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Cytarabine

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Cytarabine

Side Effects
Interactions

SIDE EFFECTS

Expected Reactions: Because cytarabine is a bone marrow suppressant, anemia, leukopenia, thrombocytopenia, megaloblastosis, and reduced reticulocytes can be expected as a result of administration of cytarabine. The severity of these reactions are dose and schedule dependent. Cellular changes in the morphology of bone marrow and peripheral smears can be expected.

Following 5-day constant infusions or acute injections of 50 to 600 mg/m2, white cell depression follows a biphasic course. Regardless of initial count, dosage level, or schedule, there is an initial fall starting the first 24 hours with a nadir at days 7 to 9. This is followed by a brief rise which peaks around day 12. A second and deeper fall reaches nadir at days 15 to 24. Then there is a rapid rise to above baseline in the next 10 days. Platelet depression is noticeable at day 5 with a peak depression occurring between days 12 to 15. Thereupon, a rapid rise to above baseline occurs in the next 10 days.

Infectious Complications:Infection - Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body may be associated with the use of cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe and at times fatal.

The Cytarabine (Ara-C) Syndrome: A cytarabine syndrome has been described by Castleberry. It is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise. It usually occurs 6 to 12 hours following drug administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are deemed treatable, corticosteroids should be contemplated, as well as continuation of therapy with cytarabine.

Most Frequent Adverse Reactions
anorexia hepatic dysfunction
nausea fever
vomiting rash
diarrhea thrombophlebitis
oral and anal or ulceration inflammation bleeding (all sites)

Nausea and vomiting are most frequent following rapid intravenous injection.

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

Experimental Doses: Severe and at times fatal CNS, GI, and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some experimental dose schedules of cytarabine. 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 cytarabine treatment programs. If experimental high-dose therapy is used, do not use a diluent 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 regimens 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 and numerous other drugs. Cytarabine could have been the causative agent.

Read the Cytarabine (cytarabine) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Reversible decreases in steady-state plasma digoxin concentrations and renal glycoside excretion were observed in patients receiving beta-acetyldigoxin and chemotherapy regimens containing cyclophosphamide, vincristine, and prednisone with or without cytarabine or procarbazine. Steady-state plasma digitoxin concentrations did not appear to change. Therefore, monitoring of plasma digoxin levels may be indicated in patients receiving similar combination chemotherapy regimens. The utilization of digitoxin for such patients may be considered as an alternative.

An in vitro interaction study between gentamicin and cytarabine showed a cytarabine- related antagonism for the susceptibility of K. pneumoniae strains. This study suggests that in patients on cytarabine being treated with gentamicin for a K. pneumoniae infection, the lack of a prompt therapeutic response may indicate the need for re-evaluation of antibacterial therapy.

Clinical evidence in one patient showed possible inhibition of fluorocytosine efficacy during therapy with cytarabine. This may be due to potential competitive inhibition of its uptake.

Last reviewed on RxList: 11/3/2008
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
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