Must-read for patients: Overview of basic information in the instructions for use of ixazomib

1. Generic name: Ixazomib

Product name:Ninlaro, Enleri

Other names: Ixazomib Citrate Capsules,Ixazomib, Ixazomib

2. Indications:

Ixazomib is indicated for use in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received at least one prior therapy.

Limitations of Use: Ixazomib is not recommended for maintenance therapy or in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma outside of controlled clinical trials.

3. Usage and dosage:

1. Recommended dose: The recommended starting dose of ixazomib is 4 mg, taken orally once a week on days 1, 8 and 15 of a 28-day treatment cycle. The recommended starting dose of lenalidomide is 25 mg administered daily on days 1 through 21 of a 28-day treatment cycle. The recommended starting dose of dexamethasone is 40 mg, administered on days 1, 8, 15, and 22 of a 28-day treatment cycle. Treatment should be continued until disease progression or unacceptable toxicity.

Ixazomib should be taken once on the same day and at about the same time during the first three weeks of the four-week cycle, and should be taken at least one hour before or two hours after a meal. When initiating treatment, the importance of carefully following all dosage instructions should be discussed with the patient and the patient should be instructed to take the recommended dose as directed, as death has occurred from overdose.

2. Medication management: If the dose of ixazomib is delayed or missed, the dose should be taken only ≥72 hours after the next scheduled dose. A missed dose should not be taken within 72 hours of the next scheduled dose. A double dose should not be taken to make up for a missed dose. If vomiting occurs after taking the medication, the patient should not take the medication again. Patients should resume dosing at the next scheduled dose.

Before starting a new round of treatment: The doctor will conduct relevant examinations on the patient. For example, the absolute neutrophil count should be at least 1000/mm3; the platelet count should be at least 75000/mm3. Non-hematological toxicity should be determined by the medical staff at their own discretion. Generally, it will return to the patient's baseline status or grade 1 or lower.

3. Dose adjustment: If the patient takes ixazomibIf adverse reactions occur, the doctor will adjust the drug dose according to the severity of the condition. The first dose can be reduced to3mg; the second dose can be reduced to 2mg; patients who cannot tolerate the 2mg dose should stop using ixazomib. An alternating dose adjustment approach is recommended for ixazomib and lenalidomide for thrombocytopenia, neutropenia, and rash.

(1) Patients with hepatic impairment: For patients with moderate (total bilirubin >1.5-3×ULN) or severe (total bilirubin >3×ULN) hepatic impairment, reduce the starting dose of ixazomib to 3 mg.

(2) Patients with renal impairment: For patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease (ESRD) requiring dialysis, reduce the starting dose of ixazomib to 3 mg. Ixazomib is not dialyzable and therefore can be administered regardless of dialysis time.

4. Adverse reactions:

In clinical studies of ixazomib combination, the most commonly reported adverse reactions (≥20%) were thrombocytopenia, neutropenia, diarrhea, constipation, peripheral neuropathy, nausea, peripheral edema, rash, vomiting, and bronchitis; serious adverse reactions reported in ≥2% of patients included diarrhea, thrombocytopenia, and bronchitis.

5. Storage:

Store ixazomib at room temperature, Do not store at temperatures above 30°C (86°F). Do not freeze. Keep capsules in original packaging until use. Ixazomib is a dangerous drug. Do not open or crush capsules. Avoid direct contact with capsule contents. If capsule ruptures, avoid direct skin or eye contact with capsule contents. If in contact with skin, wash thoroughly with soap and water. If in contact with eyes, rinse thoroughly with water. Any unused pharmaceutical products or waste materials should be disposed of in accordance with local requirements.

6. Special groups:

1. Contraception

(1) Females: Advise females of childbearing potential to use effective non-hormonal contraceptives during treatment with ixazomib and for 90 days after the last dose. Dexamethasone is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters. Sinceixazomibis administered with dexamethasone, the risk of reduced contraceptive efficacy needs to be considered.

(2) Men: Advise men with female partners to use effective contraception during treatment with ixazomib and for 90 days after the last dose.

2. Breastfeeding: Because ixazomib may cause serious adverse reactions in breastfed infants, women are advised not to breastfeed during drug treatment and within 90 days after the last dose.

7. Mechanism of action:

Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds to and inhibits the chymotrypsin-like activity of the β5 subunit of the 20S proteasome. Ixazomib induces apoptosis in multiple myeloma cells in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells derived from patients who had relapsed after prior treatment with multiple therapies, including bortezomib, lenalidomide, and dexamethasone. The combination of ixazomib and lenalidomide shows synergistic cytotoxic effects in multiple myeloma cell lines. In vivo, ixazomib showed antitumor activity in a mouse xenograft model of multiple myeloma.