DEPOCYT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEPOCYT (DEPOCYT).
Cytarabine is a nucleoside analog that inhibits DNA polymerase, leading to termination of DNA chain elongation and cell death in the S phase of the cell cycle.
| Metabolism | Primarily deaminated by cytidine deaminase in the liver and other tissues to inactive uracil arabinoside. |
| Excretion | Renal excretion of cytarabine metabolites accounts for >70% of elimination; unchanged cytarabine excretion is minimal (<10%). Biliary/fecal excretion is negligible (<5%). |
| Half-life | After intrathecal administration, the terminal half-life of cytarabine in CSF is 2.5-4.5 hours (mean 3.5 hours) due to slow clearance from CSF; systemic half-life is 10-15 minutes due to rapid deamination. |
| Protein binding | Cytarabine is approximately 13-15% bound to plasma proteins; binding to CSF proteins is negligible. |
| Volume of Distribution | Intrathecal: apparent Vd is approximately 400-600 mL (CSF volume). Systemic: Vd is 3.0-4.5 L/kg, indicating extensive distribution into total body water. |
| Bioavailability | Intrathecal: 100% (direct administration into CSF). Oral: not applicable (given intrathecally only). |
| Onset of Action | Intrathecal: onset of antimitotic effect is within 30-60 minutes as drug penetrates CSF and enters cells. |
| Duration of Action | Intrathecal: cytarabine remains cytotoxic for approximately 24-48 hours in CSF; clinical duration of effect is related to cell cycle sensitivity and dosing schedule (every 14 days). |
50 mg intrathecally via lumbar puncture or intraventricularly via Ommaya reservoir on days 1, 15, 29, 43, 57, 71, 85, and 99 for induction; followed by consolidation and maintenance doses. Administer with dexamethasone 4 mg PO/IV twice daily for 5 days starting on the day of DepoCyt injection.
| Dosage form | INJECTABLE, LIPOSOMAL |
| Renal impairment | No specific dose adjustments provided in manufacturer labeling for GFR-based modifications. Use with caution in patients with renal impairment due to potential systemic toxicity. |
| Liver impairment | No specific dosage adjustments provided for Child-Pugh classes A, B, or C. Monitor hepatic function and adjust if toxicity occurs. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. Not recommended. |
| Geriatric use | No specific dosage adjustments recommended for elderly patients. Monitor for increased toxicity due to age-related decline in organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEPOCYT (DEPOCYT).
| Breastfeeding | Cytarabine is excreted into breast milk. The M/P ratio is not specifically reported for the liposomal formulation. Due to potential serious adverse reactions in the nursing infant, including immunosuppression and carcinogenesis, breastfeeding is contraindicated during DepoCyt therapy and for at least 3 months after the last dose. |
| Teratogenic Risk | DepoCyt (cytarabine liposome) is classified as FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. Cytarabine is teratogenic in animals. First trimester exposure is associated with major congenital malformations including limb defects, cleft palate, and ear anomalies. Second and third trimester exposure may cause fetal growth restriction, myelosuppression, and neonatal pancytopenia. |
■ FDA Black Box Warning
Neurotoxicity: Chemical arachnoiditis leading to permanent neurological impairment; use only under supervision of experienced physician.
| Serious Effects |
["Hypersensitivity to cytarabine","Active meningeal infection","Chemical arachnoiditis"]
| Precautions | Neurotoxicity including myelopathy, leukoencephalopathy; chemical arachnoiditis; increased toxicity with hepatic or renal impairment; bone marrow suppression; do not substitute for other cytarabine formulations. |
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| Fetal Monitoring | Complete blood count with differential and platelets before each dose. Monitor for signs of myelosuppression, infection, bleeding, and hepatic toxicity. In pregnant patients, monitor fetal growth and amniotic fluid volume via ultrasound due to risk of intrauterine growth restriction. Monitor for preterm labor. |
| Fertility Effects | Cytarabine is gonadotoxic. In males, it may cause azoospermia or oligospermia with potential for permanent infertility. In females, it may cause ovarian failure, premature menopause, and reduced fertility. The degree of effect is dose- and duration-dependent. Preconception counseling is recommended. |