DepoCyt

Generic Name: Cytarabine
Class: Antineoplastic Agents
VA Class: AN300
CAS Number: 147-94-4

• Experience of Supervising Clinician


• 
  

  Conventional cytarabine: Use only under supervision of qualified clinicians experienced in therapy with antineoplastic agents.^{a b c c j} Consider possible benefits vs known risks of cytarabine treatment.^{a b c j}

  
  


• 
  

  Liposomal cytarabine: Use only under supervision of qualified clinicians experienced in intrathecal therapy with antineoplastic agents; adequate diagnostic and treatment facilities must be readily available for management of complications.^d

  
  

• Induction Therapy with Conventional Cytarabine


• 
  

  Patients should be treated in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity.^{a b c j}

  
  


• 
  

  Risk of serious adverse effects, including myelosuppression with leukopenia, thrombocytopenia, and anemia.^{a b c j} Less serious adverse effects include nausea, vomiting, diarrhea, abdominal pain, oral ulceration, and hepatic dysfunction.^{a b c j} (See Cautions.)

  
  

• Chemical Arachnoiditis with Intrathecal Liposomal Cytarabine


• 
  

  Chemical arachnoiditis, a syndrome manifested principally by nausea, vomiting, headache, and fever, commonly occurs.^d If left untreated, may be fatal.^d (See Chemical Arachnoiditis Related to Liposomal Cytarabine under Cautions.)

  
  


• 
  

  Administer dexamethasone to ameliorate symptoms and reduce incidence.^d (See Liposomal Cytarabine under Dosage and Administration.)

  
  

Introduction

Antimetabolite antineoplastic agent; synthetic pyrimidine antagonist.^{d f i}

Uses for DepoCyt

Acute Myeloid Leukemia (AML)

Conventional cytarabine: Remission induction (in combination with other antineoplastic agents) in AML (acute nonlymphocytic leukemia) in children and adults.^{237 a b c j}

Conventional cytarabine and either idarubicin or daunorubicin (with or without thioguanine) are currently preferred components of induction regimens.^{g h} However, various regimens have been used in combination therapy, and comparative efficacy is continually being evaluated.^g

Conventional cytarabine: Has been used with other antineoplastic agents in regimens of consolidation following induction of a complete remission†; ^{239 242 243 f g} role of such therapy in prolonging remissions and optimal dosage, schedules, and duration of consolidation chemotherapy regimens not established.^g

Conventional cytarabine: Has been used with other antineoplastic agents in the treatment of erythroleukemia.^f

Conventional cytarabine: Also has been used alone in high-dose† regimens to induce remissions in some patients with refractory AML or with secondary AML.^f

Acute Lymphocytic Leukemia (ALL)

Conventional cytarabine: Has been used alone or with other antineoplastic agents for remission induction in ALL;^{237 a b c j} however, combinations containing other antineoplastic agents are more effective.^{f h}

Conventional cytarabine: Generally has been limited to use with other antineoplastics for remission induction in some patients who do not achieve a complete remission with combinations containing other agents or who relapse during maintenance therapy.^f

Conventional cytarabine: Also has been used occasionally in regimens of consolidation and/or maintenance therapy following induction of a complete remission by combinations containing other agents.^{f h}

Conventional cytarabine: Has been used alone in high-dose† regimens to induce remissions in some patients with refractory ALL.^f

Meningeal Leukemia and Other Meningeal Neoplasms

Conventional cytarabine: Has been used effectively alone or with other chemotherapeutic agents in treatment, maintenance, and prophylactic therapy of meningeal leukemia and other meningeal neoplasms (e.g., lymphoma).^{a c f j}

Many clinicians consider intrathecal conventional cytarabine and intrathecal methotrexate to have similar efficacy in the treatment of these conditions; however, intrathecal conventional cytarabine produces less systemic toxicity than intrathecal methotrexate.^f

Liposomal cytarabine: Treatment of lymphomatous meningitis.^d

Intrathecal liposomal cytarabine appears to have greater efficacy in the treatment of neoplastic meningitis and less systemic toxicity compared with intrathecal conventional cytarabine;ⁱ however, further study is needed.^{d i}

Chronic Myelogenous Leukemia (CML)

Conventional cytarabine: Used with other antineoplastic agents (e.g., daunorubicin) in the treatment of accelerated or blast phase of CML;^{a b c f j} however, various regimens have been used in combination therapy, and comparative efficacy is continually being evaluated.^{237 246 247 253 254}

Non-Hodgkin’s Lymphomas†

Conventional cytarabine: Has been used with other antineoplastic agents for maintenance therapy of non-Hodgkin’s lymphoma in children†.^f

Conventional cytarabine: Has been used with other antineoplastic agents for remission induction and/or maintenance therapy in adults with non-Hodgkin’s lymphomas, principally advanced diffuse histiocytic lymphoma†.^f

Conventional cytarabine: Has been used alone in high-dose† regimens with some success for the treatment of refractory non-Hodgkin’s lymphomas†.^f

DepoCyt Dosage and Administration

General

• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastics.^{a b c d j}

  
  

Premedication before Intrathecal Liposomal Cytarabine

• 
  

  Initiate dexamethasone therapy on the day of the intrathecal administration of liposomal cytarabine to prevent or ameliorate chemical arachnoiditis.^{d i} Administer 4 mg of dexamethasone twice daily orally or IV for 5 days.^d

  
  

Administration

Conventional cytarabine: Administer by rapid IV injection or continuous IV infusion, sub-Q injection, or intrathecal injection; ^{a b c j} also has been administered by IM injection† and by continuous sub-Q infusion†.^f

Liposomal cytarabine: Administer only by intrathecal injection.^d

IV Administration

For solution compatibility information for conventional cytarabine see Compatibility under Stability.

Higher total doses of conventional cytarabine may be given by rapid IV injection compared with continuous IV infusion with no increase in hematologic toxicity; most effective method of administration not established.^{a b c f j}

Cytarabine injection solution containing benzyl alcohol may be used for IV administration but should not be used in high-dose regimens†.²⁵¹

Cytarabine injection solution containing benzyl alcohol should not be used in neonates.^{a b c f}

Cytarabine injection in pharmacy bulk packages is not intended for direct IV infusion; individual doses can be withdrawn with a sterile dispensing set or transfer device and used undiluted or further diluted in a compatible IV solution.^{252 f}

Reconstitution of Conventional Cytarabine

Add 5, 10, 10, or 20 mL of bacteriostatic water for injection containing 0.945% benzyl alcohol to a vial containing 100, 500, 1000, or 2000 mg cytarabine powder; resultant solutions contain 20, 50, 100, or 100 mg of cytarabine per mL, respectively.^j

Diluents containing benzyl alcohol should not be used in neonates^{f j} or in high-dose† regimens.^{a b c j} (See Benzyl Alcohol under Cautions.)

The desired dose of reconstituted solution may be given by rapid IV injection or may be further diluted with 5% dextrose or 0.9% sodium chloride injection for IV infusion.^{f j}

Dilution of Conventional Cytarabine

Cytarabine injection solution (containing 20 or 100 mg/mL) may be diluted with a compatible IV solution (e.g., 5% dextrose injection, 0.9% sodium chloride injection) for direct IV injection, rapid IV injection, or IV infusion.^{250 b c j}

Cytarabine injection in pharmacy bulk package solution (containing 20 mg/mL) should be diluted with a compatible IV solution (e.g., 5% dextrose injection, 0.9% sodium chloride injection) for IV infusion.^c

Alternatively, desired dose of the solution reconstituted from powder may be further diluted with 5% dextrose or 0.9% sodium chloride injection for IV infusion.^j

Rate of Administration of Conventional Cytarabine

Has been given over 1–3 hours when used for treatment of refractory or secondary acute leukemia and refractory non-Hodgkin’s lymphomas.^f

Also administered by rapid IV injection or continuous IV infusion.^{a b c j}

Sub-Q Administration

For solution compatibility information on conventional cytarabine see Compatibility under Stability. Consult specialized references for information on continuous sub-Q infusion†.

Cytarabine injection solution containing benzyl alcohol may be used for sub-Q administration but should not be used in high-dose regimens†.²⁵¹

Reconstitution of Conventional Cytarabine

Add 5, 10, 10, or 20 mL of bacteriostatic water for injection containing 0.945% benzyl alcohol to a vial containing 100, 500, 1000, or 2000 mg cytarabine powder; resultant solutions contain 20, 50, 100, or 100 mg of cytarabine per mL, respectively.^j

Diluents or drug solutions containing benzyl alcohol should not be used in neonates^{a b c f j} or in high-dose† regimens.^{a b c j} (See Benzyl Alcohol under Cautions.)

Intrathecal Administration

Conventional Cytarabine

Usually administered in 5–15 mL of solution, after removing an equivalent volume of CSF.^f

Only preservative-free injection solutions are suitable for intrathecal administration.^{250 a b c j}

Injection in pharmacy bulk packages should not be used for preparation of solutions for intrathecal administration.²⁵²

Reconstitution of Conventional Cytarabine

Do not use diluents containing benzyl alcohol for preparation of solutions.^{b c j}

Reconstitute cytarabine powder with preservative-free 0.9% sodium chloride injection, Elliott’s B solution, other isotonic buffered diluents that do not contain a preservative (e.g., lactated Ringer’s injection), or the patient’s spinal fluid.^{f j}

Liposomal Cytarabine

Only use for intrathecal administration.^d

Administer directly into CSF via an intraventricular reservoir or by direct injection into lumbar sac; do not use inline filters.^d

Following intrathecal administration by lumbar puncture, patient should lie flat for 1 hour.^d

Preparing Dose of Liposomal Cytarabine

Allow vials to warm to room temperature; immediately prior to withdrawing dose, gently agitate or invert to ensure resuspension of liposomes.^d Avoid aggressive agitation.^d

Withdraw dose from the vial immediately before administration.^d

Do not dilute or mix with any other drugs.^d

Rate of Administration of Liposomal Cytarabine

Inject slowly over a period of 1–5 minutes.^d

Dosage

Conventional cytarabine: Optimize results and minimize adverse effects by basing dose on clinical and hematologic response, patient tolerance, and other therapy being used.^f

Consult published protocols for dosages used in combination regimens and method and sequence of administration.

Pediatric Patients

The manufacturers make no specific dosage recommendations for pediatric patients; consult published protocols for dosages used in children.^{a b c j}

Adults

Acute Leukemia

Induction with Conventional Cytarabine

IV

Monotherapy: 200 mg/m² daily by continuous IV infusion for 5 days at approximately 2-week intervals.^f

Combination therapy: 2–6 mg/kg daily or 100–200 mg/m² daily by continuous IV infusion or in 2 or 3 divided doses by rapid IV injection or IV infusion for 5–10 days in a course of therapy or daily until a remission is attained.^f

Maintenance with Conventional Cytarabine

Initiate appropriate maintenance therapy after induction of a complete remission.^f

Dosage and schedule vary according to regimen used.^f

IV

70–200 mg/m² daily by rapid IV injection or continuous IV infusion for 2–5 days at monthly intervals.^f

IM† or Sub-Q

1 or 1.5 mg/kg IM at intervals of 1–4 weeks.^f

Refractory or Secondary Acute Leukemia†

Treatment with Conventional Cytarabine

IV

3 g/m² by IV infusion (usually over 1–3 hours) every 12 hours for up to 12 doses has been used.^f

Meningeal Leukemia and Other Meningeal Neoplasms

Treatment and Maintenance with Conventional Cytarabine

Dosage schedule usually determined by the type and severity of CNS manifestations and prior response to therapy.^{a b c j}

Intrathecal

5–75 mg/m² or 30–100 mg administered at frequencies ranging from once every 2–7 days to once daily for 4 or 5 days.^{a b c f j}

Alternatively, 30 mg/m² once every 4 days until CSF findings are normal, followed by 1 additional dose.^{a b c j}

Lymphomatous Meningitis

Induction with Liposomal Cytarabine

Intrathecal

50 mg every 14 days for 2 doses (weeks 1 and 3).^d

Consolidation with Liposomal Cytarabine

Intrathecal

50 mg every 14 days for 3 doses (weeks 5, 7, and 9) followed by 1 additional dose after 28 days (week 13).^d

Maintenance with Liposomal Cytarabine

Intrathecal

50 mg every 28 days for 4 doses (weeks 17, 21, 25, and 29).^d

Refractory Non-Hodgkin’s Lymphomas†

Treatment with Conventional Cytarabine

IV

3 g/m² by IV infusion (usually over 1–3 hours) every 12 hours for up to 12 doses has been used.^f

Dosage Modification for Toxicity

Conventional Cytarabine

Consider suspension or modification of therapy if polymorphonuclear granulocyte count <1000/mm³ or platelet count <50,000/mm³;^{a b c j} however, during remission induction therapy in acute leukemia, the drug usually is administered in a short course and therapy is not discontinued or adjusted based on peripheral blood counts.^f

When indicated, resume therapy when definite signs of marrow recovery appear (on successive bone marrow studies).^{a b c j} Withholding therapy until peripheral blood values normalize may permit escape from control.^{a b c j}

Intrathecal Liposomal Cytarabine

If drug-related neurotoxicity develops, reduce dose to 25 mg.^d If toxicity persists, discontinue therapy.^d

Special Populations

Hepatic Impairment

Conventional Cytarabine

Select dosage with caution.^{a b c j} (See Hepatic Impairment under Cautions.)

Renal Impairment

Conventional Cytarabine

Select dosage with caution.^{a b c j} (See Renal Impairment under Cautions.)

Cautions for DepoCyt

Contraindications

• 
  

  Liposomal or Conventional Cytarabine: Hypersensitivity to cytarabine or any ingredient in the formulation.^{a b c d j}

  
  


• 
  

  Liposomal Cytarabine: Active meningeal infection.^d

  
  

Warnings/Precautions

Warnings

Hematologic Effects

Conventional cytarabine: Potent myelosuppressant.^{a b c j} Initiate with caution in patients with preexisting drug-induced myelosuppression.^{a b c j} Patients must be under close medical supervision and facilities should be available for management of serious complications, possibly fatal, of myelosuppression (e.g., infection resulting from granulocytopenia, hemorrhage secondary to thrombocytopenia).^{a b c j} (See Boxed Warning.)

Risk of increased frequency of infections (e.g., viral, bacterial, fungal), as well as possible hemorrhagic complications; potentially fatal.^{a b c j}

During induction therapy, perform leukocyte and platelet counts daily.^{a b c j} (See Dosage Modification for Toxicity under Dosage and Administration.)

Perform bone marrow examinations frequently after blasts have disappeared from peripheral blood.^{a b c f j} Counts of formed elements in peripheral blood may continue to fall after drug discontinuance and reach lowest values after drug-free intervals of 12–24 days.^{a b c j}

Liposomal cytarabine: Clinically important systemic exposure to unencapsulated cytarabine unlikely following intrathecal administration.^d However, careful hematologic monitoring recommended since myelosuppression cannot be completely ruled out.^d

High-dose Regimens with Conventional Cytarabine

Severe and sometimes fatal CNS, GI, and pulmonary toxicities reported following experimental dosage regimens for refractory or secondary acute leukemia or refractory non-Hodgkin’s lymphomas; differ from reactions seen with regimens employing lower dosages.^{a b c f j}

Cerebral and cerebellar dysfunction (e.g., somnolence, coma, personality changes) reported; usually reversible.^{a b c j} Reversible, acute aseptic meningitis, combined with cerebellar dysfunction, reported in at least 1 patient.²⁰⁵

Peripheral motor and sensory neuropathies have occurred occasionally.^{202 203 204 a b c j}

Patients with renal or hepatic impairment may be at increased risk of CNS toxicity associated with high-dose cytarabine therapy.^{a b c j}

Monitor patients receiving high-dose therapy closely for signs of central or peripheral neurotoxicity.^{202 203 204 a b c j} Dosage schedule adjustment may be necessary to avoid irreversible neurologic toxicity.^{202 a b c j}

Severe GI ulceration (including pneumatosis cystoides intestinalis leading to peritonitis), bowel necrosis, necrotizing colitis, hepatic abscess or hepatic damage with increased hyperbilirubinemia reported.^{a b c j}

Pancreatitis reported in patients previously treated with asparaginase and those receiving high-dose cytarabine therapy.^{212 218 a b c j}

Pulmonary edema reported.^{a b c j} Diffuse interstitial pneumonitis reported occasionally in patients receiving relatively high doses (e.g., 1 g/m²) of cytarabine alone or in combination with other antineoplastic agents.^{213 214 215 216 217 218 219 220 221 a b c j}

A syndrome of acute respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly, which was sometimes fatal, has been reported in patients with refractory acute leukemia receiving high-dose therapy.^{a b c j}

Severe skin rash leading to desquamation has been reported rarely.^{a b c j} Complete alopecia occurs more commonly with high-dose regimens.^{a b c j}

Fatal cardiomyopathy reported in patients receiving high-dose cytarabine in combination with cyclophosphamide in preparation for bone marrow transplantation; this cardiac toxicity may be schedule dependent.^{a b c j}

Hemorrhagic conjunctivitis and reversible corneal toxicity (e.g., keratitis) reported; may be minimized or prevented by prophylaxis with ophthalmic corticosteroid preparations.^{a b c j}

Intrathecal Administration of Conventional Cytarabine

Possible systemic toxicity; carefully monitor hematologic status.^{a b c j} Dosage adjustment of concurrently administered antineoplastic agents may be necessary.^{a b c j}

Concurrent (within a few days) IV chemotherapy or cranial/spinal irradiation and intrathecal treatment with conventional cytarabine may be associated with increased risk of neurotoxicity (e.g., spinal cord toxicity).^{a b c d j}

Progressive ascending paralysis reported.^{200 a b c j} Occurred in 2 children 4–6 months after intrathecal and IV therapy with conventional cytarabine at usual doses in combination with other drugs and CNS irradiation; fatal in one patient.^{200 a b c j}

Permanent neurologic deficits reported rarely.^d

Intrathecal Administration of Liposomal Cytarabine

Observe closely for acute toxic reactions.^d

Neurotoxicity may occur after a single dose or repeated administration; most likely to occur within 5 days of intrathecal administration.^d Monitor continuously and reduce subsequent doses if neurotoxicity occurs; discontinue if neurotoxicity persists.^d CSF flow obstruction may result in increased CSF concentrations and increased risk of neurotoxicity.^d (See Dosage Modification for Toxicity under Dosage and Administration.)

At least 2 fatalities attributed to liposomal cytarabine have occurred.^d One patient died after developing encephalopathy 36 hours after receiving intraventricular liposomal cytarabine;^{d i} the other patient developed focal seizures that progressed to status epilepticus and died approximately 8 weeks after the last intraventricular dose of liposomal cytarabine.^d

Possible increased risk of adverse events in patients receiving concurrent radiation or chemotherapy.^d

Chemical Arachnoiditis Related to Liposomal Cytarabine

Common complication of intrathecal liposomal cytarabine; in clinical studies, generally occurred ≤48 hours after intrathecal administration.^{d i}

Defined in clinical studies as occurrence of any 1 of certain manifestations (i.e., neck rigidity, neck pain, meningism) or any 2 of the following: nausea, vomiting, headache, fever, back pain, or CSF pleocytosis.^{d i}

Administer dexamethasone to ameliorate symptoms and reduce incidence.^{d i} (See Intrathecal Administration under Dosage and Administration and also Chemical Arachnoiditis in Boxed Warning.)

Benzyl Alcohol

Do not use conventional cytarabine injection solution containing benzyl alcohol in neonates.^{a b c j f} Do not use diluents containing benzyl alcohol to reconstitute or dilute conventional cytarabine for use in neonates.^{a b c j} Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates.^{a b c f j}

Do not use conventional cytarabine injection solution containing benzyl alcohol for intrathecal administration.^{a b c} Do not use diluents containing benzyl alcohol to reconstitute conventional cytarabine for intrathecal administration.^j

Because of potential neurotoxicity, conventional cytarabine injection solution containing benzyl alcohol or cytarabine powder reconstituted or diluted with diluents containing benzyl alcohol should not be used for high-dose regimens.^{a b c j}

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; upper and lower distal limb defects, extremity and ear deformities, low birth weight, premature delivery, and adverse hematologic effects reported.^{a b c d j}

Avoid pregnancy during therapy with conventional or liposomal cytarabine; especially avoid cytarabine use during first trimester.^{a b c d j} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.^{a b c d j} Follow-up monitoring of infants exposed to cytarabine in utero is advised.^{a b c j}

Sensitivity Reactions

Anaphylaxis

At least one case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported after IV administration of conventional cytarabine.^d

General Precautions

Cytarabine (Ara-C) Syndrome

Cytarabine syndrome reported; may manifest as fever, myalgia, bone pain, maculopapular rash, conjunctivitis, malaise, and occasionally chest pain.^{a b c j} Generally occurs 6–12 hours after administration of conventional cytarabine.^{a b c j}

Corticosteroids are beneficial in treatment and prevention.^{a b c j} If symptoms require treatment, consider administration of corticosteroids, as well as continuation of conventional cytarabine therapy.^{a b c j}

GI Effects

Nausea and vomiting are more frequent and severe following rapid IV administration of conventional cytarabine than with continuous IV infusion.^{a b c j}

Pancreatitis

Pancreatitis reported in patients receiving conventional cytarabine and in those previously treated with asparaginase.^{a b c j} (Also see High-dose Regimens with Conventional Cytarabine under Cautions.)

Hyperuricemia

Hyperuricemia may occur in patients receiving conventional cytarabine because of extensive purine catabolism accompanying rapid cellular destruction.^{a b c f j}

Monitor serum uric acid concentrations in patients receiving conventional cytarabine.^{a b c j} Hyperuricemia may be minimized or prevented by adequate hydration, alkalinization of urine, and/or administration of allopurinol.^{a b c f j}

Alterations in CSF

Transient increases in CSF protein concentration and WBC counts reported in patients following intrathecal administration of liposomal or conventional cytarabine.^d

Specific Populations

Pregnancy

Category D.^{a b c d j} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether cytarabine is distributed into milk; discontinue nursing or the drug.^{a b c d j}

Pediatric Use

Do not use conventional cytarabine injection solution or diluents containing benzyl alcohol in neonates.^{b 250} (See Benzyl Alcohol under Cautions.)

Safety and efficacy of liposomal cytarabine not established in children.^d

Hepatic Impairment

Use with caution; increased risk of CNS toxicity after high-dose therapy with conventional cytarabine because of decreased clearance.^{a b c j} Assess hepatic function prior to and periodically during prolonged therapy.^{a b c j}

Renal Impairment

Use with caution; increased risk of CNS toxicity after high-dose therapy with conventional cytarabine because of decreased clearance.^{a b c j} Assess renal function prior to and periodically during prolonged therapy.^{a b c j}

Common Adverse Effects

IV, sub-Q, or IM administration of conventional cytarabine: Myelosuppression, anorexia, nausea, vomiting, diarrhea, oral and anal inflammation or ulceration, hepatic dysfunction, fever, rash, thrombophlebitis, bleeding (all sites).^{a b c j}

Intrathecal administration of conventional cytarabine: Nausea, vomiting, fever, transient headaches.^{a b c d f j}

Intrathecal administration of liposomal cytarabine: Chemical arachnoiditis (neck rigidity, neck pain, meningism, nausea, vomiting, headache, fever, back pain, and/or CSF pleocytosis), asthenia, pain, confusion, somnolence.^{d i}

Interactions for DepoCyt

No formal drug interaction studies conducted with liposomal cytarabine to date.^d

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Antineoplastic agents, intrathecally administered	Possible enhanced neurotoxicity when intrathecal conventional cytarabine used concomitantly with other intrathecal cytotoxic agentsd	Concomitant intrathecal use of liposomal cytarabine and other antineoplastic agents not studiedd
Digoxin	GI absorption of oral digoxin tablets may be substantially reduced when used concomitantly with conventional cytarabine207 208 a b c j	Monitor plasma digoxin concentrations closely; use of digoxin oral elixir or liquid-filled capsules may improve absorption207 208 210 a b c j
Flucytosine	Possible inhibition of anti-infective activity by competitive inhibition of uptake by fungi when flucytosine was used concomitantly with conventional cytarabinea b c j
Gentamicin	In vitro evidence of inhibition of antibacterial activity against Klebsiella pneumoniae with conventional cytarabine211 a b c j	Monitor closely; if therapeutic response is not achieved, reevaluate anti-infective therapy211 a b c j
Test, for WBC in CSF	Liposomal cytarabine vesicles are similar in size and appearance to WBC d	Interpret CSF analysis with care d

DepoCyt Pharmacokinetics

Absorption

Bioavailability

Conventional cytarabine: <20% of dose is absorbed after oral administration; not effective when administered orally.^{a b c j}

Conventional cytarabine: Continuous IV infusions produce relatively constant plasma concentrations of the drug in 8–24 hours.^{a b c f j}

Following sub-Q or IM injection of radioactively labeled conventional cytarabine, peak plasma concentrations of radioactivity occur within 20–60 minutes and are considerably lower than those attained after IV administration.^{a b c j}

Liposomal cytarabine: Negligible systemic exposure expected after intrathecal administration.^d

Liposomal cytarabine: Limited data indicate peak cytarabine concentrations occur within 5 hours in both ventricle and lumbar sac after intrathecal administration into lumbar sac or by intraventricular reservoir.^{d i}

Distribution

Extent

Conventional cytarabine: Rapidly and widely distributed into tissues and fluids, including liver, plasma, and peripheral granulocytes;^{a b c f j} crosses blood-brain barrier to a limited extent.^{a b c i j}

Conventional cytarabine: CSF concentrations are higher during continuous IV or sub-Q infusion than after rapid IV injection and are approximately 40–60% of plasma concentrations.^{a b c f j}

Conventional cytarabine: Apparently crosses placenta;^{a b}