Antineoplastic Agent, Antimetabolite

Intrathecal treatment of lymphomatous meningitis

D

Cytarabine may cause fetal harm if a pregnant woman is exposed systemically. Excretion in breast milk is unknown, however, breast-feeding is not recommended.

Hypersensitivity to cytarabine or any component of the formulation; active meningeal infection

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. The incidence and severity of chemical arachnoiditis is reduced by coadministration with dexamethasone. May cause neurotoxicity. Blockage to CSF flow may increase the risk of neurotoxicity. Safety and use in pediatric patients has not been established.

Chemical arachnoiditis is commonly observed, and may include neck pain, neck rigidity, headache, fever, nausea, vomiting, and back pain. It may occur in up to 100% of cycles without dexamethasone prophylaxis. The incidence is reduced to 33% when dexamethasone is used concurrently.

Central nervous system: Headache (28%), confusion (14%), somnolence (12%), fever (11%), pain (11%)

Gastrointestinal: Vomiting (12%), nausea (11%)

1% to 10%:

Cardiovascular: Peripheral edema (7%)

Gastrointestinal: Constipation (7%)

Genitourinary: Incontinence (3%)

Hematologic: Neutropenia (9%), thrombocytopenia (8%), anemia (1%)

Neuromuscular & skeletal: Back pain (7%), weakness (19%), abnormal gait (4%)

<1% Anaphylaxis, neck pain

No overdosage with liposomal cytarabine has been reported. Symptoms of cytarabine overdose (when administered systemically) include myelosuppression, megaloblastosis, nausea, vomiting, respiratory distress, pulmonary edema. A syndrome of sudden respiratory distress progressing to pulmonary edema and cardiomegaly has been reported following high doses. Exchange of CSF with isotonic saline, a procedure used in intrathecal cytarabine overdose, may be considered in the event of an overdose of the liposomal product.

No formal studies of interactions with other medications have been conducted. The limited systemic exposure minimizes the potential for interaction between liposomal cytarabine and other medications.

Store under refrigeration (2°C to 8°C). Protect from freezing and avoid aggressive agitation. Solutions should be used within 4 hours of withdrawal from the vial. Particles may settle in diluent over time, and may be resuspended by gentle agitation or inversion of the vial.

This is a sustained-release formulation of the active ingredient cytarabine, which acts through inhibition of DNA synthesis; cell cycle-specific for the S phase of cell division; cytosine gains entry into cells by a carrier process, and then must be converted to its active compound; cytosine acts as an analog and is incorporated into DNA; however, the primary action is inhibition of DNA polymerase resulting in decreased DNA synthesis and repair; degree of its cytotoxicity correlates linearly with its incorporation into DNA; therefore, incorporation into the DNA is responsible for drug activity and toxicity

Absorption: Systemic exposure following intrathecal administration is negligible, since the transfer rate from CSF to plasma is slow. Peak levels in the CSF occur within 5 hours.

Metabolism: In plasma, to ara-U (inactive)

Half-life: In CSF, 100-263 hours

Elimination: Primarily in urine, as metabolites (ara-U)

Adults:

Consolidation: 50 mg intrathecally every 14 days for 3 doses (weeks 5, 7, and 9), followed by an additional dose at week 13

Maintenance: 50 mg intrathecally every 28 days for 4 doses (weeks 17, 21, 25, and 29)

If drug-related neurotoxicity develops, the dose should be reduced to 25 mg. If toxicity persists, treatment with liposomal cytarabine should be discontinued.

Note: Patients should be started on dexamethasone 4 mg twice daily (oral or I.V.) for 5 days, beginning on the day of liposomal cytarabine injection

For intrathecal use only. Dose should be removed from vial immediately before administration (must be administered within 4 hours of removal). An in-line filter should not be used. Vials are intended for a single use and contain no preservative. Administer directly into the CSF via an intraventricular reservoir or by direct injection into the lumbar sac. Injection should be made slowly (over 1-5 minutes). Patients should lie flat for 1 hour after lumbar puncture. Patients should be monitored closely for immediate toxic reactions.

Monitor closely for signs of an immediate reaction

Since cytarabine liposomes are similar in appearance to WBCs, care must be taken in interpreting CSF examinations in patients receiving liposomal cytarabine

No information available to require special precautions

No effects or complications reported

Notify physician of any fever, sore throat, bleeding, or bruising; contraceptive measures are recommended during therapy

Injection: 10 mg per mL