Formulation and Specifications: Capsules: 2.3 mg, 3 mg, 4 mg
Indications: In combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
Rational dosing points:
1. The route of administration of this product is oral. Patients should take this product at approximately the same time on days 1, 8, and 15 of each treatment cycle, at least 1 hour before or at least 2 hours after a meal, and should take the entire capsule with water. Do not crush, chew or open the capsule.
2. Before starting a new treatment cycle, the following should be met: absolute neutrophil count should be ≥1×109/L, platelet count should be ≥75×109/L, and non-hematologic toxicity should generally return to the patient’s baseline status or ≤ Grade 1.
3. Treatment should be continued until disease progression or intolerable toxicity occurs. Because of the limited data related to tolerability and toxicity after 24 cycles, coadministration of therapy requiring longer than 24 cycles should be based on individual patient benefit risk assessment results.
4. If a dose of this product is delayed or missed, the missed dose should only be made up if it is ≥72 hours before the next scheduled dose. The missed dose should not be made up within 72 hours of the next scheduled dose. Do not take a double dose to make up for a missed dose. If the patient vomits after taking the drug, the dose should not be repeated but should be resumed at the next scheduled dose.
5. Antiviral prophylaxis should be considered in patients treated with this product to reduce the risk of herpes zoster virus reactivation. In the Ixazomib study, the incidence of herpes zoster infection was lower in patients receiving antiviral drug prophylaxis than in those who did not receive prophylaxis.
6. For the overlapping toxicity of izatzomib and lenalidomide thrombocytopenia, neutropenia, and rash, alternate dose adjustments of izatzomib and lenalidomide are recommended. For these toxicities, the first step in dose adjustment is to discontinue/reduce the lenalidomide dose; see the lenalidomide drug insert for dose reduction steps for these toxicities.
7. For patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin > 1 to 1.5 times any level of ULN and AST), no dose adjustment of this product is necessary. For patients with moderate (total bilirubin > 1.5 to 3 times ULN) or severe (total bilirubin > 3 times ULN) hepatic impairment, a dose reduction to 3 mg is recommended.
8. For patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min), no dose adjustment of this product is required. For patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease requiring dialysis, a dose reduction to 3 mg is recommended. isazolomib is not cleared by dialysis and therefore can be administered without regard to the duration of dialysis.
9. No dose adjustment is necessary for patients older than 65 years of age.
10. Common adverse reactions (>20%) to Ixazomib include diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, and back pain. The incidence of peripheral neuropathy is lower than that of bortezomib.
11. Dose adjustment is required for co-administration of Ixazomib with CYP3A potent inhibitors and CYP1A2 potent inhibitors.
12. The risk of reduced efficacy of oral contraceptives needs to be considered when rizazomib is co-administered with dexamethasone. Women using hormonal contraception also need to use barrier contraception.
13. Newly diagnosed multiple myeloma, amyloidosis, and Walden’s macroglobulinemia (Phase I-II clinical data only).