Ixazomib — Drug Monograph

Brand names: Ninlaro

Drug class: Proteasome Inhibitor

Mechanism of Action

Ixazomib is a reversible proteasome inhibitor that preferentially binds to and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome. At higher concentrations, it also inhibits the caspase-like activity of the beta 1 subunit and trypsin-like activity of the beta 2 subunit. Inhibition of the proteasome prevents the degradation of polyubiquitinated proteins, which leads to cell cycle arrest and apoptosis in leukemia and myeloma cell lines. It is the first orally bioavailable proteasome inhibitor.

FDA Indications

• In combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy

Common Side Effects

• Diarrhea
• Constipation
• Thrombocytopenia
• Peripheral neuropathy
• Nausea
• Peripheral edema
• Vomiting
• Back pain

Clinical Pearl

Ixazomib offers an all-oral triplet regimen when combined with lenalidomide and dexamethasone, significantly reducing the treatment burden compared to parenteral proteasome inhibitors. It has a lower incidence of peripheral neuropathy than bortezomib, particularly because it is administered weekly. Monitor for skin rash, which is a known class effect but may require dose interruption or corticosteroids. Always ensure patients are aware of the specific "on-off" weekly dosing schedule to avoid…

Related Therapies & Mechanisms

• Bortezomib (Velcade) — Proteasome Inhibitor · Myeloma
• Carfilzomib (Kyprolis) — Proteasome Inhibitor · Myeloma
• Belantamab mafodotin (Blenrep) — Myeloma
• Ciltacabtagene autoleucel (Carvykti) — Myeloma