Adzynma
Apadamtase Alfa · Kit
Uses
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
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 ) 2.1 Dosage 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. 2.2 Preparation 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 purple plastic spike pierces through the ADZYNMA powder vial stopper ( Figure G ). The vacuum will draw the diluent into the ADZYNMA powder vial. You may notice some bubbles or foam – this is normal and should soon disappear. Wait until foam or bubbles dissipate before administration. Figure G 11. Swirl the connected vials gently and continuously until the powder is completely dissolved ( Figure H ). Do not shake the vial. Figure H 12. Visually inspect the reconstituted solution for particulate matter before administration. The solution should be clear and colorless in appearance. Do not use the product if particulate matter or discoloration is observed. 13. If the dose requires more than one vial of ADZYNMA, repeat step 1 to step 12 to reconstitute each vial. Use a different BAXJECT II Hi-Flow device to reconstitute each vial of ADZYNMA and diluent. Administration Instructions 14. Take off the blue cap from the BAXJECT II Hi-Flow device ( Figure I ). Attach a Luer-lock syringe ( Figure J ). Do not inject air into the system. Figure I Figure J 15. Turn the system upside down (ADZYNMA vial is now on top). Draw the reconstituted solution into the syringe by pulling the plunger back slowly ( Figure K ). 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. Do not administer ADZYNMA in the same tubing or container at the same time with other medicinal products for infusion. Figure K 16. If a patient is to receive more than one vial of ADZYNMA, the contents of multiple vials can be drawn into the same syringe. Repeat this process for all reconstituted vials of ADZYNMA until the total volume to be administered is reached. 17. Disconnect the syringe and attach a suitable injection needle or an infusion set. 18.
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 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 ) 5.1 Hypersensitivity 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. 5.2 Neutralizing 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.
Side effects
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 . 6.1 Clinical 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) 6.2 Postmarketing 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
8.1 Pregnancy 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. 8.2 Lactation 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. 8.4 Pediatric 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. 8.5 Geriatric 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) ] .
Pregnancy
8.1 Pregnancy 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
8.4 Pediatric 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
8.5 Geriatric 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) ] .
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.
Mechanism of action
12.1 Mechanism 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
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.
Patient 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.
Label text from the FDA structured product label by TAKEDA PHARMACEUTICALS AMERICA, INC. (revised Aug 20, 2026). Long sections are shortened; the complete label is on DailyMed.
Adzynma NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 64764-140 | Kit | TAKEDA PHARMACEUTICALS AMERICA, INC. | BLA |
| 64764-145 | Kit | TAKEDA PHARMACEUTICALS AMERICA, INC. | BLA |
Frequently asked questions
What is Adzynma used for?
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”…
What are the side effects of Adzynma?
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 . 6.1 Clinical Trials Experience Because clinical trials are… See the full label for the complete list.
Who makes Adzynma?
Adzynma is listed by 1 labeler in the FDA NDC directory, including TAKEDA PHARMACEUTICALS AMERICA, INC..