Ixazomib

NINLARO ® is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Limitations of Use: NINLARO is not recommended for use in the maintenance setting or in newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasone outside of controlled clinical trials.

Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome. Ixazomib induced apoptosis of multiple myeloma cell lines in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple prior therapies, including bortezomib, lenalidomide, and dexamethasone. The combination of ixazomib and lenalidomide demonstrated synergistic cytotoxic effects in multiple myeloma cell lines. In vivo, ixazomib demonstrated antitumor activity in a mouse multiple myeloma tumor xenograft model.

Recommended starting dose of 4 mg taken orally on Days 1, 8, and 15 of a 28-day cycle. Dose should be taken at least one hour before or at least two hours after food.

None. None.

Thrombocytopenia: Monitor platelet counts at least monthly during treatment and adjust dosing, as needed. Gastrointestinal Toxicities: Adjust dosing for severe diarrhea, constipation, nausea, and vomiting, as needed. Peripheral Neuropathy: Monitor patients for symptoms of peripheral neuropathy and adjust dosing, as needed. Peripheral Edema: Monitor for fluid retention. Investigate for underlying causes, when appropriate. Adjust dosing, as needed. Cutaneous Reactions: Monitor patients for rash and adjust dosing, as needed. Thrombotic Microangiopathy: Monitor for signs and symptoms. Discontinue NINLARO if suspected. Hepatotoxicity: Monitor hepatic enzymes during treatment. Embryo-Fetal Toxicity: NINLARO can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective non-hormonal contraception.

The following adverse reactions are described in detail in other sections of the prescribing information: Thrombocytopenia Gastrointestinal Toxicities Peripheral Neuropathy Peripheral Edema Cutaneous Reactions Thrombotic Microangiopathy Hepatotoxicity The most common adverse reactions (≥20%) are thrombocytopenia, neutropenia, diarrhea, constipation, peripheral neuropathy, nausea, peripheral edema, rash, vomiting, and bronchitis.

Strong CYP3A inducers: Avoid concomitant use with NINLARO. Strong CYP3A Inducers Avoid concomitant administration of NINLARO with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John's Wort).

Store NINLARO at room temperature. Do not store above 30°C (86°F). Do not freeze. Store capsules in original packaging until immediately prior to use.