decitabine 50 mg Injection, Powder, Lyophilized, For Solution, 1 vial
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Nucleoside Metabolic Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- Decitabine targets myelodysplastic syndromes, or MDS — conditions where your bone marrow isn't producing enough healthy blood cells and instead makes abnormal ones. It works by hel...
- What exactly is decitabine treating in my body?
- Decitabine is given as an IV infusion at a clinic or infusion center — you won't be taking anything by mouth at home. Depending on which schedule your doctor chose, you'll either c...
- How will I receive this medication, and how long will treatment last?
Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
-
UNII 4J9FJ0HL51
Potassium phosphate, monobasic is a salt compound used in medicines as a pH buffer and electrolyte source. It helps stabilize the acidity level of liquid and powdered formulations.
-
UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
3 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 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 | $558.84 | — |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J0894 | $1.064 / J0894 unit | — |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| decitabine 50 mgthis 00143-9385-01 | Hikma | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/20mL 16729-0224-05 | Accord | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/20mL 25021-0219-20 | Sagent | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 31722-0304-31 | Camber | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 43598-0427-37 | Dr. | 1 vial | — | AP | FDA listed | — |
| decitabine 47335-0361-41 | Sun | 1 kit | — | — | FDA listed | — |
| Decitabine 50 mg/10mL 55111-0556-10 | Dr.Reddy's | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/26mL 55150-0376-01 | Eugia | 1 vial | — | — | FDA listed | — |
| Decitabine 50 mg/20mL 67184-0535-01 | Qilu | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/20mL 67457-0316-25 | Mylan | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg 68001-0573-41 | BluePoint | 1 vial | — | — | FDA listed | — |
| Decitabine 50 mg/20mL 68001-0618-37 | BluePoint | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 68001-0642-41 | BluePoint | 1 vial | — | AP | FDA listed | — |
| decitabine 50 mg/10mL 68083-0528-01 | Gland | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/20mL 70121-1644-01 | Amneal | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/20mL 71288-0119-20 | Meitheal | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 72162-2634-02 | Bryant | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 72205-0031-01 | Novadoz | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 72205-0036-01 | Novadoz | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/10mL 72603-0107-01 | Northstar | 1 vial | — | AP | FDA listed | — |
| Decitabine 50 mg/20mL 75834-0190-01 | Nivagen | 1 vial | — | 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)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00143-9385-01 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (0143-9385-01) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, SINGLE-DOSE | 2022-04-15 | 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
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Does this product have a billing J-code?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Decitabine for Injection is indicated for treatment of adult patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
( 1 ) Decitabine for Injection is a nucleoside metabolic inhibitor indicated for treatment of adult patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Three Day Regimen: Administer decitabine for injection at a dose of 15 mg/m 2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. Repeat cycle every 6 weeks. ( 2.1 ) Five Day Regimen: Administer decitabine for injection at a dose of 20 mg/m 2 by continuous intravenous infusion over 1 hour repeated daily for 5 days. Repeat cycle every 4 weeks. ( 2.1 )
2.1Recommended Dosage Pre-Medications and Baseline Testing Consider pre-medicating for nausea with antiemetics. Conduct baseline laboratory testing: complete blood count (CBC) with platelets, serum hepatic panel, and serum creatinine. Decitabine for Injection Regimen Options Three Day Regimen Administer decitabine for injection at a dose of 15 mg/m 2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days.
Repeat cycles every 6 weeks upon hematologic recovery (ANC at least 1,000/µL and platelets at least 50,000/µL) for a minimum of 4 cycles. A complete or partial response may take longer than 4 cycles. Delay and reduce dose for hematologic toxicity [see Dosage and Administration ( 2.2 )].
Five Day Regimen Administer decitabine for injection at a dose of 20 mg/m 2 by continuous intravenous infusion over 1 hour daily for 5 days. Delay and reduce dose for hematologic toxicity [see Dosage and Administration ( 2.2 )]. Repeat cycles every 4 weeks upon hematologic recovery (ANC at least 1,000/µL and platelets at least 50,000/µL) for a minimum of 4 cycles.
A complete or partial response may take longer than 4 cycles. Patients with Renal or Severe Hepatic Impairment Treatment with decitabine for injection has not been studied in patients with pre-existing renal or hepatic impairment. For patients with pre-existing renal or hepatic impairment, consider the potential risks and benefits before initiating treatment with decitabine for injection.
2.2Dosage Modifications for Adverse Reactions Hematologic Toxicity If hematologic recovery from a previous decitabine for injection treatment cycle requires more than 6 weeks, delay the next cycle of decitabine for injection therapy and reduce decitabine for injection dose temporarily by following this algorithm: Recovery requiring more than 6, but less than 8 weeks: delay decitabine for injection dosing for up to 2 weeks and reduce the dose temporarily to 11 mg/m 2 every 8 hours (33 mg/m 2 /day, 99 mg/m 2 /cycle) upon restarting therapy.
Recovery requiring more than 8, but less than 10 weeks: Perform bone marrow aspirate to assess for disease progression. In the absence of progression, delay decitabine for injection dosing for up to 2 more weeks and reduce the dose to 11 mg/m 2 every 8 hours (33 mg/m 2 /day, 99 mg/m 2 /cycle) upon restarting therapy, then maintain or increase dose in subsequent cycles as clinically indicated. Non-hematologic Toxicity Delay subsequent decitabine for injection treatment for any the following nonhematologic toxicities and do not restart until toxicities resolve: Serum creatinine greater than or equal to 2 mg/dL Alanine transaminase (ALT), total bilirubin greater than or equal to 2 times upper limit of normal (ULN) Active or uncontrolled infection
2.3Preparation and Administration Decitabine for injection is a cytotoxic drug. Follow special handling and disposal procedures. 1 Aseptically reconstitute decitabine for injection with room temperature (20°C to 25°C) 10 mL of Sterile Water for Injection, USP.
Upon reconstitution, the final concentration of the reconstituted decitabine for injection solution is 5 mg/mL. You must dilute the reconstituted solution with 0.9% Sodium Chloride Injection or 5% Dextrose Injection prior to administration. Temperature of the diluent (0.9% Sodium Chloride Injection or 5% Dextrose Injection) depends on time of administration after preparation.
For Administration Within 15 Minutes of Preparation If decitabine for injection is intended to be administered within 15 minutes from the time of preparation, dilu…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For Injection: 50 mg of decitabine as a lyophilized powder in a single-dose vial for reconstitution. ( 3 ) For Injection: 50 mg of decitabine as a sterile, white to almost white lyophilized powder in a single-dose vial for reconstitution.
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 ）
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Neutropenia and Thrombocytopenia: Perform complete blood counts and platelet counts. ( 5.1 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception ( 5.2 , 8.1 , 8.3 )
5.1Myelosuppression Fatal and serious myelosuppression occurs in decitabine-treated patients. Myelosuppression (anemia, neutropenia, and thrombocytopenia) is the most frequent cause of decitabine dose reduction, delay, and discontinuation. Neutropenia of any grade occurred in 90% of decitabine-treated patients with grade 3 or 4 occurring in 87% of patients.
Grade 3 or 4 febrile neutropenia occurred in 23% of patients. Thrombocytopenia of any grade occurred in 89% of patients with grade 3 or 4 occurring in 85% of patients. Anemia of any grade occurred in 82% of patients.
Perform complete blood count with platelets at baseline, prior to each cycle, and as needed to monitor response and toxicity. Manage toxicity using dose-delay, dose-reduction, growth factors, and anti-infective therapies as needed [see Dosage and Administration (2.2) ] . Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.
5.2Embryo-Fetal Toxicity Based on findings from human data, animal studies and its mechanism of action, decitabine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 ) and Nonclinical Toxicology ( 13.1 )]. In preclinical studies in mice and rats, decitabine caused adverse developmental outcomes including embryo-fetal lethality and malformations. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception while receiving decitabine and for 6 months following the last dose. Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with decitabine and for 3 months following the last dose [see Use in Specific Populations ( 8.1 , 8.3 )].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (>50%) are neutropenia, thrombocytopenia, anemia, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions ( 5.1 )]
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. The safety of decitabine was studied in 3 single-arm studies (N =66, N =98, N =99) and 1 controlled supportive care study (N =83 decitabine, N =81 supportive care). The data described below reflect exposure to decitabine in 83 patients in the MDS trial.
In the trial, patients received 15 mg/m 2 intravenously every 8 hours for 3 days every 6 weeks. The median number of decitabine cycles was 3 (range 0 to 9). Most Common Adverse Reactions: neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.
Adverse Reactions Most Frequently (≥1%) Resulting in Clinical Intervention and or Dose Modification in the Controlled Supportive Care Study in the Decitabine Arm: Discontinuation: thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardio-respiratory arrest, increased blood bilirubin, intracranial hemorrhage, abnormal liver function tests. Dose Delayed: neutropenia, pulmonary edema, atrial fibrillation, central line infection, febrile neutropenia. Dose Reduced: neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, pharyngitis.
Table 1 presents all adverse reactions occurring in at least 5% of patients in the decitabine group and at a rate greater than supportive care. Table 1 Adverse Reactions Reported in ≥5% of Patients in the Decitabine Group and at a Rate Greater than Supportive Care in the Controlled Trial in MDS Decitabine N =83 (%) Supportive Care N =81 (%) Blood and lymphatic system disorders Neutropenia 75 (90) 58 (72) Thrombocytopenia 74 (89) 64 (79) Anemia NOS 68 (82) 60 (74) Febrile neutropenia 24 (29) 5 (6) Leukopenia NOS 23 (28) 11 (14) Lymphadenopathy 10 (12) 6 (7) Thrombocythemia 4 (5) 1 (1) Cardiac disorders Pulmonary edema NOS 5 (6) 0 (0) Eye disorders Vision blurred 5 (6) 0 (0) Gastrointestinal disorders Nausea 35 (42) 13 (16) Constipation 29 (35) 11 (14) Diarrhea NOS 28 (34) 13 (16) Vomiting NOS 21 (25) 7 (9) Abdominal pain NOS 12 (14) 5 (6) Oral mucosal petechiae 11 (13) 4 (5) Stomatitis 10 (12) 5 (6) Dyspepsia 10 (12) 1 (1) Ascites 8 (10) 2 (2) Gingival bleeding 7 (8) 5 (6) Hemorrhoids 7 (8) 3 (4) Loose stools 6 (7) 3 (4) Tongue ulceration 6 (7) 2 (2) Dysphagia 5 (6) 2 (2) Oral soft tissue disorder NOS 5 (6) 1 (1) Lip ulceration 4 (5) 3 (4) Abdominal distension 4 (5) 1 (1) Abdominal pain upper 4 (5) 1 (1) Gastro-esophageal reflux disease 4 (5) 0 (0) Glossodynia 4 (5) 0 (0) General disorders and administrative site disorders Pyrexia 44 (53) 23 (28) Edema peripheral 21 (25) 13 (16) Rigors 18 (22) 14 (17) Edema NOS 15 (18) 5 (6) Pain NOS 11 (13) 5 (6) Lethargy 10 (12) 3 (4) Tenderness NOS 9 (11) 0 (0) Fall 7 (8) 3 (4) Chest discomfort 6 (7) 3 (4) Intermittent pyrexia 5 (6) 3 (4) Malaise 4 (5) 1 (1) Crepitations NOS 4 (5) 1 (1) Catheter site erythema 4 (5) 1 (1) Catheter site pain 4 (5) 0 (0) Injection site swelling 4 (5) 0 (0) Hepatobiliary disorders Hyperbilirubinemia 12 (14) 4 (5) Infections and infestations Pneumonia NOS 18 (22) 11 (14) Cellulitis 10 (12) 6 (7) Candidal infection NOS 8 (10) 1 (1) Catheter related infection 7 (8) 0 (0) Urinary tract infection NOS 6 (7) 1 (1) Staphylococcal infection 6 (7) 0 (0) Oral candidiasis 5 (6) 2 (2) Sinusitis NOS 4 (5) 2 (2) Bacteremia 4 (5) 0 (0) Injury,…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Drug interaction studies with decitabine have not been conducted. In vitro studies in human liver microsomes suggest that decitabine is unlikely to inhibit or induce cytochrome P450 enzymes. In vitro metabolism studies have suggested that decitabine is not a substrate for human liver cytochrome P450 enzymes.
As plasma protein binding of decitabine is negligible (<1%), interactions due to displacement of more highly protein bound drugs from plasma proteins are not expected.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on findings from human data, animal studies, and the mechanism of action, decitabine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology ( 13.1 )] . Limited published data on decitabine use throughout the first trimester during pregnancy describe adverse developmental outcomes including major birth defects (structural abnormalities). In animal reproduction studies, administration of decitabine to pregnant mice and rats during organogenesis caused adverse developmental outcomes including malformations and embryo-fetal lethality starting at doses approximately 7% of the recommended human dose on a mg/m 2 basis (see Data ) .
Advise pregnant women of the potential risk to a fetus.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20% of clinically recognized pregnancies, respectively.
Data Human Data A single published case report of decitabine pregnancy exposure in a 39-year old woman with a hematologic malignancy described multiple structural abnormalities after 6 cycles of therapy in the 18 th week of gestation. These abnormalities included holoprosencephaly, absence of nasal bone, mid-facial deformity, cleft lip and palate, polydactyly and rocker-bottom feet. The pregnancy was terminated.
Animal Data In utero exposure to decitabine causes temporal related defects in the rat and/or mouse, which include growth suppression, exencephaly, defective skull bones, rib/sternabrae defects, phocomelia, digit defects, micrognathia, gastroschisis, micromelia. Decitabine inhibits proliferation and increases apoptosis of neural progenitor cells of the fetal CNS and induces palatal clefting in the developing murine fetus. Studies in mice have also shown that decitabine administration during osteoblastogenesis (day 10 of gestation) induces bone loss in offspring.
In mice exposed to single IP (intraperitoneal) injections (0 mg/m 2 , 0.9 mg/m 2 and 3.0 mg/m 2 , approximately 2% and 7% of the recommended daily clinical dose, respectively) over gestation days 8, 9, 10 or 11, no maternal toxicity was observed but reduced fetal survival was observed after treatment at 3 mg/m 2 and decreased fetal weight was observed at both dose levels. The 3 mg/m 2 dose elicited characteristic fetal defects for each treatment day, including supernumerary ribs (both dose levels), fused vertebrae and ribs, cleft palate, vertebral defects, hind-limb defects and digital defects of fore- and hind-limbs.
In rats given a single IP injection of 2.4 mg/m 2 , 3.6 mg/m 2 or 6 mg/m 2 (approximately 5%, 8%, or 13% the daily recommended clinical dose, respectively) on gestation days 9 to 12, no maternal toxicity was observed. No live fetuses were seen at any dose when decitabine was injected on gestation day 9. A significant decrease in fetal survival and reduced fetal weight at doses greater than 3.6 mg/m 2 was seen when decitabine was given on gestation day 10.
Increased incidences of vertebral and rib anomalies were seen at all dose levels, and induction of exophthalmia, exencephaly, and cleft palate were observed at 6.0 mg/m 2 . Increased incidence of foredigit defects was seen in fetuses at doses greater than 3.6 mg/m 2 . Reduced size and ossification of long bones of the fore-limb and hind-limb were noted at 6.0 mg/m 2 .
The effect of decitabine on postnatal development and reproductive capacity was evaluated in mice administered a single 3 mg/m 2 IP injection (approximately 7% the recommended daily clinical dose) on day 10 of gestation. Body weights of males and females exposed in utero to decitabine were significantly reduced relati…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from human data, animal studies, and the mechanism of action, decitabine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology ( 13.1 )] . Limited published data on decitabine use throughout the first trimester during pregnancy describe adverse developmental outcomes including major birth defects (structural abnormalities). In animal reproduction studies, administration of decitabine to pregnant mice and rats during organogenesis caused adverse developmental outcomes including malformations and embryo-fetal lethality starting at doses approximately 7% of the recommended human dose on a mg/m 2 basis (see Data ) .
Advise pregnant women of the potential risk to a fetus.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20% of clinically recognized pregnancies, respectively.
Data Human Data A single published case report of decitabine pregnancy exposure in a 39-year old woman with a hematologic malignancy described multiple structural abnormalities after 6 cycles of therapy in the 18 th week of gestation. These abnormalities included holoprosencephaly, absence of nasal bone, mid-facial deformity, cleft lip and palate, polydactyly and rocker-bottom feet. The pregnancy was terminated.
Animal Data In utero exposure to decitabine causes temporal related defects in the rat and/or mouse, which include growth suppression, exencephaly, defective skull bones, rib/sternabrae defects, phocomelia, digit defects, micrognathia, gastroschisis, micromelia. Decitabine inhibits proliferation and increases apoptosis of neural progenitor cells of the fetal CNS and induces palatal clefting in the developing murine fetus. Studies in mice have also shown that decitabine administration during osteoblastogenesis (day 10 of gestation) induces bone loss in offspring.
In mice exposed to single IP (intraperitoneal) injections (0 mg/m 2 , 0.9 mg/m 2 and 3.0 mg/m 2 , approximately 2% and 7% of the recommended daily clinical dose, respectively) over gestation days 8, 9, 10 or 11, no maternal toxicity was observed but reduced fetal survival was observed after treatment at 3 mg/m 2 and decreased fetal weight was observed at both dose levels. The 3 mg/m 2 dose elicited characteristic fetal defects for each treatment day, including supernumerary ribs (both dose levels), fused vertebrae and ribs, cleft palate, vertebral defects, hind-limb defects and digital defects of fore- and hind-limbs.
In rats given a single IP injection of 2.4 mg/m 2 , 3.6 mg/m 2 or 6 mg/m 2 (approximately 5%, 8%, or 13% the daily recommended clinical dose, respectively) on gestation days 9 to 12, no maternal toxicity was observed. No live fetuses were seen at any dose when decitabine was injected on gestation day 9. A significant decrease in fetal survival and reduced fetal weight at doses greater than 3.6 mg/m 2 was seen when decitabine was given on gestation day 10.
Increased incidences of vertebral and rib anomalies were seen at all dose levels, and induction of exophthalmia, exencephaly, and cleft palate were observed at 6.0 mg/m 2 . Increased incidence of foredigit defects was seen in fetuses at doses greater than 3.6 mg/m 2 . Reduced size and ossification of long bones of the fore-limb and hind-limb were noted at 6.0 mg/m 2 .
The effect of decitabine on postnatal development and reproductive capacity was evaluated in mice administered a single 3 mg/m 2 IP injection (approximately 7% the recommended daily clinical dose) on day 10 of gestation. Body weights of males and females exposed in utero to decitabine were significantly reduced relative to controls at all postnatal time points. No consistent effect on fertil…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of decitabine in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of patients exposed to decitabine in the controlled clinical trial, 61 of 83 patients were age 65 years and over, while 21 of 83 patients were age 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE There is no known antidote for overdosage with decitabine. Higher doses are associated with increased myelosuppression including prolonged neutropenia and thrombocytopenia. Standard supportive measures should be taken in the event of an overdose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Decitabine is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation.
In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine.
12.2Pharmacodynamics Decitabine has been shown to induce hypomethylation both in vitro and in vivo. However, there have been no studies of decitabine-induced hypomethylation and pharmacokinetic parameters.
12.3Pharmacokinetics Pharmacokinetic (PK) parameters were evaluated in patients. Eleven patients received 20 mg/m 2 infused over 1 hour intravenously (treatment Option 2). Fourteen patients received 15 mg/m 2 infused over 3 hours intravenously (treatment Option 1).
PK parameters are shown in Table 3 . Plasma concentration-time profiles after discontinuation of infusion showed a biexponential decline. The clearance (CL) of decitabine was higher following treatment Option 2.
Upon repeat doses, there was no systemic accumulation of decitabine or any changes in PK parameters. Population PK analysis (N=35) showed that the cumulative AUC per cycle for treatment Option 2 was 2.3-fold lower than the cumulative AUC per cycle following treatment Option 1. Table 3 Mean (CV% or 95% CI) Pharmacokinetic Parameters of Decitabine Dose C max (ng/mL) AUC 0-INF (ng∙h/mL) T 1/2 (h) CL (L/h/m 2 ) AUC Cumulative N=35 Cumulative AUC per cycle (ng∙h/mL) 15 mg/m 2 3-hr infusion every 8 hours for 3 days (Option 1) N=14 73.8 (66) 163 (62) 0.62 (49) 125 (53) 1332 (1010-1730) 20 mg/m 2 1-hr infusion daily for 5 days (Option 2) N=11 147 (49) 115 (43) 0.54 (43) 210 (47) 570 (470-700) The exact route of elimination and metabolic fate of decitabine is not known in humans.
One of the pathways of elimination of decitabine appears to be deamination by cytidine deaminase found principally in the liver but also in granulocytes, intestinal epithelium and whole blood. Specific Populations Patients with Renal Impairment There are no data on the use of decitabine in patients with renal impairment. Patients with Hepatic Impairment There are no data on the use of decitabine in patients with hepatic impairment.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Decitabine is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation.
In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Decitabine for Injection is a sterile, white to almost white lyophilized powder for intravenous use supplied as: NDC 0143-9385-01, 50 mg single dose vial individually packaged in a carton. Store vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard unused portion.
📦 Storage and Handling ▾
Store vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard unused portion.
📋 Description ▾
11 DESCRIPTION Decitabine is a nucleoside metabolic inhibitor. Decitabine is a fine, white to almost white powder with the molecular formula of C 8 H 12 N 4 O 4 and a molecular weight of 228.21. Its chemical name is 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1 H )-one and it has the following structural formula: Decitabine is slightly soluble in ethanol/water (50/50), methanol/water (50/50) and methanol; sparingly soluble in water and soluble in dimethylsulfoxide (DMSO).
Decitabine for Injection, for intravenous use, is a sterile, white to almost white lyophilized powder supplied in a clear colorless glass single-dose vial. Each single-dose glass vial contains 50 mg decitabine, 68 mg monobasic potassium phosphate (potassium dihydrogen phosphate) and 11.6 mg sodium hydroxide. Sodium hydroxide and/or hydrochloric acid are used for pH adjustment. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Myelosuppression Advise patients of the risk of myelosuppression and to report any symptoms of infection, anemia, or bleeding to their healthcare provider as soon as possible. Advise patients for the need for laboratory monitoring [see Warnings and Precautions ( 5.1 )]. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.1 )]. Advise females of reproductive potential to use effective contraception while receiving Decitabine for Injection and for 6 months after last dose [see Use in Specific Populations ( 8.3 )]. Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with Decitabine for Injection and for 3 months after the last dose [see Use in Specific Populations ( 8.3 ) and Nonclinical Toxicology ( 13.1 )].
Lactation Advise women to avoid breastfeeding while receiving Decitabine for Injection and for at least 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )].