Cytarabine Pfizer

Cytarabine Pfizer Special Precautions





Zuellig Pharma


Full Prescribing Info
Special Precautions
Cytarabine should be administered only under constant supervision by physicians experienced in therapy with cytotoxic agents and only when the potential benefits of cytarabine therapy outweigh the possible risks. Patients should be treated in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. Appropriate facilities should be available for adequate management of complications should they arise.
The main toxic effect of cytarabine is bone marrow suppression with leukopenia, thrombocytopenia and anaemia. Less serious toxicity includes nausea, vomiting, diarrhoea and abdominal pain, oral ulceration, and hepatic dysfunction.
Myelosuppression: Cytarabine is a potent bone marrow suppressant and the severity depends on the dose of the drug and schedule of administration. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients should undergo close medical supervision including daily assessment of leucocyte and platelet levels. 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 defences and haemorrhage secondary to thrombocytopenia). Consider suspending or modifying therapy when drug-induced marrow depression has resulted in a platelet count under 50 × 109 L or a polymorphonuclear granulocyte count under 1 × 109 L. 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.
Intrathecal Use: Cytarabine given intrathecally may cause systemic toxicity and careful monitoring of the haemopoietic system is indicated. Modification of other anti-leukaemia therapy may be necessary (see DOSAGE & ADMINISTRATION). When cytarabine is administered both intrathecally and intravenously within a few days, there is an increased risk of spinal cord toxicity.
Hepatic and/or Renal Effects: The liver is the main site of inactivation of cytarabine and the normal dosage regimen should be used with caution in patients with pre-existing liver dysfunction or poor renal function. In particular, patients with renal or hepatic function impairment may have higher likelihood of CNS toxicity after high-dose treatment with cytarabine.
Monitoring: Periodic checks of bone marrow, liver and kidney functions should be performed in patients receiving cytarabine.
Neurological: Cases of severe neurological adverse reactions that ranged from headache to paralysis, coma and stroke-like episodes have been reported mostly in juveniles and adolescents given intravenous cytarabine in combination with intrathecal methotrexate.
Hyperuricaemia: Like other cytotoxic drugs, cytarabine may induce hyperuricaemia 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 pharmacological measures as might be necessary to control this problem.
Anaphylaxis: Anaphylactic reactions have occurred with cytarabine treatment. Anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after intravenous administration of cytarabine.
Acute Pancreatitis: Acute pancreatitis has been reported to occur in patients being treated with cytarabine who have had prior treatment with L-asparaginase.
Immunosuppressant Effects/Increased Susceptibility to Infections: Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including cytarabine, may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving cytarabine. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
Vomiting: When large intravenous doses are given quickly, patients are frequently nauseated and may vomit for several hours post-injection. The severity is less if the solution is infused.
Conventional Dose Schedules: Abdominal tenderness (peritonitis) and guaiac positive colitis, with concurrent neutropenia and thrombocytopenia, have been reported in patients treated with conventional doses of cytarabine in combination with other drugs. Patients have responded to non-operative medical management. Delayed progressive ascending paralysis resulting in death has been reported in children with AML following intrathecal and intravenous cytarabine at conventional doses in combination with other drugs.
Experimental Doses: Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) have been reported following some experimental dose schedules of cytarabine. These reactions include reversible corneal toxicity, and haemorrhagic conjunctivitis (which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop); usually reversible cerebral and cerebellar dysfunction (including personality changes, somnolence and coma); severe gastrointestinal ulceration (including pneumatosis cystoides intestinalis leading to peritonitis); sepsis and liver abscess; pulmonary oedema, liver damage with increased hyperbilirubinaemia; bowel necrosis; and necrotising colitis.
Severe sometimes fatal pulmonary toxicity, adult respiratory distress syndrome and pulmonary oedema have occurred following high dose schedules with cytarabine therapy. A syndrome of sudden respiratory distress, rapidly progressing to pulmonary oedema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukaemia. The outcome of this syndrome can be fatal.
Cases of cardiomyopathy with subsequent death have been reported following experimental high dose therapy with cytarabine and cyclophosphamide therapy when used for bone marrow transplant preparation. This may be schedule dependent.
Peripheral motor and sensory neuropathies after consolidation with high dose cytarabine, daunorubicin and asparaginase have occurred in adult patients with non-lymphocytic leukaemia. Patients treated with high dose cytarabine should be observed for neuropathy since dose schedule alterations may be needed to avoid irreversible neurologic disorders.
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.
Use in Pregnancy: Pregnancy Category D.
Cytarabine is known to be teratogenic in some animal species and its use in pregnant women is not recommended. Cytarabine should only be used in women of child-bearing potential if the expected benefits outweigh the risks of therapy and adequate contraception is used.
Australian categorisation definition of Category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
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 6 weeks to 7 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, haematocrit 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 foetus 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.
Use in Lactation: It is not known whether cytarabine is excreted in breast milk so breast feeding should be discontinued during cytarabine therapy in lactating women.
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