Precautions of Ixazomib

1.Thrombocytopenia

Monitor platelet counts at least monthly during treatment with Ixazomib. Consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines.

2.Gastrointestinal Toxicities

Diarrhea, constipation, nausea, and vomiting have been reported with Ixazomib, occasionally requiring use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea was reported in 52% of patients in the Ixazomib regimen and 43% in the placebo regimen, constipation in 35%  and 28%, respectively, nausea in 32% and 23%, respectively, and vomiting in 26% and 13%, respectively. Diarrhea resulted in discontinuation of one or more of the three drugs in 3% of patients in the Ixazomib regimen and 2% of patients in the placebo regimen. Adjust dosing for Grade 3 or 4 symptoms.

3.Peripheral Neuropathy

The most commonly reported reaction was peripheral sensory neuropathy (24% and 17% in the Ixazomib and placebo regimen, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more  of the three drugs in 4% of patients in the Ixazomib regimen and <1% of patients in the placebo  regimen. Patients should be monitored for symptoms of neuropathy. Patients experiencing new or  worsening peripheral neuropathy may require dose modification. 

4.Peripheral Edema

Grade 3 peripheral edema was reported in 2% and 1% of patients in the Ixazomib and placebo regimens, respectively. Peripheral edema resulted in discontinuation of one or more of the three drugs in <1% of patients in both regimens. Evaluate for underlying causes and provide supportive care, as necessary. Adjust dosing of dexamethasone per its prescribing  information or Ixazomib for Grade 3 or 4 symptoms.

5.Cutaneous Reactions

The most common type of rash reported in both regimens included maculo-papular and macular rash. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification if Grade 2 or higher.

Stevens-Johnson syndrome and toxic epidermal necrolysis, including fatal cases, have been reported with Ixazomib. If Stevens-Johnson syndrome or toxic epidermal necrolysis occurs, discontinue Ixazomib and manage as clinically indicated.

6.Thrombotic Microangiopathy

Cases, sometimes fatal, of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in patients who received Ixazomib. Monitor for signs and symptoms of TTP/HUS. If the  diagnosis is suspected, stop Ixazomib and evaluate. If the diagnosis of TTP/HUS is excluded,  consider restarting Ixazomib. The safety of reinitiating Ixazomib therapy in patients previously  experiencing TTP/HUS is not known.

from FDA,2024.07