Note: Azacitidine is associated with a moderate emetic potential (ASCO [Hesketh 2020; MASCC/ESMO [Roila 2016]); antiemetics are recommended to prevent nausea and vomiting. Do not substitute azacitidine tablets for azacitidine injection (or vice versa); indications and dosing regimens are different.
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 (Wei 2020). 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):
IV, SubQ: Adults ≥75 years of age and/or with comorbidities: 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 (DiNardo 2020).
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 (Fenaux 2010). Dose reductions and/or therapy interruption may be required for hematologic toxicity; refer to protocol for 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.
Dosage adjustment based on serum electrolytes: If serum bicarbonate falls to <20 mEq/L (unexplained decrease): Reduce dose by 50% for next treatment course.
Note: Alternate (off-label) schedules (which have produced hematologic response) have been used for convenience in community oncology centers (Lyons 2009): 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
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
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.
Injection:
Renal impairment at baseline:
CrCl ≥30 mL/minute: No dosage adjustment necessary (Douvali 2012).
CrCl <30 mL/minute: No dosage adjustment necessary for cycle 1; azacitidine and its metabolites are excreted renally, monitor closely for toxicity.
Renal toxicity during treatment: Unexplained increases in BUN or serum creatinine: Delay next cycle until values reach baseline or normal, then reduce dose by 50% for next treatment course.
Oral: CrCl 15 to 89 mL/minute: No dosage adjustment necessary; monitor patients with CrCl 15 to 29 mL/minute more frequently and modify dosage for adverse reactions.
Injection: No dosage adjustment provided in the manufacturer’s labeling (has not been studied). Use is contraindicated in patients with advanced malignant hepatic tumors.
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).
(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 (POGO [Dupuis 2011]); antiemetics are recommended to prevent nausea and vomiting.
Acute myeloid leukemia (AML): Limited data available; efficacy results variable:
SubQ: Children ≥2 years and Adolescents: 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 (Soriano 2007)
IV: Dosing regimens variable: Children and Adolescents: 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 (Ravindranath 2005; Ribiero 2005). Note: Frequency of use of azacitidine therapy for AML (newly diagnosed) has decreased as newer therapies have replaced previous protocols.
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: The presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.
Hematologic toxicity:
Adult:
For baseline WBC ≥3,000/mm3, ANC ≥1,500/mm3, and platelets ≥75,000/mm3:
Nadir count: ANC <500/mm3 or platelets <25,000/mm3: Administer 50% of dose during next treatment course
Nadir count: ANC 500/mm3 to 1,500/mm3 or platelets 25,000 to 50,000/mm3: Administer 67% of dose during next treatment course
Nadir count: ANC >1,500/mm3 or platelets >50,000/mm3: Administer 100% of dose during next treatment course
For baseline WBC <3,000/mm3, ANC <1,500/mm3, or platelets <75,000/mm3 : Adjust dose as follows based on nadir counts and bone marrow biopsy cellularity at the time of nadir, unless clear improvement in differentiation at the time of the next cycle:
WBC or platelet nadir decreased 50% to 75% from baseline and bone marrow biopsy cellularity at time of nadir 30% to 60%: Administer 100% of dose during next treatment course
WBC or platelet nadir decreased 50% to 75% from baseline and bone marrow biopsy cellularity at time of nadir 15% to 30%: Administer 50% of dose during next treatment course
WBC or platelet nadir decreased 50% to 75% from baseline and bone marrow biopsy cellularity at time of nadir <15%: Administer 33% of dose during next treatment course
WBC or platelet nadir decreased >75% from baseline and bone marrow biopsy cellularity at time of nadir 30% to 60%: Administer 75% of dose during next treatment course
WBC or platelet nadir decreased >75% from baseline and bone marrow biopsy cellularity at time of nadir 15% to 30%: Administer 50% of dose during next treatment course
WBC or platelet nadir decreased >75% from baseline and bone marrow biopsy cellularity at time of nadir <15%: Administer 33% of dose during next treatment course
Note: If a nadir defined above occurs, administer the next treatment course 28 days after the start of the preceding course as long as WBC and platelet counts are >25% above the nadir and rising. If a >25% increase above the nadir is not seen by day 28, reassess counts every 7 days. If a 25% increase is not seen by day 42, administer 50% of the scheduled dose.
Electrolyte disturbances: Adult: If serum bicarbonate falls to <20 mEq/L (unexplained decrease): Reduce dose by 50% for next treatment course
There are no pediatric-specific recommendations; refer to pediatric specific protocols if available. Based on experience in adult patients, dosing adjustment suggested; monitor closely for toxicity.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use is contraindicated in patients with advanced malignant hepatic tumors.
Refer to adult dosing. Due to the potential for decreased renal function in the elderly, select dose carefully and closely monitor renal function.
Azacitidine injection:
Hematologic toxicity: Myelodysplastic syndromes:
For baseline WBC ≥3,000/mm3, ANC ≥1,500/mm3, and platelets ≥75,000/mm3:
Nadir count: ANC <500/mm3 or platelets <25,000/mm3: Administer 50% of dose during next treatment course.
Nadir count: ANC 500/mm3 to 1,500/mm3 or platelets 25,000 to 50,000/mm3: Administer 67% of dose during next treatment course.
Nadir count: ANC >1,500/mm3 or platelets >50,000/mm3: Administer 100% of dose during next treatment course.
For baseline WBC <3,000/mm3, ANC <1,500/mm3, or platelets <75,000/mm3: Adjust dose as follows based on nadir counts and bone marrow biopsy cellularity at the time of nadir, unless clear improvement in differentiation at the time of the next cycle:
WBC or platelet nadir decreased 50% to 75% from baseline and bone marrow biopsy cellularity at time of nadir 30% to 60%: Administer 100% of dose during next treatment course.
WBC or platelet nadir decreased 50% to 75% from baseline and bone marrow biopsy cellularity at time of nadir 15% to 30%: Administer 50% of dose during next treatment course.
WBC or platelet nadir decreased 50% to 75% from baseline and bone marrow biopsy cellularity at time of nadir <15%: Administer 33% of dose during next treatment course.
WBC or platelet nadir decreased >75% from baseline and bone marrow biopsy cellularity at time of nadir 30% to 60%: Administer 75% of dose during next treatment course.
WBC or platelet nadir decreased >75% from baseline and bone marrow biopsy cellularity at time of nadir 15% to 30%: Administer 50% of dose during next treatment course.
WBC or platelet nadir decreased >75% from baseline and bone marrow biopsy cellularity at time of nadir <15%: Administer 33% of dose during next treatment course.
Note: If a nadir defined above occurs, administer the next treatment course 28 days after the start of the preceding course as long as WBC and platelet counts are >25% above the nadir and rising. If a >25% increase above the nadir is not seen by day 28, reassess counts every 7 days. If a 25% increase is not seen by day 42, administer 50% of the scheduled dose.
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. |
|
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 | |
|
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. |
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
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 (ASCO [Hesketh 2020; MASCC/ESMO [Roila 2016]); 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 (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 (POGO [Dupuis 2011]); 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 2016 [group 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 2016; USP-NF 2020).
Acute myeloid leukemia (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.
Myelodysplastic syndromes (injection): Treatment of myelodysplastic syndromes (MDS) in patients 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
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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%), nausea (48% to 71%), vomiting (27% to 60%)
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%; more common with IV administration), 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%), dizziness (11% to 19%), fatigue (≤44%), headache (22%), insomnia (9% to 11%), malaise (11%)
Neuromuscular & skeletal: Arthralgia (14% to 22%), asthenia (≤44%), limb pain (11%), myalgia (16%)
Respiratory: Dyspnea (5% to 29%), nasopharyngitis (15%), pneumonia (8% to 27%), upper respiratory infection (9% to 13%)
Miscellaneous: Fever (30% to 52%)
1% to 10%:
Cardiovascular: Atrial fibrillation (<5%), cardiac failure (<5%), chest wall pain (5%), congestive cardiomyopathy (<5%), hypertension (9%), hypotension (7%), orthostatic hypotension (<5%), septic shock (<5%)
Dermatologic: Cellulitis (<5%), cutaneous nodule (5%), pruritic rash (<5%), pyoderma gangrenosum (<5%), rash at injection site (6%), skin discoloration at injection site (5%), skin sclerosis (<5%), urticaria (6%), xeroderma (5%)
Endocrine & metabolic: Dehydration (<5%), hypokalemia (6%; more common with IV administration), weight loss (4% to 8%)
Gastrointestinal: Cholecystectomy (<5%), cholecystitis (<5%), diverticulitis of the gastrointestinal tract (<5%), dyspepsia (6%), gastrointestinal hemorrhage (<5%), gingival hemorrhage (10%), loose stools (6%), melena (<5%), stomatitis (8%)
Genitourinary: Abscess of rectum and/or peri-rectal area (<5%), hematuria (6%), urinary tract infection (9%)
Hematologic & oncologic: Agranulocytosis (<5%), bone marrow failure (<5%), hematoma (9%), leukemia cutis (<5%), oral hemorrhage (5%), pancytopenia (<5%), postprocedural hemorrhage (6%), splenomegaly (<5%)
Hypersensitivity: Anaphylactic shock (<5%), hypersensitivity reaction (<5%)
Infection: Bacterial infection (<5%), blastomycosis (<5%), limb abscess (<5%), neutropenic sepsis (<5%), sepsis (<5%, including Klebsiella sepsis), staphylococcal bacteremia (<5%), staphylococcal infection (<5%), systemic inflammatory response syndrome (<5%), toxoplasmosis (<5%)
Local: Catheter site hemorrhage (<5%), hematoma at injection site (6%), induration at injection site (5%), injection site granuloma (5%), injection site infection (<5%), itching at injection site (7%), swelling at injection site (5%)
Nervous system: Aggravated bone pain (<5%), cerebral hemorrhage (<5%), flank pain (<5%), intracranial hemorrhage (<5%), lethargy (7% to 8%), myasthenia (<5%), seizure (<5%)
Neuromuscular & skeletal: Neck pain (<5%)
Ophthalmic: Subconjunctival hemorrhage (<5%)
Renal: Renal failure syndrome (<5%)
Respiratory: Hemoptysis (<5%), Klebsiella pneumoniae infection (<5%), pharyngolaryngeal pain (6%), pneumonitis (<5%), pulmonary infiltrates (<5%), respiratory distress (<5%), rhinitis (6%), streptococcal pharyngitis (<5%)
Miscellaneous: Physical health deterioration (<5%)
Frequency not defined:
Hepatic: Hepatic coma
Nervous system: Rigors (more common with IV administration)
Postmarketing:
Dermatologic: Sweet's syndrome
Hematologic & oncologic: Differentiation syndrome, tumor lysis syndrome
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. Hematologic toxicity may require treatment interruption, dose reduction, and/or discontinuation. If appropriate, consider supportive care with hematopoietic growth factors.
• 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). Use is contraindicated in patients with advanced malignant hepatic tumors.
• Injection-site reactions: Injection site reactions commonly occurred with SubQ azacitidine administration.
• Nephrotoxicity: Renal 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 renal failure (some fatal), have been reported with IV azacitidine when used in combination with other chemotherapy agents. Withhold or reduce the dose with unexplained decreases in serum bicarbonate <20 mEq/L or if elevations in BUN or serum creatinine occur. Patients with renal impairment may be at increased risk for renal toxicity. Monitor closely for toxicity in patients with severe renal impairment (azacitidine and metabolites are excreted renally).
• Tumor lysis syndrome: May cause serious or fatal tumor lysis syndrome (TLS). TLS has occurred in patients despite receiving antihyperuricemic therapy (eg, allopurinol). Assess TLS risk at baseline and monitor for TLS symptoms; treat accordingly.
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 and dosages 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.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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 diminish the therapeutic effect 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
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect 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
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect 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 diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to therapy. Females of reproductive potential should use effective contraception during therapy and for at least 6 months after the last azacitidine dose. Males with female partners of reproductive potential 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. Assess for tumor lysis syndrome (TLS) risk 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: IV, SubQ: ~4 hours; Oral: ~0.5 hours.
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).
Renal function impairment: 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.
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): $1,895.16
300 mg (per each): $1,895.16
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