Dacogen

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.

Dacogen

a trademark for decitabine.
Mentioned in ?
References in periodicals archive ?
The combination of MGI PHARMA and Janssen-Cilag as global developers and marketers of Dacogen should accelerate the availability of this product to patients worldwide.
The primary reason for the decrease in total costs and operating expenses for 2005 was a decrease in development, selling and marketing expenses associated with the Orathecin and Dacogen programs, lower cost of product revenue resulting from reduced distribution charges offset by an increase in sales and marketing expenses for Nipent commercialization efforts with the Company's European operations.
Astex Pharmaceuticals, formerly SuperGen, developed Dacogen and receives significant royalties on global sales.
Dacogen injection is a product candidate that belongs to a class of drugs called hypomethylating agents that is currently being evaluated in a broad clinical development program in patients with MDS, acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and solid tumors.
Dacogen injection was the subject of five oral presentations and 10 poster presentations.
MGI PHARMA and SuperGen have submitted their response to the Approvable Letter received for Dacogen injection to the U.
The primary reason for the decrease in total costs and operating expenses for the 2005 third quarter was a decrease in development and marketing expenses associated with the Orathecin(TM) (rubitecan) capsules and Dacogen programs, lower cost of product revenue resulting from a change in product mix and reduced distribution charges offset by an increase in selling, general and administrative expenses associated primarily with additional sales and marketing efforts for Nipent commercialization scale-up efforts with the Company's European operations.
SuperGen developed Dacogen and receives significant royalties on global sales.
The primary reason for the decrease in total costs and operating expenses for the 2005 second quarter was a decrease in development and marketing expenses associated with the Orathecin(TM) (rubitecan) capsules and Dacogen programs, lower cost of product revenue resulting from a change in product mix and reduced distribution charges.
The application is based on the Phase III randomized open-label, multi-center trial (DACO-016) comparing DACOGEN versus patient's choice with physician's advice of either supportive care or low-dose cytarabine in patients 65 years and older with newly diagnosed de novo or secondary AML and with poor- or intermediate-risk cytogenetics.
sales of DACOGEN were approximately $251 million for the twelve months ending in April 2014.
Dacogen is an intravenous formulation of decitabine which has received approval for sale in the United States.