Decitabine

Pronunciation: dee-SYE-ta-been
Class: Antineoplastic

Trade Names

Dacogen
- Injection, lyophilized powder for solution 50 mg

Pharmacology

May cause hypomethylation of DNA and cellular differentiation or apoptosis by phosphorylation and direct incorporation into DNA.

Slideshow: 18 Herbal Supplements with Risky Drug Interactions

Herbal and Dietary Supplements Deserve Your Attention

Pharmacokinetics

Absorption

C max is approximately 73.8 ng/mL (treatment option 1, see Route/Dosage) and approximately 147 ng/mL (treatment option 2, see Route/Dosage). Cumulative AUC per cycle for treatment option 2 was 2.3-fold lower than for treatment option 1.

Distribution

Undergoes biphasic distribution. Plasma protein binding is less than 1%.

Elimination

May be eliminated through deamination by cytidine deaminase. Half-life is approximately 0.62 h (treatment option 1) and 0.54 h (treatment option 2).

Special Populations

Hepatic/Renal Function Impairment

Have not been studied.

Indications and Usage

Treatment of myelodysplastic syndromes.

Contraindications

Standard considerations.

Dosage and Administration

Adults Treatment regimen – option 1

IV 15 mg/m 2 by continuous IV infusion over 3 h repeated every 8 h for 3 days. Repeat this treatment cycle every 6 wk for a minimum of 4 cycles. However, complete or partial response may take longer than 4 cycles. Treatment may be continued as long as there is continued benefit.

Treatment regimen – option 2

IV 20 mg/m 2 by continuous IV infusion over 1 h repeated daily for 5 days. Repeat this treatment cycle every 4 wk for a minimum of 4 cycles. However, complete or partial response may take longer than 4 cycles.

Dose Adjustments or Delays
Adults Hematologic toxicity (treatment regimen – option 1)

IV If hematologic recovery (absolute neutrophil count [ANC] 1,000/mcL or more and platelets 50,000/mcL or more) from a previous treatment cycle requires more than 6 wk, then delay the next cycle of therapy and temporarily reduce dosing as follows:

Recovery requiring more than 6 wk but less than 8 wk

Delay decitabine dosing for up to 2 wk and temporarily reduce the dose to 11 mg/m 2 every 8 h (33 mg/m 2 /day; 99 mg/m 2 /cycle) upon restarting of therapy.

Recovery requiring more than 8 wk but less than 10 wk

Assess for disease progression using bone marrow aspirates. In the absence of progression, delay the decitabine dose up to 2 more wk and reduce the dose to 11 mg/m 2 every 8 h (33 mg/m 2 /day; 99 mg/m 2 /cycle) upon restarting therapy, then maintain or increase dose in subsequent cycles as clinically indicated.

Hematologic toxicity (treatment regimen – option 2)

IV If myelosuppression is present, subsequent treatment cycles of decitabine should be delayed until there is hematologic recovery (ANC at least 1,000/mcL and platelets at least 50,000/mcL).

Nonhematologic toxicity

IV Treatment should not be restarted until the toxicity is resolved: serum creatinine at least 2 mg/dL; ALT, total bilirubin at least 2 times ULN; and active or uncontrolled infection.

General Advice

  • Unless used within 15 min of reconstitution, diluted solution must be prepared using cold (36° to 46°F) infusion fluids and stored at 36° to 46°F for a max of 7 h until administration.
  • Use procedures for proper handling and disposal of antineoplastic drugs.
  • Premedicate with standard antiemetic therapy before treatment.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Storage/Stability

Store vials at 59° to 86°F.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiac murmur (16%); hypotension (11%); tachycardia (8%); hypertension, pulmonary edema (6%); congestive cardiac failure, hematoma (5%); atrial fibrillation, cardiomyopathy, cardiorespiratory arrest, intracranial hemorrhage, MI, supraventricular tachycardia.

CNS

Pyrexia (53%); fatigue (46%); headache, insomnia (28%); dizziness (21%); chills (16%); asthenia (15%); confusional state, lethargy (12%); anxiety, hypesthesia (11%); depression (9%); fall (8%); intermittent pyrexia (6%); malaise (5%); mental status changes.

Dermatologic

Petechiae (39%); pallor (23%); ecchymosis (22%); rash (19%); erythema (14%); pruritus, skin lesion (11%); contusion (9%); alopecia, dry skin (8%); swelling face, urticaria (6%); night sweats (5%).

EENT

Pharyngitis (16%); epistaxis (13%); pharyngolaryngeal pain (8%); blurred vision, ear pain (6%); postnasal drip (5%).

GI

Nausea (42%); constipation (35%); diarrhea (34%); vomiting (25%); anorexia, decreased appetite (16%); abdominal pain (14%); oral mucosal petechiae (13%); dyspepsia, stomatitis (12%); ascites (10%); gingival bleeding, hemorrhoids (8%); loose stools, tongue ulceration (7%); dysphagia, oral candidiasis, oral soft tissue disorder, toothache, upper abdominal pain (6%); abdominal distension, gastroesophageal reflux disease, glossodynia, lip ulceration, oral pain, tooth abscess (5%); upper GI hemorrhage.

Genitourinary

UTI (7%); dysuria (6%); urinary frequency (5%); renal failure, urethral hemorrhage.

Hematologic-Lymphatic

Neutropenia (90%); thrombocytopenia (89%); anemia (82%); febrile neutropenia (29%); leukopenia (28%); lymphadenopathy (12%); pancytopenia, thrombocythemia (5%); myelosuppression, splenomegaly.

Hepatic

Hyperbilirubinemia (14%); cholecystitis.

Lab Tests

Increased blood alkaline phosphatase (11%); increased AST, increased blood urea (10%); increased blood LDH (8%); decreased blood albumin (7%); decreased blood chloride, increased blood bicarbonate, increased blood bilirubin (6%); decreased blood bicarbonate, decreased blood bilirubin, decreased total protein (5%).

Local

Catheter-related infections (8%); catheter-site erythema, catheter-site pain, injection-site swelling (5%); catheter-site hemorrhage.

Metabolic-Nutritional

Hyperglycemia (33%); anorexia (23%); peripheral edema (27%); hypoalbuminemia, hypomagnesemia (24%); hypokalemia (22%); hyponatremia (19%); edema (18%); hyperkalemia (13%); decreased weight (9%); dehydration (8%).

Musculoskeletal

Rigors (22%); arthralgia (20%); limb pain (19%); back pain, pain in extremity (18%); myalgia (9%); chest wall pain, muscle spasms (7%); bone pain, musculoskeletal discomfort (6%); musculoskeletal pain, muscular weakness, myalgia (5%).

Respiratory

Cough (40%); dyspnea (29%); pneumonia (22%); lung crackles (14%); decreased breathing sounds, hypoxia, upper respiratory tract infection (10%); respiratory tract infection (9%); rales (8%); pulmonary edema, sinusitis (6%); abnormal breath sounds, sinus congestion (5%); bronchopulmonary aspergillosis, hemoptysis, lung infiltration, pseudomonal lung infection, pulmonary embolism, pulmonary mass, respiratory arrest, upper respiratory tract infection.

Miscellaneous

Pain (13%); cellulitis (12%); tenderness (11%); candidal infections, fall, mucosal inflammation, staphylococcal bacteremia (8%); chest discomfort, staphylococcal infection, transfusion reaction (7%); chest pain (6%); abrasion, bacteremia, crepitations, pleural effusion (5%); hypersensitivity (eg, anaphylactic reaction), Mycobacterium avium complex infection, sepsis.

Precautions

Monitor

Perform CBCs and platelet counts as needed to monitor response and toxicity, but at least prior to each cycle. Obtain liver chemistries and serum creatinine prior to initiation of treatment.


Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Hematologic toxicity

Neutropenia and thrombocytopenia may occur.

Overdosage

Symptoms

Myelosuppression, including prolonged neutropenia and thrombocytopenia.

Patient Information

  • Caution patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
  • Advise patients to notify health care provider of any underlying liver or kidney disease.
  • Advise men not to father a child while receiving treatment and for 2 mo after. Advise men with female partners of childbearing potential to use effective contraception.
  • Women of childbearing potential should be advised to avoid becoming pregnant while receiving decitabine and for 1 month following completion of treatment.
  • Advise women to consult health care provider before breast-feeding.

Copyright © 2009 Wolters Kluwer Health.

Hide
(web5)