| Boxed warning |
The most common adverse reactions that occurred in patients treated with Itvisma® were upper respiratory tract infection, fever, upper gastrointestinal symptoms, increased liver enzymes, headache, dizziness, pain in extremity, low platelet counts, and sensory disturbance. |
| Warnings and precautions |
If any of the following signs occur after Itvisma® injection, consult your healthcare provider immediately: fever, lethargy, decreased feeding, decreased urination, seizures, or easy bruising or bleeding.
1.) Hepatotoxicity, with elevated ALT and/or AST levels, can occur. Patients with preexisting hepatic impairment or acute hepatic viral infection may be at higher risk of liver injury. In order to mitigate potential aminotransferase elevations, administer systemic corticosteroid before and after Itvisma® injection. Immune-mediated hepatotoxicity may require adjustment of the corticosteroid treatment regimen, including longer duration, increased dose, or prolongation of the corticosteroid taper.
2.) Low platelet counts (thrombocytopenia) can occur. Platelet counts are expected to return to baseline two weeks following Itvisma® injection.
3.) Peripheral sensory neuropathy has occurred with Itvisma® administration. Signs and symptoms may include numbness, tingling, prickling, or pain in the arms, hands, legs and/or feet, with onset seen at approximately three weeks post-injection in clinical studies. Patients and caregivers should promptly notify their physician if such symptoms occur.
4.) Thrombotic microangiopathy (TMA) may occur with Itvisma® administration. TMA is characterized by thrombocytopenia (low platelet count), microangiopathic hemolytic anemia (bleeding), and acute kidney injury.
5.) Troponin I levels may increase without clinical symptoms. Consider cardiac evaluation and consult a cardiologist if needed.
6.) integration of AAV vector DNA into the genome. Random integration of recombinant AAV-vector DNA into human DNA has been reported with AAV gene therapies like Itvisma®. Long-term studies in animals show rare, clonal integration events can occur, especially in the liver, raising theoretical concerns for high-dose treatments. Long-term studies assessing cancer risk in humans are limited.
|
| Monitoring |
Prior to Itvisma® injection:
- Assess for illness, and do not give Itvisma® if concurrent infection is suspected until the infection has resolved
- Assess vaccination status
- Obtain Anti-AAV9 antibodies testing
- Assess liver function (exam and blood testing for liver enzymes, albumin, clotting
- Obtain blood for creatinine, complete blood count, including hemoglobin and platelet count
After Itvisma® injection:
- Monitor liver function (AST, ALT, total bilirubin) weekly for the month after Itvisma® injection and during the corticosteroid taper period (over the next 28 days or longer if needed).
- If the patient is clinically stable with unremarkable findings (normal clinical exam, total bilirubin, and ALT and AST levels below 2 × ULN) at the end of the corticosteroid taper period, continue to monitor liver function every other week for another month.
- Monitor platelet counts weekly for the first month and as clinically indicated until platelet counts return to baseline.
|
