Dacogen (decitabine)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Decitabine, a synthetic nucleoside analog of 2'-deoxycytidine, is an antineoplastic agent.
Decitabine, a synthetic nucleoside analog of 2'-deoxycytidine, is an antineoplastic agent. The antineoplastic activity of decitabine depends on intracellular conversion of the drug to its 5'-triphosphate metabolite. Following conversion to decitabine triphosphate, the drug appears to exert its antineoplastic effect by incorporating into DNA and inhibiting DNA methyltransferase (the enzyme responsible for methylating newly synthesized DNA in mammalian cells), thereby causing hypomethylation of DNA.
The concentration of decitabine required for inhibition of DNA methylation in vitro does not appear to cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes silenced by aberrant DNA methylation (e.g., tumor suppressor genes) that are critical for cellular differentiation, proliferation, senescence, and apoptosis. In rapidly dividing cells, decitabine that has been incorporated into DNA also may exert a direct cytotoxic effect by forming covalent adducts with DNA methyltransferase.
Nonproliferating cells are relatively insensitive to decitabine. Decitabine is cell-cycle specific, acting principally in the S phase of the cell cycle; the drug does not inhibit progression of cells from G1 into S phase.
Following IV administration, decitabine rapidly enters cells by a nucleoside-specific transport mechanism; the drug distributes into body fluids and crosses the blood-brain barrier. The exact route of elimination and the metabolic fate of decitabine in humans are not known. One possible elimination pathway is deamination by cytidine deaminase, an enzyme found principally in the liver and to a lesser extent in granulocytes, intestinal epithelium, and whole blood.
In vitro studies indicate that decitabine is not a substrate for, and is unlikely to inhibit or induce, cytochrome P-450 (CYP) isoenzymes. Less than 1% of decitabine is bound to plasma proteins. The terminal elimination half-life of decitabine is approximately 0.51 hour.
USES: This medication is used to treat a group of blood/bone marrow disorders (myelodysplastic syndromes-MDS) in which the bone marrow does not produce enough healthy blood cells. People with MDS may have problems such as infections, anemia, and easy bleeding/bruising. Decitabine is a chemotherapy drug.
It is believed to work by helping your bone marrow grow normal blood cells so you will need fewer blood transfusions. Decitabine also kills abnormal blood cells that have grown too fast and do not work properly.
Generic name: decitabine
Pronunciation: (dee-SYE-ta-been)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Dacogen
Indications
The following indications are listed for Dacogen:
- Myelodysplastic Syndrome
Also known as: Preleukemia.
Dosing
The recommended dosage of decitabine for the treatment of myelodysplastic syndrome (MDS) in adults is 15 mg/m2 (administered by IV infusion over 3 hours) every 8 hours for 3 consecutive days (total dose per treatment cycle: 135 mg/m2); the treatment cycle should be repeated every 6 weeks. The manufacturer recommends that patients receive at least 4 treatment cycles, although additional treatment cycles may be needed to achieve complete or partial response. Decitabine should be continued as long as the patient is deriving benefit from therapy. In the phase 3 study, the median duration of response to decitabine was 288 days.
Alternative dosages of decitabine are being investigated in patients with MDS, and the optimum dosage remains to be established.
Patients receiving decitabine therapy should be monitored for hematologic and nonhematologic toxicities; treatment should be delayed or dosage reduced accordingly. (` Dosage Modification for Hematologic Toxicity and also see Dosage Modification for Nonhematologic Toxicity under Dosage and Administration: Dosage.)
If hematologic recovery (i.e., absolute neutrophil count (ANC) of at least 1000/mm3, platelet count of at least 50,000/mm3) from the previous treatment cycle requires more than 6 weeks but less than 8 weeks, the next treatment cycle should be delayed for up to 2 weeks, and dosage of decitabine should be temporarily reduced at the start of the next cycle to 11 mg/m2 every 8 hours for 3 consecutive days (total dosage during treatment cycle: 99 mg/m2). If hematologic recovery from the previous treatment cycle requires more than 8 weeks but less than 10 weeks, the patient should be evaluated for disease progression (i.e., by bone marrow aspirates). In the absence of progression, the next treatment cycle should be delayed for up to 2 more weeks, and dosage of decitabine in the next cycle should be reduced to 11 mg/m2 every 8 hours for 3 consecutive days (total dosage during treatment cycle: 99 mg/m2). This reduced dosage may be maintained or increased in subsequent treatment cycles as clinically indicated.
If serum creatinine concentration increases to 2 mg/dL or greater, serum ALT or total bilirubin concentration increases to 2 or more times the upper limit of normal, or active or uncontrolled infection occurs, decitabine therapy should not be restarted until the toxicity has been resolved.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
No formal drug interaction studies have been performed to date.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to decitabine or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects reported in clinical trials of decitabine are neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia. Other adverse effects reported in 20% or more of patients receiving decitabine in the phase 3 study and occurring more frequently with decitabine than with supportive care alone include febrile neutropenia, leukopenia, headache, insomnia, vomiting, peripheral edema, hypoalbuminemia, hypomagnesemia, pallor, rigors, pneumonia, hypokalemia, ecchymosis, and arthralgia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of decitabine have not been established in pediatric patients.
Category D. (See Users Guide and also see Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)
It is not known whether decitabine or its metabolites are distributed into milk. Because of the potential for serious adverse reactions to decitabine in nursing infants, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the woman.
Of the 83 patients receiving decitabine in the phase 3 study, 61 (73%) were 65 years of age or older and 21 (25%) were 75 years of age or older. No overall differences in efficacy or safety were observed between geriatric and younger patients, but the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.