Azacitidine Dosage

Medically reviewed by Drugs.com. Last updated on Oct 9, 2024.

Applies to the following strengths: 100 mg; 200 mg; 300 mg

Usual Adult Dose for Myelodysplastic Syndrome

PARENTERAL:
FIRST TREATMENT CYCLE: 75 mg/m2 IV or subcutaneously daily for 7 days, repeat cycles every 4 weeks
SUBSEQUENT CYCLES: After 2 cycles, may increase dose to 100 mg/m2 if no beneficial effect is seen and if no toxicity other than nausea and vomiting has occurred

DURATION OF THERAPY:
Parenteral: Minimum of 4 to 6 cycles, may continue treatment if the patient continues to benefit.

Comments:

Premedicate patients for nausea and vomiting 30 minutes prior to each dose for the first two cycles.
IV administration: Administer the total dose over a period of 10 to 40 minutes, complete the administration within 1 hour of reconstitution.

Use: Treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome (MDS) subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions, refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL)

Usual Adult Dose for Acute Myeloid Leukemia

ORAL:
300 mg orally once daily for 14 days in a 28-day cycle

DURATION OF THERAPY: Until disease progression or unacceptable toxicity.

Comments:

Premedicate patients for nausea and vomiting 30 minutes prior to each dose for the first two cycles.
If the absolute neutrophil count (ANC) is less than 0.5 Gi/L on Day 1 of a cycle, do not administer this drug product. Delay the therapy until the ANC is 0.5 Gi/L or more.

Use: Treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy

Usual Pediatric Dose for Leukemia

1 month to less than 1 year or weighing less than 10 kg:
2.5 mg/kg IV or subcutaneously daily for 7 days in a 28-day cycle

1 year and older and weighing 10 kg or greater:
75 mg/m2 IV or subcutaneously daily for 7 days in a 28-day cycle

Duration of therapy: 3 to 6 cycles.

Comments:

Premedicate patients for nausea and vomiting prior to each dose for the first two cycles.
IV administration: Administer the total dose over a period of 10 to 40 minutes, complete the administration within 1 hour of reconstitution.

Use: Treatment of pediatric patients aged one month and older with newly diagnosed Juvenile Myelomonocytic Leukemia (JMML)

Renal Dose Adjustments

Unexplained reductions in serum bicarbonate levels to less than 20 mEq/L: Reduce dose by 50% for the next course.
Unexplained elevations of BUN or serum creatinine: Delay the next cycle until values return to normal or baseline and reduce dose by 50% for the next course.

Liver Dose Adjustments

Patients with severe preexisting hepatic impairment are at higher risk for toxicity.
Advanced malignant hepatic tumors: Use is contraindicated.
Oral tablet formulation: No dose adjustment is recommended for patients with mild hepatic impairment.

Dose Adjustments

Parenteral:
Adults:
Baseline WBC 3 x 10(9)/L or greater, absolute neutrophil count (ANC) 1.5 x 10(9)/L or greater, AND platelets 75 x 10(9)/L or greater:

ANC less than 0.5 x 10(9)/L and platelets less than 25 x 10(9)/L: Administer 50% of the dose in the next course.
ANC 0.5 to 1.5 x 10(9)/L and platelets 25 to 50 x 10(9)/L: Administer 67% of the dose in the next course.
ANC greater than 1.5 x 10(9)/l and platelets greater than 50 x 10(9)/L: Administer 100% of the dose in the next course.

Baseline WBC less than 3 x 10(9)/L, ANC less than 1.5 x 10(9)/L, OR platelets less than 75 x 10(9)/L, base dose adjustments on nadir counts and bone marrow biopsy cellularity at the time of the nadir unless there is clear improvement in differentiation (percentage of mature granulocytes is higher and ANC is higher than at onset of that course) at the time of the next cycle, in which case continue the current dose:

Bone marrow biopsy cellularity (BMBC) of 30% to 60% at time of nadir: Administer 100% of the dose in the next course.
BMBC of 15% to 30% at time of nadir: Administer 50% of the dose in the next course.
BMBC Less Than 15% at time of nadir: Administer 33% of the dose in the next course.

BASELINE WBC less than 3 x 10(9)/L, ANC less than 1.5 x 10(9)/L, OR platelets less than 75 x 10(9)/L AND WBC or platelet nadir 50% to 75% decrease in counts from baseline:

BMBC of 30% to 60% at nadir time: Administer 100% of the dose in the next course.
BMBC of 15% to 30% at nadir time: Administer 50% of the dose in the next course.
BMBC Less Than 15% at nadir time: Administer 33% of the dose in the next course.

BASELINE WBC less than 3 x 10(9)/L, ANC less than 1.5 x 10(9)/L, OR platelets less than 75 x 10(9)/L AND WBC or platelet nadir greater than 75% decrease in counts from baseline:

BMBC of 30% to 60% at nadir time: Administer 75% of the dose in the next course.
BMBC of 15% to 30% at nadir time: Administer 50% of the dose in the next course.
BMBC Less Than 15% at nadir time: Administer 33% of the dose in the next course.
Give the next course 28 days after the start of the preceding course provided that both the WBC and platelet counts are greater than 25% above the nadir and rising.
At the time of the next cycle, continue the current dose if there is clear improvement in differentiation (i.e., percentage of mature granulocytes and ANC is higher than at onset of that course).
If greater than 25% increase above the nadir is not seen by Day 28: Reassess counts every 7 days.
If 25% increase is not seen by Day 42: Reduce the scheduled dose by 50%.

Pediatric:

First three cycles: Dose reductions are not recommended.
Neutrophil count of less than 0.5 x 10(9)/L at end of Cycle 3 or on Day 1 of Cycles 5 or 6: Discontinue the treatment.

Based on Serum Electrolytes and Renal Toxicity:

Serum bicarbonate levels less than 20 mEq/L: Reduce the dose by 50% in the next course.
Elevations of BUN or serum creatinine: Delay the next cycle until values return to normal and reduce the dose by 50% in the next course.

Oral:
Adult:
Myelosuppression:

Neutrophils less than 0.5 Gi/L on Cycle Day 1:
Stop therapy and resume at the same dose once neutrophils return to 0.5 Gi/L or higher.
Neutrophils less than 1 Gi/L with fever at any time:
At first occurrence, stop therapy and resume at the same dose once neutrophils return to 1 Gi/L or higher.
If occurred in two consecutive cycles,
Stop therapy and after neutrophils return to 1 Gi/L or higher, resume at reduced dose of 200 mg.
If a patient continues to experience febrile neutropenia after dose reduction, reduce the treatment duration by 7 days.
If febrile neutropenia reoccurs after dose and schedule reduction, discontinue treatment with this drug product.
Platelets less than 50 Gi/L with bleeding:
At first occurrence, stop therapy and resume at the same dose once platelets return to 50 Gi/L or higher.
If occurred in two consecutive cycles,
Stop therapy and after platelets return to 50 Gi/L or higher, resume at reduced dose of 200 mg.
If a patient continues to experience thrombocytopenia with bleeding after dose reduction, reduce the treatment duration by 7 days.
If thrombocytopenia with bleeding reoccurs after dose and schedule reduction, discontinue treatment with this drug product.

Gastrointestinal toxicity:

Grade 3 or 4 Nausea or Vomiting:
Stop therapy and resume at the same dose once toxicity has resolved to Grade 1 or lower.
If toxicity reoccurs, stop therapy until resolved to Grade 1 or lower. Resume at reduced dose of 200 mg.
If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days.
If the toxicity continues or reoccurs after dose and schedule reduction, discontinue treatment with this drug product.

Grade 3 or 4 Diarrhea:
Stop therapy and resume at the same dose once toxicity has resolved to Grade 1 or lower.
If toxicity reoccurs, stop therapy until resolved to Grade 1 or lower. Resume at reduced dose of 200 mg.
If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days.
If the toxicity continues or reoccurs after dose and schedule reduction, discontinue treatment with this drug product.

Other Adverse Reactions:
Grade 3 or 4:

Stop therapy and provide medical support. Resume at the same dose once toxicity has resolved to Grade 1 or lower.
If toxicity reoccurs, stop therapy until resolved to Grade 1 or lower. Resume at reduced dose of 200 mg.
If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days.
If the toxicity continues or reoccurs after dose and schedule reduction, discontinue treatment with this drug product.

Precautions

CONTRAINDICATIONS:

Hypersensitivity to the active component or any of the ingredients
Hypersensitivity to mannitol
Advanced malignant hepatic tumors

Safety and efficacy have not been established in patients younger than 1 month for the treatment of JMML.
Safety and efficacy have not been established in patients younger than 18 years for the treatment of myelodysplastic syndrome and acute myeloid leukemia.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available.

Other Comments

Administration advice:

Do not cut, crush, or chew the tablets.
Take a dose about the same time each day.
If a dose is missed or not taken at the usual time, take it as soon as possible on the same day and resume your normal schedule the next day.
Do not take 2 doses on the same day.
If a dose is vomited, do not take another dose on the same day. Resume the normal schedule the following day.
Do not substitute this drug's tablet form for the intravenous or subcutaneous forms. Tablet indication and dosing regimen differ from those of the intravenous or subcutaneous forms.
Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.
Subcutaneous administration: Divide doses greater than 4 mL equally into 2 syringes and inject into 2 separate sites. Rotate sites (thigh, abdomen, upper arm) for each injection, give new injections at least 1 inch/2.5 cm from the previous site and avoid areas that are tender, bruised, red, or hardened.
Oral: Antiemetic prophylaxis may be omitted after 2 cycles if there has been no nausea and vomiting.
In older patients select the dose carefully and monitor renal function.

Storage requirements:
Vials:

Store unreconstituted vials at 25C (77F), excursions permitted to 15C to 30C (59F to 86F) in original bottle.

Tablets:

Store at 20C to 25C (68F to 77F), excursions permitted between 15C to 30C (59F to 86F).

Reconstitution:
Subcutaneous:

Aseptically inject 4 mL sterile water for injection slowly into the vial and mix this drug until a uniform suspension is achieved.
Do not filter the suspension after reconstitution.
The manufacturer product information should be consulted.

Intravenous:

Reconstitute each vial with 10 mL Sterile Water for Injection, USP.
Vigorously shake or roll the vial until all solids are dissolved and a clear solution is formed.
Withdraw required volume of drug solution and inject into a 50-100 mL infusion bag of either 0.9% Sodium Chloride Injection, USP or Lactated Ringer's Injection, USP.
The manufacturer product information should be consulted.

General:

Follow appropriate special handling and disposal procedures.

Monitoring:

Hematologic: Complete blood counts (prior to therapy initiation and with each cycle), signs and symptoms of bleeding (during therapy)
Hepatic: Liver chemistries (prior to therapy initiation and with each cycle)
Metabolic: Signs and symptoms of tumor lysis syndrome (during therapy)
Renal: Serum creatinine, serum bicarbonate, and electrolytes (prior to therapy initiation and with each cycle)

Patient Advice:

Read the FDA-approved patient labeling (Patient Information).
Inform healthcare provider about any underlying liver or renal disease.
Do not breastfeed during therapy and for 1 week after the last dose.
This drug may impair fertility.
Inform females of reproductive potential to notify their healthcare provider if they are pregnant or suspect pregnancy.
There is a risk of myelosuppression and gastrointestinal toxicity, consider use of anti-emetic or anti-diarrheal medications during treatment.