Azacitidine 100 mg/30mL Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Nucleoside Metabolic Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Azacitidine is used to treat myelodysplastic syndrome (a group of conditions in which the bone marrow produces blood cells that are misshapen and does not produce enough healthy blood cells). Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow.
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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100 mg / 30 mL
UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
1 inactive ingredient listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $45.89 | $1,376.74 / 30 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9025 | $0.401 / J9025 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Azacitidine 100 mg 00143-9606-01 | Hikma | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 00781-3491-94 | Sandoz | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 16714-0927-01 | NorthStar | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 16729-0306-10 | Accord | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 31722-0365-31 | Camber | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 43598-0305-62 | Dr. | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 43598-0465-62 | Dr. | 1 injection | — | AP | FDA listed | — |
| Azacitidine Azacitidine 100 mg 43598-0678-11 | Dr. | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg/50mL 43817-0906-01 | Panacea | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg/4mL 55150-0393-01 | Eugia | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 58458-0002-02 | Reliance | 1 vial | — | AP | FDA listed | — |
| Vidaza 100 mg 59572-0102-01 | Celgene | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 60505-6271-01 | Apotex | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg/30mLthis 63323-0771-39 | Fresenius | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 68001-0313-56 | BluePoint | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 68001-0527-54 | BluePoint | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 68001-0620-54 | BluePoint | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 69539-0112-01 | MSN | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 70069-0857-01 | Somerset | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 70121-1237-01 | Amneal | 1 injection | — | — | FDA listed | — |
| Azacitidine 100 mg 71288-0115-30 | Meitheal | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 71288-0153-95 | Meitheal | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 72485-0201-01 | Armas | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 72572-0020-01 | Civica, | 1 injection | — | AP | FDA listed | — |
| Azacitidine 100 mg 75907-0225-11 | Dr. | 1 vial | — | AP | FDA listed | — |
| Azacitidine 100 mg 83774-0102-01 | Pilnova | 1 injection | — | AP | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63323-0771-39 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (63323-771-39) / 30 mL in 1 VIAL, SINGLE-DOSE | 2017-03-16 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Azacitidine for injection is a nucleoside metabolic inhibitor indicated for the treatment of: • Adult patients with the following FAB myelodysplastic syndrome (MDS) subtypes: Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). ( 1.1 )
1.1Myelodysplastic Syndromes (MDS) Azacitidine for injection is indicated for treatment of adult patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection).
However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Do not substitute Azacitidine for injection for oral azacitidine. The indications and dosing regimen for Azacitidine for injection differ from that of oral azacitidine ( 2.1 , 5.1 ). • MDS: The recommended starting dosage for the first treatment cycle, for all patients regardless of baseline hematology values, is Azacitidine for injection 75 mg/m 2 daily for 7 days to be administered by subcutaneous injection or intravenous infusion. See full prescribing information for schedule for subsequent cycles.
Premedicate for nausea and vomiting ( 2.2 ). • Continue treatment as long as the patient continues to benefit ( 2.3 ). • Monitor all patients for hematologic response and for renal toxicity; delay or reduce dosage as appropriate ( 2.3 , 2.6 , 2.7 ).
2.1Important Administration Information Do not substitute Azacitidine for injection for oral azacitidine. The indications and dosing regimen for Azacitidine for injection differ from that of oral azacitidine [see Warnings and Precautions ( 5.1 )]
2.2First Treatment Cycle for Adults The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m 2 subcutaneously or intravenously, daily for 7 days. Premedicate patients for nausea and vomiting. Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.
2.3Subsequent Treatment Cycles for Adults Repeat cycles every 4 weeks. The dose may be increased to 100 mg/m 2 if no beneficial effect is seen after 2 treatment cycles and if no toxicity other than nausea and vomiting has occurred. It is recommended that patients be treated for a minimum of 4 to 6 cycles.
However, complete or partial response may require additional treatment cycles. Treatment may be continued as long as the patient continues to benefit. Monitor patients for hematologic response and renal toxicities [see Warnings and Precautions ( 5.4 )], and delay or reduce dosage if necessary [see Dosage and Administration ( 2.6 )] .
Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
2.5Dosage Adjustment Based on Hematology Laboratory Values • For adult patients with baseline (start of treatment) WBC greater than or equal to 3 x 10 9 /L, ANC greater than or equal to 1.5 x 10 9 /L, and platelets greater than or equal to 75 x 10 9 /L, adjust the dose as follows, based on nadir counts for any given cycle: Nadir Counts % Dose in the Next Course ANC (x10 9 /L) Less than 0.5 0.5 -
1.5 Greater than
1.5Platelets (x10 9 /L) Less than 25 25 - 50 Greater than 50 50% 67% 100% • For adult patients whose baseline counts are WBC less than 3 x 10 9 /L, ANC less than 1.5 x 10 9 /L, or platelets less than 75 x 10 9 /L, base dose adjustments on nadir counts and bone marrow biopsy cellularity at the time of the nadir as noted below, unless there is clear improvement in differentiation (percentage of mature granulocytes is higher and ANC is higher than at onset of that course) at the time of the next cycle, in which case continue the current dose.
WBC or Platelet Nadir % decrease in counts from baseline Bone Marrow Biopsy Cellularity at Time of Nadir (%) 30-60 15-30 Less than 15 50 - 75 Greater than 75 % Dose in the Next Course 100 50 33 75 50 33 If a nadir as defined in the table above has occurred, give the next course 28 days after the start of the preceding course, provided that both the WBC and the platelet counts are greater than 25% above the nadir and rising. If a greater than 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, reduce the scheduled dose by 50%. Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivit…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Azacitidine for injection is supplied as lyophilized powder in 100 mg single-dose vials. • Lyophilized powder in 100 mg single-dose vials ( 3 ).
⛔ Contraindications ▾
4 CONTRAINDICATIONS • Advanced Malignant Hepatic Tumors ( 4.1 ). • Hypersensitivity to Azacitidine or Mannitol ( 4.2 ).
4.1Advanced Malignant Hepatic Tumors Azacitidine is contraindicated in patients with advanced malignant hepatic tumors [see Warnings and Precautions ( 5.3 )].
4.2Hypersensitivity to Azacitidine or Mannitol Azacitidine is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Risks of Substitution with Other Azacitidine Products : Do not substitute Azacitidine for oral azacitidine ( 2.1 , 5.1 ). • Anemia, Neutropenia and Thrombocytopenia : Monitor complete blood counts (CBC) frequently ( 5.2 ). • Hepatotoxicity : Patients with severe preexisting hepatic impairment are at higher risk for toxicity ( 5.3 ). • Renal Toxicity : Monitor patients with renal impairment for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys ( 5.4 ). • Tumor Lysis Syndrome : Azacitidine may cause fatal or serious tumor lysis syndrome, including in patients with MDS.
Assess baseline risk and monitor and treat as appropriate ( 5.5 ). • Embryo-Fetal Toxicity : Azacitidine can cause fetal harm. Advise female patients and male patients with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception ( 5.6 ).
5.1Risks of Substitution with Other Azacitidine Products Due to substantial differences in the pharmacokinetic parameters [see Clinical Pharmacology ( 12.3 )] , the recommended dose and schedule for Azacitidine for Injection are different from those of oral azacitidine products. Treatment of patients using Azacitidine for Injection at the recommended dosage of oral azacitidine may result in a fatal adverse reaction. Treatment of patients using oral azacitidine at the doses recommended for Azacitidine may not be effective.
Do not substitute Azacitidine for Injection for oral azacitidine [see Dosage and Administration ( 2.1 )] .
5.2Anemia, Neutropenia and Thrombocytopenia Azacitidine causes anemia, neutropenia and thrombocytopenia in adult patients with MDS. Monitor complete blood counts frequently for response and/or toxicity, at a minimum, prior to each dosing cycle. In adult patients with MDS, after administration of the recommended dosage for the first cycle, adjust dosage for subsequent cycles based on nadir counts and hematologic response [see Dosage and Administration ( 2.5 ) ].
Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
5.3Hepatotoxicity in Patients with Severe Pre-existing Hepatic Impairment Because azacitidine is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution is needed in patients with liver disease. Patients with extensive tumor burden due to metastatic disease have been reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline albumin <30 g/L. Azacitidine is contraindicated in patients with advanced malignant hepatic tumors [see Contraindications ( 4.1 )].
Monitor liver chemistries prior to initiation of therapy and with each cycle. Safety and effectiveness of Azacitidine in patients with MDS and hepatic impairment have not been studied as these patients were excluded from the clinical trials. Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection).
However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
5.4Renal Toxicity Renal toxicity ranging from elevated serum creatinine to renal failure and death have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for non-MDS conditions. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to <20 mEq/L in association with an alkaline urine and hypokalemia (serum potassium <3 mEq/L) developed in 5 patients with CML treated with azacitidine and etoposide. Monitor serum creatinine and electrolytes prior to initiation of therapy and with each cycle.
If unexplained reductions in serum bicarbonate <20 mEq/L or elevations of BUN or serum creatinine occur, reduce or hold the dose [see…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described in other labeling sections: ͦ Anemia, Neutropenia and Thrombocytopenia [see Warnings and Precautions ( 5.2 )] ͦ Hepatotoxicity in Patients with Severe Pre-existing Hepatic Impairment [see Warnings and Precautions ( 5.3 )] ͦ Renal Toxicity [see Warnings and Precautions ( 5.4 )] ͦ Tumor Lysis Syndrome [see Warnings and Precautions ( 5.5 )] Most common adverse reactions (>30%) in adult patients with MDS by subcutaneous route are: nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia and ecchymosis.
Most common adverse reactions by intravenous route also included petechiae, rigors, weakness and hypokalemia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. MDS The data described below reflect exposure to Azacitidine in 443 patients with MDS from 4 clinical studies. Study 1 was a supportive-care controlled trial (subcutaneous administration), Studies 2 and 3 were single arm studies (one with subcutaneous administration and one with intravenous administration), and Study 4 was an international randomized trial (subcutaneous administration) [see Clinical Studies ( 14.1 )].
In Studies 1, 2 and 3, a total of 268 patients were exposed to Azacitidine, including 116 exposed for 6 cycles (approximately 6 months) or more and 60 exposed for greater than 12 cycles (approximately one year). Azacitidine was studied primarily in supportive-care controlled and uncontrolled trials (n=150 and n=118, respectively). The population in the subcutaneous studies (n=220) was 23 to 92 years old (mean 66.4 years), 68% male, and 94% white, and had MDS or AML.
The population in the intravenous study (n=48) was 35 to 81 years old (mean 63.1 years), 65% male, and 100% white. Most patients received average daily doses between 50 and 100 mg/m 2 . In Study 4, a total of 175 patients with higher-risk MDS (primarily RAEB and RAEB-T subtypes) were exposed to Azacitidine.
Of these patients, 119 were exposed for 6 or more cycles, and 63 for at least 12 cycles. The mean age of this population was 68.1 years (ranging from 42 to 83 years), 74% were male, and 99% were white. Most patients received daily Azacitidine doses of 75 mg/m 2 .
Most Commonly Occurring Adverse Reactions (Subcutaneous or Intravenous Route) in Adult Patients with MDS: nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia, ecchymosis. The most common adverse reactions by intravenous route also included petechiae, rigors, weakness and hypokalemia. Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (Subcutaneous or Intravenous Route) in Adult Patients with MDS: Discontinuation: leukopenia, thrombocytopenia, neutropenia.
Dose Held: leukopenia, neutropenia, thrombocytopenia, pyrexia, pneumonia, febrile neutropenia. Dose Reduced: leukopenia, neutropenia, thrombocytopenia. Table 3 presents adverse reactions occurring in at least 5% of patients treated with Azacitidine (subcutaneous) in Studies 1 and 2.
It is important to note that duration of exposure was longer for the Azacitidine-treated group than for the observation group: patients received Azacitidine for a mean of 11.4 months while mean time in the observation arm was 6.1 months. Table 3: Most Frequently Observed Adverse Reactions (≥ 5% in All Subcutaneous Azacitidine Treated Patients; Studies 1 and 2) a Multiple terms of the same preferred terms for a patient are only counted once within each treatment group. b Includes adverse reactions…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed ( 8.2 ). Pediatric use information is approved for Celgene Corporation’s Vidaza (azacitidine for injection). However, due to Celgene Corporation’s marketing exclusivity rights, this drug product is not labeled with that information.
8.1Pregnancy Risk Summary Based on its mechanism of action and findings in animals, Azacitidine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no data on the use of azacitidine in pregnant women. Azacitidine was teratogenic and caused embryo-fetal lethality in animals at doses lower than the recommended human daily dose ( see Data ).
Advise pregnant women of the potential risk to the fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single IP (intraperitoneal) injection of 6 mg/m 2 (approximately 8% of the recommended human daily dose on a mg/m 2 basis) azacitidine on gestation day 10. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation day 15 at doses of ~3-12 mg/m 2 (approximately 4%-16% the recommended human daily dose on a mg/m 2 basis).
In rats, azacitidine was clearly embryotoxic when given IP on gestation days 4-8 (postimplantation) at a dose of 6 mg/m 2 (approximately 8% of the recommended human daily dose on a mg/m 2 basis), although treatment in the preimplantation period (on gestation days 1-3) had no adverse effect on the embryos. Azacitidine caused multiple fetal abnormalities in rats after a single IP dose of 3 to 12 mg/m 2 (approximately 8% the recommended human daily dose on a mg/m 2 basis) given on gestation day 9, 10, 11 or 12. In this study azacitidine caused fetal death when administered at 3-12 mg/m 2 on gestation days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation day 9.
Fetal anomalies included: CNS anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities).
8.2Lactation Risk Summary There is no information regarding the presence of azacitidine in human milk, the effects of Azacitidine on the breastfed infant, or the effects of Azacitidine on milk production. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for azacitidine in animal studies [see Nonclinical Toxicology ( 13.1 )] and the potential for serious adverse reactions in nursing infants from Azacitidine, advise patients not to breastfeed during treatment with Azacitidine and for 1 week after the last dose.
8.3Females and Males of Reproductive Potential Based on its mechanism of action and findings in animals, Azacitidine can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating azacitidine. Contraception Females Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with azacitidine and for 6 months after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with azacitidine and for 3 months after the last dose. Infertility Based on animal data, azacitidine could have an effect on male or female fertility [see Nonclinical Toxicology ( 13.1 )].
8.4 Pediatr…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on its mechanism of action and findings in animals, Azacitidine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no data on the use of azacitidine in pregnant women. Azacitidine was teratogenic and caused embryo-fetal lethality in animals at doses lower than the recommended human daily dose ( see Data ).
Advise pregnant women of the potential risk to the fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single IP (intraperitoneal) injection of 6 mg/m 2 (approximately 8% of the recommended human daily dose on a mg/m 2 basis) azacitidine on gestation day 10. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation day 15 at doses of ~3-12 mg/m 2 (approximately 4%-16% the recommended human daily dose on a mg/m 2 basis).
In rats, azacitidine was clearly embryotoxic when given IP on gestation days 4-8 (postimplantation) at a dose of 6 mg/m 2 (approximately 8% of the recommended human daily dose on a mg/m 2 basis), although treatment in the preimplantation period (on gestation days 1-3) had no adverse effect on the embryos. Azacitidine caused multiple fetal abnormalities in rats after a single IP dose of 3 to 12 mg/m 2 (approximately 8% the recommended human daily dose on a mg/m 2 basis) given on gestation day 9, 10, 11 or 12. In this study azacitidine caused fetal death when administered at 3-12 mg/m 2 on gestation days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation day 9.
Fetal anomalies included: CNS anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of azacitidine in pediatric patients with MDS have not been established. Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of patients in Studies 1, 2 and 3, 62% were 65 years and older and 21% were 75 years and older. No overall differences in effectiveness were observed between these patients and younger patients. In addition, there were no relevant differences in the frequency of adverse reactions observed in patients 65 years and older compared to younger patients.
Of the 179 patients randomized to azacitidine in Study 4, 68% were 65 years and older and 21% were 75 years and older. Survival data for patients 65 years and older were consistent with overall survival results. The majority of adverse reactions occurred at similar frequencies in patients < 65 years of age and patients 65 years of age and older.
Elderly patients are more likely to have decreased renal function. Monitor renal function in these patients [see Dosage and Administration ( 2.7 ) and Warnings and Precautions ( 5.4 )].
🆘 Overdosage ▾
10 OVERDOSAGE One case of overdose with Azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single intravenous dose of approximately 290 mg/m 2 , almost 4 times the recommended starting dose. The events resolved without sequelae, and the correct dose was resumed the following day.
In the event of overdosage, the patient should be monitored with appropriate blood counts and should receive supportive treatment, as necessary. There is no known specific antidote for Azacitidine overdosage.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Azacitidine is a pyrimidine nucleoside analog of cytidine. Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis.
Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Nonproliferating cells are relatively insensitive to azacitidine.
12.2Pharmacodynamics Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information.
12.3Pharmacokinetics The pharmacokinetics of azacitidine were studied in 6 adult patients with MDS following a single 75 mg/m 2 subcutaneous dose and a single 75 mg/m 2 intravenous dose. Absorption Azacitidine is rapidly absorbed after subcutaneous administration; the peak plasma azacitidine concentration of 750 ± 403 ng/ml occurred in 0.5 hour after subcutaneous administration. Distribution The bioavailability of subcutaneous azacitidine relative to intravenous azacitidine is approximately 89%, based on area under the curve.
Mean volume of distribution following intravenous dosing is 76 ± 26 L. Mean apparent subcutaneous clearance is 167 ± 49 L/hour and mean half-life after subcutaneous administration is 41 ± 8 minutes. The AUC and C max of subcutaneous administration of azacitidine in 21 patients with cancer were approximately dose proportional within the 25 to 100 mg/m 2 dose range.
Multiple dosing at the recommended dose-regimen does not result in drug accumulation with intravenous or subcutaneous administration. Elimination Metabolism An in vitro study of azacitidine incubation in human liver fractions indicated that azacitidine is not metabolized by the cytochrome P450 (CYP) enzymes. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase.
Excretion Published studies indicate that urinary excretion is the primary route of elimination of azacitidine and its metabolites. Following intravenous administration of radioactive azacitidine to 5 cancer patients, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for <1% of administered radioactivity over 3 days.
Mean excretion of radioactivity in urine following subcutaneous administration of 14 C-azacitidine was 50%. The mean elimination half-lives of total radioactivity (azacitidine and its metabolites) were similar after intravenous and subcutaneous administrations, about 4 hours. Specific Populations The effects of hepatic impairment, gender, or race/ethnicity on the pharmacokinetics of intravenous and subcutaneous azacitidine have not been studied.
Pediatric Patients Pediatric use information is approved for Celgene Corporation's Vidaza (azacitidine for injection). However, due to Celgene Corporation's marketing exclusivity rights, this drug product is not labeled with that information. Patients with Renal Impairment In adult patients with cancer, the pharmacokinetics of azacitidine in 6 patients with normal renal function (CLcr >80 mL/min) and 6 patients with severe renal impairment (CLcr <30 mL/min) were compared following daily subcutaneous dosing (Days 1 through 5) at 75 mg/m 2 /day.
Severe renal impairment increased azacitidine exposure by approximately 70% after single and 41% after multiple subcutaneous administrations. This increase in exposure was not correlated with an increase in adverse events. The exposure was similar to exposure in patients with normal renal function receiving 100 mg/m 2 .…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Azacitidine is a pyrimidine nucleoside analog of cytidine. Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis.
Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Nonproliferating cells are relatively insensitive to azacitidine.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Azacitidine for injection is supplied as a lyophilized powder in 100 mg single-dose vials as follows: Product Code Unit of Sale Strength 771139 NDC 63323-771-39 Individually packaged 100 mg per vial Storage Store unreconstituted vials at 25º C (77º F); excursions permitted to 15º-30º C (59º-86º F) (See USP Controlled Room Temperature). Handling and Disposal Azacitidine for injection is a hazardous drug. Follow applicable special handling and disposal procedures.
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📦 Storage and Handling ▾
Storage Store unreconstituted vials at 25º C (77º F); excursions permitted to 15º-30º C (59º-86º F) (See USP Controlled Room Temperature). Handling and Disposal Azacitidine for injection is a hazardous drug. Follow applicable special handling and disposal procedures. 1
📋 Description ▾
11 DESCRIPTION Azacitidine for injection contains azacitidine, which is a nucleoside metabolic inhibitor. Azacitidine is 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one. The structural formula is as follows: The empirical formula is C 8 H 12 N 4 O 5 .
The molecular weight is 244. Azacitidine is a white to off-white solid. Azacitidine was found to be insoluble in acetone, ethanol, and methyl ethyl ketone; slightly soluble in ethanol/water (50/50), propylene glycol, and polyethylene glycol; sparingly soluble in water, water saturated octanol, 5% dextrose in water, N-methyl-2-pyrrolidone, normal saline and 5% Tween 80 in water; and soluble in dimethylsulfoxide (DMSO).
The finished product is supplied in a sterile form for reconstitution as a suspension for subcutaneous injection or reconstitution as a solution with further dilution for intravenous infusion. Vials of Azacitidine for injection contain 100 mg of azacitidine and 100 mg mannitol as a sterile lyophilized powder. azaci-struc-01.jpg
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Hepatotoxicity in Patients with Severe Pre-Existing Hepatic Impairment Instruct patients to inform their physician about any underlying liver disease [see Warnings and Precautions ( 5.3 )]. Renal Toxicity Instruct patients to inform their physician about any underlying renal disease [see Warnings and Precautions ( 5.4 )]. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.1 )].
Advise females of reproductive potential to use effective contraception during treatment with Azacitidine for injection and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Azacitidine for injection and for 3 months after the last dose. Advise patients to report known or suspected pregnancy to their physicians immediately [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.3 )].
Lactation Advise patients to avoid breastfeeding while receiving Azacitidine for injection and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )]. Infertility Advise males and females that Azacitidine for injection may impair fertility [see Use in Specific Populations ( 8.3 ) and Nonclinical Toxicology ( 13.1 )] . Manufactured for: Lake Zurich, IL 60047 Made in India www.fresenius-kabi.com/us 451537E Revised: 08/2024 4502035 azaci-img-02.jpg