Version May 2024
Congenital thrombotic thrombocytopenic purpura (cTTP): Note: Calculate dose and volume for administration using the actual potency printed on the vial, not the nominal potency.
Prophylactic therapy: Children ≥2 years and Adolescents: IV: 40 units/kg/dose once every other week; may increase frequency to once weekly based on prior prophylactic regimen or clinical response.
On-demand therapy (treatment of acute event): Children ≥2 years and Adolescents:
Day 1: IV: 40 units/kg once.
Day 2: IV: 20 units/kg once.
Day 3 and beyond: IV: 15 units/kg/dose once daily; continue for 2 days after the acute event has resolved.
Children ≥2 years and Adolescents: IV: No dosage adjustment necessary.
Children ≥2 years and Adolescents: IV: No dosage adjustment necessary.
(For additional information see "ADAMTS13, recombinant: Drug information")
Dosage guidance:
Dosing: Calculate administration dose and volume based on the patient's body weight using the actual potency (and not the nominal potency) as printed on ADAMTS13 (recombinant) vial. Each vial is labeled with the actual ADAMTS13 activity (potency is measured in international units).
Congenital thrombotic thrombocytopenic purpura:
Prophylactic therapy: IV: 40 units/kg once every other week; may adjust to 40 units/kg once weekly based on prior prophylactic regimen or clinical response.
On demand therapy:
Treatment day 1: IV: 40 units/kg.
Treatment day 2: IV: 20 units/kg.
Treatment day 3 and beyond: IV: 15 units/kg once daily until 2 days after acute event is resolved.
No dosage adjustment necessary.
No dosage adjustment necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for children, adolescents, and adults.
>10%:
Gastrointestinal: Abdominal pain (13%), diarrhea (17%), nausea (13%)
Nervous system: Headache (31%), migraine (15%)
Respiratory: Upper respiratory tract infection (13%)
1% to 10%:
Gastrointestinal: Vomiting (10%)
Nervous system: Dizziness (10%)
History of life-threatening hypersensitivity reactions to ADAMTS13 (recombinant) or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity: Allergic-type hypersensitivity including anaphylactic reactions may occur with ADAMTS13 (recombinant). Inform patients of early signs of hypersensitivity, including but not limited to tachycardia, chest tightness, wheezing and/or acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and/or restlessness.
• Immunogenicity: ADAMTS13 (recombinant) has a potential for immunogenicity. Patients may develop neutralizing antibodies, which may result in a decreased or lack of response to ADAMTS13. Neutralizing antibodies were not reported in the congenital thrombotic thrombocytopenic purpura (cTTP) clinical trials and all subjects had been previously exposed to ADAMTS13 via plasma-based products. There are no data on immunogenicity with ADAMTS13 (recombinant) in previously untreated patients. Antibodies to host cell proteins may develop, which could potentially result in adverse reactions. Data are lacking on immunogenicity to host cell proteins in previously untreated patients.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Ref). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Ref). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intravenous [preservative free]:
Adzynma: ADAMTS13 (recombinant)-krhn 500 units, ADAMTS13 (recombinant)-krhn 1500 units [latex free; contains polysorbate 80]
Yes
ADAMTS13 (recombinant) is available through specialty pharmacies/distributors and various specialty institutions/accounts. Examples from the manufacturer may be found at: https://www.adzynma.com/how-to-order.
IV: For IV administration only. Gently remove air bubbles from syringe prior to administration. Infuse at a rate of 2 to 4 mL/minute. A syringe pump may be used to control administration rate. Do not administer ADAMTS13 in the same infusion line at the same time with other medications. If severe hypersensitivity reactions including anaphylaxis occur, immediately discontinue infusion and provide appropriate supportive care.
IV: Administer at a rate of 2 to 4 mL/minute. Gently remove air bubbles from syringe prior to administration. A syringe pump may be used to control administration rate. Do not administer ADAMTS13 (recombinant) in the same infusion line at the same time with other medications.
Store intact vial(s) at 2°C to 8°C (36°F to 46°F) for up to 36 months from the date of manufacture until the expiration date on the vial and carton; do not freeze. Within this period, may be stored at ≤30°C (≤86°F) for a period up to 6 months; do not return to refrigerator after storing at room temperature. Store in original carton and protect from extreme exposure to light. Reconstituted solutions should be used within 3 hours after reconstitution when stored at room temperature.
Prophylactic or on-demand enzyme replacement therapy (ERT) in patients with congenital thrombotic thrombocytopenic purpura (cTTP) (FDA approved in ages ≥2 years and adults).
Adzynma may be confused with Adthyza, Adzenys, Akynzeo, Andexxa.
None known.
There are no known significant interactions.
Data related to the use of ADAMTS13 (recombinant) in pregnant patients are limited (Ref).
Untreated thrombotic thrombocytopenic purpura (TTP) is associated with adverse pregnancy outcomes. Agents other than recombinant ADAMTS13 are currently recommended to treat TTP during pregnancy (Ref).
Monitor for signs and symptoms of hypersensitivity (eg, tachycardia, chest tightness, wheezing, acute respiratory distress, hypotension, generalized urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paresthesia, and/or restlessness) and for the development of immunogenicity (development of neutralizing antibodies or antibodies to host cell proteins).
ADAMTS13 (recombinant) is a bivariant human recombinant form of endogenous ADAMTS13 (a plasma zinc metalloprotease with thrombospondin motifs 13), which regulates von Willebrand factor (VWF) activity by cleaving large and ultra-large VWF multimers into smaller units, reducing VWF platelet binding properties and therefore the propensity to form microthrombi.
Onset: Adults: Following a single IV dose of 5 units/kg, 20 units/kg, or 40 units/kg, dose-related increases in individual ADAMTS13 activity were observed and reached maximum activity at ≤1 hour post infusion.
Duration: Adults: Following an IV dose (at the recommended dose), von Willebrand factor (VWF): antigen and VWF:ristocetin cofactor activity are transiently decreased for 1 to 2 days with a 15% to 25% change from baseline; duration of ADAMTS13 activity above 10%: 5.8 days (range: 4.5 to ~9 days).
Half-life elimination: Adults: ~48 hours (40 units/kg dose; range: ~30 to ~90 hours); mean residence time: ~64 hours (40 units/kg dose; range: ~45 to 113 hours).
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