Ixazomib

Ixazomib is an oral proteasome inhibitor used in the treatment of multiple myeloma. It is the citrate prodrug ixazomib, which is converted in the body to the active boronic acid compound that inhibits the 20S proteasome. By blocking proteasome activity, ixazomib disrupts protein degradation, leading to the accumulation of ubiquitinated proteins and inducing apoptosis in malignant plasma cells. Its oral formulation provides an all‑oral option in appropriate regimens.

Medical uses

Ixazomib is approved for adults with multiple myeloma that has progressed after at least one prior therapy. It is most commonly used in combination with lenalidomide and dexamethasone for relapsed or refractory disease, offering an all‑oral regimen compared with injectable proteasome inhibitors. It may be used as part of other regimens in certain contexts, but is not generally used as initial therapy for newly diagnosed disease.

Administration and pharmacology

As an oral agent, ixazomib is taken in cycles that are defined by the accompanying regimen. It is absorbed with moderate bioavailability and is extensively metabolized in the liver, with elimination mainly via feces. The drug is metabolized by hepatic enzymes, including CYP pathways, and potential drug interactions or hepatic impairment may necessitate dose adjustments and monitoring.

Adverse effects

Common adverse events include thrombocytopenia, nausea, diarrhea, vomiting, fatigue, peripheral neuropathy, rash, and edema. Infections and elevations in liver enzymes can occur. Regular monitoring of blood counts and organ function is recommended during treatment.

Development and regulation

Ixazomib citrate was developed for use by Takeda/Millennium Pharmaceuticals and received regulatory approval in the United States in 2015 for use with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma, with subsequent approvals in other regions. It remains one of several proteasome inhibitors used in myeloma therapy.