Ixazomib

Indications

Ixazomib is used for: Multiple Myeloma Indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy

Adult Dose

Multiple Myeloma Indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy Treatment should be continued until disease progression or unacceptable toxicity Starting doses Ixazomib: 4 mg PO on days 1, 8, and 15 of a 28-day cycle; take 1 hr ac or 2 hr pc Lenalidomide: 25 mg PO on days 1-21 of a 28-day cycle; take with or without food Dexamethasone: 40 mg PO in morning on days 1, 8, 15, and 22 of a 28-day cycle Hepatic impairment Mild: No dosage adjustment required Moderate (TB >1.5-3 x ULN) or severe (TB >3 ULN): Decrease starting dose to 3 mg

Child Dose

Renal Dose

Renal impairment Mild-to-moderate: No dosage adjustment required Severe (CrCl <30 mL/min) or ESRD requiring dialysis: Decrease starting dose to 3 mg; ixazomib is not dialyzable and therefore can be administered without regard to the timing of dialysis

Administration

Oral Administration Take once a week on the same day and at approximately the same time for the first 3 weeks of a 4-week cycle Taken at least 1 hr before or at least 2 hr after food Swallow capsule whole with water; do not crush, chew, or open

Contra Indications

Hypersensitivity

Precautions

Cutaneous reactions reported, the most common types being maculopapular and macular rash; manage with supportive care or with dose modification if ≥grade 2 Rare occurrence of drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic, and hepatotoxicity reported; monitor hepatic enzymes regularly and adjust dosing for grade 3 or 4 symptoms Can cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings in animals Thrombocytopenia reported with platelet nadirs typically occurring between days 14 and 21 of each 28-day cycle and recovery to baseline by the start of the next cycle; monitor platelet counts at least monthly during treatment; consider more frequent monitoring during the first 3 cycles Diarrhea, constipation, nausea, and vomiting reported, occasionally requiring use of antidiarrheals, antiemetics, and supportive care Peripheral neuropathy was reported (majority grade 1); the most commonly reported reaction was peripheral sensory neuropathy; monitor for symptoms; new or worsening peripheral neuropathy may require dose modification Peripheral edema reported; adjust dosing of dexamethasone per its prescribing information or ixazomib for grade 3 or 4 symptoms Lactation No data are available in human milk; effects of drug on breast fed infant, or effects of drug on milk production; because potential for serious adverse reactions from drug in breastfed infants is unknown, advise nursing women not to breastfeed during treatment and for 90 days after last dose

Pregnancy-Lactation

Pregnancy Can cause fetal harm when administered to a pregnant woman There are no human data available regarding the potential effect of ixazomib on pregnancy or development of the embryo or fetus Animal studies Ixazomib caused embryofetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose Increases in fetal skeletal variations/abnormalities (fused caudal vertebrae, number of lumbar vertebrae, and full supernumerary ribs) in rabbit studies Decrease fetal weights, a trend towards decreased fetal viability, and increased postimplantation losses were observed in rat studies Contraception Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated Male and female patients of childbearing potential must use effective contraceptive measures during and for 90 days following the final dose Dexamethasone is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters; because drug is administered with dexamethasone, consider risk for reduced efficacy of contraceptives; advise women using hormonal contraceptives to also use a barrier method of contraception Lactation No data are available in human milk; effects of drug on breast fed infant, or effects of drug on milk production; because potential for serious adverse reactions from drug in breastfed infants is unknown, advise nursing women not to breastfeed during treatment and for 90 days after last dose

Interactions

Adverse Effects

Side effects of Ixazomib : >10% Thrombocytopenia (78%) Neutropenia (67%) Diarrhea (42%) Constipation (34%) Peripheral neuropathies (28%) Nausea (26%) Thrombocytopenia, grade 3-4 (26%) Neutropenia, grade 3-4 (26%) Peripheral edema (25%) Vomiting (22%) Back pain (21%) Upper respiratory tract infection (19%) Rash (19%) 1-10% Diarrhea, grade 3 (6%) Blurred vision (6%) Conjunctivitis (6%) Dry eye (5%) Herpes zoster, without antiviral prophylaxis (4%) Rash, grade 3 (3%) Peripheral edema (2%) Peripheral neuropathies, grade 3 (2%) Nausea, grade 3 (2%) Vomiting, grade 3 (1%) <1% Herpes zoster, with antiviral prophylaxis Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic, and hepatotoxicity Upper respiratory tract infection, grade 3 Constipation, grade 3 Back pain, grade 3 Acute febrile neutrophilic dermatosis (Sweet syndrome) Stevens-Johnson syndrome Transverse myelitis Posterior reversible encephalopathy syndrome Tumor lysis syndrome Thrombotic thrombocytopenic purpura

Mechanism of Action

Reversible proteasome inhibitor; preferentially binds and inhibits the chymotrypsinlike activity of the beta 5 subunit of the 20S proteasome