Azacitidine Injection 150 mg (Azacitidine)

Adult dosage

Due to differences in exposure, dosage, and dosing schedule, this drug must not be substituted for oral azacitidine. Verify the product name, dose, and route of administration. 1. Myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia with 20∼30% bone marrow blasts 1) First treatment cycle The recommended initial dose for all patients, regardless of pretreatment hematologic laboratory values, is 75mg/m2/day administered by subcutaneous or intravenous injection for 7 days. Patients should receive premedication for nausea and vomiting before administration of this drug. 2) Subsequent treatment cycles Treatment cycles should be repeated at 4-week intervals. 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, more treatment cycles may be required to achieve complete or partial remission. Treatment may continue as long as the patient benefits. The patient's hematologic response and renal toxicity must be monitored, and treatment may need to be delayed or the dose reduced as described below. 2. Acute myeloid leukemia (AML) with more than 30% bone marrow blasts in adults aged 65 years or older who are not candidates for hematopoietic stem cell transplantation or intensive chemotherapy and have poor cytogenetics 1) First treatment cycle The recommended initial dose for all patients, regardless of pretreatment hematologic laboratory values, is 75mg/m2/day administered by subcutaneous or intravenous injection for 7 days. Patients should receive premedication for nausea and vomiting before administration of this drug. 2) Subsequent treatment cycles Treatment cycles should be repeated at 4-week intervals. Administration for at least 6 treatment cycles is recommended; however, more treatment cycles may be required to achieve complete or partial remission. Treatment may continue as long as the patient benefits. The patient's hematologic response and renal toxicity must be monitored, and treatment may need to be delayed or the dose reduced as described below. 4. Dose adjustment based on hematologic laboratory values 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 cell lineage in which hematologic toxicity was observed to at least the nadir plus half the difference between the nadir and the pretreatment value (i.e., blood cell count ≥ nadir + (0.5 x [pretreatment value – nadir]). 1) 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 based on the nadir during all treatment cycles, as shown in the following table. (Table 1) Nadir Dose % in the next cycle ANC(x109/L) Platelets(x109/L) ＜0.5 ＜25.0 50% 0.5-1.5 25.0-50.0 67% ＞1.5 ＞50.0 100% • 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 (i.e., the percentage of mature granulocytes and the ANC are higher than at the start of the treatment cycle). Otherwise, adjust the dose based on the nadir and the bone marrow biopsy cellularity at the time of nadir, as shown in the following table. (Table 2) WBC or platelet nadir % decrease from pretreatment value Bone marrow biopsy cellularity (%) at the time of nadir 30-60 15-30 <15 Dose % in the next cycle 50-75 100 50 33 ＞75 75 50 33 When a nadir as defined in the table above occurs, the next treatment should be started 28 days after the start of the preceding treatment cycle, provided that the WBC and platelet counts are more than 25% above the nadir and are increasing. If the nadir has not increased by at least 25% by day 28, the counts should be reassessed every 7 days. If they have still not increased by at least 25% by day 42, treat the patient with 50% of the scheduled dose. 2) AML with more than 30% bone marrow blasts in adults aged 65 years or older who are not candidates for hematopoietic stem cell transplantation or intensive chemotherapy and have poor cytogenetics • Patients whose baseline blood cell counts before the first dose of this drug are not decreased (i.e., white blood cell (WBC) count is 3.0 x 109/L or higher, ANC is 1.5 x 109/L or higher, and platelet count is 75.0 x 109/L or higher) If hematologic toxicity is observed after administration of this drug, the next treatment cycle should be delayed until the platelet and ANC counts recover. If recovery occurs within 14 days, no dose adjustment is needed. However, if recovery does not occur within 14 days, reduce the dose according to the following table. After a dose change, the treatment cycle duration should be adjusted back to 28 days. Nadir Dose % in the next cycle if recovery does not occur within 14 days ANC (x 109/L) Platelets (x 109/L) ≤ 1.0 ≤ 50.0 50 % > 1.0 > 50.0 100 % *Recovery = blood cell count ≥ nadir + (0.5 x [pretreatment value – nadir]) • Patients whose baseline blood cell counts before the first dose of this drug 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 drug, do not delay the next treatment cycle or adjust the dose if the WBC, ANC, or platelet count decreases by 50 % or less compared with the pretreatment value, or if it decreases by more than 50 % but cell-lineage differentiation improves. If the WBC, ANC, or platelet count decreases by more than 50 % compared with the pretreatment value and there is no improvement in cell-lineage differentiation, delay the next treatment cycle of this drug until the platelet and ANC counts recover. If recovery occurs within 14 days, no dose adjustment is needed. However, if recovery does not occur within 14 days, assess bone marrow cellularity. If bone marrow cellularity is greater than 50 %, no dose adjustment is required. If bone marrow cellularity is 50 % or less, delay treatment and reduce the dose according to the following table. Bone marrow cellularity Dose % in the next cycle if recovery does not occur within 14 days Recovery within 21 days* Recovery after more than 21 days* 15-50 % 100 % 50 % < 15 % 100 % 33 % *Recovery = blood cell count ≥ nadir + (0.5 x [pretreatment value – nadir]) After a dose change, the treatment cycle duration should be adjusted back to 28 days. 5. 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 must be reduced by 50% in the next treatment. 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. 6. Use in older adults: Azacitidine and its metabolites are known to be excreted primarily by the kidneys, and the risk of toxicity is greater in patients with renal impairment. Since renal function may be reduced in older patients, select the dose carefully and monitor renal function closely. ※ Method of administration ① Subcutaneous injection: Add 6mL of water for injection to each vial of this drug to prepare a cloudy suspension (25mg/mL). For volumes greater than 6mL, divide the volume equally between 2 syringes and inject alternately at 2 separate injection sites (thigh, abdomen, or upper arm). New injections should be given at least 2.54 centimeters from a previous injection site. Never inject into an area that is tender, red, bruised, or hardened. (See 13. Precautions for use). ② Intravenous injection: Add 15mL of water for injection to each vial of this drug to prepare a clear diluent (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 after preparation of the diluted solution. (See 13. Precautions for use).

This drug should not be used during pregnancy as it may cause severe harm to the fetus. Women and men of childbearing potential must exercise caution to avoid pregnancy while taking this drug. Patients with allergies to azacitidine or mannitol, those with advanced malignant liver tumors, and breastfeeding women should not be administered this drug. Patients with renal or liver function issues should use this drug with extra caution, and a blood test should confirm sufficient blood cell counts before treatment. This medication may commonly cause various side effects such as nausea, vomiting, anemia, thrombocytopenia, leukopenia, diarrhea, fatigue, and occasionally serious infections, bleeding, or hypersensitivity reactions. Hematologic adverse reactions frequently occur, so regular blood tests are necessary to monitor conditions and adjust dosages or discontinue treatment if necessary. In particular, the risk of infection may increase due to neutropenia, so any signs of infection should be reported to healthcare professionals immediately. Rash, inflammation, or itching may occur at injection sites, and in severe cases, serious infections such as cellulitis or necrotizing fasciitis can occur, so caution is advised. Renal and liver dysfunctions have also been reported, so liver enzyme tests and serum creatinine tests must be performed before and during administration. Patients with a history of heart or lung diseases may experience increased cardiac-related side effects when taking this drug, so careful evaluation and monitoring are required. This medication is highly cytotoxic; therefore, care must be taken to avoid contact with skin or mucous membranes during preparation, and if contact occurs, it should be washed off immediately. Patients should avoid driving or operating machinery if they experience dizziness or any unusual symptoms while taking this medication. In case of overdose, there is no specific antidote, so blood conditions should be closely monitored, and appropriate supportive treatment should be administered if needed. This drug may potentially be excreted in breast milk, so breastfeeding should be avoided during treatment, and safety in pediatric patients has not been sufficiently established. Elderly patients or those with decreased kidney function are at higher risk of toxic reactions, so renal function should be periodically checked during administration. This drug may cause carcinogenicity, mutagenicity, and reproductive dysfunction, so caution is necessary during long-term use. Regular blood tests and liver and renal function tests should be performed before and during treatment to identify and manage any abnormal signs early.

Nausea, anemia, thrombocytopenia, vomiting, fever, leukopenia, diarrhea, fatigue, redness at the injection site, constipation, neutropenia, petechiae, purpura, rigidity, weakness, hypokalemia, febrile neutropenia, pneumonia, neutropenic sepsis, hypersensitivity reaction, brain hemorrhage, gastrointestinal bleeding, intracranial hemorrhage, elevated serum creatinine, renal tubular acidosis, hypokalemia, hepatic encephalopathy, renal failure, necrotizing fasciitis, neutropenic sepsis, sepsis, urinary tract infection, cellulitis, dizziness, dyspnea, febrile neutropenia, pneumonia, fever, sepsis, anemia, neutropenic sepsis, urinary tract infection, cellulitis, dizziness, dyspnea, constipation, nausea, diarrhea, fever, redness at the injection site, pain at the injection site, reaction at the injection site, necrosis at the injection site, agranulocytosis, bone marrow suppression, pancytopenia, splenomegaly, atrial fibrillation, heart failure, congestive heart failure, cardiac arrest, congestive cardiomyopathy, diverticulitis, gastrointestinal bleeding, melena, perianal abscess, bleeding at the catheter site, systemic health deterioration, systemic inflammatory response syndrome, cholecystitis, anaphylactic shock, limb abscess, bacterial infection, soft tissue infection, candidiasis, injection site infection, Klebsiella sepsis, pharyngeal streptococcus infection, Klebsiella pneumonia, sepsis, septic shock, staphylococcemia, staphylococcal infection, toxoplasmosis, dehydration, worsening of bone pain, muscle weakness, neck pain, skin leukemia, brain hemorrhage, seizures, intracranial hemorrhage, ocular hemorrhage, low back pain, hemoptysis, pulmonary infiltration, pneumonia, respiratory disease, necrotizing fasciitis, pruritic rash, scleroderma, cholecystectomy, orthostatic hypotension, interstitial lung disease, tumor lysis syndrome, necrosis at the injection site, Sweet's syndrome, necrotizing fasciitis, febrile neutropenia, neutropenia, pneumonia, fungal pneumonia, septic shock, bloody stools, colitis, jejunal ulcer, oral hemorrhage, vomiting, mechanical bowel obstruction, abdominal pain, epigastric pain, upper gastrointestinal bleeding, diarrhea, pruritus, drug rash, purpura, petechiae, adipose tissue inflammation, dyspnea, interstitial lung disease, voice disorder, pulmonary edema, sneezing, pneumothorax, rapid breathing, pharyngeal bleeding, thrombocytosis, osteoarthritis, flank pain, tendinitis, temporomandibular joint disorder, osteonecrosis, crystalline arthropathy, osteoporosis, joint stiffness, joint swelling, musculoskeletal rigidity, bursitis, spinal stenosis, rotator cuff syndrome, rhabdomyolysis, sensory loss, paresthesia, peripheral neuropathy, sensory disturbances, tremors, stuttering, hypersomnia, cerebral infarction, brain hemorrhage, cerebrovascular stenosis, carotid artery stenosis, seizures, radiculopathy, neuralgia, facial paralysis, sciatica, dementia, hypophosphatemia, hypocalcemia, hypomagnesemia, hypoglycemia, hyperglycemia, diabetes, iron overload, gout, hemosiderosis, impaired glucose tolerance, acromegaly, metabolic acidosis, acidosis, hyponatremia, hypoalbuminemia, elevated ALT, elevated AST, elevated CRP, increased serum ferritin, elevated blood bilirubin, hyperkalemia, decreased oral intake, tinnitus, chest discomfort, phlebitis, rectal pain, toothache, oral ulcer, gastroesophageal reflux disease, dry mouth, colitis, glossitis, gingival swelling, dental discomfort, anal fissure, jejunal ulcer, mechanical bowel obstruction, fecal incontinence, small intestine ulcer bleeding, duodenitis, aphthous ulcer, reflux, hiatal hernia, gastritis, gastrointestinal disorders, lip ulcers, gingival ulcers, small intestine-large intestine inflammation, mucous stools, rectal ulcer, anal discomfort, bowel obstruction, dental caries, periodontal disease, rectal bleeding, obstipation, hematemesis, ischemic colitis, dry tongue, tongue discoloration, tongue bleeding, tongue pain, glossitis, oral ulcer, rectal pain, jejunal ulcer, small intestine ulcer bleeding, duodenitis, gastroesophageal reflux disease, gastritis, gingival ulcers, small intestine-large intestine inflammation, facial swelling, warmth, systemic edema, sudden death, influenza-like syndrome, death, tonsillitis, oral candidiasis, membranous colitis, influenza, gingivitis, meibomian cyst, fungal pneumonia, dental abscess, Aspergillus infection, periodontitis, sepsis, hepatitis B, infectious scleritis, infectious colitis, acute pyelonephritis, acute otitis media, bronchopulmonary aspergillosis, Pneumocystis jirovecii pneumonia, rickettsiosis, chronic otitis media, viral gastroenteritis, cystitis, bronchiolitis, aspergillosis sinusitis, endophthalmitis, streptococcal pneumonia, latent syphilis, fungal sepsis, mite dermatitis, pericoronitis, dermatophyte infection, peritonsillar abscess, skin infection, epiglottitis, laryngitis, shingles, bronchopulmonary aspergillosis, membranous colitis, dental abscess, septic shock, sepsis, laryngitis, purpura, vesicles, contact dermatitis, seborrheic dermatitis, facial swelling, dry eczema, senile purpura, acne, adipose tissue inflammation, blood vesicles, voice disorder, pharyngeal bleeding, febrile neutropenia, thrombocytosis, osteoarthritis, flank pain, joint stiffness, joint swelling, flank pain, tremors, peripheral neuropathy, facial paralysis, neuralgia, hyperglycemia, metabolic acidosis, acidosis, hyperkalemia, hypomagnesemia, iron overload, nitrogenemia, hematuria, hypotension, phlebitis, subdural hemorrhage, subdural hematoma, spinal compression fracture, skin abrasion, traffic accident, femoral fracture, hair damage, post-procedural contusion, ocular contusion, compression fracture, anal wound, dry eyes, cataract, blurred vision, presbyopia, eyelid dysfunction, retinal dysfunction, decreased vision, ocular irritation, palpitations, bradycardia, heart failure, cardiomyopathy, cardiac arrest, dilated cardiomyopathy, open ear-nasopharyngeal canal, ear discomfort, abnormal liver function, hepatotoxicity, liver disease, hyperbilirubinemia, cholangitis, cholelithiasis, toxic hepatitis, benign prostatic hyperplasia, vulvar pain, nipple pain, endometrial neoplasm, vaginal bleeding, adrenal insufficiency, secondary adrenal cortical insufficiency, hypoaldosteronism, hepatocellular carcinoma, cholangiocarcinoma

This drug should be stored in an airtight container to prevent exposure to air and is safely stored at room temperature between 1°C and 30°C. This helps maintain the drug's efficacy and prevent degradation.

Appearance

This medicine is a freeze-dried powder or cake contained in a colorless and transparent vial, formulated as a freeze-dried injection.

Package unit

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