Bosulif 400 mg (Bosutinib Hydrate)

Adult dose

1. Recommended Dosage This drug is administered orally once daily with food. The tablets must be swallowed whole and must not be crushed or cut. Continue treatment with this drug until disease progression or treatment intolerance occurs. If a dose of this drug is missed by 12 hours or more, the patient should skip that dose and take the prescribed dose the next day. 1) Newly diagnosed chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (CP Ph+ CML) The recommended dosage of this drug is 400 mg of bosutinib once daily, administered orally with food. 2) Chronic-, accelerated-, or blast-phase Philadelphia chromosome-positive chronic myeloid leukemia (CP, AP, BP Ph+ CML) resistant or intolerant to prior therapy The recommended dosage of this drug is 500 mg of bosutinib once daily, administered orally with food. 2. Dose Escalation In clinical trials in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML), an increase of 100 mg once daily, up to a maximum of 600 mg once daily, was permitted for patients who did not achieve or maintain a hematologic, cytogenetic, or molecular response and had no Grade 3 or higher adverse reactions at the recommended starting dose. 3. Dose Adjustments for Nonhematologic Adverse Reactions 1) Elevated liver aminotransferases: If liver aminotransferases rise to more than 5 times the upper limit of normal, temporarily interrupt treatment until they recover to 2.5 times the upper limit of normal or lower, and then resume treatment at 400 mg once daily. Discontinue treatment if recovery takes more than 4 weeks. If elevated aminotransferases of at least 3 times the upper limit of normal occur concurrently with elevated bilirubin of more than 2 times the upper limit of normal and alkaline phosphatase of less than 2 times the upper limit of normal (Hy's law case), discontinue treatment. 2) Diarrhea: For Grade 3-4 diarrhea according to NCI CTCAE* criteria (an increase of 7 or more bowel movements per day compared with pretreatment/baseline), temporarily interrupt treatment with this drug until recovery to Grade 1 or lower. Treatment with this drug may be resumed at 400 mg once daily. (* National Cancer Institute Common Terminology Criteria for Adverse Events) 3) For clinically significant, moderate, or severe nonhematologic toxicity, temporarily interrupt treatment until the toxicity resolves, then consider resuming treatment once daily at a dose reduced by 100 mg. If clinically appropriate, consider increasing the dose again to the starting dose. Doses below 300 mg/day have been used in patients, but efficacy has not been established. 4. Dose Adjustments for Myelosuppression Dose adjustments for severe or persistent neutropenia and thrombocytopenia are shown in Table 1 below. [Table 1] Dose Adjustments for Neutropenia and Thrombocytopenia Absolute neutrophil count (ANC) below 1000x106/L or Platelets below 50,000x106/L Temporarily interrupt treatment with this drug until the ANC is at least 1,000×106/L and the platelet count is at least 50,000×106/L. If recovery occurs within 2 weeks, resume treatment at the same dose. If blood counts remain low for more than 2 weeks, resume treatment at a dose reduced by 100 mg once recovery occurs. If cytopenia recurs, reduce the dose by an additional 100 mg and resume treatment. Doses below 300 mg/day have been used in patients, but efficacy has not been established. 5. Dose Adjustments for Renal Impairment Patients with serum creatinine levels greater than 1.5 times the upper limit of normal were excluded from chronic myeloid leukemia clinical trials. Increased exposure (AUC) was observed in patients with moderate and severe renal impairment during the study period. 1) Newly diagnosed chronic-phase (CP) Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) For patients with moderate renal impairment (creatinine clearance [CLcr] 30-50mL/min, estimated by Cockcroft-Gault (C-G)), the recommended dosage of this drug is 300mg once daily, administered with food. For patients with severe renal impairment (CLCr < 30mL/min, estimated by C-G), the recommended dosage of this drug is 200mg once daily, administered with food. If there are no severe or persistent moderate adverse reactions and an adequate hematologic, cytogenetic, or molecular response has not been achieved, an increase to 400mg once daily with food may be considered for patients with moderate renal impairment, and an increase to 300mg once daily may be considered for patients with severe renal impairment. 2) Chronic-, accelerated-phase (AP), or blast-phase (BP) Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) resistant or intolerant to prior therapy For patients with moderate renal impairment (CLCr 30~50mL/min, estimated by C-G), the recommended dosage of this drug is 400mg once daily. For patients with severe renal impairment (CLCr < 30mL/min, estimated by C-G), the recommended dosage of this drug is 300mg once daily. If there are no severe or persistent moderate adverse reactions and an adequate hematologic, cytogenetic, or molecular response has not been achieved, an increase to 500mg once daily may be considered for patients with moderate renal impairment, and an increase to 400mg once daily may be considered for patients with severe renal impairment.

This medication should not be used in patients with a history of hypersensitivity or liver impairment. It should be used with caution in patients with impaired liver function, especially during the first 3 months, where monthly liver function tests must be conducted to carefully monitor for liver damage. Patients with impaired kidney function or those taking medications that may induce nephrotoxicity should also be administered with caution and their kidney function monitored regularly. Hepatitis B virus carriers should be closely monitored for reactivation of infection before and during treatment and consult a specialist if necessary. Patients at high risk for bleeding should exercise caution when using this medication in conjunction with drugs that inhibit platelet function. Patients with heart disease or at risk of heart failure should be administered cautiously after correcting any hypokalemia or hypomagnesemia. Patients with gastrointestinal disorders or those who have recently experienced gastrointestinal problems should be careful as this medication can exacerbate symptoms such as diarrhea and vomiting. Common side effects of this medication include diarrhea, rash, nausea, abdominal pain, vomiting, fatigue, liver dysfunction, respiratory infections, fever, headaches, etc. Routine blood tests may show decreased platelets, hemoglobin, lymphocytes, and increased liver enzymes, necessitating regular check-ups. Liver dysfunction may occur, so liver enzyme levels should be periodically checked and dosage adjustment or discontinuation should be considered if abnormalities occur. Cardiovascular side effects such as heart failure or myocardial ischemia have been reported, making it necessary to carefully monitor heart conditions. Fluid retention may occur, so symptoms of edema, pleural effusion, or pulmonary edema should be reported to medical staff immediately. Impaired kidney function may arise, thus regular kidney function tests are necessary, and dose adjustments may be required in cases of kidney impairment. During pregnancy, this medication can harm the fetus, so women with childbearing potential should practice effective contraception during and at least 2 weeks after taking this medication. Nursing mothers should refrain from breastfeeding during and at least 2 weeks after taking this medication for safety. Safety in children has not been established, thus it is not recommended for those under 18 years. No special differences are noted in the elderly, but some elderly individuals may be more sensitive to side effects. In case of overdose, there is no specific treatment, and the patient should be observed while receiving appropriate supportive care. This medication may interact with other drugs, thus caution is necessary when used with CYP3A inhibitors or inducers, proton pump inhibitors, and some medications should be avoided concomitantly. When storing, keep out of reach of children, store in the original container, and handle safely during disposal due to its nature as an anticancer drug.

Diarrhea, rash, nausea, abdominal pain, vomiting, fatigue, liver dysfunction, respiratory infection, fever, headache, increased creatinine, decreased hemoglobin, decreased lymphocyte count, decreased platelet count, increased ALT, decreased calcium, decreased white blood cell count, decreased absolute neutrophil count, increased AST, increased glucose, decreased phosphate, increased uric acid, increased alkaline phosphatase, increased lipase, increased creatine kinase, increased amylase, pneumonia, coronary artery disease, gastroenteritis, acute heart failure, renal failure, thrombocytopenia, neutropenia, constipation, itching, edema, chest pain, cough, shortness of breath, decreased appetite, hypertension, influenza, pneumonia, pleural effusion, dizziness, arthralgia, back pain, pain, drug hypersensitivity, anaphylactic shock, bronchitis, prolonged QT interval on electrocardiogram, dehydration, myalgia, dysgeusia, acute kidney injury, renal impairment, renal failure, pulmonary hypertension, acute pulmonary edema, respiratory failure, interstitial lung disease, erythema multiforme, thrombotic microangiopathy, Stevens-Johnson syndrome

This medication should be stored in a tightly closed container to prevent exposure to air or moisture. It is important to maintain the storage temperature between 1 and 30 degrees Celsius to effectively preserve the drug's efficacy and safety.

Appearance

Orange, oval-shaped, biconvex, film-coated tablets

Package unit

28 tablets/box [14 tablets/blister x 2]