decitabine


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decitabine

(de-sit-a-been) ,

Dacogen

(trade name)

Classification

Therapeutic: antineoplastics
Pregnancy Category: D

Indications

Treatment of various myelodysplastic syndromes (MDS).

Action

Inhibits DNA methyltransferase, causing apoptosis. Has more effect on rapidly replicating cells.

Therapeutic effects

Improved hematologic and clinical manifestations of MDS.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Mostly metabolized by the liver.
Half-life: 0.5 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IVrapidend of infusionunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Patients with child-bearing potential (males and females);Impaired hepatic/renal function; Geriatric: May be more sensitive to effects; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • confusion (most frequent)
  • fatigue (most frequent)
  • insomnia (most frequent)
  • depression
  • lethargy

Ear, Eye, Nose, Throat

  • blurred vision

Respiratory

  • cough (most frequent)

Cardiovascular

  • atrial fibrillation
  • pulmonary edema
  • tachycardia

Gastrointestinal

  • abdominal pain (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • ↑ liver enzymes

Dermatologic

  • petechiae (most frequent)
  • rash

Fluid and Electrolyte

  • edema (most frequent)
  • hypokalemia (most frequent)
  • hypomagnesemia (most frequent)
  • ascites

Hematologic

  • bleeding (life-threatening)
  • anemia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Local

  • injection site irritation

Metabolic

  • hyperglycemia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • myalgia (most frequent)

Miscellaneous

  • infection (life-threatening)
  • fever (most frequent)
  • lymphadenopathy

Interactions

Drug-Drug interaction

↑ risk of myelosuppression with other antineoplastics, immunosuppressants, or radiation therapy.May ↓ antibody response to and ↑ risk of adverse reactions from live virus vaccines.

Route/Dosage

Intravenous (Adults) 15 mg/m2 as a continuous infusion over 3 hr repeated q 8 hr for 3 days; cycle should be repeated q 6 wk for a minimum of 4 cycles or 20 mg/m2 as a continuous infusion over 1 hr repeated daily for 5 days; cycle should be repeated q 4 wk for a minimum of 4 cycles.

Availability (generic available)

Lyophilized powder for injection (requires reconstitution): 50 mg/vial

Nursing implications

Nursing assessment

  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Lab Test Considerations: Monitor CBC prior to each dosing cycle and periodically as needed. May cause neutropenia, thrombocytopenia, and anemia; occur more frequently in 1st or 2nd treatment cycles. Use early institution of growth factors and antimicrobial agents to prevent infections.
    • Obtain liver chemistries and serum creatinine prior to initiation of treatment. May cause hyperbilirubinemia and hypoalbuminemia.
    • May cause hyperglycemia, hypomagnesemia, hyponatremia, hypokalemia, and hyperkalemia.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • high alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
    • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers (see ).
    • Premedicate patient with standard antiemetic therapy.
    • If hematologic recovery (ANC ≥1,000 cells/mm3 and platelets ≥50,000 cells/mm3) from previous treatment cycle requires more than 6, but less than 8 wk—delay dosing for up to 2 wk and temporarily reduce dose to 11 mg/m2 (33 mg/m2/day, 99 mg/m2/cycle) upon restarting therapy.
    • If hematologic recovery requires more than 8, but less than 10 wk—Patient should be assessed for disease progression (by bone marrow aspirates); in the absence of progression, delay dose for up to 2 more wk and reduce dose as above upon restarting, then maintain or increase in subsequent cycles as clinically indicated.
  • Intravenous Administration
  • pH: 6.7–7.3.
  • Intermittent Infusion: Reconstitute with 10 mL of sterile water for injection for a concentration of 5 mg/mL. Diluent: Immediately after reconstitution, dilute further with 0.9% NaCl, D5W, or LR.Concentration: 0.1–1.0 mg/mL. Unless used within 15 min of reconstitution, dilute solution must be prepared using cold infusion fluids and refrigerated until administration (maximum of 7 hr).
  • Rate: Administer over 3 hr or over 1 hr, depending on treatment regimen chosen.

Patient/Family Teaching

  • Caution patient to avoid crowds and persons with known infections. Report symptoms of infection (fever, chills, cough, hoarseness, sore throat, lower back or side pain, painful or difficult urination) immediately.
  • Instruct patient to report unusual bleeding. Advise patient of thrombocytopenia precautions (use soft toothbrush and electric razor, avoid falls, do not drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding).
  • Inform patient that this medication may have teratogenic effects. Advise women to use effective contraception and avoid becoming pregnant during treatment. Advise men not to father a child during or for 2 mo after treatment.

Evaluation/Desired Outcomes

  • Improved hematologic and clinical manifestations of MDS.
Drug Guide, © 2015 Farlex and Partners

decitabine

Oncology An antimetabolic anticancer agent
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.
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References in periodicals archive ?
Trovagene has an ongoing Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML that was accepted by the National Library of Medicine (NLM) and is now posted to www.clinicaltrials.gov, with a NCT number of NCT03303339.
"These can improve blood counts, decrease transfusions, reduce the risk of AML, and improve quality of life and survival." Options include azacitidine (Vidaza[R]), decitabine (Dacogen[R]), and lenalidomide (Revlimid[R]).
The amended Phase 2 study will continue evaluating the safety of prexigebersen in combination with decitabine in both cohorts of patients at a dose of 60 mg/m2 in combination with decitabine.
It is running two Phase 2 trials for onvansertib combo therapies: one in combination with low-dose cytarabine or decitabine for acute myeloid leukemia , and another in combination with Zytiga for mCRPC.
AbbVie achieved a number of regulatory milestones for several key products in 2018, including regulatory approvals for cancer drugVenclexta in combination with Rituxan (rituximab) and in combination with azacitidine or decitabine; Imbruvica was also approved in combination with rituximab for cancer treatment.
The oral, fixed-dose-combination drug candidate ASTX727 comprises the active ingredient of the DNA methylation inhibitor Dacogen[R] (decitabine) in combination with the novel metabolic enzyme inhibitor cedazuridine that suppresses the degradation of decitabine.
Oncology pipeline company Taiho Oncology Inc reported on Friday the launch of a commercialisation agreement with Otsuka Pharmaceuticals Co Ltd for the novel fixed-dose combination of cedazuridine and decitabine (ASTX727) and guadecitabine (SGI-110) in the US and Canada.
Food and Drug Administration (FDA) granted accelerated approval to VENCLEXTA (venetoclax) in combination with azacitidine, or decitabine, or low-dose cytrabine (LDAC) for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
Decitabine, the only other inhibitor with more than two supporting references, was inactive against HDAC1, but review of the literature showed it was a synergist with HDAC inhibitors but acting as a hypomethylating agent independent of direct effects on the HDAC enzyme (Kalac et al., 2011).
Despite these findings, a recent study indicated that AML patients with cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had a favorable clinical response to decitabine (49,50).
Criteria enforced included a requirement for a 99.25 chemotherapy administration procedure code to be greater than or equal to the date of AML diagnosis, minimum 7-day length of stay (LOS) during first treatment, and absence of outpatient administration of azacitidine or decitabine (hypo-methylating agents) within the first 60 days following diagnosis.
The multitude of SDH alterations described here have opened up potential targets for future therapies: decitabine, a demethylase inhibitor, has shown a role in reversing SDH-mutant methylation profiles in mouse models (10); a glutaminase inhibitor is currently undergoing trial as an adjunct to chemotherapy in SDH-mutated tumors; and a third trial using a DNA methyltransferase inhibitor, guadecitabine, to target SDH-deficient tumors is also in the preliminary stages.