AzaCITIDine

Dosage Forms

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)

Pharmacology

Mechanism of Action

Antineoplastic effects may be a result of azacitidine's ability to promote hypomethylation of DNA, restoring normal gene differentiation and proliferation. Azacitidine also exerts direct toxicity to abnormal hematopoietic cells in the bone marrow.

Pharmacokinetics/Pharmacodynamics

Absorption

SubQ: Rapid and complete

Distribution

V_d: IV: 76 ± 26 L; does not cross blood-brain barrier

Metabolism

Hepatic; hydrolysis to several metabolites

Excretion

Urine (50% to 85%); feces (<1%)

Time to Peak

SubQ: 30 minutes

Half-Life Elimination

IV, SubQ: ~4 hours

Use in Specific Populations

Special Populations: Renal Function Impairment

The AUC was increased by 70% after a single subcutaneous dose and by 41% after multiple subcutaneous 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.

Use: Labeled Indications

Myelodysplastic syndromes: 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.

Use: Off Label

Acute myeloid leukemia (AML) in patients requiring low-intensity therapya

Data from a phase III randomized trial supports the use of azacitidine in the management of patients requiring low-intensity therapy for AML Fenaux 2010.

Contraindications

Hypersensitivity to azacitidine, mannitol, or any component of the formulation; advanced malignant hepatic tumors

Dosage and Administration

Dosing: Adult

Note: Azacitidine is associated with a moderate emetic potential (Hesketh 2017; Roila 2016); antiemetics are recommended to prevent nausea and vomiting.

Myelodysplastic syndromes (MDS): IV, SubQ: Initial cycle: 75 mg/m²/day for 7 days. 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 (Lyons 2009): SubQ:

75 mg/m²/day for 5 days (Mon-Fri), 2 days rest (Sat, Sun), then 75 mg/m²/day for 2 days (Mon, Tues); repeat cycle every 28 days or

50 mg/m²/day for 5 days (Mon-Fri), 2 days rest (Sat, Sun), then 50 mg/m²/day for 5 days (Mon-Fri); repeat cycle every 28 days or

75 mg/m²/day for 5 days (Mon-Fri), repeat cycle every 28 days

Acute myeloid leukemia (AML) (off-label use): SubQ: 75 mg/m²/day for 7 days every 4 weeks 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.

Dosage adjustment based on serum electrolytes: If serum bicarbonate falls to <20 mEq/L (unexplained decrease): Reduce dose by 50% for next treatment course.

Dosing: Geriatric

Refer to adult dosing. Due to the potential for decreased renal function in the elderly, select dose carefully and closely monitor renal function.

Dosing: Pediatric

Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.

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.

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

Dosing: Adjustment for Toxicity

Hematologic toxicity: MDS:

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.

Reconstitution

If reconstituted solution comes in contact with skin, wash immediately and thoroughly with soap and water; if comes in contact with mucous membranes, flush thoroughly with water.

IV: Reconstitute vial with 10 mL SWFI to form a 10 mg/mL solution; vigorously shake or roll vial until solution is dissolved and clear. Mix in 50 to 100 mL of NS or lactated Ringer's injection for infusion.

SubQ: Slowly add 4 mL SWFI to each vial, resulting in a concentration of 25 mg/mL. Vigorously shake or roll vial until a suspension is formed (suspension will be cloudy). The manufacturer recommends dividing doses requiring more than one vial equally into 2 syringes. Do not filter after reconstitution (may remove active drug). Resuspend contents of syringe by vigorously rolling between palms immediately prior to administration.

Discard unused portion (does not contain preservatives); do not save unused portions for later administration.

Administration

Azacitidine is associated with a moderate emetic potential (Dupuis 2011; Hesketh 2017; Roila 2016); antiemetics are recommended to prevent 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 comes in contact with the skin, immediately wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water.

Storage

Prior to reconstitution, store intact vials at room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

IV solution: Solutions for IV administration have very limited stability and must be prepared immediately prior to each dose. Administration must be completed within 1 hour of (vial) reconstitution.

SubQ suspension: Following reconstitution, suspension may be stored at room temperature for up to 1 hour prior to immediate administration (administer within 1 hour of reconstitution). If administration is delayed, refrigerate reconstituted suspension immediately (either in vial or syringe); may be stored for up to 8 hours (if reconstituted with room temperature SWFI) or up to 22 hours (if reconstituted with refrigerated SWFI). After removal from refrigerator, may be allowed up to 30 minutes to reach room temperature prior to immediate administration.

Drug Interactions

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. 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. 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. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (7% to 19%), chest pain (16%)

Central nervous system: Fatigue (13% to 36%), rigors (26%), headache (22%), dizziness (19%), anxiety (5% to 13%), depression (12%), malaise (11%), pain (11%), insomnia (9% to 11%)

Dermatologic: Erythema (7% to 17%), pallor (16%), skin lesion (15%), skin rash (10% to 14%), pruritus (12%), diaphoresis (11%)

Endocrine & metabolic: Weight loss (≤16%), pitting edema (15%), hypokalemia (6% to 13%)

Gastrointestinal: Nausea (48% to 71%), vomiting (27% to 54%), constipation (34% to 50%), diarrhea (36%), anorexia (13% to 21%), abdominal pain (11% to 16%), abdominal tenderness (12%)

Hematologic & oncologic: Thrombocytopenia (66% to 70%; grades 3/4: 58%), anemia (51% to 70%; grades 3/4: 14%), neutropenia (32% to 66%; grades 3/4: 61%), leukopenia (18% to 48%; grades 3/4: 15%), bruise (19% to 31%), petechia (11% to 24%), febrile neutropenia (14% to 16%; grades 3/4: 13%), bone marrow depression (nadir: days 10 to 17; recovery: days 28 to 31)

Local: Injection site reactions (14% to 29%): Erythema (35% to 43%; more common with IV administration), pain (19% to 23%; more common with IV administration), bruising (5% to 14%)

Neuromuscular & skeletal: Weakness (29%), arthralgia (22%), limb pain (20%), back pain (19%), myalgia (16%)

Respiratory: Cough (11% to 30%), dyspnea (5% to 29%), pharyngitis (20%), epistaxis (16%), nasopharyngitis (15%), upper respiratory infection (9% to 13%), pneumonia (11%), rales (9% to 11%)

Miscellaneous: Fever (30% to 52%)

5% to 10%:

Cardiovascular: Heart murmur (10%), tachycardia (9%), hypertension (≤9%), hypotension (7%), syncope (6%), chest wall pain (5%)

Central nervous system: Lethargy (7% to 8%), hypoesthesia (5%), postoperative pain (5%)

Dermatologic: Night sweats (9%), cellulitis (8%), rash at injection site (6%), urticaria (6%), skin nodules (5%), xeroderma (5%)

Gastrointestinal: Gingival hemorrhage (10%), stomatitis (8%), hemorrhoids (7%), dyspepsia (6% to 7%), abdominal distention (6%), loose stools (6%), dysphagia (5%), tongue ulcer (5%)

Genitourinary: Urinary tract infection (8% to 9%), dysuria (8%), hematuria (≤6%)

Hematologic & oncologic: Lymphadenopathy (10%), hematoma (9%), oral mucosal petechiae (8%), postprocedural hemorrhage (6%), oral hemorrhage (5%)

Hypersensitivity: Transfusion reaction (7%)

Infection: Herpes simplex infection (9%)

Local: Itching at injection site (7%), hematoma at injection site (6%), induration at injection site (5%), injection site granuloma (5%), skin discoloration at injection site (5%), swelling at injection site (5%)

Neuromuscular & skeletal: Muscle cramps (6%)

Respiratory: Rhinorrhea (10%), wheezing (9%), abnormal breath sounds (8%), nasal congestion (6%), pharyngolaryngeal pain (6%), pleural effusion (6%), post nasal drip (6%), rhinitis (6%), rhonchi (6%), atelectasis (5%), sinusitis (5%)

Miscellaneous: Lymphadenopathy (10%), herpes simplex (9%), night sweats (9%), transfusion reaction (7%), mouth hemorrhage (5%)

<5%, postmarketing, and/or case reports: Abscess (limb, perirectal), aggravated bone pain, agranulocytosis, anaphylactic shock, atrial fibrillation, azotemia, bacterial infection, blastomycosis, bone marrow failure, cardiac failure, catheter site hemorrhage, cellulitis, cerebral hemorrhage, cholecystectomy, cholecystitis, congestive cardiomyopathy, decreased serum bicarbonate, dehydration, diverticulitis, fibrosis (interstitial and alveolar), gastrointestinal hemorrhage, glycosuria, hemophthalmos, hemoptysis, hepatic coma, hypersensitivity reaction, hypophosphatemia, increased serum creatinine, injection site infection, interstitial pulmonary disease, intracranial hemorrhage, leukemia cutis, melena, necrotizing fasciitis, neutropenic sepsis, orthostatic hypotension, pancytopenia, pneumonitis, polyuria, pulmonary infiltrates, pyoderma gangrenosum, renal failure, renal tubular acidosis, respiratory distress, seizure, sepsis, sepsis syndrome, septic shock, splenomegaly, Sweet's syndrome, tissue necrosis at injection site, toxoplasmosis, tumor lysis syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia, thrombocytopenia, and anemia are common; may cause therapy delays and/or dosage reductions. Monitor blood counts prior to each cycle (at a minimum), and as clinically indicated. Adjust dose in subsequent cycles based on nadir counts and hematologic response.
• 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. Monitor liver function tests prior to therapy initiation and before each cycle.
• Gastrointestinal toxicity: Azacitidine is associated with a moderate emetic potential (Dupuis 2011; Hesketh 2017; Roila 2016); antiemetics are recommended to prevent nausea and vomiting.
• Injection site reactions: Injection site reactions commonly occurred with subcutaneous 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 intravenous azacitidine when used in combination with other chemotherapy agents. Monitor serum creatinine and electrolytes prior to therapy initiation and before each cycle. 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• 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.

Monitoring Parameters

Monitor liver function tests, electrolytes, CBC with differential and platelets, renal function (BUN and serum creatinine) at baseline, prior to each cycle, and more frequently if indicated. Also monitor for hematologic response, nausea/vomiting, and for injection site reactions.

Pregnancy

Pregnancy Considerations

Based on its mechanism of action, azacitidine may cause fetal harm if administered during pregnancy.

Evaluate pregnancy status prior to therapy. Women of childbearing potential should be advised to avoid pregnancy during treatment. Males with female partners of reproductive potential should not father a child and should use effective contraception during therapy.

Patient Education

What is this drug used for?

• It is used to treat a health problem called myelodysplastic syndrome (MDS).
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Mouth sores
• Mouth irritation
• Trouble sleeping
• Constipation
• Diarrhea
• Lack of appetite
• Dry skin
• Stuffy nose
• Sore throat
• Joint pain
• Muscle pain
• Anxiety
• Weight loss
• Abdominal pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.
• Necrotizing fasciitis like warm skin with red or purple areas of swelling that spread quickly; ulcers, blisters, black spots on the skin; or any other skin changes.
• Chest pain
• Shortness of breath
• Severe dizziness
• Passing out
• Severe headache
• Tumor lysis syndrome like fast heartbeat or abnormal heartbeat; any passing out; unable to pass urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish.
• Severe injection site irritation
• Severe loss of strength and energy
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.