ADAMTS13, Recombinant

ADAMTS13, Recombinant is an enzyme indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).

• ADAMTS13, Recombinant is available under the following different brand names: Adzynma, ADAMTS13, Recombinant-krhn.

Common side effects of ADAMTS13, Recombinant include:

• headache
• diarrhea
• migraine
• abdominal pain
• nausea
• upper respiratory tract infection
• dizziness
• vomiting

Serious side effects of ADAMTS13, Recombinant include:

• rash
• hives
• itching
• tightness of the throat
• chest pain or tightness
• difficulty breathing
• lightheadedness
• dizziness
• nausea
• fainting

Rare side effects of ADAMTS13, Recombinant include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injectable, lyophilized powder for reconstitution

• Nominally 500 IU/vial
• Nominally 1500 IU/vial
• Each vial labeled with actual rADAMTS13 activity, measured in terms of its potency in International Units (IU)

Congenital Thrombotic Thrombocytopenic Purpura

Adult and pediatric dosage

• Prophylactic therapy
  • 40 IU/kg IV every 2 weeks
  • The dosing frequency may be adjusted to once weekly based on prior prophylactic dosing regimens or clinical response
• On-demand therapy
  • Treatment day 1: 40 IU/kg IV
  • Treatment day 2: 20 IU/kg IV
  • Treatment day 3 and thereafter: 15 IU/kg IV every day until 2 days after acute event resolved

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first

• ADAMTS13, Recombinant has no noted severe interactions with any other drugs
• ADAMTS13, Recombinant has no noted serious interactions with any other drugs
• ADAMTS13, Recombinant has no noted moderate interactions with any other drugs
• ADAMTS13, Recombinant has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

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

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using ADAMTS13, Recombinant?”

Long-Term Effects

• See “What Are Side Effects Associated with Using ADAMTS13, Recombinant?”

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 and Lactation

• 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 the study to comply with protocol requirements
  • 2 additional cTTP patients were treated in a compassionate use program during pregnancy
  • Patient 1
    • The 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
    • The 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
    • The 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
    • The 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
    • The infant was delivered by cesarean section at week 29 and the treating physician reported no adverse events
• Lactation
  • There is no information regarding the presence of ADAMTS13, Recombinant in human milk, its effects on milk production, or breastfed infants