decitabine (Rx)

>10%

Neutropenia (90%)

Thrombocytopenia (89%)

Anemia (82%)

Pyrexia (53%)

Nausea (42%)

Cough (40%),

Petechiae (39%)

Constipation (35%)

Diarrhea (34%)

Hyperglycemia (33%)

Febrile neutropenia (29%)

Headache (28%)

Insomnia (28%)

Leukopenia (28%)

Vomiting (25%)

Peripheral edema (25%)

Hypoalbuminemia (24%)

Hypomagnesemia (24%)

Pallor (23%)

Hypokalemia (22%)

Pneumonia (22%)

Rigors (22%)

Ecchymosis (22%)

Arthralgia (20%)

Limb pain (19%)

Hyponatremia (19%)

Rash (19%)

Edema (18%)

Dizziness (18%)

Back pain (17%)

Appetite decreased (16%)

Pharyngitis (16%)

Cardiac murmur (16%)

Anorexia (16%)

Hyperbilirubinemia (14%)

Abdominal pain (14%)

Erythema (14%)

Crackles in lung (14%)

Oral mucosal petechiae (13%)

Pain (13%)

Hyperkalemia (13%)

Confusional state (12%)

Lethargy (12%)

Stomatitis (12%)

Dyspepsia (12%)

Lymphadenopathy (12%)

Cellulitis (12%)

Anxiety (11%)

Hypoesthesia (11%)

Tenderness (11%)

Blood alkaline phosphatase increased (11%)

Skin lesion (11%)

Pruritus (11%)

1-10%

Aspartate aminotransferase increase (10%)

Blood urea increase (10%)

Breath sounds decrease (10%)

Hypoxia (10%)

Candidal infection (10%)

Ascites (10%)

Blood lactate dehydrogenase increase (8%)

Catheter related infection (8%)

Gingival bleeding (8%)

Hemorrhoids (8%)

Alopecia (8%)

Fall (8%)

Rales (8%)

Loose stools (7%)

Transfusion reaction (7%)

Tongue ulceration (7%)

Chest discomfort (7%)

Chest wall pain (7%)

Blood albumin decrease (7%)

Urinary tract infection (7%)

Staphylococcal infection (7%)

Oral candidiasis (6%)

Dysuria (6%)

Dysphagia (6%)

Pulmonary edema (6%)

Blurred vision (6%)

Oral soft tissue disorder (6%)

Urticaria (6%)

Swelling of face (6%)

Blood Cl decrease (6%)

Blood bicarbonate increase (6%)

Musculoskeletal discomfort (6%)

Hypotension (6%)

Dehydration (6%)

Intermittent pyrexia (6%)

Lip ulceration (5%)

Thrombocythemia (5%)

Hematoma (5%)

Abdominal distension (5%)

Upper abdominal pain (5%)

Gastro-esophageal reflux disease (5%)

Glossodynia (5%)

Myalgia (5%)

Malaise (5%)

Crepitations (5%)

Catheter site erythema (5%)

Catheter site pain (5%)

Injection site swelling (5%)

Urinary frequency (5%)

Sinusitis (5%)

Postnasal drip (5%)

Bacteremia (5%)

Abrasion (5%)

Protein total decrease (5%)

Blood bicarbonate decrease (5%)

Blood bilirubin decreased (5%)

Postmarketing Reports

Sweet’s syndrome (acute febrile neutrophilic dermatosis)

Differentiation syndrome

Interstitial lung disease

Contraindications

Hypersensitivity

Cautions

Use caution in renal/hepatic impairment

Fatal and serious myelosuppression occurs in treated patients; myelosuppression (anemia, neutropenia, and thrombocytopenia) is the most frequent cause of dose reduction, delay, and discontinuation; manage toxicity using dose-delay, dose-reduction, growth factors, and anti-infective therapies as needed; myelosuppression and worsening neutropenia may occur more frequently in first or second treatment cycles, and may not necessarily indicate progression of underlying MDS

Therapy can cause fetal harm when administered to a pregnant woman; based on mechanism of action, drug alters DNA synthesis and is expected to result in adverse reproductive effects; advise men with female partners of childbearing potential to avoid fathering a child while receiving treatment and for 3 months following the last dose; counsel patients of childbearing potential to use effective contraception during this time

Bone marrow suppression may occur (dose limiting); dose adjustment may be necessary

Pregnancy

Based on findings from human data, animal studies, and the mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; limited published data on use throughout first trimester during pregnancy describe adverse developmental outcomes including major birth defects (structural abnormalities); advise pregnant women of potential risk to fetus

Based on findings of decitabine in animals, male fertility may be compromised by treatment; reversibility of effect on fertility is unknown

Conduct pregnancy testing of females of reproductive potential prior to initiating treatment

Advise females of reproductive potential to avoid pregnancy and use effective contraception while receiving therapy and for 6 months following last dose

Advise males with female partners of reproductive potential to use effective contraception while receiving treatment and for 3 months following last dose

Animal data

• In animal reproduction studies, administration of decitabine to pregnant mice and rats during organogenesis caused adverse developmental outcomes and was teratogenic, fetotoxic, and embryotoxic starting at doses approximately 7% of the recommended human dose on a mg/m2 basis

Lactation

There are no data on presence of drug or metabolites in human milk, effects on breastfed child, or on milk production; because many drugs are excreted in human milk, and because of potential for serious adverse reactions in a nursing child, advise lactating women to avoid breastfeeding during treatment and for at least 1 week after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits DNA methyltransferase, causing hypomethylation of DNA & cellular differentiation or apoptosis

Pharmacokinetics

Protein Bound: <1%

Vd: 63-89 L/m²

Half-life: 30-35 min

IV Compatibilities

Solution: NS, D5W, LR

IV Preparation

Aseptically reconstitute drug with room temperature (20°C to 25°C) 10 mL of Sterile Water for Injection, USP.

Upon reconstitution, the final concentration of the reconstituted drug solution is 5 mg/mL; you must dilute the reconstituted solution with 0.9% sodium chloride injection or 5% dextrose injection prior to administration

Temperature of the diluent (0.9% sodium chloride injection or 5% dextrose injection) depends on time of administration after preparation

For administration within 15 minutes of preparation

• If drug is intended to be administered within 15 minutes from time of preparation, dilute reconstituted solution with room temperature (20-25 ^oC) 0.9% sodium chloride injection or 5% dextrose injection to a final concentration of 0.1 mg/mL to 1 mg/mL; discard unused portion

For delayed administration

• If drug is intended to be administered after 15 minutes of preparation, dilute reconstituted solution with cold (2-8 ^oC) 0.9% sodium chloride injection or 5% dextrose injection to a final concentration of 0.1 mg/mL to1 mg/mL
• Store at 2-8 ^oC for up to 4 hours; diluted stored solution must be used within 4 hours from time of preparation; discard unused portion
• Use the diluted, refrigerated solution within 4 hours from time of preparation or discard; parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
• Do not use if there is evidence of particulate matter or discoloration

IV Administration

Infuse IV continuously over 3 hr

Storage

Store diluted solution at 2-8°C (36-46°F) not to exceed 7 hr

Store vials at 25°C (77°F)