Cytarabine (Page 3 of 4)

Less Frequent Adverse Reactions

sepsis sore throat conjunctivitis (may occur with rash)
pneumonia esophageal ulceration dizziness
cellulitis at injection site esophagitis alopecia
skin ulceration chest pain anaphylaxis (see WARNINGS)
urinary retention pericarditis allergic edema
renal dysfunction bowel necrosis pruritis
neuritis abdominal pain shortness of breath
neural toxicity pancreatitis urticaria
freckling headache
jaundice sinus bradycardia

Experimental Doses

Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine injection) has been reported following some experimental dose schedules of cytarabine injection. These reactions include reversible corneal toxicity and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis. Rarely, severe skin rash, leading to desquamation has been reported. Complete alopecia is more commonly seen with experimental high dose therapy than with standard treatment programs using cytarabine. If experimental high dose therapy is used, do not use a preparation containing benzyl alcohol.

Cases of cardiomyopathy with subsequent death have been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation. This cardiac toxicity may be schedule dependent.

A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients. The outcome of this syndrome can be fatal.

Two patients with adult acute non-lymphocytic leukemia developed peripheral motor and sensory neuropathies after consolidation with high-dose cytarabine, daunorubicin, and asparaginase. Patients treated with high-dose cytarabine should be observed for neuropathy since dose schedule alterations may be needed to avoid irreversible neurologic disorders.

Ten patients treated with experimental intermediate doses of cytarabine (1 g/m2) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, etoposide) at various dose regimes developed a diffuse interstitial pneumonitis without clear cause that may have been related to the cytarabine.

Two cases of pancreatitis have been reported following experimental doses of cytarabine injection and numerous other drugs. Cytarabine injection could have been the causative agent.

OVERDOSAGE

There is no antidote for overdosage of Cytarabine Injection. Doses of 4.5 g/m2 by intravenous infusion over 1 hour every 12 hours for 12 doses have caused an unacceptable increase in irreversible CNS toxicity and death.

Single doses as high as 3 g/m2 have been administered by rapid intravenous infusion without apparent toxicity.

DOSAGE AND ADMINISTRATION

Cytarabine Injection is not active orally. The schedule and method of administration varies with the program of therapy to be used. Cytarabine Injection may be given by intravenous infusion or injection, subcutaneously, or intrathecally (preservative free preparation only).

Thrombophlebitis has occurred at the site of drug injection or infusion in some patients, and rarely patients have noted pain and inflammation at subcutaneous injection sites. In most instances, however, the drug has been well tolerated.

Patients can tolerate higher total doses when they receive the drug by rapid intravenous injection as compared with slow infusion. This phenomenon is related to the drug’s rapid inactivation and brief exposure of susceptible normal and neoplastic cells to significant levels after rapid injection. Normal and neoplastic cells seem to respond in somewhat parallel fashion to these different modes of administration and no clear-cut clinical advantage has been demonstrated for either.

In the induction therapy of acute non-lymphocytic leukemia, the usual cytarabine dose in combination with other anti-cancer drugs is 100 mg/m2 /day by continuous intravenous infusion (Days 1–7) or 100 mg/m2 intravenous every 12 hours (Days 1–7).

The literature should be consulted for the current recommendations for use in acute lymphocytic leukemia.

Intrathecal Use in Meningeal Leukemia

Cytarabine injection has been used intrathecally in acute leukemia in doses ranging from 5 mg/m2 to

75 mg/m2 of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment. The dosage schedule is usually governed by the type and severity of central nervous system manifestations and the response to previous therapy.

Cytarabine injection given intrathecally may cause systemic toxicity and careful monitoring of the hematopoietic system is indicated. Modification of other anti-leukemia therapy may be necessary. Major toxicity is rare. The most frequently reported reactions after intrathecal administration were nausea, vomiting and fever; these reactions are mild and self-limiting. Paraplegia has been reported. Necrotizing leukoencephalopathy occurred in 5 children; these patients had also been treated with intrathecal methotrexate and hydrocortisone, as well as by central nervous system radiation. Isolated neurotoxicity has been reported. Blindness occurred in two patients in remission whose treatment had consisted of combination systemic chemotherapy, prophylactic central nervous system radiation and intrathecal cytarabine injection.

When cytarabine injection is administered both intrathecally and intravenously within a few days, there is an increased risk of spinal cord toxicity, however, in serious life-threatening disease, concurrent use of intravenous and intrathecal Cytarabine Injection is left to the discretion of the treating physician.

Focal leukemic involvement of the central nervous system may not respond to intrathecal cytarabine injection and may better be treated with radiotherapy.

Chemical Stability of Infusion Solutions

Chemical stability studies were performed by ultraviolet assay on Cytarabine Injection in infusion solutions. These studies showed that when Cytarabine Injection was added to Water for Injection, 5% Dextrose in Water or Sodium Chloride Injection, 94 to 96 percent of the cytarabine was present after 192 hours storage at room temperature.

Parenteral drugs should be inspected visually for particulate matter and discoloration, prior to administration, whenever solution and container permit.

HANDLING AND DISPOSAL

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.1–7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED

Cytarabine Injection is available as follows:

Unit of Sale Total Strength/Total Volume
(Concentration)
NDC 61703-305-38
5 Single dose flip top vials in a carton
100 mg/5 mL
(20 mg/mL)

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