Version July 2025
Dosage guidance:
Dosage forms information: Do not substitute azacitidine tablets for azacitidine injection (or vice versa); indications, dosing regimens, and pharmacokinetics are different.
Clinical considerations: Azacitidine is associated with a moderate emetic potential (Ref); antiemetics are recommended to prevent nausea and vomiting.
Acute myeloid leukemia, maintenance (tablet): Oral: 300 mg once daily on days 1 to 14 of a 28-day treatment cycle (if complete remission following induction chemotherapy and unable to complete intensive curative therapy); continue until disease progression or unacceptable toxicity (Ref). If ANC is <500/mm3 prior to the start of a cycle, delay the treatment cycle until ANC is ≥500/mm3.
Antiemetic prophylaxis : During the first 2 oral azacitidine cycles, administer an antiemetic 30 minutes prior to each dose; antiemetic prophylaxis may be omitted after 2 cycles if there has been no nausea and vomiting.
Missed dose: If an oral azacitidine dose is missed or not administered at the usual time, administer the dose as soon as possible on the same day and resume the normal schedule the following day; do not administer 2 doses on the same day. If the oral azacitidine dose is vomited, do not administer another dose on the same day; resume the normal schedule the following day.
Acute myeloid leukemia in patients requiring low-intensity therapy (injection; off-label use):
In combination with venetoclax: Adults ≥75 years of age and/or with comorbidities: IV, SUBQ: 75 mg/m2/day on days 1 to 7 of a 28-day treatment cycle (in combination with venetoclax); continue until disease progression or unacceptable toxicity (Ref).
Single-agent therapy: SUBQ: 75 mg/m2/day for 7 days of a 28-day treatment cycle for at least 6 cycles; treatment may be continued as long as patient continues to benefit or until disease progression or unacceptable toxicity (Ref). Dose reductions and/or therapy interruption may be required for hematologic toxicity; refer to protocol for details.
IDH1-mutated disease (in combination with ivosidenib): Adults ≥75 years of age and/or with comorbidities: IV, SUBQ: 75 mg/m2/day on days 1 to 7 of a 28-day treatment cycle or 75 mg/m2/day on days 1 to 5 and days 8 and 9 of a 28-day treatment cycle (in combination with ivosidenib) for a minimum of 6 cycles or until relapse, disease progression, or unacceptable toxicity (Ref). Refer to protocol for additional details.
Myelodysplastic syndromes (injection): IV, SUBQ: Initial cycle: 75 mg/m2/day for 7 days of a 28-day treatment cycle. Subsequent cycles: 75 mg/m2/day for 7 days every 4 weeks; dose may be increased to 100 mg/m2/day if no benefit is observed after 2 cycles and no toxicity other than nausea and vomiting have occurred. Patients should be treated for a minimum of 4 to 6 cycles; treatment may be continued as long as patient continues to benefit.
Note: Alternate (off-label) schedules (which have produced hematologic response) have been used for convenience in community oncology centers (Ref):
SUBQ: 75 mg/m2/day for 5 days (Monday to Friday), 2 days rest (Saturday, Sunday), then 75 mg/m2/day for 2 days (Monday, Tuesday); repeat cycle every 28 days or
SUBQ: 50 mg/m2/day for 5 days (Monday to Friday), 2 days rest (Saturday, Sunday), then 50 mg/m2/day for 5 days (Monday to Friday); repeat cycle every 28 days or
SUBQ: 75 mg/m2/day for 5 days (Monday to Friday), repeat cycle every 28 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function prior to treatment:
Altered kidney function: IV, Oral, SUBQ:
CrCl ≥30 mL/minute: No dose adjustment necessary (Ref).
CrCl <30 mL/minute: No dose adjustment necessary; AUC may be increased by as much as ~70%, monitor closely for increased myelosuppression (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal SCr concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV, Oral, SUBQ: No dose adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (% unknown) (Ref):
IV, Oral, SUBQ: No dosage adjustment necessary; when scheduled dose falls on dialysis days, administer after dialysis (Ref). Monitor closely for increased myelosuppression (Ref).
Peritoneal dialysis: IV, Oral, SUBQ: No data available; no dosage adjustment necessary. Monitor closely for increased myelosuppression (Ref).
CRRT: IV, Oral, SUBQ: No data available; no dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV, Oral, SUBQ: No dosage adjustment necessary; when scheduled dose falls on a PIRRT day, administer after PIRRT (Ref).
Kidney toxicity during treatment:
IV, SUBQ: Unexplained increases in BUN or serum creatinine: Delay next cycle until values reach normal or baseline, then reduce azacitidine dose by 50% for next treatment course.
Injection: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Advanced malignant hepatic tumors: Use is contraindicated.
The following adjustments have also been recommended:
Mild or moderate impairment: No need for dosage adjustment is expected (Ref).
Albumin <30 g/L: Use is not recommended (Ref).
Oral:
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST): No dosage adjustment recommended.
Moderate impairment (total bilirubin >1.5 to 3 times ULN): A recommended dosage adjustment has not been established.
Severe impairment (total bilirubin >3 times ULN): There is no dosage adjustment provided in the manufacturer’s labeling (has not been studied).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 (excludes oral dosage form): Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Azacitidine injection:
Hematologic toxicity:
For patients with baseline WBC ≥3,000/mm3, ANC ≥1,500/mm3, and platelets ≥75,000/mm3, adjust the dosage based on nadir counts for any given cycle.
|
Nadir counts |
% dose in the next course | |
|---|---|---|
|
ANC and platelets | ||
|
<500/mm3 |
<25,000/mm3 |
50% |
|
500 to 1,500/mm3 |
25,000 to 50,000/mm3 |
67% |
|
>1,500/mm3 |
>50,000/mm3 |
100% |
For patients whose baseline counts are WBC <3,000/mm3, ANC <1,500/mm3, or platelets <75,000/mm3, dose adjustments should be based 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 the dose of the current treatment should be continued.
|
WBC or platelet nadir % decrease in counts from baseline |
Bone marrow biopsy cellularity at time of nadir | ||
|---|---|---|---|
|
30% to 60% |
15% to 30% |
<15% | |
|
50% to 75% |
Administer 100% of the previous dose. |
Administer 50% of the previous dose. |
Administer 33% of the previous dose. |
|
>75% |
Administer 75% of the previous dose. |
Administer 50% of the previous dose. |
Administer 33% of the previous dose. |
If a nadir, as defined in the previous table, has occurred, the next course of treatment should be given 28 days after the start of the preceding course, providing that both the WBC and the platelet counts are >25% above the nadir and rising. If a >25% increase above nadir is not seen by day 28, counts should be reassessed every 7 days. If a 25% increase is not seen by day 42, then the patient should be treated with 50% of the scheduled dose.
Nonhematologic toxicity:
Dosage adjustment for electrolyte imbalance: If serum bicarbonate falls to <20 mEq/L (unexplained decrease): Reduce azacitidine dose by 50% for next treatment course.
Azacitidine tablets:
|
Adverse reaction |
Severity |
Recommended azacitidine dosage modification |
|---|---|---|
|
Hematologic toxicity |
Neutrophils <500/mm3 on day 1 of cycle |
Interrupt azacitidine treatment; resume at the same dose after neutrophils return to ≥500/mm3. May require WBC growth factor support. |
|
Neutrophils <1,000/mm3 with fever at any time |
First occurrence: Interrupt azacitidine treatment; resume at the same dose after neutrophils return to ≥1,000/mm3. Occurrence on 2 consecutive cycles: Interrupt azacitidine treatment; resume at a reduced dose of 200 mg after neutrophils return to ≥1,000/mm3. If a patient continues to experience neutropenic fever following dose reduction, reduce the treatment duration by 7 days. If neutropenic fever recurs after dose and schedule reduction, discontinue oral azacitidine. May require WBC growth factor support. | |
|
Platelets <50,000/mm3 with bleeding |
First occurrence: Interrupt azacitidine treatment; resume at the same dose after platelets return to ≥50,000/mm3. Occurrence on 2 consecutive cycles: Interrupt azacitidine treatment; resume at a reduced dose of 200 mg after platelets return to ≥50,000/mm3. If thrombocytopenia with bleeding continues following dose reduction, reduce the treatment duration by 7 days. If thrombocytopenia with bleeding recurs after dose and schedule reduction, discontinue oral azacitidine. | |
|
GI toxicity |
Grade 3 or 4 nausea and vomiting |
Interrupt azacitidine treatment; once toxicity has resolved to ≤ grade 1, resume azacitidine at the same dose. If toxicity recurs, interrupt azacitidine treatment until resolved to ≤ grade 1 and resume azacitidine at reduced dose of 200 mg. If nausea/vomiting continue after dose reduction, reduce the treatment duration by 7 days. If nausea/vomiting continue or recur after dose and schedule reduction, discontinue oral azacitidine. |
|
Grade 3 or 4 diarrhea |
Interrupt azacitidine treatment; once toxicity has resolved to ≤ grade 1, resume azacitidine at the same dose. If toxicity recurs, interrupt azacitidine treatment until resolved to ≤ grade 1 and resume azacitidine at reduced dose of 200 mg. If diarrhea continues after dose reduction, reduce the treatment duration by 7 days. If diarrhea continues or recurs after dose and schedule reduction, discontinue oral azacitidine. | |
|
Other adverse reactions |
Grade 3 or 4 |
Interrupt azacitidine treatment and provide supportive care; once toxicity has resolved to ≤ grade 1, resume azacitidine at the same dose. If toxicity recurs, interrupt azacitidine treatment until resolved to ≤ grade 1 and resume azacitidine at reduced dose of 200 mg. If the toxicity continues after dose reduction, reduce the treatment duration by 7 days. If the toxicity continues or recurs after dose and schedule reduction, discontinue oral azacitidine. |
Refer to adult dosing. Due to the potential for decreased kidney function, select dose carefully and closely monitor renal function.
(For additional information see "Azacitidine: Pediatric drug information")
Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. Azacitidine is associated with a moderate emetic potential (Ref); antiemetics are recommended to prevent nausea and vomiting. Oral (adult patients only) and injectable azacitidine dosage forms are not substitutable on a mg:mg basis due to pharmacokinetic differences and unique dosing regimens (indications). Pediatric dosing presented as mg/kg and mg/m2; use caution.
Acute myeloid leukemia (AML): Limited data available; efficacy results variable:
SUBQ:
Children ≥2 years and Adolescents: SUBQ: 75 mg/m2/dose once daily for 7 days; dosing from a patient population (n=53) that included adults up to 84 years; the minimum age of subjects in the trial was 5 years, although minimum inclusion criteria was 2 years; used in combination with tretinoin and valproic acid for refractory or relapsed cases with clinical activity observed (Ref).
IV: Reported dosing regimens variable:
Children and Adolescents: IV: 300 mg/m2/dose once daily for 2 consecutive days has been used for induction and intensive consolidation therapy in various combinations in newly diagnosed patients (Ref). Note: Frequency of use of azacitidine therapy for AML (newly diagnosed) has decreased as newer therapies have replaced previous protocols.
Juvenile myelomonocytic leukemia (JMML):
Infants: IV: 2.5 mg/kg once daily on days 1 through 7 of a 28-day cycle; treat for at least 3 cycles up to a maximum of 6 cycles.
Children weighing <10 kg: IV: 2.5 mg/kg/dose once daily on days 1 through 7 of a 28-day cycle; treat for at least 3 cycles up to a maximum of 6 cycles.
Children weighing ≥10 kg: IV: 75 mg/m2/dose once daily on days 1 through 7 of a 28-day cycle; treat for at least 3 cycles up to a maximum of 6 cycles.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Juvenile myelomonocytic leukemia (JMML): Note: A delay in dose not exceeding 14 days can be considered for nonhematologic toxicities.
Hematologic toxicity:
Pediatric patients: Dosage adjustment not recommended based on hematologic toxicity within the first 3 cycles because drug toxicity is difficult to differentiate from disease.
ANC <500/mm3 at end of cycle 3 or day 1 of cycles 5 or 6: Discontinue treatment.
Electrolyte disturbances: If serum bicarbonate falls to <20 mEq/L (unexplained decrease): Reduce dose by 50% for next treatment course.
Acute myeloid leukemia (AML): Refer to specific protocols.
Infants, Children, and Adolescents: Injection: There are no dosage adjustments provided in the manufacturer's labeling for pediatric patients (pediatric patients with kidney impairment were excluded from the juvenile myelomonocytic leukemia clinical trials); based on adult data, the following dose adjustments may be considered: If unexplained increases in BUN or serum creatinine occur, delay next cycle until values return to normal or baseline, then reduce azacitidine dose by 50% for next treatment course.
Infants, Children, and Adolescents: Injection: There are no dosage adjustments provided in the manufacturer's labeling for pediatric patients (pediatric patients with hepatic impairment were excluded from the juvenile myelomonocytic leukemia clinical trials); use with caution (potentially hepatotoxic in patients with preexisting liver impairment); use is contraindicated in patients with advanced malignant hepatic tumors.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Chest pain (16%)
Dermatologic: Ecchymoses (31%), erythema of skin (7% to 17%), pruritus (12%), skin rash (10% to 14%)
Gastrointestinal: Abdominal pain (13% to 22%), abdominal tenderness (12%), anorexia (21%), constipation (34% to 50%), decreased appetite (13%), diarrhea (36% to 50%; grades 3/4: 5%), nausea (48% to 71%; grades 3/4: 2% to 3%), vomiting (27% to 60%; grades 3/4: 3%)
Hematologic & oncologic: Anemia (25% to 70%; grades 3/4: 4% to 14%), febrile neutropenia (7% to 16%; grades 3/4: 11% to 13%), leukopenia (18% to 48%; grades 3/4: 15%), neutropenia (32% to 74%; grades 3/4: 49% to 61%), petechia (11% to 24%), thrombocytopenia (65% to 70%; grades 3/4: 21% to 58%)
Local: Bruising at injection site (5% to 14%), erythema at injection site (35% to 43%), injection-site reaction (14% to 29%), pain at injection site (19% to 23%)
Nervous system: Anxiety (5% to 13%), asthenia (≤44%), dizziness (11% to 19%), fatigue (≤44%), headache (22%), insomnia (9% to 11%), malaise (11%)
Neuromuscular & skeletal: Arthralgia (14% to 22%), limb pain (11%), myalgia (16%)
Respiratory: Dyspnea (15% to 29%; dyspnea on exertion: 5%), nasopharyngitis (15%), pneumonia (8% to 27%), upper respiratory tract infection (9% to 13%)
Miscellaneous: Fever (30% to 52%)
1% to 10%:
Cardiovascular: Atrial fibrillation (<5%), chest wall pain (5%), congestive cardiomyopathy (<5%), heart failure (<5%), hypertension (9%), hypotension (7%), orthostatic hypotension (<5%)
Dermatologic: Cellulitis (<5%), cutaneous nodule (5%), pruritic rash (<5%), pyoderma gangrenosum (<5%), skin sclerosis (<5%), urticaria (6%), xeroderma (5%)
Endocrine & metabolic: Dehydration (<5%), hypokalemia (6%), weight loss (4% to 8%)
Gastrointestinal: Abscess of rectum and/or perirectal area (<5%), cholecystectomy (<5%), cholecystitis (<5%), diverticulitis of the gastrointestinal tract (<5%), dyspepsia (6%), gastrointestinal hemorrhage (<5%), gingival hemorrhage (10%), loose stools (6%), melena (<5%), oral hemorrhage (5%), stomatitis (8%)
Genitourinary: Hematuria (6%), urinary tract infection (9%)
Hematologic & oncologic: Agranulocytosis (<5%), bone marrow failure (<5%), exacerbation of anemia (6%), hematoma (9%), leukemia cutis (<5%), pancytopenia (<5%), postprocedural hemorrhage (6%), splenomegaly (<5%)
Hypersensitivity: Anaphylactic shock (<5%), hypersensitivity reaction (<5%)
Infection: Bacterial infection (<5%), blastomycosis (<5%), Klebsiella pneumoniae infection (<5%), limb abscess (<5%), neutropenic sepsis (<5%), sepsis (<5%; including Klebsiella sepsis), septic shock (<5%), staphylococcal bacteremia (<5%), staphylococcal infection (<5%), systemic inflammatory response syndrome (<5%), toxoplasmosis (<5%)
Local: Hematoma at injection site (6%), induration at injection site (5%), injection-site granuloma (5%), injection-site infection (<5%), injection-site pruritus (7%), rash at injection site (6%), skin discoloration at injection site (5%), swelling at injection site (5%)
Nervous system: Cerebral hemorrhage (<5%), debility (<5%), intracranial hemorrhage (<5%), lethargy (7% to 8%), myasthenia (<5%), seizure (<5%)
Neuromuscular & skeletal: Aggravated bone pain (<5%), neck pain (<5%)
Ophthalmic: Subconjunctival hemorrhage (eye hemorrhage: <5%)
Renal: Flank pain (<5%), kidney failure (<5%)
Respiratory: Hemoptysis (<5%), pharyngolaryngeal pain (6%), pneumonitis (<5%), pulmonary infiltrates (<5%), respiratory distress (<5%), rhinitis (6%), streptococcal pharyngitis (<5%)
Frequency not defined:
Hepatic: Hepatic coma
Nervous system: Rigors
Postmarketing:
Cardiovascular: Pericardial effusion, pericarditis
Dermatologic: Sweet syndrome
Hematologic & oncologic: Differentiation syndrome, tumor lysis syndrome
Hypersensitivity: Hypersensitivity angiitis
Infection: Necrotizing fasciitis
Local: Tissue necrosis at injection site
Respiratory: Interstitial pulmonary disease
Hypersensitivity to azacitidine or any component of the formulation; hypersensitivity to mannitol (injection only); advanced malignant hepatic tumors (injection only).
Concerns related to adverse effects:
• Bone marrow suppression: Neutropenia, thrombocytopenia, and anemia commonly occur; neutropenic fever has been reported.
• Hepatotoxicity: May cause hepatotoxicity in patients with preexisting hepatic impairment. Progressive hepatic coma leading to death has been reported in patients with extensive tumor burden due to metastatic disease, especially those with a baseline albumin <30 g/L. Patients with hepatic impairment were excluded from clinical studies for myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML).
• Injection-site reactions: Injection site reactions commonly occurred with SUBQ azacitidine administration.
• Nephrotoxicity: Kidney toxicities, including serum creatinine elevations, renal tubular acidosis (serum bicarbonate decrease to <20 mEq/L associated with alkaline urine and serum potassium <3 mEq/L), and kidney failure (some fatal), have been reported with IV azacitidine when used in combination with other chemotherapy agents. Patients with kidney impairment may be at increased risk for kidney toxicity. Patients with kidney impairment were excluded from clinical studies for MDS and JMML.
• Tumor lysis syndrome: May cause serious or fatal tumor lysis syndrome (TLS). TLS has occurred despite receiving antihyperuricemic therapy (eg, allopurinol).
Disease-related concerns:
• Myelodysplastic syndromes: In a clinical trial of patients with RBC transfusion-dependent anemia and thrombocytopenia due to MDS, patients were randomized to receive oral azacitidine (300 mg once daily for 21 days every 28 days) versus placebo; patients received oral azacitidine for a median of 5 cycles. Enrollment was discontinued early in the trial due to a higher incidence of early fatal and/or serious adverse reactions in the azacitidine arm; sepsis was the most frequent fatal adverse reaction. Safety and efficacy of oral azacitidine for treatment of MDS have not been established, and treatment of MDS with oral azacitidine outside of a clinical trial is not recommended.
Dosage form specific issues:
• Do not substitute: Do not substitute azacitidine tablets for azacitidine injection (or vice versa); indications, dosages, and pharmacokinetics are different. Treatment of patients using IV or SUBQ azacitidine at the recommended tablet dosage may result in a fatal adverse reaction; treatment of patients using azacitidine tablets at the doses recommended for IV or SUBQ azacitidine may not be effective.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Injection:
Generic: 100 mg (1 ea)
Suspension Reconstituted, Injection [preservative free]:
Vidaza: 100 mg (1 ea)
Generic: 100 mg (1 ea)
Tablet, Oral:
Onureg: 200 mg, 300 mg
May be product dependent
Suspension (reconstituted) (azaCITIDine Injection)
100 mg (per each): $46.80 - $617.62
Suspension (reconstituted) (Vidaza Injection)
100 mg (per each): $702.29
Tablets (Onureg Oral)
200 mg (per each): $2,248.12
300 mg (per each): $2,248.12
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Injection:
Vidaza: 100 mg (1 ea)
Generic: 100 mg (1 ea)
Tablet, Oral:
Onureg: 200 mg, 300 mg
Azacitidine is associated with a moderate emetic potential (Ref); antiemetics are recommended to prevent nausea and vomiting.
Oral: Swallow whole; do not split, crush, or chew tablets. Administer at approximately the same time each day, with or without food. During the first 2 cycles, administer an antiemetic 30 minutes prior to each dose; antiemetic prophylaxis may be omitted after 2 cycles if there has been no nausea and vomiting.
IV: Infuse over 10 to 40 minutes; infusion must be completed within 1 hour of (vial) reconstitution.
SUBQ: The manufacturer recommends equally dividing doses requiring more than one vial into 2 syringes and injecting into 2 separate sites. Rotate sites for each injection (thigh, abdomen, or upper arm). Administer subsequent injections at least 1 inch from previous injection sites; do not inject into tender, bruised, red, or hard areas. Allow refrigerated suspensions to come to room temperature (for up to 30 minutes) prior to administration. Resuspend by vigorously rolling the syringe between the palms until a cloudy suspension is achieved.
If azacitidine suspension (injection) comes in contact with the skin, immediately wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water.
If azacitidine suspension comes in contact with the skin, immediately wash with soap and water; if it comes into contact with mucous membranes, flush thoroughly with water. Azacitidine is associated with a moderate emetic potential (Ref); antiemetics are recommended to prevent nausea and vomiting.
SubQ: The manufacturer recommends equally dividing volumes >4 mL into two syringes and injecting into two separate sites; however, policies for maximum SubQ administration volume may vary by institution; interpatient variations may also apply. Rotate sites for each injection (thigh, abdomen, or upper arm). Administer subsequent injections at least 1 inch from previous injection sites and never into areas where the site is tender, bruised, red, or hardened. Allow refrigerated suspensions to come to room temperature up to 30 minutes prior to administration; suspension stored at room temperature must be administered within 1 hour after reconstitution. Resuspend by inverting the syringe 2 to 3 times and then rolling the syringe between the palms for 30 seconds.
IV: Infuse over 10 to 40 minutes; infusion must be completed within 1 hour of vial reconstitution.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Acute myeloid leukemia, maintenance (tablet): Treatment (maintenance) of acute myeloid leukemia in adults 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.
Juvenile myelomonocytic leukemia, newly diagnosed (injection): Treatment of newly diagnosed juvenile myelomonocytic leukemia in pediatric patients ≥1 month of age.
Myelodysplastic syndromes (injection): Treatment of myelodysplastic syndromes (MDS) in adults with the following French-American-British (FAB) classification subtypes: Refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
Acute myeloid leukemia in patients requiring low-intensity therapy (injection)
AzaCITIDine may be confused with azaTHIOprine, decitabine
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Cedazuridine: May increase serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to therapy in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 6 months after the last azacitidine dose. Patients with partners who could become pregnant should use effective contraception during therapy and for at least 3 months after the last azacitidine dose.
Based on its mechanism of action and data from animal reproduction studies, in utero exposure to azacitidine may cause fetal harm. Information related to the use of azacitidine for the treatment of acute myeloid leukemia (AML) in pregnancy is limited (Alrajhi 2019; Mahdi 2018).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy (ESMO [Peccatori 2013]). Guidelines are also available for the treatment of AML in pregnancy (BCSH [Ali 2015]). The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). If chemotherapy is indicated, it should not be administered in the first trimester but may begin in the second trimester. There should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Ali 2015; ESMO [Peccatori 2013]).
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (1-877-635-4499).
It is not known if azacitidine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during treatment and for 1 week after the last azacitidine dose.
Monitor LFTs, electrolytes, CBC with differential and platelets at baseline and prior to each cycle (at a minimum) and as clinically indicated (injection). For oral azacitidine, monitor blood counts every other week for 2 cycles, then prior to each cycle; increase to every other week for 2 cycles after any myelosuppression-related dose reduction. Monitor renal function (BUN and serum creatinine) at baseline, prior to each cycle, and more frequently if indicated; monitor closely for toxicities, particularly in patients with severe renal impairment (azacitidine and metabolites are excreted renally). Assess risk for tumor lysis syndrome (TLS) prior to treatment and monitor for signs/symptoms of TLS. Also monitor for hematologic response, nausea/vomiting, and for injection-site reactions. Monitor adherence (tablets).
The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Azacitidine (a hypomethylating agent) is a pyrimidine nucleoside analog of cytidine that inhibits DNA/RNA methyltransferases; it is incorporated into DNA and RNA and inhibits DNA and RNA methyltransferases, reduces DNA and RNA methylation, alters DNA gene expression (including re-expression of genes that regulate tumor suppression and cell differentiation), and decreases RNA stability and decreases protein synthesis.
Absorption: SUBQ: Rapid and complete.
Distribution: Vd: IV: 76 ± 26 L; does not cross blood-brain barrier; Oral: Vz/F: 881 L.
Protein binding: Oral: 6% to 12%.
Metabolism: Hepatic; spontaneous hydrolysis and deamination (mediated by cytidine deaminase) to several metabolites.
Bioavailability: SUBQ: ~89%; Oral: ~11% (compared to SUBQ).
Half-life elimination:
Infants and children <7 years: IV: Geometric mean: 0.3 hours (azacytidine) (Niemeyer 2021).
Adults: IV, SUBQ: 41 ± 8 minutes (azacitidine); ~4 hours (azacitidine and metabolites); ~4 hours; Oral: ~0.5 hours (azacitidine).
Time to peak, plasma: SUBQ: 30 minutes; Oral: 1 hour.
Excretion: IV, SUBQ: Urine (50% to 85%); feces (<1%); Oral: Urine (<2% as unchanged drug).
Altered kidney function: The AUC was increased by ~70% after a single SUBQ dose and by 41% after multiple SUBQ doses in patients with severe renal impairment (CrCl <30 mL/minute) compared to patients with normal renal function. This increase in exposure did not correlate with increased adverse effects.
