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Decitabine

Pronunciation

(de SYE ta been)

Index Terms

  • 5 - Aza - 2' - deoxycytidine
  • 5 - Aza - dCyd
  • Deoxyazacytidine
  • Dezocitidine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Dacogen: 50 mg (1 ea)

Generic: 50 mg (1 ea)

Brand Names: U.S.

  • Dacogen

Pharmacologic Category

  • Antineoplastic Agent, Antimetabolite
  • Antineoplastic Agent, DNA Methylation Inhibitor

Pharmacology

After phosphorylation, decitabine is incorporated into DNA and inhibits DNA methyltransferase causing hypomethylation and subsequent cell death (within the S-phase of the cell cycle).

Distribution

~63 to 89 L/m2 (Cashen 2008)

Metabolism

Possibly via deamination by cytidine deaminase

Half-Life Elimination

~30 to 35 minutes

Use: Labeled Indications

Myelodysplastic syndromes: Treatment of myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) 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 (IPSS) groups

Use: Unlabeled

Treatment of acute myelogenous leukemia (AML), sickle cell anemia

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Dosage

Myelodysplastic syndromes (MDS): Adults: IV:

15 mg/m2 over 3 hours every 8 hours (45 mg/m2/day) for 3 days (135 mg/m2/cycle) every 6 weeks; treatment is recommended for at least 4 cycles and may continue until the patient no longer benefits.

Adjustment for prolonged hematologic toxicity (ANC <1,000/mm3 and platelets <50,000/mm3):

>6 weeks but <8 weeks: Delay dose for up to 2 weeks and temporarily reduce dose to 11 mg/m2 every 8 hours (33 mg/m2/day) for 3 days (99 mg/m2/cycle)

>8 weeks but <10 weeks: Assess for disease progression; if no disease progression, delay dose for up to 2 weeks and reduce dose to 11 mg/m2 every 8 hours (33 mg/m2/day) for 3 days (99 mg/m2/cycle); maintain or increase dose with subsequent cycles if clinically indicated

or

20 mg/m2 over 1 hour daily for 5 days every 28 days (delay subsequent treatment cycles until hematologic recovery [ANC ≥1,000/mm3 and platelets ≥50,000/mm3]); treatment is recommended for at least 4 cycles and may continue until the patient no longer benefits.

Acute myeloid leukemia (AML) (off-label use): Adults ≥60 years: IV: 20 mg/m2 over 1 hour daily for 5 days every 28 days until relapse, disease progression, or unacceptable toxicity (Cashen 2010; Kantarjian 2012)

Dosage adjustment for toxicity:

Hematologic toxicity (ANC <1,000/mm3 and platelets <50,000/mm3): Delay and/or reduce dose; see recommendations specific to each MDS dosing regimen above

Nonhematologic toxicity: Temporarily hold treatment until resolution for any of the following toxicities:

Serum creatinine ≥2 mg/dL

ALT, bilirubin ≥2 times ULN

Active or uncontrolled infection

Dosage adjustment in renal impairment:

Preexisting impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Renal toxicity during treatment: Serum creatinine ≥2 mg/dL: Temporarily hold treatment until resolution.

Dosage adjustment in hepatic impairment:

Preexisting impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Hepatotoxicity during treatment: ALT and/or bilirubin ≥2 times ULN: Temporarily hold treatment until resolution.

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Vials should be reconstituted with 10 mL SWFI to a concentration of 5 mg/mL. Immediately further dilute with NS, D5W, or lactated Ringer’s to a final concentration of 0.1 to 1 mg/mL. Use appropriate precautions for handling and disposal. Solutions not administered within 15 minutes of preparation should be prepared with cold (2°C to 8°C [36°F to 46°F]) infusion solutions.

Administration

Infuse over 1 to 3 hours. For the treatment of myelodysplastic syndromes, administer by IV infusion over 3 hours (15 mg/m2 dose) or over 1 hour (20 mg/m2 dose). For the treatment of acute myeloid leukemia (off-label use), administer by IV infusion over 1 hour (Cashen 2010; Kantarjian 2012). Premedication with antiemetics is recommended according to the manufacturer.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Compatibility

Stable in NS, D5W, and lactated Ringer’s.

Storage

Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Solutions diluted for infusion may be stored for up to 4 hours prior to infusion refrigerated at 2°C to 8°C (36°F to 46°F) if prepared with cold infusion fluids. Infusion should begin within 15 minutes of preparation if room temperature infusion solutions are utilized.

Drug Interactions

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

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

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

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

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (25% to 27%), pallor (23%), edema (5% to 18%), cardiac murmur (16%), hypotension (6% to 11%)

Central nervous system: Fever (6% to 53%), fatigue (46%), headache (23% to 28%), insomnia (14% to 28%), dizziness (18% to 21%), chills (16%), pain (5% to 13%), confusion (8% to 12%), lethargy (12%), anxiety (9% to 11%), hypoesthesia (11%)

Dermatologic: Petechiae (12% to 39%), bruising (9% to 22%), rash (11% to 19%), erythema (5% to 14%), cellulitis (9% to 12%), lesions (5% to 11%), pruritus (9% to 11%)

Endocrine & metabolic: Hyperglycemia (6% to 33%), hypoalbuminemia (7% to 24%), hypomagnesemia (5% to 24%), hypokalemia (12% to 22%), hyperkalemia (13%), hyponatremia (19%)

Gastrointestinal: Nausea (40% to 42%), constipation (30% to 35%), diarrhea (28% to 34%), vomiting (16% to 25%), anorexia/appetite decreased (8% to 23%), abdominal pain (5% to 14%), oral mucosal petechiae (13%), stomatitis (11% to 12%), dyspepsia (10% to 12%)

Hematologic: Neutropenia (38% to 90%; grades 3/4: 37% to 87%; recovery 28-50 days), thrombocytopenia (27% to 89%; grades 3/4: 24% to 85%), anemia (31% to 82%; grades 3/4: 22%), febrile neutropenia (20% to 29%; grades 3/4: 23%), leukopenia (6% to 28%; grades 3/4: 22%), lymphadenopathy (12%)

Hepatic: Hyperbilirubinemia (6% to 14%), alkaline phosphatase increased (11%)

Local: Tenderness (11%)

Neuromuscular & skeletal: Rigors (22%), arthralgia (17% to 20%), limb pain (18% to 19%), back pain (17% to 18%), weakness (15%)

Respiratory: Cough (27% to 40%), dyspnea (29%), pneumonia (20% to 22%), pharyngitis (16%), lung crackles (14%), epistaxis (13%)

5% to 10%:

Cardiovascular: Tachycardia (8%), chest pain/discomfort (6% to 7%), facial edema (6%), hypertension (6%), heart failure (5%)

Central nervous system: Depression (9%), malaise (5%)

Dermatologic: Alopecia (8%), dry skin (8%), urticaria (6%)

Endocrine & metabolic: Hyperuricemia (10%), LDH increased (8%), bicarbonate increased (6%), dehydration (6% to 8%), hypochloremia (6%), bicarbonate decreased (5%), hypoproteinemia (5%)

Gastrointestinal: Mucosal inflammation (9%), weight loss (9%), gingival bleeding (8%), hemorrhoids (8%), loose stools (7%), tongue ulceration (7%), dysphagia (5% to 6%), oral candidiasis (6%), toothache (6%), abdominal distension (5%), gastroesophageal reflux (5%), glossodynia (5%), lip ulceration (5%), oral pain (5%), tooth abscess (5%)

Genitourinary: Urinary tract infection (7%), dysuria (6%), polyuria (5%)

Hematologic: Bacteremia (5% to 8%), hematoma (5%), pancytopenia (5%), thrombocythemia (5%)

Hepatic: Ascites (10%), AST increased (10%), hypobilirubinemia (5%)

Local: Catheter infection (8%), catheter site erythema (5%), catheter site pain (5%), injection site swelling (5%)

Neuromuscular & skeletal: Myalgia (5% to 9%), falling (8%), chest wall pain (7%), muscle spasm (7%), bone pain (6%), musculoskeletal pain/discomfort (5% to 6%), crepitation (5%)

Ocular: Blurred vision (6%)

Otic: Ear pain (6%)

Respiratory: Breath sounds abnormal (5% to 10%), hypoxia (10%), upper respiratory tract infection (10%), pharyngolaryngeal pain (8%), rales (8%), pulmonary edema (6%), sinusitis (5% to 6%), pleural effusion (5%), postnasal drip (5%), sinus congestion (5%)

Miscellaneous: Candidal infection (10%), staphylococcal infection (7%), transfusion reaction (7%), night sweats (5%)

<5% (Limited to important or life-threatening): Anaphylactic reaction, atrial fibrillation, bronchopulmonary aspergillosis, cardiomyopathy, cardiorespiratory arrest/failure, catheter site hemorrhage, cholecystitis, fungal infection, gastrointestinal hemorrhage, gingival pain, hemoptysis, hypersensitivity, intracranial hemorrhage, mental status change, MI, mycobacterium avium complex infection, peridiverticular abscess, pseudomonal lung infection, pulmonary embolism, pulmonary infiltrates, pulmonary mass, renal failure, respiratory arrest, sepsis, splenomegaly, supraventricular tachycardia, Sweet’s syndrome (acute febrile neutrophilic dermatosis), urethral hemorrhage

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia and thrombocytopenia commonly occur; anemia and neutropenic fever have also been reported. Myelosuppression and worsening neutropenia are more common in first two treatment cycles and may not correlate with progression of underlying MDS. Hematologic toxicity may require dosage adjustment (after the first cycle), growth factor support, and/or antimicrobial agents. Monitor for infection.

Concurrent drug therapy issues:

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

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Monitoring Parameters

CBC with differential and platelets (with each cycle and more frequently if needed); liver enzymes (prior to treatment initiation and periodically); serum creatinine (prior to treatment initiation and periodically)

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Based on the mechanism of action, decitabine may cause fetal harm if administered during pregnancy. Women of childbearing potential should be advised to use effective contraception to avoid pregnancy during treatment and for 1 month after treatment. In addition, males should be advised to avoid fathering a child while on decitabine therapy and for 2 months after treatment.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, asthenia, dyspepsia, stomatitis, insomnia, lack of appetite, headache, arthralgia, or back pain. Have patient report immediately to prescriber signs of infection, signs of hepatic impairment, dyspnea, severe nausea, considerable constipation, intolerable diarrhea, ecchymosis, hemorrhaging, significant edema, signs of hyperglycemia, or signs of fluid and electrolyte imbalance (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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