Apadamtase Alfa

FDA Drug Information • Also known as: Adzynma

Brand Names: Adzynma
Dosage Form: KIT
Product Type: HUMAN PRESCRIPTION DRUG

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...

What Is Apadamtase Alfa Used For?

1 INDICATIONS AND USAGE 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) [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. 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 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Most common adverse reactions (>5% of subjects) reported in clinical trials were headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. 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). 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)

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 )

Pregnancy and Breastfeeding

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. 1 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. 1 The second patient had an exacerbation of her cTTP during her second trimester of pregnancy...

How Supplied

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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.