosphoric acid that acts as a buffer and pH adjuster in medicines. It helps keep the product at the correct acidity level for stability and effectiveness.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $70,059.37 | $56,047.49 / 0.8 ml |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Dawnzera 80 mg/.8mLthis 71860-0103-01 | Ionis | 1 syringe | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 10294477 ↗ | Drug substance | U-3010 | May 1, 2035 |
| US 9315811 ↗ | Method of use | U-3010 | Oct 21, 2032 |
| US 9670492 ↗ | Drug substance | — | Aug 28, 2034 |
| US 9127276 ↗ | Drug substance | — | May 1, 2034 |
| US 9181549 ↗ | Drug substance | — | May 1, 2034 |
| Code | What it grants | Expires |
|---|---|---|
| ODE-550 | Orphan Drug Exclusivity (7-year) | Aug 21, 2032 |
Is there a generic version of DAWNZERA 80 MG/0.8 ML PEN?
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 71860-0103-01 You're viewing this | 1 SYRINGE, GLASS in 1 CARTON (71860-103-01) / .8 mL in 1 SYRINGE, GLASS | 2025-08-21 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 )
⏱️ Dosage and Administration ▾
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 )
2.1Recommended 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. Resume treatment at the recommended dosing frequency from the date of the most recently administered dose.
2.2Administration Instructions For subcutaneous use. DAWNZERA is intended for self-administration or administration by a caregiver. Prior to treatment initiation, train patients and/or caregivers on proper preparation and subcutaneous administration technique of DAWNZERA autoinjector [see Instructions for Use ] .
Remove the single‑dose autoinjector from the refrigerator 30 minutes prior to the injection and allow to warm to room temperature. Do not use other warming methods. Inspect DAWNZERA visually for particulate matter and discoloration prior to administration.
The solution should appear clear and colorless to yellow. Do not use if cloudiness, particulate matter, or discoloration is observed prior to administration. Administer DAWNZERA subcutaneously into the abdomen or upper thigh region.
The back of the upper arm can also be used as an injection site if a caregiver or healthcare provider administers the injection.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 80 mg/0.8 mL of donidalorsen as a sterile, clear, colorless to yellow solution in a single-dose autoinjector. Injection: 80 mg/0.8 mL solution in a single-dose autoinjector. ( 3 )
⛔ 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.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions including anaphylaxis have been reported following use of DAWNZERA. Advise patients to discontinue DAWNZERA and seek immediate medical attention if serious hypersensitivity reactions occur. ( 5.1 )
5.1Risk of Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with DAWNZERA [see Adverse Reactions (6.1) ] . If signs and symptoms of serious hypersensitivity reactions occur, discontinue DAWNZERA and institute appropriate therapy.
🤒 Adverse Reactions ▾
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 .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of DAWNZERA reflects the exposure in a total of 171 adult and pediatric patients 12 years and older with hereditary angioedema (HAE) from a placebo-controlled trial (OASIS-HAE) [see Clinical Studies (14) ] , and 2 other clinical studies.
The average duration of DAWNZERA treatment exposure across the 3 clinical studies was 14 months. The safety data below is based on the 24-week multicenter, randomized, double-blind, placebo-controlled trial (OASIS-HAE), in which patients received at least one subcutaneous dose of DAWNZERA 80 mg once every 4 weeks (n=45), DAWNZERA 80 mg once every 8 weeks (n=23), or matching placebo (n=22). Demographics of the patients in OASIS-HAE are summarized in Clinical Studies [see Clinical Studies (14) ] .
Table 1 provides the most common adverse reactions with DAWNZERA with incidence ≥5% and more common than placebo. Table 1: Adverse Reactions with DAWNZERA with Incidence ≥5% and More Common than Placebo in Patients with HAE (OASIS-HAE) N = number of patients; n = number of patients experiencing the event; q4wks = every 4 weeks; q8wks = every 8 weeks. * Injection site reactions include: erythema, discoloration, pain, pruritus, induration, bruising, haematoma, hypersensitivity, swelling, reaction, and urticaria. † All injection site reactions were mild, nonserious, and the majority of them resolved without receiving any treatment.
Adverse Reaction DAWNZERA Placebo (N=22) 80 mg q4wks (N=45) 80 mg q8wks (N=23) n (%) n (%) n (%) Injection site reactions*† 11 (24) 1 (4) 1 (5) Upper respiratory tract infection 4 (9) 2 (9) 1 (5) Urinary tract infection 4 (9) 2 (9) 0 Abdominal discomfort 3 (7) 0 0 Specific Adverse Reactions Hypersensitivity Reactions, Including Anaphylaxis In clinical trials, hypersensitivity reactions, including anaphylaxis, have occurred. Symptoms included generalized rash, dyspnea, chest pain, and peri-oral swelling. Laboratory Tests Decrease in Platelet Count : DAWNZERA can cause reductions in platelet count.
In OASIS-HAE, the mean platelet count at baseline was 266,000/mm 3 for the DAWNZERA 80 mg every 4 weeks group, 265,000/mm 3 for the DAWNZERA 80 mg every 8 weeks group, and 245,000/mm 3 for the placebo group. The mean percent change in platelet count at Week 25 was -9.6% for the DAWNZERA 80 mg every 4 weeks group, -7.9% for the DAWNZERA 80 mg every 8 weeks group, and -1.4% for the placebo group. In OASIS-HAE and 2 other clinical studies no DAWNZERA-treated patient had a platelet count of <50,000/mm 3 , and there were no major bleeding events associated with a low platelet count.
Increase in Liver Function Tests : Increases from baseline in liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase) were observed with DAWNZERA use. The increased levels were generally below 3 times the upper limit of normal and stabilized. Discontinuations due to liver function test increases were infrequent.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Hepatic Impairment: Use in patients with moderate and severe hepatic impairment is not recommended. ( 8.7 )
8.1Pregnancy Risk Summary There are no available data on DAWNZERA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 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.
Donidalorsen does not cross the placental barrier (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
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. Data Animal Data In reproductive toxicity studies with donidalorsen, the unconjugated form was not detected (below the limit of quantitation) in fetal tissues. Donidalorsen does not cross the placental barrier.
In a combined fertility and embryofetal development study, subcutaneous administration of donidalorsen (up to 10 mg/kg/week [2.5-times the MRHD on a BSA basis]) or a mouse‑specific surrogate (4 mg/kg/week) to male and female F0 mice weekly, prior to and during mating, and continuing every other day in females throughout the periods of implantation and organogenesis (Gestation Days 0 to 16), resulted in no adverse effects on embryofetal development. There was no evidence of maternal toxicity with doses up to 10 mg/kg/week.
In a pre- and postnatal development study, subcutaneous administration of donidalorsen (up to 20 mg/kg/week [5-times the MRHD on a BSA basis]) or a mouse-specific surrogate (5 mg/kg/week) to F0 female mice every other day throughout pregnancy (from Gestation Day 6 to 18) and weekly throughout lactation (from Lactation Day 1 to 20) produced no adverse effects on behavioral, fertility, and reproductive development in the F1 offspring. There was no evidence of maternal toxicity with doses up to 20 mg/kg/week.
8.2Lactation Risk Summary 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. 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 (see Data) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DAWNZERA and any potential adverse effects on the breast‑fed infant from DAWNZERA or from the underlying maternal condition.
Data Animal Data In the mouse pre‑ and postnatal development study, the concentrations of donidalorsen in breast milk from lactating mice on Lactation Day 15 increased in a dose‑dependent manner at doses ≥10 mg/kg/week, but these concentrations of donidalorsen in breast milk were lower than the observed concentrations in the liver where the drug is preferentially taken up. Even though donidalorsen was detected in the maternal mouse milk, systemic exposure in pups was not expected due to the lack of oral absorption of donidalorsen.
8.4Pediatric Use The safety and effectiveness of DAWNZERA for prophylaxis to prevent attacks of HAE have been established in pediatric patients aged 12 years and older. Use of DAWNZERA for this indication is supported by evidence from an adequate and well‑controlled trial (OASIS…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on DAWNZERA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 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.
Donidalorsen does not cross the placental barrier (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
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. Data Animal Data In reproductive toxicity studies with donidalorsen, the unconjugated form was not detected (below the limit of quantitation) in fetal tissues. Donidalorsen does not cross the placental barrier.
In a combined fertility and embryofetal development study, subcutaneous administration of donidalorsen (up to 10 mg/kg/week [2.5-times the MRHD on a BSA basis]) or a mouse‑specific surrogate (4 mg/kg/week) to male and female F0 mice weekly, prior to and during mating, and continuing every other day in females throughout the periods of implantation and organogenesis (Gestation Days 0 to 16), resulted in no adverse effects on embryofetal development. There was no evidence of maternal toxicity with doses up to 10 mg/kg/week.
In a pre- and postnatal development study, subcutaneous administration of donidalorsen (up to 20 mg/kg/week [5-times the MRHD on a BSA basis]) or a mouse-specific surrogate (5 mg/kg/week) to F0 female mice every other day throughout pregnancy (from Gestation Day 6 to 18) and weekly throughout lactation (from Lactation Day 1 to 20) produced no adverse effects on behavioral, fertility, and reproductive development in the F1 offspring. There was no evidence of maternal toxicity with doses up to 20 mg/kg/week.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of DAWNZERA for prophylaxis to prevent attacks of HAE have been established in pediatric patients aged 12 years and older. Use of DAWNZERA for this indication is supported by evidence from an adequate and well‑controlled trial (OASIS-HAE) that included 7 pediatric patients (aged 12 to 17 years) who received DAWNZERA 80 mg subcutaneously every 4 weeks (n=4) or every 8 weeks (n=3). The safety and effectiveness of DAWNZERA in pediatric patients aged 12 years and older is extrapolated from adults from OASIS-HAE with support from pharmacokinetic analysis and pharmacodynamic response [see Clinical Pharmacology (12.2 , 12.3) and Clinical Studies (14) ] .
No new safety signals were identified in pediatric patients aged 12 years and older who received DAWNZERA [see Adverse Reactions (6.1) ] . The safety and effectiveness of DAWNZERA have not been established in pediatric patients younger than 12 years of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of DAWNZERA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics In OASIS-HAE in adult and pediatric patients (≥12 years) with HAE‑1 or HAE‑2 [see Clinical Studies (14) ] , a decrease in plasma PKK concentrations was observed at the first assessment (Week 4) following treatment with DAWNZERA 80 mg. The mean percentage reduction from baseline at Week 4 across both treatment groups was 48%. The mean percentage change from baseline to Week 24 in trough plasma PKK concentrations indicated reductions of 73% and 47% following treatment with DAWNZERA 80 mg every 4 weeks and every 8 weeks, respectively, compared with a slight increase (2%) observed in the placebo group.
Cardiac Electrophysiology At the maximum recommended dose of DAWNZERA 80 mg every 4 weeks, clinically significant QTc interval prolongation was not observed.
12.3Pharmacokinetics The pharmacokinetic properties of DAWNZERA were evaluated following subcutaneous administration of multiple doses every 4 weeks in healthy subjects and every 4 weeks or every 8 weeks in patients with HAE. The pharmacokinetics of DAWNZERA were similar between healthy subjects and patients with HAE. Donidalorsen exposure (area under the plasma concentration‑time curve [AUC]) at steady state following subcutaneous administration in healthy subjects increased in a greater than dose‑proportional manner over the dose range of 0.25 times the maximum recommended dosage to 80 mg every 4 weeks.
Geometric Mean (Coefficient of Variation [CV%]) of steady‑state maximum plasma concentration (C max,ss ), trough plasma concentration (C trough,ss ), and area under the plasma concentration‑time curve over the dosing interval (AUC τ ,ss ) are presented in Table 2. No accumulation of donidalorsen C max and AUC was observed in plasma after repeated dosing every 4 weeks. However, a 2-fold increase of plasma donidalorsen C trough was observed following repeated dosing every 4 weeks.
Table 2: Summary of Geometric Mean (CV%) Steady-State Donidalorsen Pharmacokinetic Parameters Following Dosage of DAWNZERA 80 mg Every 4 Weeks or 80 mg Every 8 Weeks in Patients with HAE AUC τ,ss = area under the plasma concentration time curve over each dosing interval at steady state; C max,ss = maximum plasma concentration at steady state; C trough,ss = trough plasma concentration at steady state; q4wks = every 4 weeks; q8wks = every 8 weeks. Pharmacokinetic Parameters (Geometric Mean) DAWNZERA 80 mg q4wks 80 mg q8wks C max,ss (ng/mL) 417 (81%) 416 (78%) C trough,ss (ng/mL) 0.755 (63%) 0.255 (73%) AUC τ,ss (ng·h/mL) 5240 (52%) 5210 (52%) Absorption Following subcutaneous administration, donidalorsen is absorbed with the median (range) time to maximum plasma concentration of approximately 2 (0.25, 8) hours post dose.
Distribution Donidalorsen is expected to distribute primarily to the liver and kidney cortex after subcutaneous dosing. The apparent volume of distribution for the central (V c /F) and peripheral (V p /F) compartment were
69.8L and 1840 L, respectively. Donidalorsen is highly bound to human plasma proteins (>98% bound) in vitro. Elimination The terminal plasma elimination half-life of donidalorsen in a typical patient with HAE is approximately 1 month. The half-life of the initial rapid clearance phase, reflecting tissue distribution, was approximately 5 hours. Metabolism The oligonucleotide moiety of donidalorsen is expect…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
📋 Description ▾
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. Donidalorsen sodium is a white to yellow solid and it is freely soluble in water and in sodium phosphate buffer.
The molecular formula of donidalorsen sodium is C 296 H 415 N 83 O 151 P 20 S 15 Na 20 and the molecular weight is 9112.27 daltons. The chemical name of donidalorsen is DNA, d([2′- O -(2-methoxyethyl)]m 5 rU-s p -[2′- O -(2-methoxyethyl)]rG-s p -[2′- O -(2-methoxyethyl)]m 5 rC-[2′- O -(2-methoxyethyl)]rA-[2′- O -(2-methoxyethyl)]rA-s p -G-s p -T-s p -m 5 C-s p -T-s p -m 5 C-s p -T-s p -T-s p -G-s p -G-s p -m 5 C-s p -[2′- O -(2-methoxyethyl)]rA-[2′- O -(2-methoxyethyl)]rA-[2′- O -(2methoxyethyl)]rA-s p -[2′- O -(2-methoxyethyl)]m 5 rC-s p -[2′- O -(2-methoxyethyl)]rA), 5′-[26-[[2-(acetylamino)-2-deoxy-β-d-galactopyranosyl]oxy]-14,14-bis[[3-[[6-[[2-(acetylamino)-2-deoxy-β-d-galactopyranosyl]oxy]hexyl]amino]-3-oxopropoxy]methyl]-8,12,19-trioxo-16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate], sodium salt (1:20).
The chemical structure of donidalorsen sodium is presented below: DAWNZERA (donidalorsen) injection is a sterile, preservative‑free solution for subcutaneous injection supplied as a single-dose autoinjector. Each single‑dose autoinjector contains 80 mg of donidalorsen (equivalent to 84 mg donidalorsen sodium) in 0.8 mL of solution. The solution also contains disodium hydrogen phosphate; sodium chloride; sodium dihydrogen phosphate; water for injection; and may include hydrochloric acid and/or sodium hydroxide for pH adjustment between 6.9 to 7.9.
Each dose of DAWNZERA injection contains 6 mg of phosphorous and 5 mg of sodium. Chemical structure.jpg
💬 Information for Patients ▾
Patient Information PATIENT INFORMATION DAWNZERA TM (dawn-ZAIR-ah) (donidalorsen) injection, for subcutaneous use What is DAWNZERA? DAWNZERA is a prescription medicine used to prevent hereditary angioedema (HAE) attacks in adults and children 12 years of age and older. It is not known if DAWNZERA is safe and effective in children under 12 years of age.
Do not use DAWNZERA if you: have had a serious allergic reaction, including anaphylaxis to donidalorsen or any of the ingredients in DAWNZERA. See the end of this Patient Information leaflet for a complete list of ingredients in DAWNZERA. Before using DAWNZERA, tell your healthcare provider about all your medical conditions, including if you: are pregnant or plan to become pregnant.
It is not known if DAWNZERA can harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with DAWNZERA. are breastfeeding or plan to breastfeed. It is not known if DAWNZERA passes into your breast milk.
Talk to your healthcare provider about the best way to feed your baby while using DAWNZERA. Tell your healthcare provider about any other medications you take, including prescription and over‑the‑counter medicines, vitamins, and herbal supplements. Know the medicines you take.
Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use DAWNZERA? Read the detailed Instructions for Use that comes with your DAWNZERA single-dose autoinjector.
Your healthcare provider will show you and your caregiver how to inject DAWNZERA the first time. DAWNZERA is injected under your skin (subcutaneous use) in your stomach area (abdomen) or the front of your upper legs (thighs). Only a healthcare provider or caregiver may give you an injection in the back of your upper arm.
Use DAWNZERA exactly as your healthcare provider tells you to take it. You, your caregiver, or healthcare provider should inject DAWNZERA 1 time every 4 weeks or 1 time every 8 weeks depending on your prescribed dosing frequency. If you miss a dose of DAWNZERA, take the missed dose as soon as possible.
Then inject DAWNZERA on the regular dosing schedule from the date of the most recently injected dose. What are the possible side effects of DAWNZERA? DAWNZERA can cause serious side effects, including: Allergic reactions.
DAWNZERA can cause allergic reactions. Stop taking DAWNZERA and call your healthcare provider or go to your nearest emergency room right away if you have symptoms of serious allergic reaction. Symptoms of serious allergic reaction may include: o rash o trouble breathing o fainting, dizziness, feeling lightheaded (low blood pressure) o swelling of your face, lips, or tongue o chest pain o itching The most common side effects of DAWNZERA include: o injection site reactions o upper respiratory tract infection o urinary tract infection o abdominal discomfort These are not the only possible side effects of DAWNZERA.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away while using DAWNZERA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store DAWNZERA? Store DAWNZERA in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton. If needed, DAWNZERA can be stored at room temperature up to 86°F (30°C) in the original carton for up to 6 weeks.
If not used within 6 weeks, throw away DAWNZERA. Do not freeze. Do not expose the autoinjector to heat.
Protect from direct light. Keep DAWNZERA and all medicines out of the reach of children. General information about the safe and effective use of DAWNZERA.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use DAWNZERA for a condition for which it was not prescribed. Do not give DAWNZERA to other people, even if they have the same symptoms or condition that you have.
It may harm them. You can ask your pharmacist or he…