ADAMTS13, recombinant (Rx)

>10%

Headache (31.3%)

Diarrhea (16.7%)

Migraine (14.7%)

Abdominal pain (12.5%)

Nausea (12.5%)

Upper respiratory tract infection (12.5%)

Dizziness (10.4%)

Vomiting (10.4%)

Contraindications

History of life-threatening hypersensitivity to ADAMTS13 recombinant or its components

Cautions

Hypersensitivity

• Allergic-type hypersensitivity including anaphylactic reactions may occur
• Inform patient 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 restlessness
• If signs and symptoms of severe allergic reactions occur, immediately discontinue recombinant ADAMTS13 and provide appropriate supportive care

Immunogenicity

• Patients may develop neutralizing antibodies to ADAMTS13, which could potentially result in decreased or lack of response; antibodies to host cell proteins may also result in adverse reactions
• Neutralizing antibodies were not reported in cTTP clinical trials
• All participants had been previously exposed to ADAMTS13 through plasma-based products

Pregnancy

Limited data with use during pregnancy are insufficient to inform a drug-associated risk of adverse developmental outcome

Human data

• There have been 4 patients exposed during pregnancy
• 2 patients in a long-term extension study were found to be pregnant early in the first trimester while receiving prophylaxis; both patients were discontinued from study to comply with protocol requirements
• 2 additional cTTP patients were treated in a compassionate use program during pregnancy

• Patient 1

  • First patient had no further exposure and had a first trimester miscarriage ~2 months after study discontinuation; assessment by the investigator determined the miscarriage was unrelated to recombinant ADAMTS13

• Patient 2

  • Second patient resumed treatment with ADAMTS13, recombinant under a compassionate use program and delivered a healthy full-term baby with no safety concerns reported by the investigator

• Patient 3

  • 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, recombinant ADAMTS13 treatment was started once weekly in a compassionate use program
  • ADAMTS13 activity levels normalized, thrombocytopenia resolved, and a healthy baby was delivered at 37 weeks with no safety concerns reported by the treating physician

• Patient 4

  • Patient had an exacerbation of her cTTP during her second trimester of pregnancy despite prior daily plasma exchange
  • Her pregnancy was at risk with inadequate response to plasma-based therapies
  • Recombinant ADAMTS13 was started once weekly and induced clinical remission
  • Infant was delivered by cesarean section at week 29 and treating physician reported no adverse events

Lactation

There is no information regarding the presence in human milk, effects on milk production, or breastfed infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant form of endogenous ADAMTS13

Congenital thrombotic thrombocytopenic purpura (cTTP), is an ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) gene deficiency disorder

ADAMTS13 enzyme splices von Willebrand factor to regulate its interaction with platelets; this action is involved in platelet adhesion to form temporary clots at the site of an injury

Absorption

Peak plasma concentration: 1.15 IU/mL (≥12 yr); 1.02 IU/mL (<12 yr)

AUC: 57.2-57.6 IU⋅h/mL (≥12 yr); 54 IU⋅h/mL (<12 yr)

Elimination

Half-life: 47.8 hr

IV Incompatibilities

Do not administer in same tubing or container at the same time with other medicinal products for infusion

IV Preparation

Check expiration date of product prior to use; do not use if date expired

Allow vial(s) and diluent to reach room temperature before use

Reconstitute each vial with provided diluent (5-mL vial of sterile water for injection) according to detailed instructions and diagrams in the prescribing information

Inspect reconstituted solution for particulate matter and discoloration before administration; solution should appear clear and colorless

Discard if particulate matter or discoloration observed

Calculate dose and volume based on patient’s body weight using actual potency (not the nominal potency) as printed on label

Use within 3 hr after reconstitution and keep at room temperature not to exceed 86ºF/30ºC

IV Administration

Infuse slowly at rate of 2-4 mL/min

May use syringe pump to control infusion rate

Storage

Unopened vial

• Refrigerate at 2-8ºC (36-46ºF) for up to 36 months from date of manufacture until expiration date stated on vial label and carton
• Within this period, may store at room temperature not to exceed 30ºC/86ºF for up to 6 months
• After storage at room temperature, do not return to refrigerator
• Do not freeze
• Store in original box and protect from extreme exposure to light

Reconstituted vial

• Use within 3 hr after reconstitution and keep at room temperature not to exceed 86ºF/30ºC
• Do not store at any other temperature
• Discard any unused reconstituted product if not used within 3 hr after reconstitution