Ninlaro Capsule 3 mg (Ixazomib Citrate)

Adult dose

1. Recommended Dosage 1) Combination therapy with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one or more prior therapies • This drug is administered in combination with lenalidomide and dexamethasone in 28-day cycles. • The recommended starting dose of this drug is 4 mg, administered orally once weekly on Days 1, 8, and 15 of each 28-day cycle. • The recommended starting dose of lenalidomide is 25 mg, administered orally once daily on Days 1 through 21 of each 28-day cycle. • The recommended starting dose of dexamethasone is 40 mg, administered orally once weekly on Days 1, 8, 15, and 22 of each 28-day cycle. • Continue treatment until disease progression or unacceptable toxicity occurs. • Refer to the respective prescribing information for additional information on lenalidomide and dexamethasone. Table 1. Combination therapy with this drug, lenalidomide, and dexamethasone (∨: drug administration) 28-day cycle (4-week cycle) Week 1 Week 2 Week 3 Week 4 Day 1 Days 2-7 Day 8 Days 9-14 Day 15 Days 16-21 Day 22 Days 23-28 Ixazomib ∨ ∨ ∨ Lenalidomide ∨ ∨ (daily) ∨ ∨ (daily) ∨ ∨ (daily) Dexamethasone ∨ ∨ ∨ ∨ 2) Maintenance therapy for patients with multiple myeloma who have undergone autologous hematopoietic stem cell transplantation and patients with multiple myeloma who have not undergone autologous hematopoietic stem cell transplantation • This drug is administered as maintenance therapy in 28-day cycles. • The recommended starting dose of this drug is 3 mg, administered orally once weekly on Days 1, 8, and 15 of each 28-day cycle and maintained through Cycle 4. • If tolerability through Cycle 4 is good, increase the dose to 4 mg on Day 1 of Cycle 5. • Treatment should continue for 24 months or until disease progression or unacceptable toxicity occurs. 2. Method of Administration This drug should be administered once weekly on the same day of the week at approximately the same time during the first 3 weeks of each 4-week cycle. It should be administered at least 1 hour before or 2 hours after a meal. Do not crush or open the capsule. Swallow the capsule whole with water without chewing. If a dose is missed, administer the missed dose only if at least 72 hours remain before the next scheduled dose. If fewer than 72 hours remain, do not administer the missed dose, and do not take a double dose at the next scheduled administration to make up for the missed dose. If vomiting occurs after administration, do not administer another dose; resume administration at the next scheduled time. Before starting a new treatment cycle, the following conditions must be met. ● Absolute neutrophil count of at least 1,000/mm3 ● Platelet count of at least 75,000/mm3 ● Nonhematologic toxicities must have recovered to the patient's baseline level or Grade 1 or lower, as determined by the physician. Patients receiving treatment with this drug should receive antiviral vaccination to reduce the risk of herpes zoster reactivation. 3. Dosage Modification Guidelines 1) Combination therapy with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one or more prior therapies For combination therapy with this drug, follow the dose reduction levels in Table 2 below; refer to Table 3 below for dosage modification guidelines. Table 2. Dose reductions of this drug due to adverse reactions during combination therapy Recommended starting dose* 1st dose reduction 2nd dose reduction Discontinue 4mg 3mg 2.3mg * The recommended starting dose is 3mg in patients with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis. For thrombocytopenia, neutropenia, or rash, dosage modification of this drug and lenalidomide is recommended; dosage modification guidelines for this drug are described in Table 3. If lenalidomide dosage modification is required, refer to the prescribing information for lenalidomide. Table 3. Dosage modification guidelines for combination administration of lenalidomide, dexamethasone, and this drug Hematologic toxicity Recommended action Thrombocytopenia (platelet count) Platelet count below 30,000/mm3 ● Withhold this drug and lenalidomide until the platelet count is at least 30,000/mm3. ● After platelet count recovery, resume lenalidomide at one dose level lower according to the lenalidomide prescribing information, and resume this drug at the most recent dose administered. ● If the platelet count again decreases to below 30,000/mm3, withhold this drug and lenalidomide until the platelet count is at least 30,000/mm3. ● After recovery, resume this drug at one dose level lower and resume lenalidomide at the most recent dose administered.1) Neutropenia (absolute neutrophil count) below 500/mm3 ● Withhold this drug and lenalidomide until the absolute neutrophil count is at least 500/mm3. Consider adding G-CSF according to clinical guidelines. ● After recovery, resume lenalidomide at one dose level lower according to the lenalidomide prescribing information, and resume this drug at the most recent dose administered. ● If the absolute neutrophil count again decreases to below 500/mm3, withhold this drug and lenalidomide until the absolute neutrophil count is at least 500/mm3. ● After recovery, resume this drug at one dose level lower and resume lenalidomide at the most recent dose administered.1) Nonhematologic toxicity Recommended action Rash Grade 2 or 3 2) ● Withhold lenalidomide until the rash recovers to Grade 1 or lower. ● After recovery, resume lenalidomide at one dose level lower according to the lenalidomide prescribing information. ● If Grade 2 or 3 rash recurs, withhold this drug and lenalidomide until the rash recovers to Grade 1 or lower. ● After recovery, resume this drug at one dose level lower and resume lenalidomide at the most recent dose administered.1) Grade 4 Discontinue treatment. Peripheral neuropathy Grade 1 peripheral neuropathy with pain or Grade 2 peripheral neuropathy ● Withhold this drug until recovery to Grade 1 or lower without pain or to the patient's baseline level. ● After recovery, resume this drug at the most recent dose administered. Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy ● Withhold this drug. Before resuming this drug, toxicity should generally have recovered to the patient's baseline level or Grade 1 or lower, as determined by the physician. ● After recovery, resume this drug at one dose level lower. Grade 4 peripheral neuropathy Discontinue treatment. Other nonhematologic toxicity Other Grade 3 or 4 nonhematologic toxicity ● Withhold this drug. Before resuming this drug, toxicity should generally have recovered to the patient's baseline level or Grade 1 or lower, as determined by the physician. ● If the toxicity is due to administration of this drug, resume this drug at one dose level lower after recovery. 1) For subsequent occurrences, alternate dose reductions of this drug and lenalidomide. 2) Grades are according to the National Cancer Institute Common Terminology Criteria (CTCAE). 2) Maintenance therapy for patients with multiple myeloma who have undergone autologous hematopoietic stem cell transplantation and patients with multiple myeloma who have not undergone autologous hematopoietic stem cell transplantation For maintenance therapy with this drug, follow the dose reduction levels in Table 4 below; refer to Table 5 below for dosage modification guidelines. Table 4. Dose reductions of this drug due to adverse reactions during maintenance therapy Recommended starting dose* 1st dose reduction 2nd dose reduction Discontinue Cycles 1~4 3mg 2.3mg Discontinue Cycle 5~ 4mg 3mg 2.3mg * For patients with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis, the recommended starting dose is 2.3mg for Cycles 1~4, increasing to 3mg or more in Cycle 5. Table 5. Dosage modification guidelines for maintenance therapy with this drug Hematologic toxicity Recommended action Thrombocytopenia (platelet count) Platelet count 50,000/mm3 or lower ● Withhold this drug until the platelet count is at least 75,000/mm3. ● After platelet count recovery, resume treatment at one dose level lower. Neutropenia (absolute neutrophil count 750mm3 or lower) ● Withhold this drug until the absolute neutrophil count is at least 1000/mm3. ● After recovery, resume treatment at one dose level lower. Nonhematologic toxicity Recommended action Rash Grade 2 1) ● Administer oral or topical symptomatic treatment. If ineffective, reduce the dose of this drug by one dose level. Grade 3 ● Withhold this drug until the rash recovers to Grade 1 or lower. ● After recovery, resume treatment at one dose level lower. Grade 4 Discontinue treatment. Peripheral neuropathy Grade 1 peripheral neuropathy with pain or Grade 2 peripheral neuropathy ● Withhold this drug until recovery to Grade 1 or lower without pain or to the patient's baseline level. ● After recovery, resume this drug at the most recent dose administered. Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy ● Withhold this drug. Before resuming this drug, toxicity should generally have recovered to the patient's baseline level or Grade 1 or lower, as determined by the physician. ● After recovery, resume this drug at one dose level lower. Grade 4 peripheral neuropathy Discontinue treatment. Other nonhematologic toxicity Grade 2 or 3 nonhematologic toxicity ● Withhold this drug. Before resuming this drug, toxicity should generally have recovered to the patient's baseline level or Grade 1 or lower, as determined by the physician. ● After recovery, resume this drug at one dose level lower. Grade 4 nonhematologic toxicity ● Consider permanent discontinuation of the drug unless, in the physician's judgment, the patient is deriving clinical benefit. In such cases, resume this drug at one dose level lower. 1) Grades are according to the National Cancer Institute Common Terminology Criteria (CTCAE). 4. Administration to Patients with Hepatic Impairment Refer to Table 6 below for the starting dose of this drug in patients with hepatic impairment. Table 6. Starting dose of this drug in patients with hepatic impairment Maintenance therapy Combination therapy with lenalidomide and dexamethasone Mild (total bilirubin<ULN, AST> ULN or total bilirubin>ULN 1~1.5 times, any AST) No dosage adjustment No dosage adjustment Moderate (total bilirubin > ULN 1.5~3 times) or severe (total bilirubin > ULN 3 times) Start at 2.3mg and, if tolerated during the first 4 cycles, increase to 3mg on Day 1 of the next Cycle 5. 3mg *ULN (Upper Limit of Normal)=upper limit of normal, AST = Aspartate Aminotransferase 5. Administration to Patients with Renal Impairment Refer to Table 7 below for the starting dose of this drug in patients with renal impairment. Table 7. Starting dose of this drug in patients with renal impairment Maintenance therapy Combination therapy with lenalidomide and dexamethasone Mild or moderate (creatinine clearance (CrCl) ≥ 30mL/min) No dosage adjustment No dosage adjustment Severe (creatinine clearance (CrCl) < 30mL/min) or end-stage renal disease (ESRD) requiring dialysis Start at 2.3mg and, if tolerated during the first 4 cycles, increase to 3mg on Day 1 of the next Cycle 5. 3mg This drug is not removed by dialysis and may therefore be administered regardless of the timing of dialysis. For the dose of lenalidomide in patients with renal impairment during combination therapy, refer to the lenalidomide prescribing information.

This medication should not be taken by individuals allergic to the active ingredient or additives. During treatment, platelet counts may decrease, so regular blood tests should be conducted to monitor platelet levels. Gastrointestinal side effects such as diarrhea, constipation, nausea, and vomiting may occur, and severe symptoms should be discussed with a doctor. Peripheral neuropathy, such as tingling or sensory abnormalities in the hands and feet, may occur. Notify a doctor if these symptoms develop or worsen. Peripheral edema, or swelling of the hands and feet, may occur, and in severe cases, appropriate treatment may be necessary. Skin rashes or allergic reactions may occur; especially severe rashes or serious skin reactions like Stevens-Johnson syndrome require immediate discontinuation and consultation with healthcare professionals. As it may affect liver function, regular liver function tests are important. It can be harmful to the fetus during pregnancy, so women with a possibility of pregnancy must ensure effective contraception and should not take it during pregnancy. Taking this medication with strong CYP3A4 inducers may reduce its effectiveness, so co-administration with these drugs is not recommended. It is advised to discontinue breastfeeding during the use of this medication. Elderly patients can use it, but attention should be given as they may experience more severe side effects. Patients with severely impaired liver or kidney function may require dosage adjustments, so they should follow their physician's instructions. Severe side effects may occur in the case of overdose, so adherence to prescribed dosages is crucial, and medical professionals should be notified immediately in case of overdose. This medication is cytotoxic, so capsules must never be opened or crushed, and care should be taken to avoid contact with skin or eyes. If the contents come into contact with the skin, wash thoroughly with soap and water, and if it gets into the eyes, rinse thoroughly with running water.

Thrombocytopenia, neutropenia, diarrhea, constipation, peripheral neuropathy, peripheral edema, rash, vomiting, bronchitis, lower back pain, upper respiratory infection, shingles, cataract, conjunctivitis, blurred vision, dry eyes, pneumonia, arthralgia, acute febrile neutrophilic dermatosis, Stevens-Johnson syndrome, transverse myelitis, reversible posterior leukoencephalopathy syndrome, tumor lysis syndrome, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, anaphylactic reaction, angioedema, febrile neutropenia, anemia, asthenia, fatigue, pruritus, sensory disturbances, decreased appetite, reduced food intake, insomnia, flushing of the face, pneumonia, COVID-19 pneumonia, gastroenteritis, sepsis, dyspepsia, abdominal discomfort, stomatitis, epigastric pain, hemorrhoids, acute kidney injury, chronic kidney disease, spinal fracture, pulmonary inflammation, cough, erythema multiforme, purpura, urticaria, muscle weakness, dizziness, sensory loss, somnolence, hyperkalemia, deep vein thrombosis, thrombosis, vertigo, drug-induced liver injury, hepatocellular injury, fatty liver, cholestasis, liver dysfunction, severe nausea, aspiration pneumonia, multiple organ failure, death

This medication may be sensitive to air or moisture, so it should be stored in a tightly closed container. It is recommended to maintain storage temperatures between 1 and 30 degrees Celsius at room temperature. This way, the effectiveness and safety of the drug can be preserved for a long time.

Appearance

Light gray hard capsule with bright upper and lower parts

Package unit

3 capsules (1 capsule/PTP packaging x 3 per box), 1 capsule (1 capsule/PTP packaging) per box, 3 capsules (3 capsules/PTP packaging) per box