DECITABINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DECITABINE (DECITABINE).
Decitabine is a hypomethylating agent that incorporates into DNA, inhibiting DNA methyltransferase, leading to DNA hypomethylation and reactivation of silenced genes, thereby restoring normal growth control and differentiation in hematopoietic cells.
| Metabolism | Decitabine is primarily metabolized via deamination by cytidine deaminase in the liver and other tissues. It is not extensively metabolized by cytochrome P450 enzymes. |
| Excretion | Renal: 45% as unchanged drug; biliary/fecal: negligible (<5%). Hepatic metabolism accounts for remainder. |
| Half-life | Terminal half-life: 0.5-1.5 hours. Short half-life; administered over 1 hour IV to maintain cytotoxic levels. |
| Protein binding | 30-40% bound, primarily to albumin. |
| Volume of Distribution | Vd: 20-40 L/kg (extensive tissue distribution, including CNS). |
| Bioavailability | IV: 100%; oral: not clinically relevant (<10% due to deamination). |
| Onset of Action | IV: 3-7 days for hematologic recovery; epigenetic effects occur within hours of infusion. |
| Duration of Action | Duration: 2-4 weeks (myelosuppression cycle); epigenetic changes persist for several days post-infusion. |
Decitabine 15 mg/m² intravenously over 3 hours every 8 hours for 3 days, repeated every 6 weeks for myelodysplastic syndromes.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended for GFR ≥30 mL/min. Insufficient data for GFR <30 mL/min. Monitor renal function and use caution. |
| Liver impairment | No dose adjustment specified for Child-Pugh Class A or B. For Child-Pugh Class C, use is not recommended due to lack of data. Monitor hepatic function. |
| Pediatric use | Safety and efficacy not established in pediatric patients. Dosing not defined. |
| Geriatric use | No specific dose adjustment. Monitor for increased toxicity, especially myelosuppression, in elderly patients with impaired organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DECITABINE (DECITABINE).
| Breastfeeding | No data on presence in human milk. Due to potential for serious adverse reactions in breastfed infants (e.g., myelosuppression, carcinogenesis), breastfeeding is contraindicated during therapy and for at least 2 weeks after last dose. M/P ratio unknown. |
| Teratogenic Risk | Decitabine is teratogenic in animals and has the potential to cause fetal harm in humans. In first trimester, there is a high risk of major malformations and fetal death. Second and third trimester exposure may cause growth restriction, myelosuppression, and neurodevelopmental effects. Use contraindicated in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Decitabine should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Myelosuppression and worsening neutropenia may occur. Monitor complete blood counts frequently. There is no known safe level of exposure in pregnancy; women of childbearing potential should be advised to avoid pregnancy during treatment.
| Serious Effects |
["Hypersensitivity to decitabine or any component of the formulation.","Breastfeeding: Not recommended due to potential for serious adverse reactions in nursing infants.","Pregnancy: Should not be used in pregnant women or those planning pregnancy due to risk of fetal harm."]
| Precautions | ["Myelosuppression: Neutropenia, thrombocytopenia, and anemia may worsen during treatment; monitor blood counts regularly.","Hepatotoxicity: Elevations of liver enzymes and bilirubin have been reported; monitor hepatic function.","Renal toxicity: Serum creatinine elevations may occur; monitor renal function.","Fetal harm: Can cause fetal harm; advise contraception in women of reproductive potential and avoid pregnancy during treatment.","Tumor lysis syndrome: May occur; ensure adequate hydration and monitor uric acid levels.","Infusion reactions: Hypersensitivity reactions including rash, urticaria, and dyspnea have been reported."] |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential, serum creatinine, and liver function tests at baseline and periodically during therapy. Obtain pregnancy test before initiation. In pregnant patients, monitor fetus with serial ultrasounds for growth and anomalies, and consider antenatal testing (e.g., nonstress test, biophysical profile) if clinically indicated. |
| Fertility Effects | Decitabine is genotoxic and may cause impaired fertility in males and females based on animal studies. It can cause ovarian failure, azoospermia, and menstrual cycle disruption. Use effective contraception during treatment and for at least 6 months after last dose for both sexes. |