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Pharmacologic class: Pyrimidine antimetabolite
Therapeutic class: Antineoplastic
Pregnancy risk category D
Unclear. Thought to exert antineoplastic effect by causing DNA hypomethylation and direct cytotoxicity on abnormal hematopoietic bone marrow cells. Cytotoxicity causes death of rapidly growing cells, including cancer cells no longer responsive to normal growth control mechanisms.
Powder for injection (lyophilized): 100-mg single-use vials
⊘Indications and dosages
➣ Treatment of the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusion), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia
Adults: For first treatment cycle: 75 mg/m2 subcutaneously or I.V. daily for 7 days; for subsequent treatment cycles, repeat cycle every 4 weeks. Dosage may be increased to 100 mg/m2 if beneficial effect doesn't occur after two cycles and no toxicity (other than nausea and vomiting) develops. Patient should be treated for at least four cycles. Continue therapy as long as patient benefits from it.
• Based on hematologic response (after administration of recommended dosage for first cycle)
• Unexplained serum bicarbonate reduction below 20 mEq/L
• Unexplained blood urea nitrogen or serum creatinine elevation
• Acute myeloid leukemia
• Hypersensitivity to drug or mannitol
• Advanced malignant hepatic tumor
Use cautiously in:
• impaired renal or hepatic function, myelodysplastic syndrome
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
• Obtain CBC, liver function tests, and serum creatinine level before starting drug.
• For subcutaneous administration, reconstitute with 4 ml sterile water for injection. Inject diluent slowly into vial; invert vial two or three times and rotate gently until uniform suspension appears. Resulting suspension (which will be cloudy) contains azacitidine 25 mg/ml.
• Invert syringe two to three times and gently roll between palms for 30 seconds immediately before administration.
• When giving subcutaneously, divide doses above 4 ml equally in two syringes, and inject subcutaneously in separate sites.
• Administer within 1 hour after reconstitution.
• When giving subcutaneously, rotate sites for each injection (thigh, abdomen, or upper arm). Give new injection at least 1″ from old site and never into tender, bruised, red, or hard area.
• For I.V. administration, reconstitute each vial with 10 ml sterile water for injection. Vigorously shake or roll bottle until all solids have dissolved.
• Prepare I.V. solution by adding reconstituted drug to 50- to 100-ml infusion bag of normal saline solution injection or lactated Ringer's injection.
• Administer I.V. solution over 10 to 40 minutes; administration must be completed within 1 hour of vial reconstitution.
CNS: fatigue, headache, confusion, dizziness, anxiety, depression, insomnia, lethargy, weakness, rigors, malaise, hypoesthesia, cerebral hemorrhage
CV: chest pain, cardiac murmur, tachycardia, hypotension, peripheral edema, syncope
EENT: rhinorrhea, epistaxis, sinusitis, nasopharyngitis, pharyngitis, postnasal drip, eye hemorrhage
GI: nausea, vomiting, diarrhea, constipation, anorexia, abdominal pain or tenderness, abdominal distention, dyspepsia, hemorrhoids, dysphagia, gingival bleeding, oral mucosal petechiae, stomatitis, tongue ulcers, mouth hemorrhage
GU: dysuria, urinary tract infection
Hematologic: anemia, thrombocytopenia, leukopenia, neutropenia, febrile neutropenia, lymphadenopathy, aggravated anemia, postprocedural hemorrhage, pancytopenia, bone marrow failure
Musculoskeletal: myalgia, muscle cramps, arthralgia, limb pain, back pain
Respiratory: cough (possibly productive), dyspnea, exertional or exacerbated dyspnea, upper respiratory tract infection, pneumonia, crackles, wheezing, decreased breath sounds, pleural effusion, rhonchi, atelectasis
Skin: lesion, rash, pruritus, herpes simplex, increased sweating, urticaria, dry skin, skin nodule, erythema, pallor, cellulitis
Other: decreased appetite, weight loss, fever, pitting edema, hematoma, night sweats, peripheral swelling, injection-site reactions, tumor lysis syndrome, Sweet's syndrome (acute febrile neutrophilic dermatosis) transfusion reaction, chest-wall pain, postprocedural or other pain, neutropenic sepsis, septic shock
Drug-diagnostic tests.Potassium: decreased
• Monitor CBC during therapy.
• Monitor liver function tests and serum creatinine frequently.
• Watch for renal tubular acidosis (serum bicarbonate level below 20 mEq/L associated with alkaline urine and hypokalemia, and serum potassium level below 3 mEq/L).
• Monitor patient for signs and symptoms of tumor lysis syndrome (such as irregular heartbeat, shortness of breath, high potassium level, high uric acid level, impaired mental ability, kidney failure).
☞ Instruct patient to call prescriber immediately if shortness of breath, high potassium level, impaired mental ability, rash, easy bruising or bleeding, or respiratory symptoms develop.
• Advise male patient not to father a child during therapy.
• Caution female of childbearing potential to avoid pregnancy and breastfeeding during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions, especially those related to the tests mentioned above.
azacitidineA nucleoside analogue that may be used to treat beta-thalassemia, as it stimulates foetal globin production and myelodysplastic syndromes.
Neutropaenia, thrombocytopaenia, liver failure, renal failure.