Ninlaro Capsule 2.3 milligrams (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 from Day 1 through Day 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 administered) 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 it whole with water without chewing. If a dose is missed, administer the dose only if the next scheduled dose is at least 72 hours away. If the next dose is due within 72 hours, 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 the dose again; resume dosing at the next scheduled time. Before starting a new treatment cycle, the following criteria must be met. ● Absolute neutrophil count of at least 1,000/mm3 ● Platelet count of at least 75,000/mm3 ● Nonhematologic toxicities must have resolved 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 prophylaxis to reduce the risk of herpes zoster reactivation. 3. Dose 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 steps in Table 2 below; refer to Table 3 below for dose modification guidelines. Table 2. Dose reduction 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 in patients with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis is 3mg. If thrombocytopenia, neutropenia, or rash occurs, dose modification of this drug and lenalidomide is recommended. Dose modification guidelines for this drug are described in Table 3. If lenalidomide dose modification is needed, refer to the lenalidomide prescribing information. Table 3. Dose modification guidelines for concomitant administration of lenalidomide, dexamethasone, and this drug Hematologic toxicity Recommended action Thrombocytopenia (platelet count) Platelet count less than 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 recently administered dose. ● If the platelet count again decreases to less than 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 recently administered dose.1) Neutropenia (absolute neutrophil count) less than 500/mm3 ● Withhold this drug and lenalidomide until the absolute neutrophil count is at least 500/mm3. Consider adding G-CSF in accordance with clinical guidelines. ● After recovery, resume lenalidomide at one dose level lower according to the lenalidomide prescribing information, and resume this drug at the most recently administered dose. ● If the absolute neutrophil count again decreases to less than 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 recently administered dose.1) Nonhematologic toxicity Recommended action Rash Grade 2 or 3 2) ● Withhold lenalidomide until the rash resolves 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 resolves to Grade 1 or lower. ● After recovery, resume this drug at one dose level lower and resume lenalidomide at the most recently administered dose.1) Grade 4 Discontinue treatment. Peripheral neuropathy Grade 1 peripheral neuropathy with pain or Grade 2 peripheral neuropathy ● Withhold this drug until the condition resolves to Grade 1 or lower without pain or to the patient's baseline level. ● After recovery, resume this drug at the most recently administered dose. Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy ● Withhold this drug. Before resuming this drug, the toxicity should generally have resolved 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 toxicities Other Grade 3 or 4 nonhematologic toxicities ● Withhold this drug. Before resuming this drug, the toxicity should generally have resolved to the patient's baseline level or Grade 1 or lower, as determined by the physician. ● If the toxicity was caused by this drug, resume this drug at one dose level lower after recovery. 1) For additional 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 steps in Table 4 below; refer to Table 5 below for dose modification guidelines. Table 4. Dose reduction 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 higher in Cycle 5. Table 5. Dose 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) ● Provide 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 resolves 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 the condition resolves to Grade 1 or lower without pain or to the patient's baseline level. ● After recovery, resume this drug at the most recently administered dose. Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy ● Withhold this drug. Before resuming this drug, the toxicity should generally have resolved 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 toxicities Grade 2 or 3 nonhematologic toxicities ● Withhold this drug. Before resuming this drug, the toxicity should generally have resolved 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 derives 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 in 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 dose adjustment No dose 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, 5th cycle. 3mg *ULN (Upper Limit of Normal) = upper limit of normal range, AST = Aspartate Aminotransferase 5. Administration in Patients with Renal Impairment Refer to Table 7 below for the 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 dose adjustment No dose 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, 5th cycle. 3mg This drug is not removed by dialysis and may therefore be administered regardless of the timing of dialysis. For the lenalidomide dose in patients with renal impairment during combination therapy, refer to the lenalidomide prescribing information.

This drug should not be administered to patients who are allergic to the active ingredient or excipients. Platelet counts may decrease, therefore regular monitoring of platelet levels is necessary, and dosage adjustment or transfusion may be required as needed. Gastrointestinal symptoms such as diarrhea, constipation, nausea, and vomiting are common, and medication adjustment or supportive care may be needed based on symptoms. Peripheral neuropathy may occur, so neurological symptoms should be closely monitored, and dosage adjustments should be made if symptoms worsen. Peripheral edema may develop, so symptoms should be checked, and treatment or dosage adjustment should be performed if necessary. Skin rashes may occur, and in severe cases, serious skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis may arise, necessitating immediate cessation of the drug. Liver dysfunction may occur, so regular liver enzyme testing is recommended, and dosage should be adjusted if abnormalities are found. Use during pregnancy may harm the fetus, so both women and men of childbearing potential must use effective contraception during and for a period after treatment. Co-administration with strong CYP3A4 inducers may reduce drug efficacy, so concurrent use should be avoided. Nursing women are advised to discontinue breastfeeding as this drug may be passed into breast milk. Older adults can use the medication, however, some elderly may be more sensitive to drugs, requiring caution. Patients with severely impaired liver or kidney function should use reduced doses, and dialysis patients should also take care when administering. In cases of overdose, severe nausea, pneumonia, and multiple organ failure may occur, so dosage guidelines must be strictly followed, and immediate consultation with healthcare providers is necessary in case of adverse effects. This drug is cytotoxic; therefore, do not open or crush capsules, and avoid skin or eye contact with the contents, washing immediately if contact occurs.

Thrombocytopenia, neutropenia, diarrhea, constipation, peripheral neuropathy, peripheral edema, rash, vomiting, nausea, bronchitis, upper respiratory infection, lower back pain, 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, toxic epidermal necrolysis, anaphylactic reaction, angioedema, fever, asthenia, fatigue, pruritus, dysesthesia, decreased appetite, reduced intake, insomnia, facial flushing, pneumonia, COVID-19 pneumonia, gastroenteritis, sepsis, dyspepsia, abdominal discomfort, stomatitis, upper abdominal pain, hemorrhoids, acute kidney injury, chronic kidney disease, spinal fracture, pulmonary inflammation, cough, erythema multiforme, purpura, urticaria, arthralgia, muscle weakness, dizziness, sensory loss, somnolence, hyperkalemia, deep vein thrombosis, thrombosis, vertigo, drug-induced liver injury, hepatocellular injury, fatty liver, cholestasis, liver disorder

This medication should be stored in a tightly sealed container to protect it from air and moisture, and it is best to keep it at room temperature between 1 to 30 degrees Celsius. Storing it this way will help maintain the drug's efficacy for a longer period.

Appearance

Bright pink hard capsule with upper and lower parts

Package unit

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