ADZYNMA Apadamtase Alfa Kit
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
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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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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $4.85 | — |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J7171 | $36.214 / J7171 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Adzynmathis 64764-0140-05 | TAKEDA | 1 kit | — | — | FDA listed | — |
| Adzynma 64764-0145-05 | TAKEDA | 1 kit | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Nov 9, 2035 |
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 64764-0140-05 You're viewing this | 1 KIT in 1 CARTON (64764-140-05) * 500 [iU] in 1 VIAL, SINGLE-DOSE (64764-130-01) * 5 mL in 1 VIAL, GLASS (64764-515-50) | 2023-11-09 | Active |
🧭 About this NDC listing & data coverage
Kit / multi-component package
This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.
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 | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: NEUTRALIZING ANTIBODIES TO ADAMTS13 Neutralizing antibodies to ADAMTS13 with serious outcomes, including death, have been reported in patients treated with ADZYNMA. Neutralizing antibodies may result in decreased or lack of response to recombinant or plasma-derived ADAMTS13 see [ Warnings and Precautions (5.2) , Postmarketing Experience (6.2) ] . Monitor all patients closely for ADAMTS13 activity and development of ADAMTS13 neutralizing antibodies [see Warnings and Precautions (5.2) ] .
WARNING: NEUTRALIZING ANTIBODIES TO ADAMTS13 Neutralizing antibodies to ADAMTS13 with serious outcomes, including death, have been reported in patients treated with ADZYNMA. Neutralizing antibodies may result in decreased or lack of response to recombinant or plasma-derived ADAMTS13 ( 5.2 , 6.2 ). Monitor all patients closely for ADAMTS13 activity and development of ADAMTS13 neutralizing antibodies ( 5.2 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ADZYNMA is indicated for prophylactic or on demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP) [see Use in Specific Populations (8.4) , Clinical Studies (14) ]. ADZYNMA (ADAMTS13, recombinant-krhn) is a human recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (rADAMTS13) indicated for prophylactic or on demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For intravenous use after reconstitution only. ( 2 ) Prophylactic Therapy Administer 40 IU/kg body weight once every other week intravenously at a rate of 2 to 4 mL per minute. ( 2.1 ) The prophylaxis dosing frequency may be adjusted to 40 IU/kg body weight once weekly based on prior prophylactic dosing regimen or clinical response.
( 2.1 ) On-Demand Therapy Administer intravenously at a rate of 2 to 4 mL per minute: 40 IU/kg body weight on day 1. ( 2.1 ) 20 IU/kg body weight on day 2. ( 2.1 ) 15 IU/kg body weight on day 3 and beyond until two days after the acute event is resolved.
( 2.1 )
2.1Dosage For intravenous use after reconstitution only. Each vial of ADZYNMA is labeled with the actual rADAMTS13 activity, measured in terms of its potency in International Units (IU). Calculate administration dose and volume based on the patient's body weight using the actual potency (and not the nominal potency) as printed on ADZYNMA vial.
For Intravenous (IV) Infusion at a rate of 2 to 4 mL per minute. Prophylactic Therapy The recommended prophylactic dosage regimen of ADZYNMA is as follows: Administer 40 IU/kg body weight once every other week. The prophylactic dosing frequency may be adjusted to 40 IU/kg body weight once weekly based on prior prophylactic dosing regimen or clinical response [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) , Clinical Studies (14) ].
On-Demand Therapy A guide for dosing ADZYNMA for on demand treatment of an acute event is provided in Table 1 . Table 1: Dosing for On-Demand Therapy Treatment Day 1 Treatment Day 2 Treatment Day 3 and Beyond 40 IU/kg 20 IU/kg 15 IU/kg once daily until two days after the acute event is resolved.
2.2Preparation and Administration Use aseptic technique (clean and germ-free) throughout the procedure. Check the expiration date of the product prior to use. Do not use ADZYNMA if the expiration date has passed.
Reconstitution 1. Prepare a clean, germ-free, flat surface and gather all the materials you will need for the reconstitution and infusion. Figure A depicts the materials provided in the carton box.
Figure A 2. Do not use ADZYNMA if the expiration date has passed. Use ADZYNMA within 3 hours after reconstitution and keep at room temperature not to exceed 86°F/30°C.
Do not store at any other temperature. Discard any unused reconstituted product if not used within 3 hours after reconstitution. 3.
Allow the vials of ADZYNMA and diluent to reach room temperature before use. If the patient needs more than one vial of ADZYNMA per injection, reconstitute each vial according to the instructions stated under ‘Reconstitution’. Inspect the reconstituted ADZYNMA solution for particulate matter and discoloration prior to administration.
The solution should be clear and colorless in appearance. Do not administer if particulate matter or discoloration is observed. 4.
Wash and dry your hands thoroughly, and put on clean exam gloves. 5. Remove plastic caps from the ADZYNMA and diluent vials and place the vials on a flat surface ( Figure B ).
Figure B 6. Wipe the rubber stoppers with an alcohol swab and allow them to dry prior to use ( Figure C ). Figure C 7.
Open the BAXJECT II Hi-Flow device package by peeling away the lid, without touching the inside ( Figure D ). Do not remove the BAXJECT II Hi-Flow device from the package. Do not touch the clear plastic spike.
Figure D 8. Turn the package with the BAXJECT II Hi-Flow device upside down and place it over the top of the diluent vial. Press straight down until the clear plastic spike pierces through the diluent vial stopper ( Figure E ).
Figure E 9. Grip the BAXJECT II Hi-Flow device package at its edge and pull the package off the device ( Figure F ). Do not remove the blue cap from the BAXJECT II Hi-Flow device.
Do not touch the exposed purple plastic spike. Figure F 10. Turn the system over so that the diluent vial is now on top.
Press the BAXJECT II Hi-Flow device straight down until the…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS ADZYNMA is a lyophilized powder in single-dose vials containing nominally 500 or 1500 International Units (IU) per vial and comes with 5 mL of Sterile Water for Injection. Each carton and vial label for ADZYNMA states the actual potency of ADAMTS13 in IU. ADZYNMA is available as a lyophilized powder in single-dose vials containing nominally 500 or 1500 international units. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS ADZYNMA is contraindicated in patients who have manifested life-threatening hypersensitivity reactions to ADZYNMA or its components [see Description (11) ] . Do not use in patients who have manifested life-threatening hypersensitivity reactions to ADZYNMA or its components. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions may occur. Discontinue ADZYNMA if hypersensitivity symptoms occur and administer appropriate emergency treatment. ( 5.1 ) Neutralizing antibodies to ADAMTS13 with serious outcomes including death have been reported in patients with cTTP following administration of ADZYNMA.
Monitor all patients, including those who were previously exposed or naïve to plasma-based products, by assessing ADAMTS13 activity and ADAMTS13 neutralizing antibodies prior to initiation of ADZYNMA and periodically during the course of treatment. ( 5.2 , 6.2 )
5.1Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis may occur with ADZYNMA. Monitor patients for sign and symptoms of hypersensitivity reactions which may include tachycardia, tightness of the chest, wheezing and/or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. If signs and symptoms of severe hypersensitivity reactions occur, immediately discontinue administration of ADZYNMA and provide appropriate supportive care.
5.2Neutralizing Antibodies Neutralizing antibodies to ADAMTS13 with serious outcomes including death have occurred following ADZYNMA administration [see Postmarketing Experience (6.2) ] . Neutralizing antibodies may result in a decreased or lack of response to ADZYNMA which could lead to serious disease related outcomes. Neutralizing antibodies were not reported in the cTTP clinical trials.
All subjects had been previously exposed to ADAMTS13 through plasma-based products. There are no data on immunogenicity with ADZYNMA in previously untreated patients (subjects naïve to plasma-based products) [see Clinical Pharmacology (12.6) ] . Monitor all patients, including those who were previously exposed or naïve to plasma-based products, by assessing ADAMTS13 activity and ADAMTS13 neutralizing antibodies prior to initiation of ADZYNMA and periodically during the course of treatment.
If expected ADAMTS13 activity levels are not attained or if acute TTP exacerbation occurs despite appropriate dose, perform an assay that measures ADAMTS13 neutralizing antibody concentrations. Laboratory tests for monitoring neutralizing antibody levels are not capable of distinguishing between inhibitors directed against ADZYNMA, the patient’s endogenous ADAMTS13, or ADAMTS13 from other plasma sources.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (incidence >5%) are headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) 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 profile of ADZYNMA was evaluated in one, prospective, randomized, active-controlled, open-label, multicenter, two-period crossover study (Study 1) that treated 48 patients who had been previously exposed to ADAMTS13 through plasma-based products.
Patients received ADZYNMA at the dose of 40 IU/kg/dose. The adverse drug reactions (ADR) are listed in Table 2 . Table 2: Adverse Reactions Reported in >5% of Patients Treated with ADZYNMA Adverse Reaction ADZYNMA (N= 48) n (%) Percentages by patient were calculated using the number of all subjects who had the listed adverse event.
N = Total number of patients treated with ADZYNMA in Study 1. n = Number of patients who had at least one event in the category. Headache 15 (31.3) Diarrhea 8 (16.7) Migraine 7 (14.6) Abdominal pain 6 (12.5) Nausea 6 (12.5) Upper respiratory tract infection 6 (12.5) Dizziness 5 (10.4) Vomiting 5 (10.4)
6.2Postmarketing Experience The following adverse reactions have been reported during the post-approval use of ADZYNMA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. Blood and lymphatic system: Neutralizing antibodies to ADAMTS13 with serious outcomes including death [see Warnings and Precautions (5.2) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data with ADZYNMA use during pregnancy are insufficient to inform a drug-associated risk of adverse developmental outcomes. In determining whether ADZYNMA should be used in pregnancy, healthcare providers should balance the potential benefits with the potential risks.
The background rate of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data There have been four cTTP patients exposed to ADZYNMA during pregnancy.
Two patients in a long-term extension study were found to be pregnant early in the first trimester while receiving prophylaxis with ADZYNMA. Both patients were discontinued from the study to comply with the protocol requirements. The first patient had no further exposure to ADZYNMA and had a first trimester miscarriage approximately two months after study discontinuation.
The investigator assessed the event was unrelated to ADZYNMA. The second patient resumed treatment with ADZYNMA under a compassionate use program and delivered a healthy full-term baby with no safety concerns reported by the investigator. Two additional cTTP patients were treated with ADZYNMA in a compassionate use program during pregnancy.
The first patient, in the third trimester of her second pregnancy, experienced a stroke and thrombocytopenia that was refractory to daily plasmapheresis. At 33 weeks of gestation, ADZYNMA treatment was started once weekly. ADAMTS13 activity levels normalized, thrombocytopenia resolved, and a healthy baby was delivered at 37 weeks with no safety concerns reported by the treating physician due to ADZYNMA.
The second patient had an exacerbation of her cTTP during her second trimester of pregnancy despite prior daily plasma exchange. Her pregnancy was considered to be at risk, with inadequate response to plasma-based therapies. ADZYNMA was started once weekly and induced clinical remission.
The baby was delivered by a cesarean section at week 29 and the treating physician reported no adverse events due to ADZYNMA. Whether ADZYNMA should be used in pregnancy is solely up to the medical judgment of the healthcare provider. Nonclinical Data In an embryo-fetal development study in rats, ADZYNMA was administered in female rats at 80, 200, or 400 IU/kg [up to 10x human equivalent dose (HED)] every third day from 2 weeks before mating through Day 16 of gestation and was not associated with any adverse maternal findings or treatment-related effects on embryo-fetal development.
In a pre- and post-natal development study in rats, ADZYNMA was administered at 80, 200, or 400 IU/kg [up to 10x HED] by intravenous (IV) bolus injection every three days from Day 6 of gestation to weaning at approximately Day 21 of lactation. There were no adverse maternal effects or findings in F1 or F2 offspring.
8.2Lactation Risk Summary There is no information regarding the presence of ADZYNMA in human milk, its effects on milk production or the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ADZYNMA and any potential adverse effects to the breastfed child.
8.4Pediatric Use The safety and effectiveness of ADZYNMA has been established in pediatric patients. Clinical trials included patients aged 2 years and older. Based on data from population pharmacokinetic (PK) analysis, no additional dose adjustments beyond body weight are required for this age group. The recommended body-weight based dosing regimen in pediatric patients is the same as that in adults.
8.5Geriatric Use Clinical studies of ADZYNMA did not include patients 65 years of age and older to determine whether they respo…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The safety of ADZYNMA for use during pregnancy has not been established in controlled clinical trials. Limited data with ADZYNMA use during pregnancy are insufficient to inform a drug-associated risk of adverse developmental outcomes. In determining whether ADZYNMA should be used in pregnancy, healthcare providers should balance the potential benefits with the potential risks.
The background rate of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data There have been four cTTP patients exposed to ADZYNMA during pregnancy.
Two patients in a long-term extension study were found to be pregnant early in the first trimester while receiving prophylaxis with ADZYNMA. Both patients were discontinued from the study to comply with the protocol requirements. The first patient had no further exposure to ADZYNMA and had a first trimester miscarriage approximately two months after study discontinuation.
The investigator assessed the event was unrelated to ADZYNMA. The second patient resumed treatment with ADZYNMA under a compassionate use program and delivered a healthy full-term baby with no safety concerns reported by the investigator. Two additional cTTP patients were treated with ADZYNMA in a compassionate use program during pregnancy.
The first patient, in the third trimester of her second pregnancy, experienced a stroke and thrombocytopenia that was refractory to daily plasmapheresis. At 33 weeks of gestation, ADZYNMA treatment was started once weekly. ADAMTS13 activity levels normalized, thrombocytopenia resolved, and a healthy baby was delivered at 37 weeks with no safety concerns reported by the treating physician due to ADZYNMA.
The second patient had an exacerbation of her cTTP during her second trimester of pregnancy despite prior daily plasma exchange. Her pregnancy was considered to be at risk, with inadequate response to plasma-based therapies. ADZYNMA was started once weekly and induced clinical remission.
The baby was delivered by a cesarean section at week 29 and the treating physician reported no adverse events due to ADZYNMA. Whether ADZYNMA should be used in pregnancy is solely up to the medical judgment of the healthcare provider. Nonclinical Data In an embryo-fetal development study in rats, ADZYNMA was administered in female rats at 80, 200, or 400 IU/kg [up to 10x human equivalent dose (HED)] every third day from 2 weeks before mating through Day 16 of gestation and was not associated with any adverse maternal findings or treatment-related effects on embryo-fetal development.
In a pre- and post-natal development study in rats, ADZYNMA was administered at 80, 200, or 400 IU/kg [up to 10x HED] by intravenous (IV) bolus injection every three days from Day 6 of gestation to weaning at approximately Day 21 of lactation. There were no adverse maternal effects or findings in F1 or F2 offspring.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of ADZYNMA has been established in pediatric patients. Clinical trials included patients aged 2 years and older. Based on data from population pharmacokinetic (PK) analysis, no additional dose adjustments beyond body weight are required for this age group. The recommended body-weight based dosing regimen in pediatric patients is the same as that in adults.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of ADZYNMA did not include patients 65 years of age and older to determine whether they respond differently from younger patients. Based on the results from population pharmacokinetics analysis, no dose adjustment is required for elderly patients [see Clinical Pharmacology (12.3) ] .
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action ADZYNMA is a recombinant form of the endogenous ADAMTS13. ADAMTS13 is a plasma zinc metalloprotease that regulates the activity of von Willebrand factor (VWF) by cleaving large and ultra-large VWF multimers to smaller units and thereby reducing the platelet binding properties of VWF and its propensity to form microthrombi.
12.2Pharmacodynamics VWF antigen (VWF:AG) and VWF:ristocetin cofactor activity (VWF:RCo) were used to assess VWF platelet binding activity. Following IV doses of ADZYNMA at the recommended dose, both VWF:AG and VWF:RCo transiently decreased for 1 to 2 days with a 15% to 25% change from baseline.
12.3Pharmacokinetics The PK profile of ADZYNMA was determined based on clinical trial ADAMTS13 activity data analyses. Following single-dose IV administration of ADZYNMA at 5 IU/kg, 20 IU/kg, and 40 IU/kg to adults and adolescents, dose-related increases in individual ADAMTS13 activity were observed and reached a maximum at approximately 1-hour post-infusion or earlier. At a dose of 40 IU/kg the mean (SD) half-life and mean residence time (MRT) in adults and adolescents were 47.8 (13.7) hours and 63.8 (16.0) hours, respectively.
The PK parameters of ADAMTS13 activity following IV administration of ADZYNMA at 40 IU/kg in adults and adolescents are described in Table 3 . Table 3: Pharmacokinetic Parameters of ADAMTS13 Activity following IV Administration of ADZYNMA in cTTP Patients ≥12 Years Old Parameter (unit) Mean (SD) Min; Max (N=23) AUC = area under ADAMTS13 activity-time curve; C ave (0-168 h) = average ADAMTS13 activity from 0 to 168 hours dosing interval; C max = maximum ADAMTS13 activity; IR = incremental recovery; MRT = mean residence time; t 1/2 = half-life.
Note: 1 IU/mL ADAMTS13 activity corresponds to 100% average normal activity. C max (IU/mL) 1.15 (0.25) 0.78;
1.56IR [(IU/mL)/(IU/kg)] 0.03 (0.01) 0.02; 0.04 t ½ (h) 47.8 (13.70) 30.1;
90.8AUC 0-inf (IUxh/mL) 57.6 (13.9) 37.0;
88.2AUC (0-168 h) (IUxh/mL) 57.2 (13.67) 36.2;
87.2MRT 0-inf N=22 (h) 63.8 (16.0) 44.8; 113 C ave (0-168 h) (IU/mL) 0.30 (0.07) 0.20;
0.46Duration ADAMTS13 Activity above 10% (days) 5.8 (1.2) 4.5;
8.9ADZYNMA IV administration at 40 IU/kg resulted in approximately 4- to 5-fold higher ADAMTS13 activity exposures (C max , AUC) and lower inter-subject variability when compared to plasma-based therapies. Mean time duration above 10% ADAMTS13 activity and mean average ADAMTS13 activity (C ave ) were both approximately 3- to 4-fold higher following ADZYNMA IV administration than plasma-based therapies. Based on Population PK analysis leveraging available data (N=65) from adults, adolescents and pediatric patients below 12 years of age, the mean (SD) steady state C max , AUC all , C ave , and duration of ADAMTS13 activity above 10% following IV administration of ADZYNMA every other week in cTTP patients below 12 years of age were 1.02 (0.19) IU/mL, 54.0 (12.2) IU*h/mL, 0.16 (0.04) IU/mL, and 6.8 (2.1) days, respectively.
ADAMTS13 antigen and activity PK characteristics (MRT, V ss , and CL) were similar across age groups in patients with cTTP. Body-weight based ADZYNMA dosing provides similar ADAMTS13 activity PK parameters (C max and C ave ) across the different age groups including pediatric patients <12 years of age. Specific Populations Besides body-weight dosing regimen, no dose adjustment is required since no intrinsic factors such as age, gender, race, baseline estimated glomerular filtration rate (eGFR), and baseline bilirubin were identified as covariates impacting ADAMTS13 PK.
Pediatric Patients Population pharmacokinetics (PK) analysis leveraging available data from adults, adolescents and pediatric patients below 12 years of age (N=65), suggests comparable ADAMTS13 activity exposures between patients below 12 years of age and patients aged 12 years and above receiving the recommended ADZYNMA dosing regimen [see Use in Specific Populations (8.4) ] .
12.6 Immunogenicity The…
🧬 Mechanism of Action ▾
12.1Mechanism of Action ADZYNMA is a recombinant form of the endogenous ADAMTS13. ADAMTS13 is a plasma zinc metalloprotease that regulates the activity of von Willebrand factor (VWF) by cleaving large and ultra-large VWF multimers to smaller units and thereby reducing the platelet binding properties of VWF and its propensity to form microthrombi.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ADZYNMA (rADAMTS13) is a sterile, nonpyrogenic, preservative free, white powder supplied in single-dose vials packaged with: one vial with 5 mL sterile water for injection, USP one BAXJECT II Hi-FLOW needleless transfer device one syringe one 25 gauge infusion set two individually packaged alcohol swabs one package insert ADZYNMA (rADAMTS13) is available in the following strengths: Color Code Nominal rADAMTS13 Potency rADAMTS13 vial NDC Carton NDC Syringe Fill Size Eggplant 500 IU 64764-130-01 64764-140-05 10 mL Marigold 1500 IU 64764-135-01 64764-145-05 20 mL The actual ADAMTS13 potency in international units is printed on the label of each ADZYNMA vial and carton.
Components are not made with natural rubber latex. Storage and Handling Store at refrigerated temperature 2°C to 8°C (36°F to 46°F) for up to 36 months from the date of manufacture until expiration date stated on the ADZYNMA vial label and carton. Within this period, ADZYNMA may be stored at room temperature not to exceed 30°C/86°F for a period up to 6 months.
After storage at room temperature, do not return to the refrigerator. Do not use beyond the expiration date printed on the ADZYNMA vial label or carton or if not stored properly. Do not freeze.
Store in the original box and protect from extreme exposure to light. Use reconstituted product immediately or within 3 hours after reconstitution when stored at room temperature. Do not use if the solution in the syringe is cloudy or contains particles.
Discard any unused reconstituted product after 3 hours.
📋 Description ▾
11 DESCRIPTION ADZYNMA is a purified bivariant human recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (rADAMTS13) expressed in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology (a mixture of Native rADAMTS13 Q23 and Variant rADAMTS13 R23 with a controlled range of the two variants ratio). ADZYNMA is produced and formulated without the addition of any exogenous raw materials of human or animal origin in the cell culture, purification, or formulation of the final product.
The purification process for rADAMTS13 does not include use of a monoclonal antibody reagent. To enhance viral safety, the production process also incorporates two dedicated viral clearance steps – a solvent/detergent treatment step for inactivation and a 20 nm filtration step for removal of viruses. Recombinant ADAMTS13 has a molecular weight of approximately 172 kDa.
Proteins that may be present in the final product, other than rADAMTS13, are trace quantities of host cell (CHO) proteins. ADZYNMA (rADAMTS13) is a sterile, nonpyrogenic, preservative free, white powder supplied in single-dose vials for IV use after reconstitution. Each single-dose vial contains nominally 500 IU or 1500 IU of rADAMTS13, sodium chloride (9.4 mg), calcium chloride dihydrate (1.6 mg), L-histidine (16.7 mg), mannitol (161.4 mg), sucrose (53.8 mg), and polysorbate 80 (2.7 mg).
Each vial of ADZYNMA is labeled with the specific number of units of ADAMTS13 potency expressed in IU as measured with a fluorescence resonance energy transfer (FRET) assay using a synthetic 73-amino-acid peptide (FRETS-VWF73). The potency assignment employs an ADAMTS13 concentrate standard that is referenced to a WHO (World Health Organization) international standard for ADAMTS13 concentrates and is evaluated by appropriate methodology to ensure accuracy of the results. After reconstitution with 5 mL of Sterile Water for Injection, USP, the 500 IU and the 1500 IU vials result in a nominal potency of 100 IU/mL and 300 IU/mL, respectively.
All dosage strengths yield a clear, colorless solution, free from particles with a pH of approximately 7.0.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient: To read the FDA-approved patient labeling ( Patient Information ). About early signs of hypersensitivity reactions, including tachycardia, tightness of the chest, wheezing and/or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and restlessness. Advise patients to discontinue use of the product if these symptoms occur and seek immediate emergency treatment with appropriate supportive care.
To consult with their physicians or healthcare provider prior to traveling. While traveling, advise patients to bring an adequate supply of ADZYNMA based on their current regimen of treatment.