"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
See boxed "WARNINGS" at top of insert. Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving this drug must be under close medical supervision and, during induction therapy, should have leukocyte and platelet counts performed daily. Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood. Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defenses, and hemorrhage secondary to thrombocytopenia). One case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after the intravenous administration of cytarabine.
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 cytarabine dose schedules. 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.
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.
Benzyl alcohol is contained in the diluent for this product. Benzyl alcohol has been reported to be associated with fatal "Gasping Syndrome" in premature infants. Two patients with childhood acute myelogenous leukemia who received intrathecal and intravenous cytarabine at conventional doses (in addition to a number of other concomitantly administered drugs) developed delayed, progressive ascending paralysis resulting in death in one of the two patients.
Use in Pregnancy
Cytarabine can cause fetal harm when administered to a pregnant woman. Cytarabine causes abnormal cerebellar development in the neonatal hamster and is teratogenic to the rat fetus. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant.
Patients receiving cytarabine must be monitored closely. Frequent platelet and leukocyte counts and bone marrow examinations are mandatory. Consider suspending or modifying therapy when drug-induced marrow depression has resulted in a platelet count under 50,000/mm3 or a polymorphonuclear granulocyte count under 1000/mm3. Counts of formed elements in the peripheral blood may continue to fall after the drug is stopped and reach lowest values after drug-free intervals of 12 to 24 days. When indicated, restart therapy when definite signs of marrow recovery appear (on successive bone marrow studies). Patients whose drug is withheld until "normal" peripheral blood values are attained may escape from control.
When large intravenous doses are given quickly, patients are frequently nauseated and may vomit for several hours post-injection. This problem tends to be less severe when the drug is infused.
The human liver apparently detoxifies a substantial fraction of an administered dose. In particular, patients with renal or hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose cytarabine treatment. Use the drug with caution and possibly at reduced dose in patients whose liver or kidney function is poor.
Periodic checks of bone marrow, liver, and kidney functions should be performed in patients receiving cytarabine.
Like other cytotoxic drugs, cytarabine may induce hyperuricemia secondary to rapid lysis of neoplastic cells. The clinician should monitor the patient's blood uric acid level and be prepared to use such supportive and pharmacologic measures as might be necessary to control this problem. Acute pancreatitis has been reported to occur in a patient receiving cytarabine by continuous infusion and in patients being treated with cytarabine who have had prior treatment with L-asparaginase.
See"General Precautions" Subsection.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Extensive chromosomal damage, including chromatoid breaks have been produced by cytarabine and malignant transformation of rodent cells in culture has been reported.
Usage in Pregnancy
"Pregnancy Category D." See "WARNINGS" Section.
A review of the literature has shown 32 reported cases where cytarabine was given during pregnancy, either alone or in combination with other cytotoxic agents.
Eighteen normal infants were delivered. Four of these had first trimester exposure. Five infants were premature or of low birth weight. Twelve of the 18 normal infants were followed up at ages ranging from six weeks to seven years and showed no abnormalities. One apparently normal infant died at 90 days of gastroenteritis.
Two cases of congenital abnormalities have been reported, one with upper and lower distal limb defects and the other with extremity and ear deformities. Both of these cases had first trimester exposure.
There were seven infants with various problems in the neonatal period, including pancytopenia; transient depression of WBC, hematocrit or platelets; electrolyte abnormalities; transient eosinophilia; and one case of increased IgM levels and hyperpyrexia possibly due to sepsis. Six of the seven infants were also premature. The child with pancytopenia died at 21 days of sepsis.
Therapeutic abortions were done in five cases. Four fetuses were grossly normal, but one had an enlarged spleen and another showed Trisomy C chromosome abnormality in the chorionic tissue.
Because of the potential for abnormalities with cytotoxic therapy, particularly during the first trimester, a patient who is or who may become pregnant while on cytarabine should be apprised of the potential risk to the fetus and the advisability of pregnancy continuation. There is a definite but considerably reduced risk if therapy is initiated during the second or third trimester. Although normal infants have been delivered to patients treated in all three trimesters of pregnancy, follow-up of such infants would be advisable.
Labor and Delivery
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from cytarabine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
See "INDICATIONS" Section.
Last reviewed on RxList: 11/3/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Cytarabine Information
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