Azacitidine Injection 100 mg

Adult dosage

This medication must not be substituted for oral azacitidine. Verify the product name, dose, and route of administration. For myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia with 20~30% bone marrow blasts — First treatment cycle: The recommended initial dose for all patients, regardless of pretreatment hematologic laboratory values, is 75mg/m2/day by subcutaneous or intravenous injection for 7 days. Patients should receive premedication to prevent nausea and vomiting. For myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia with 20~30% bone marrow blasts — Subsequent treatment cycles: Treatment cycles should be repeated every 4 weeks. If no treatment effect is observed after 2 treatment cycles and no toxicity other than nausea or vomiting is observed, the dose may be increased to 100mg/m2. Administration for at least 4~6 treatment cycles is recommended; however, achieving complete or partial remission may require additional treatment cycles. Treatment may continue for as long as the patient benefits. The patient's hematologic recovery and renal toxicity must be monitored, and treatment may need to be delayed or the dose reduced as described below. For acute myeloid leukemia (AML) with >30% bone marrow blasts in adults aged 65 years or older who are not eligible for hematopoietic stem cell transplantation or intensive chemotherapy and have poor cytogenetics — First treatment cycle: The recommended initial dose for all patients, regardless of pretreatment hematologic laboratory values, is 75mg/m2/day by subcutaneous or intravenous injection for 7 days. Patients should receive premedication to prevent nausea and vomiting. For acute myeloid leukemia (AML) with >30% bone marrow blasts in adults aged 65 years or older who are not eligible for hematopoietic stem cell transplantation or intensive chemotherapy and have poor cytogenetics — Subsequent treatment cycles: Treatment cycles should be repeated every 4 weeks. Administration for at least 6 treatment cycles is recommended; however, achieving complete or partial remission may require additional treatment cycles. Treatment may continue for as long as the patient benefits. The patient's hematologic recovery and renal toxicity must be monitored, and treatment may need to be delayed or the dose reduced as described below. Liver function tests, serum creatinine, and serum bicarbonate should be checked before treatment initiation and before each treatment cycle. A complete blood count should be performed before treatment initiation and when needed to monitor response and toxicity, and must be performed before each treatment cycle at a minimum. Hematologic toxicity is defined as the nadir observed during the treatment cycle when the platelet count is 50.0 x 109/L or less and/or the absolute neutrophil count (ANC) is 1 x 109/L or less. Recovery is defined as an increase in the blood cell line in which hematologic toxicity was observed to a value at least equal to the nadir plus half the difference between the pretreatment value and the nadir (i.e., blood cell count ≥ nadir + (0.5 x [pretreatment value – nadir]). For MDS, CMML, and AML with 20~30% bone marrow blasts: For patients whose hematologic laboratory values before starting the first treatment cycle are WBC≥3.0x109/L, ANC≥1.5x109/L, and platelets ≥75.0x109/L, the dose is adjusted as shown in the following table based on the nadir during all treatment cycles. Nadir ANC (x109/L) ＜0.5, Platelets (x109/L) ＜25.0: dose for the next cycle 50%; ANC (x109/L) 0.5-1.5, Platelets (x109/L) 25.0-50.0: dose for the next cycle 67%; ANC (x109/L) ＞1.5, Platelets (x109/L) ＞50.0: dose for the next cycle 100%. For MDS, CMML, and AML with 20~30% bone marrow blasts: For patients whose hematologic laboratory values before starting the first treatment cycle are WBC<3.0x109/L, ANC<1.5x109/L, or platelets <75x109/L, continue the current treatment dose when starting the next treatment cycle if there is clear improvement in differentiation (the percentage of mature granulocytes and ANC are higher than at the start of the treatment cycle); otherwise, adjust the dose as shown in the following table based on the nadir and bone marrow biopsy cellularity at the nadir. Percentage decrease from pretreatment value in WBC or platelet nadir 50-75: dose for the next cycle for bone marrow biopsy cellularity (%) of 30-60, 15-30, and <15 at the time of nadir is 100, 50, and 33, respectively; percentage decrease from pretreatment value in WBC or platelet nadir ＞75: dose for the next cycle for bone marrow biopsy cellularity (%) of 30-60, 15-30, and <15 at the time of nadir is 75, 50, and 33, respectively. If the nadir defined in the table above occurs, the next treatment should begin 28 days after the start of the preceding treatment cycle, provided that the WBC and platelet counts are >25% above the nadir and are rising. If the nadir has not increased by 25% or more by day 28, the counts should be reassessed every 7 days. If they have not increased by 25% or more by day 42, treat the patient with 50% of the scheduled dose. For AML with >30% bone marrow blasts in adults aged 65 years or older who are not eligible for hematopoietic stem cell transplantation or intensive chemotherapy and have poor cytogenetics: Patients whose baseline blood counts before the first dose of this medication are not decreased (i.e., white blood cell (WBC) count is at least 3.0 x 109/L, ANC is at least 1.5 x 109/L, and platelet count is at least 75.0 x 109/L). If hematologic toxicity is observed after administration of this medication, the next treatment cycle should be delayed until the platelet and ANC counts recover. If recovery occurs within 14 days, no dose adjustment is necessary. However, if recovery does not occur within 14 days, the dose should be reduced according to the following table. After a dose change, the treatment cycle duration should be adjusted to the original 28 days. Nadir ANC (x 109/L) ≤ 1.0, platelets (x 109/L) ≤ 50.0: if recovery does not occur within 14 days, dose for the next cycle 50 %; ANC (x 109/L) > 1.0, platelets (x 109/L) > 50.0: if recovery does not occur within 14 days, dose for the next cycle 100 %. *Recovery = blood cell count ≥ nadir + (0.5 x [pretreatment value – nadir]) For AML with >30% bone marrow blasts in adults aged 65 years or older who are not eligible for hematopoietic stem cell transplantation or intensive chemotherapy and have poor cytogenetics: Patients whose baseline blood counts before the first dose of this medication are decreased (i.e., WBC is less than 3.0 x 109/L, or ANC is less than 1.5 x 109/L, or platelets are less than 75.0 x 109/L). After administration of this medication, if WBC, ANC, or platelets decrease by 50 % or less compared with pretreatment values, or decrease by more than 50 % but there is improved differentiation of the cell line, the next treatment cycle should not be delayed and the dose should not be adjusted. If WBC, ANC, or platelets decrease by more than 50 % compared with pretreatment values and there is no improvement in cell line differentiation, the next treatment cycle should be delayed until the platelet and ANC counts recover. If recovery occurs within 14 days, no dose adjustment is necessary. However, if recovery does not occur within 14 days, bone marrow cellularity should be assessed. If bone marrow cellularity is greater than 50 %, no dose adjustment should be made. If bone marrow cellularity is 50 % or less, treatment should be delayed and the dose reduced according to the following table. Bone marrow cellularity 15-50 %: dose for the next cycle is 100 % if recovery* occurs within 21 days, and 50 % if recovery* occurs after more than 21 days; bone marrow cellularity < 15 %: dose for the next cycle is 100 % if recovery* occurs within 21 days, and 33 % if recovery* occurs after more than 21 days. *Recovery = blood cell count ≥ nadir + (0.5 x [pretreatment value – nadir]). After a dose change, the treatment cycle duration should be adjusted to the original 28 days. Dose adjustment based on renal function and serum electrolytes: If the serum bicarbonate concentration decreases to 20mEq/L or less for an unexplained reason, the dose for the next treatment must be reduced by 50%. Similarly, if an unexplained increase in BUN or serum creatinine occurs, delay the next treatment cycle until the values return to normal or to pretreatment levels, and reduce the dose by 50% in the next treatment cycle. Use in older adults: Azacitidine and its metabolites are known to be largely excreted by the kidneys, and the risk of toxicity is greater in patients with renal impairment. Renal function may be decreased in older patients; therefore, select the dose carefully and monitor renal function closely. Subcutaneous injection: Add 4mL of Sterile Water for Injection to each vial of this medication to prepare a cloudy suspension (25mg/mL). If the volume is greater than 4mL, divide it equally between 2 syringes and inject alternately at 2 separate injection sites (thigh, abdomen, upper arm). A new injection should be given at least 2.54 centimeters from the previous injection site. Never inject into an injection site that is tender, red, bruised, or hardened. Intravenous injection: Add 10mL of Sterile Water for Injection to each vial of this medication to prepare a clear diluent solution (10mg/mL), then add the required amount to a 50-100mL infusion bag of 0.9% sodium chloride or Lactated Ringer’s Injection and administer intravenously over 10-40 minutes. Administration must be completed within 1 hour of preparing the diluted solution.

This medication should not be used during pregnancy as it may cause serious harm to the fetus. Both males and females of childbearing potential are advised to avoid pregnancy while taking this medication. Patients allergic to azacitidine or mannitol, those with progressive liver cancer, and breastfeeding women should not use this medication. Patients with renal or hepatic function issues should exercise caution when using this medication and should confirm adequate blood counts through blood tests before administration. Various side effects such as nausea, vomiting, diarrhea, anemia, thrombocytopenia, leukopenia, and fever may commonly occur, so any unusual symptoms should be immediately discussed with a doctor. Especially, due to neutropenia, there may be an increased risk of infection, and prompt treatment is necessary if any symptoms of infection occur. Due to the risk of bleeding, careful monitoring for bleeding signs is necessary. This medication can cause allergic reactions such as skin rash or injection site reactions, so if abnormalities occur, administration should be stopped immediately, and treatment should be sought. During treatment, regular blood tests, along with liver and kidney function tests, should be conducted, especially for elderly patients or those with reduced kidney function. This medication may cause dizziness or drowsiness while driving or operating machinery, so dangerous activities should be avoided if these symptoms occur. In case of overdose, since there is no specific antidote, medical assistance should be sought immediately for appropriate treatment. When preparing or handling this medication, caution should be exercised as it is cytotoxic; avoid contact with skin or mucous membranes, and if contact occurs, wash the area thoroughly right away. Prepared solutions should be stored under strict conditions, and leftover medication should not be reused and should be disposed of properly. This medication may potentially cause carcinogenicity, mutagenicity, or reproductive toxicity, so caution is required with prolonged or repeated use.

• Nausea
• Anemia
• Thrombocytopenia
• Vomiting
• Fever
• Leukopenia
• Diarrhea
• Fatigue
• Erythema at injection site
• Constipation

This medication should be stored in a sealed container to prevent exposure to air and is best kept at room temperature between 1 to 30 degrees Celsius. This helps maintain the medication's effectiveness and prevents degradation.

Appearance

A white freeze-dried powder or lump contained in a colorless and transparent vial as a freeze-dried injection.

Package unit

1 vial/carton, 10 vials (1 vial x 10)/carton