Cytarabine (cytarabine/PF)

Dosage of conventional (unencapsulated) cytarabine must be based on the clinical and hematologic response and tolerance of the patient to obtain optimum therapeutic results with minimum adverse effects. Although higher total doses of cytarabine can be given by rapid IV injection compared with continuous IV infusion with similar hematologic toxicity, the most effective dosage schedule and method of administration have not been established. Clinicians should consult published protocols for the dosage of cytarabine and other chemotherapeutic agents and the method and sequence of administration.

Reduction of cytarabine dosage in patients with impaired renal function does not appear to be necessary. The manufacturers state that cytarabine should be used with caution and in reduced dosage in patients with poor hepatic function, but some clinicians believe that dosage adjustment is not necessary in patients with impaired hepatic function.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

Formal studies of drug interactions have not been conducted for liposomal cytarabine.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Conventional cytarabine is contraindicated in patients with known hypersensitivity to the drug. Liposomal cytarabine is contraindicated in patients who are hypersensitive to cytarabine or any component of the formulation, and in patients with active meningeal infection.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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No enhanced messaging available.

Cytarabine can cause fetal toxicity when administered to pregnant women, but potential benefits from use of the drug may be acceptable in certain conditions despite the possible risks to the fetus. Because systemic exposure to cytarabine is negligible during intrathecal therapy with liposomal cytarabine, the risk of fetal toxicity is thought to be low. However, there are no formal studies assessing the reproductive toxicity of liposomal cytarabine.

Congenital abnormalities have been reported, particularly when the fetus has been exposed to systemic therapy with cytarabine during the first trimester. There is a definite, but considerably reduced risk to the fetus when therapy is initiated during the second or third trimester. At least 3 cases of major limb malformations have been reported in infants of mothers who received IV cytarabine, alone or in combination with other agents, during the first trimester. One infant had extremity and ear deformities, and another infant had upper and lower distal limb defects. A few women have received cytarabine with other antineoplastic agents during the second and third trimesters (20th-28th week of gestation) and delivered apparently normal infants. However, in one patient a trisomy C chromosomal abnormality was found in the chorionic tissue following a therapeutic abortion at 24 weeks of gestation after 4 weeks of therapy with cytarabine and thioguanine; the fetus appeared to have no congenital abnormalities.

In animal studies, cytarabine has been shown to cause abnormal cerebellar development in the neonatal hamster. Cytarabine has been shown to be teratogenic in mice and rats. Abnormalities including cleft palate, phocomelia, deformed appendages, and skeletal abnormalities have been observed in the offspring of mice given cytarabine doses of at least 2 mg/kg daily (about 0.2 times the recommended human dose on a mg/m2 basis) administered intraperitoneally during the period of organogenesis. Deformed appendages have been observed in the offspring of rats given cytarabine 20 mg/kg (about 4 times the recommended human dose on a mg/m2 basis) as a single intraperitoneal dose on day 12 of gestation. Reduced prenatal and postnatal brain size and permanent impairment of learning ability were observed in rats given single intraperitoneal doses of cytarabine 50 mg/kg (about 10 times the recommended human dose on a mg/m2 basis) on day 14 of gestation.

Cytarabine was embryotoxic in mice when given during the period of organogenesis. Decreased fetal weight was observed in mice given cytarabine 0.5 mg/kg daily (about 0.05 times the recommended human dose on a mg/m2 basis), and increased early and late resorptions and decreased live litter sizes were observed in mice given cytarabine 8 mg/kg daily (approximately equal to the recommended human dose on a mg/m2 basis).

There are no adequate and well-controlled studies to date using conventional or liposomal cytarabine in pregnant women. Cytarabine should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. When the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus. Women receiving systemic therapy with cytarabine, particularly during the first trimester, should be counseled on the advisability of continuing the pregnancy. The manufacturers suggest that infants delivered by women who received cytarabine therapy during pregnancy receive follow-up monitoring. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug.

It is not known whether cytarabine is distributed into human milk. Because of the potential for serious adverse reactions to conventional cytarabine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. Systemic exposure to free cytarabine following intrathecal administration of liposomal cytarabine is negligible, so the risk of the drug being distributed into human milk is thought to be low. However, because many drugs are distributed into human milk and because of the potential for serious adverse reactions in nursing infants, the use of liposomal cytarabine is not recommended in nursing women.

No enhanced messaging available.