Decitabine is a pyrimidine antimetabolite. It is indicated for the treatment of adult patients with myelodysplastic syndrome. Severe myelosuppression has been reported with decitabine therapy; monitor complete blood counts during therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
-Low
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Decitabine is available as a single-use 50-mg lyophilized powder vial from multiple manufacturers.
-Recommended vial diluent, dilution solutions, and storage following reconstitution and dilution differ among products; refer to the manufacturer package insert for specific instructions.
Reconstitution:
-Add 10 mL of diluent to the 50-mg lyophilized powder vial for a final concentration of 5 mg/mL.
Dilution:
-Immediately after reconstitution, withdraw the appropriate dose from the vial and further dilute to a final admixture concentration between 0.1 to 1 mg/mL.
-Storage following dilution: The diluted admixture may be used within 15 minutes or stored refrigerated (2 to 8 degrees C; 36 to 46 degrees F) for a maximum of 4 hours or 7 hours until administration (depending on the product used).
Intravenous (IV) Infusion:
-Administer the diluted admixture IV over 1 or 3 hours; infusion time depends on the treatment regimen.
Hematologic toxicity has been reported in patients with myelodysplastic syndrome (MDS) who received decitabine therapy in clinical trials; some cases were fatal. Myelosuppression and worsening neutropenia occur most frequently in the first or second treatment cycle and may not indicate progression or underlying MDS. Obtain complete blood counts at baseline, prior to each cycle of therapy, and as clinically indicated to monitor for response and toxicity. Therapy delay or a dose reduction may be necessary in patients who experience delayed hematologic recovery. Start growth factors as clinically indicated. In a pooled analysis of 3 single arm studies, neutropenia (90% vs. 72%), febrile neutropenia (29% vs. 6%), thrombocytopenia (89% vs. 79%), anemia (82% vs. 74%), leukopenia (28% vs. 14%), lymphadenopathy (12% vs. 7%), and thrombocythemia (5% vs. 1%) occurred more often in patients with MDS who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81). Grade 3 or 4 neutropenia (87%), thrombocytopenia (85%), and febrile neutropenia (23%) were also reported in decitabine-treated patients in this analysis. Anemia (31%), thrombocytopenia (27%), febrile neutropenia (20%), leukopenia (6%), neutropenia (38%), pancytopenia (5%), and thrombocythemia (5%) were reported in patients with MDS who received a 5-day decitabine regimen in another single-arm study. Myelosuppression and splenomegaly were also reported with decitabine therapy in clinical trials.
Infection has been reported with decitabine therapy in clinical trials. In patients who have an active or uncontrolled infection, hold decitabine therapy until the infection resolves. Start growth factors and anti-infective therapies as clinically indicated. Infectious events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include pneumonia (22% vs. 14%), cellulitis (12% vs. 7%), candidiasis (10% vs. 1%) and oral candidiasis (6% vs. 2%), urinary tract infection (7% vs. 1%), Staphylococcal infection (7% vs. 0%), sinusitis (5% vs. 2%), and bacteremia (5% vs. 0%). Additionally, pneumonia (20%), upper respiratory tract infection (10%), cellulitis (9%), Staphylococcal bacteremia (8%), oral candidiasis (6%), urinary tract infection (7%), sinusitis (6%), and tooth abscess (5%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Fungal infection, sepsis, bronchopulmonary aspergillosis, peridiverticular abscess, respiratory tract infection, pseudomonal lung infection, and Mycobacterium avium complex infection were also reported in decitabine-treated patients.
Gastrointestinal (GI) adverse events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include nausea (42% vs. 16%), constipation (35% vs. 14%), diarrhea (34% vs. 16%), vomiting (25% vs. 9%), anorexia (16% vs. 10%), appetite decreased (16% vs. 15%), abdominal pain (14% vs. 6%), upper abdominal pain (5% vs. 1%), oral mucosal petechiae (13% vs. 5%), stomatitis (12% vs. 6%), dyspepsia (12% vs. 1%), gingival bleeding (8% vs. 6%), hemorrhoids (8% vs. 4%), loose stools (7% vs. 4%), oral ulceration such as tongue (7% vs. 2%) or lip ulceration (5% vs. 4%), dysphagia (6% vs. 2%), oral soft tissue disorder (6% vs. 1%), abdominal distension (5% vs. 1%), gastroesophageal reflux disease (5% vs. 0%), and glossodynia (5% vs. 0%). Additionally, nausea (40%), constipation (30%), diarrhea (28%), vomiting (16%), anorexia (23%), abdominal pain (14%), upper abdominal pain (6%), stomatitis (11%), dyspepsia (10%), mucosal inflammation (9%), gastroesophageal reflux disease (5%), dysphagia (5%), oral pain (5%), and toothache (6%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Gingival pain was also reported with decitabine therapy in clinical trials. Prophylactic antiemetic therapy is recommended.
Metabolic and laboratory/electrolyte abnormalities reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include hyperglycemia (33% vs. 20%); hypoalbuminemia (24% vs. 17%); hypomagnesemia (24% vs. 7%); hypokalemia (22% vs. 12%); hyponatremia (19% vs. 16%); hyperkalemia (13% vs. 4%); increased urea (10% vs. 1%), lactate dehydrogenase (8% vs. 6%), and bicarbonate (metabolic alkalosis) (6% vs. 1%) levels; dehydration (6% vs. 5%); decreased albumin (7% vs. 0%), chloride (hypochloremia) (6% vs. 1%), total protein (hypoproteinemia) (5% vs. 4%), bicarbonate (metabolic acidosis) (5% vs. 1%), and bilirubin (5% vs. 1%) levels. Additionally, hypokalemia (12%), weight loss (9%), dehydration (8%), hyperglycemia (6%), and hypomagnesemia (5%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99).
Musculoskeletal adverse events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include arthralgia (20% vs. 10%), limb pain (19% vs. 10%), back pain (17% vs.6%), pain (13% vs. 6%), tenderness (11% vs. 0%), chest wall pain (7% vs. 1%), chest discomfort (7% vs. 4%), musculoskeletal pain/discomfort (6% vs. 0%), and myalgia (5% vs. 1%). Additionally, arthralgia (17%), back pain (18%), bone pain (6%), muscle spasms (7%), pain (5%), muscular weakness (5%), musculoskeletal pain (5%), myalgia (9%), and extremity pain (18%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99).
Peripheral edema (25% vs. 16%), heart murmur (16% vs. 11%), edema (18% vs. 6%), and hypotension (6% vs. 5%) were reported in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care compared with patients who received supportive care alone in a randomized trial (n = 164). Peripheral edema (27%), hypotension (11%), hypertension (6%), sinus tachycardia (8%), chest pain (unspecified) (6%), congestive heart failure (5%), and edema (5%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Myocardial infarction, cardiac arrest, cardiomyopathy, atrial fibrillation, and supraventricular tachycardia (SVT) were also reported with decitabine therapy in clinical trials.
Nervous system adverse events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include headache (28% vs. 14%), dizziness (18% vs. 12%), falls (8% vs. 4%), and hypoesthesia (11% vs. 1%). Additionally, dizziness (21%) and headache (23%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99).
Nephrotoxicity has been reported with decitabine therapy. Obtain renal function tests at baseline (e.g., serum creatinine (SCr) level) and as clinically indicated during therapy. Hold decitabine therapy until nephrotoxicity resolves in patients who develop renal impairment (i.e., SCr level of 2 mg/dL or higher). Dysuria (6% vs. 4%) and increased urinary frequency (5% vs. 1%) were reported more often in patients with myelodysplastic syndrome who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial. Renal failure (unspecified) and urethral hemorrhage were also reported with decitabine therapy in clinical trials.
Dermatologic adverse events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include ecchymosis (22% vs. 15%), rash (19% vs. 9%), erythema (14% vs. 6%), skin lesion (11% vs. 4%), pruritus (11% vs. 2%), alopecia (8% vs. 1%), urticaria (6% vs. 1%), face swelling (6% vs. 0%), and injection site reaction such as catheter-related infection (8% vs. 0%), catheter-site erythema (5% vs. 1%), abrasion (5% vs. 1%), catheter-site pain (5% vs. 0%), and injection site swelling (5% vs. 0%). Additionally, rash (11%), pruritus (9%), ecchymosis (9%), xerosis (8%), erythema (5%), night sweats (5%), and skin lesion (5%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Catheter-site hemorrhage has been reported in clinical studies and cases of Sweet's Syndrome (acute febrile neutrophilic dermatosis) have been reported with decitabine use in postmarketing surveillance.
Serious bleeding events including intracranial bleeding and upper GI bleeding have been reported with decitabine therapy in clinical trials. Petechiae (39% vs. 16%) and hematoma (5% vs. 4%) occurred more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial. Petechiae was reported in 12% of MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Additionally, post procedure hemorrhage has been reported with decitabine therapy in clinical trials.
Hepatotoxicity has been reported with decitabine therapy. Obtain liver function tests at baseline and as clinically indicated during therapy. Hold decitabine therapy until hepatotoxicity resolves in patients who develop hepatic impairment (i.e., ALT level or total bilirubin level 2-times the upper limit of normal or greater). Liver toxicity reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial included elevated hepatic enzymes such as increased AST level (10% vs. 9%) and increased alkaline phosphatase level (11% vs. 9%), ascites (10% vs. 2%), and hyperbilirubinemia (14% vs. 5%). Increased bilirubin levels occurred in 6% of MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Cholecystitis was also reported with decitabine therapy in clinical trials.
Blurred vision was reported in 6% of patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care compared with no patients who received supportive care alone in a randomized trial (n = 164).
Otalgia occurred in 6% of patients with myelodysplastic syndrome who received a 5-day decitabine regimen in a single-arm study (n = 99).
Psychiatric system adverse events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include insomnia (28% vs. 14%), confusion (12% vs. 4%), and anxiety (11% vs. 10%). Additionally, insomnia (14%), anxiety (9%), depression (9%), and confusion (8%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Mental status changes were also reported with decitabine therapy in clinical trials.
Respiratory adverse events reported more often in patients with myelodysplastic syndrome (MDS) who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial include cough (40% vs. 31%), pharyngitis (16% vs. 7%), lung crackles (14% vs. 1%), decreased breath sounds (10% vs. 9%), hypoxia (10% vs. 5%), rales (8% vs. 2%), pulmonary edema (6% vs. 0%), crepitations (5% vs. 1%), and postnasal drip (5% vs. 2%). Additionally, cough (27%), dyspnea (29%), epistaxis (13%), pharyngolaryngeal pain (8%), pleural effusion (5%), abnormal breath sounds (5%), and nasal congestion (5%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99). Hemoptysis, lung infiltration, pulmonary embolism, respiratory arrest, and pulmonary mass were also reported with decitabine therapy in clinical trials. Interstitial lung disease has been reported with decitabine use in postmarketing surveillance.
Transfusion reactions (7% vs. 4%) were reported more often in patients with myelodysplastic syndrome who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial. Additionally, hypersensitivity reactions (e.g., anaphylactoid reactions) have been reported with decitabine therapy in a phase 2 trial.
Lethargy (12% vs. 4%) and malaise (5% vs. 1%) were reported more often in patients with myelodysplastic syndrome who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial.
Fatigue (46%) and asthenia (15%) occurred in patients with myelodysplastic syndrome who received a 5-day decitabine regimen in a single-arm study (n = 99).
Fever (53% vs. 28%), intermittent fever (6% vs. 4%), and chills (22% vs. 17%) were reported more often in patients with myelodysplastic syndrome who received a 3-day decitabine regimen plus supportive care (n = 83) compared with supportive care alone (n = 81) in a randomized trial. Additionally, fever (36%) and chills (16%) occurred in MDS patients who received a 5-day decitabine regimen in a single-arm study (n = 99).
Differentiation syndrome has been reported with decitabine use in postmarketing surveillance.
Severe bone marrow suppression/myelosuppression (e.g., anemia, thrombocytopenia, and neutropenia) has been reported with decitabine therapy; some cases were fatal. Myelosuppression and worsening neutropenia occur frequently in the first or second treatment cycle and may not indicate progression or underlying MDS. Obtain complete blood counts at baseline, prior to each cycle of therapy, and as clinically indicated to monitor for response and toxicity. Therapy delay or a dose reduction may be necessary in patients who experience delayed hematologic recovery. Severe infection (e.g., pneumonia) has also been reported with decitabine therapy. In patients who have an active or uncontrolled infection, hold decitabine therapy until the infection resolves. Start growth factor and/or anti-infective therapy as clinically indicated.
The use of decitabine in patients with hepatic disease has not been studied. Obtain liver function tests at baseline and as clinically indicated during therapy. Hold decitabine therapy until hepatotoxicity resolves in patients who develop hepatic impairment (i.e., ALT level or total bilirubin level 2-times the upper limit of normal or greater).
The use of decitabine in patients with renal disease has not been studied. Obtain renal function tests at baseline (e.g., serum creatinine (SCr) level) and as clinically indicated during therapy. Hold decitabine therapy until nephrotoxicity resolves in patients who develop renal impairment (i.e., SCr level of 2 mg/dL or higher).
Decitabine may cause fetal harm when administered to a pregnant woman, based on human and animal data and its mechanism of action. Advise females of reproductive potential to avoid becoming pregnant while taking decitabine. Discuss the potential hazard to the fetus if decitabine is used during pregnancy or if a patient becomes pregnant while taking this drug. Limited published data of decitabine use in the first trimester during pregnancy describe adverse developmental fetal outcomes including major birth defects (i.e., structural abnormalities). In a single case report, structural abnormalities (i.e., holoprosencephaly, absence of nasal bone, mid-facial deformity, cleft lip and palate, polydactyly and rocker-bottom feet) were reported in a fetus (gestational age, 18 weeks) following use of 6 cycles of decitabine therapy in a 39-year old woman with a hematologic malignancy. Additionally, decitabine caused adverse developmental outcomes including malformations and embryo-fetal lethality in mice and rats in animal studies.
Discuss contraception requirements with both male and female patients due to the potential for reproductive risk with decitabine. Females of reproductive potential should undergo pregnancy testing prior to initiation of decitabine. These patients should be advised to use effective contraception while taking decitabine and for 6 months after the last dose. Because of the potential risk of male-mediated teratogenicity, men with female partners of reproductive potential should be advised to use effective contraception while on treatment and for 3 months after their last dose. Infertility may occur in male patients based on data from animal studies.
It is not known if decitabine or its active metabolites are secreted in human milk or if it has effects on the breast-fed infant or milk production. Because there is a potential for adverse reactions in nursing infants from decitabine, women should discontinue breast-feeding during decitabine therapy and for at least 2 weeks after the last dose.
For the treatment myelodysplastic syndrome (MDS):
NOTE: Decitabine is designated an orphan drug by the FDA for the treatment of MDS.
-for the treatment of previously treated or untreated and de novo or secondary MDS including all French-American-British subtypes and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups:
Intravenous dosage:
Adults: 3-day regimen, 15 mg/m2 IV over 3 hours every 8 hours for 3 days; repeated every 6 weeks; or 5-day regimen, 20 mg/m2 IV over 1 hour daily on days 1, 2, 3, 4, and 5 repeated every 4 weeks. Continue therapy for at least 4 cycles; a complete or partial response may take longer than 4 cycles. Do not start a new cycle until the absolute neutrophil count is 1,000 cells/microL or greater and the platelet count is 50,000 cells/microL or greater. Therapy delay or a dose reduction may be necessary in patients who experience toxicity. Consider prophylactic antiemetics prior to each dose of decitabine. The overall response (ORR) rate was significantly improved (17% vs. 0%; p less than 0.001) in patients who received a 3-day regimen of decitabine (n = 89) compared with best supportive care (n = 81) in a randomized trial. However, the median time to AML transformation or death was not significantly delayed in the decitabine arm (12.1 months vs. 7.8 months). The ORR was 32% and the overall hematologic improvement rate was 51%in patients who received a 5-day regimen of decitabine in a single-arm trial (n = 99). Among patients experiencing a hematologic improvement, 82% achieved their best response within the first 2 cycles.
For the treatment of chronic myelogenous leukemia (CML)*:
Intravenous infusion:
Adults: In 1 clinical trial in 35 patients with CML (all phases) resistant or intolerant to imatinib, decitabine 10 to 15 mg/m2 IV over 1 hour 5 days a week for 2 weeks every 6 weeks was given. Complete hematologic responses were seen in 12 patients (34%) and partial hematologic responses in 7 patients (20%), for an overall response rate of 54%. Of the patients responding, 83% were in chronic phase, 41% in accelerated phase, and 34% in blast phase. Some patients were treated with hydroxyurea during the first 1 to 2 cycles. The overall cytogenic response was 46% (major cytogenic response in 6 patients and minor response in 10 patients). Median duration of response was 3.5 months, range 2 to 13+ months. There did not appear to cross-sensitivity to imatinib. In another clinical trial of 28 patients with either accelerated phase (AP) or myeloid blastic phase (BP) CML, decitabine 15 mg/m2 IV over 1 hour 5 days a week for 2 weeks every 6 weeks was administered in combination with imatinib 600 mg PO once daily. Complete hematological responses were observed in 32% of patients (7 patients in AP, 2 patients in BP), while a cytogenetic response was observed in 33% and 20% of patients in AP and BP, respectively. Of note, out of 7 patients with BCR-ABL kinase mutation, only 1 patient exhibited a hematologic response (14%) compared to 10 out of 19 patients (53%) with no BCR-ABL kinase mutation detected. Other doses of decitabine have been studied for the treatment of CML and have shown activity. In a study of 130 patients with CML (all phases), decitabine 50 mg/m2 IV over 6 hours every 12 hours for 5 days every 4 to 8 weeks produced objective responses in 63%, 55%, and 28% of patients in chronic phase, accelerated phase, and blastic phase CML, respectively. Higher doses of decitabine (75 mg/m2 and 100 mg/m2) were also administered in this study, but did not show an increase in response rates. Myelosuppression was significant with each of the 3 decitabine dosage regimens considered in this study.
For the treatment of acute myelogenous leukemia (AML)*:
NOTE: Decitabine has been designated an orphan drug by the FDA for the treatment of AML.
-for the treatment of newly-diagnosed AML in adults who are age 75 years or older or who have comorbidities that make them ineligible for intensive induction chemotherapy, in combination with venetoclax*:
NOTE: Venetoclax is FDA approved in combination with decitabine for this indication.
Intravenous dosage:
Adults: 20 mg/m2 IV daily on days 1, 2, 3, 4, and 5 repeated every 28 days starting on day 1 of cycle 1 in combination with oral venetoclax. The venetoclax dose is increased during a ramp-up phase as follows: 100 mg on day 1; 200 mg on day 2; 400 mg on day 3; and 400 mg once daily on day 4 and beyond. Continue treatment until disease progression. Treatment with venetoclax plus decitabine was evaluated in patients with newly diagnosed AML who were 75 years of age or older or had comorbidities in a nonrandomized trial (n = 13; median age, 75 years; range, 68 to 86 years). The complete remission (CR) and CR with partial hematological recovery (CRh) rates were 54% and 7.7%, respectively; the median time to first CR or CRh was 1.9 months (range, 0.8 to 4.2 months). At a median follow-up was 11 months (range, 0.7 to 38.8 months), the median duration of CR was 12.7 months in patients who received venetoclax plus decitabine. Comorbidities included severe cardiac disease (7.7%) or a creatinine clearance of less than 45 mL/min (7.7%).
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Hematologic Toxicity (3-day Regimen)
Delayed hematologic recovery (absolute neutrophil count of less than 1,000 cells/microL and the platelet count of less than 50,000 cells/microL or greater)
-lasting more than 6 weeks but less than 8 weeks from last treatment cycle: hold therapy for up to 2 weeks then resume decitabine at a reduced dose of 11 mg/m2 IV every 8 hours for 3 days; increase the dose in subsequent cycles as clinically indicated.
-lasting more than 8 weeks but less than 10 weeks from last treatment cycle: Assess patient for disease progression. If no disease progression, hold therapy for up to 2 weeks then resume decitabine at a reduced dose of 11 mg/m2 IV every 8 hours for 3 days; maintain or increase the dose in subsequent cycles as clinically indicated.
Non-Hematologic Toxicity
Infection (active or uncontrolled): hold decitabine therapy until the toxicity resolves.
Maximum Dosage Limits:
-Adults
Myelodysplastic syndrome
3-day regimen: 15 mg/m2 IV every 8 hours for 3 days repeated every 6 weeks.
5-day regimen: 20 mg/m2 IV daily on days 1, 2, 3, 4, and 5 repeated every 4 weeks.
-Geriatric
Myelodysplastic syndrome
3-day regimen: 15 mg/m2 IV every 8 hours for 3 days repeated every 6 weeks.
5-day regimen: 20 mg/m2 IV daily on days 1, 2, 3, 4, and 5 repeated every 4 weeks.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in patients with baseline hepatic impairment are not available; it appears that no initial dosage adjustments are needed.
Treatment-related hepatic impairment (ALT level or total bilirubin level 2-times the upper limit of normal or greater): hold decitabine therapy until the toxicity resolves.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in patients with baseline renal impairment are not available; it appears that no initial dosage adjustments are needed.
Treatment-related renal impairment (serum creatinine level of 2 mg/dL or higher): hold decitabine therapy until the toxicity resolves.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dichlorphenamide: (Moderate) Use dichlorphenamide and decitabine together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Decitabine is an antimetabolite that can replace cytosine in DNA but, unlike cytosine, it cannot be methylated. The exact mechanism of decitabine activity has not been determined and may involve multiple pathways. Decitabine is thought to primarily act by correcting DNA methylation, a major mechanism for gene expression. In some cancer cells, hypermethylation blocks the activity of tumor suppressor genes, which regulate cell division and differentiation to prevent malignant transformation. When suppressor gene activity is blocked, cell division becomes unregulated, leading to the formation of neoplastic cells. Decitabine regulates DNA methylation (specifically targets methyltransferase), effectively demethylating and reactivating different tumor suppressor genes. Because hypermethylation occurs early in the malignant transformation of cells, decitabine may have activity in chemoprevention. Other possible mechanisms for decitabine activity include cytotoxicity due to incorporation into DNA similar to other antimetabolites, methylation-independent induction of gene expression, and degradation of DNA methyltransferase 1.
Decitabine is administered by intravenous (IV) infusion. Plasma protein binding of decitabine is less than 1%. In a pharmacokinetic evaluation, the mean clearance values were 125 L/hour/m2 (coefficient of variance (CV), 53%) and 210 L/hour/m2 (CV, 47%) in 11 patients who received 15 mg/m2 IV over 3 hours every 8 hours for 3 days (option 1) and 14 patients who received 20 mg/m2 IV over 1 hour daily for 5 days (option 2), respectively. The half-life values were 0.62 hour (CV, 49%) and 0.54 hour (CV, 43%) with option 1 and option 2, respectively. Decitabine appears to be eliminated via deamination by cytidine deaminase, which is found intracellularly in the liver, granulocytes, intestinal epithelium, and whole blood. Decitabine is unlikely to inhibit or induce cytochrome P450 enzymes.
-Route-Specific Pharmacokinetics
Intravenous Route
Pharmacokinetic (PK) parameters were evaluated in 11 patients who received 15 mg/m2 IV over 3 hours every 8 hours for 3 days (option 1) and 14 patients who received 20 mg/m2 IV over 1 hour daily for 5 days (option 2). The Cmax values were 73.8 ng/mL (CV, 66%) and 147 ng/mL (CV, 49%) with option 1 and 2, respectively. Plasma concentration-time profiles following the decitabine infusion showed a biexponential decline. Systemic accumulation of decitabine or significant changes in PK parameters did not occur with repeat doses. The cumulative decitabine AUC value per cycle was 2.3-fold lower with option 2 (570 ng/mL X hour) compared with option 1 (1,332 ng/mL X hour).