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  • Cytosar 1 g
    / Pfizer


    Active Ingredient
    Cytarabine 1g/Vial

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1 X 1g/Vial

    partial basket chart 3761

    Dosage

    Cytarabine is not active orally. The schedule and method of administration vary with the program of therapy to be used. Cytarabine may be given by intravenous infusion or injection. Thrombophlebitis has occurred at the site of drug infusion in some patients. 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. If high dose therapy is used, do not use a diluent containing benzyl alcohol.
    Conventional dose: 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 I.V. infusion (Days 1-7) or 100 mg/m² I.V. every 12 hours (Days 1-7).
    High dose: 2-3 g/m² as an I.V. infusion over 1-3 hours given every 12 hours for 2-6 days with or without additional cancer chemotherapeutic agents. The literature should be consulted for the current recommendations for use in leukemia and pediatric non-Hodgkin’s lymphoma.
    Drug compatibilities: Cytarabine is compatible with the following drugs, at the specified concentrations, in Dextrose 5% in water for eight hours; cytarabine 0.8 mg/ml and Sodium Cephalothin 1.0 mg/ml; cytarabine 0.4 mg/ml and prednisolone sodium phosphate 0.2 mg/ml, cytarabine 16 mcg/ml and Vincristine Sulfate 4 mcg/ml. Cytarabine is also physically compatible with methotrexate.
    Use in Children: Similar to use in adults.


    Indications

    Induction and maintenance of remission in acute myelocytic leukemia of adults and children. Treatment of other leukemias.


    Contra-Indications

    Therapy with cytarabine should not be considered in patients with pre‑existing drug‑induced bone marrow suppression, unless the clinician feels that such management offers the most hopeful alternative for the patient. Cytarabine should not be used in the management of non‑malignant disease, except for immunosuppression. Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    General: Only physicians experienced in cancer chemotherapy should use cytarabine.
    Warnings: Haematologic Effects: Cytarabine is a potent bone marrow suppressant; the severity depends on the dose of the drug and the schedule of administration. 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 leucocyte and platelet counts performed daily. Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood.
    The main toxic effect of cytarabine is bone marrow suppression with leukopenia, thrombocytopenia, anaemia, megaloblastosis and reduced reticulocytes. Less serious toxicity includes nausea, vomiting, diarrhoea and abdominal pain, oral ulceration, and hepatic dysfunction. Following 5-day constant infusions or acute injections of 50 mg/m2 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 7-9. This is followed by a brief rise which peaks around the twelfth day. A second and deeper fall reaches nadir at days 15-24. Then there is rapid rise to above baseline in the next 10 days. Platelet depression is noticeable at 5 days with a peak depression occurring between days 12-15. Thereupon, a rapid rise to above baseline occurs in the next 10 days.
    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). Anaphylactic reactions have occurred with cytarabine treatment. Anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after the intravenous administration of Cytarabine.
    High Dose Schedules: 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 high dose (2-3 g/m2) schedules with Cytarabine. These reactions include reversible corneal toxicity; cerebral and cerebellar dysfunction, usually reversible; somnolence; convulsion; severe gastro-intestinal ulceration, including pneumatosis cystoides intestinalis, leading to peritonitis; sepsis and liver abscess; and pulmonary oedema.
    Cytarabine has been shown to be carcinogenic in animals. The possibility of a similar effect should be borne in mind when designing the long‑term management of the patient.
    Precautions: Patients receiving Cytarabine must be monitored closely. Frequent platelet and leucocyte counts are mandatory. Suspend or modify therapy when drug‑induced marrow depression has resulted in a platelet count under 50,000 or a polymorphonuclear granulocyte count under 1,000 per cubic mm. 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. If 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.
    Peripheral motor and sensory neuropathies after consolidation with high doses of cytarabine, daunorubicin, and asparaginase have occurred in adult patients with acutenon lymphocytic leukemia. Patients treated with high doses of cytarabine should be observed for neuropathy since dose schedule alterations may be needed to avoid irreversible neurologic disorders.
    Severe and sometimes fatal pulmonary toxicity, sudden respiratory distress syndrome and pulmonary oedema have occurred following experimental high dose schedules with cytarabine therapy.
    Cases of cardiomyopathy with subsequent death have been reported following experimental high dose cytarabine and cyclophosphamide therapy when used for bone marrow transplant preparation. This may be schedule dependent.
    When intravenous doses are given quickly, patients are frequently nauseated and may vomit for several hours afterwards. This problem tends to be less severe when the drug 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 nonoperative 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.
    Hepatic and/or Renal Function: The human liver apparently detoxifies a substantial fraction of an administered dose of cytarabine. In particular, patients with renal or hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose treatment with cytarabine. Use the drug with caution and at reduced dose in patients whose liver function is poor. 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. The safety of this drug for use in infants is not established.
    Tumour Lysis Syndrome: 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 may be necessary to control this problem.
    Pancreatitis: Cases of pancreatitis have been observed with the induction of cytarabine.
    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.


    Side Effects

    Most frequent adverse reactions include nausea, vomiting, diarrhoea, fever, rash, anorexia, oral and anal inflammation or ulceration, and hepatic dysfunction.
    Blood and lymphatic system disorders: Because cytarabine is a bone marrow suppressant, anaemia, leukopenia, thrombocytopenia, megaloblastosis and reduced reticulocytes can be expected as a result of its administration. The severity of these reactions are dose and schedule dependent. Cellular changes in the morphology of bone marrow and peripheral smears can be expected.
    Infections and infestations: 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.
    Musculoskeletal and connective tissue disorders: A Cytarabine syndrome has been described. It is characterised by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6‑12 hours following drug administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated as well as continuation of therapy with cytarabine.
    See prescribing information for full details.


    Drug interactions

    5-Fluorocytosine should not be administered with Cytarabine as the therapeutic efficacy of 5-Fluorocytosine has been shown to be abolished during such therapy. 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 utilisation 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. In patients on Cytarabine being treated with gentamicin for a K.pneumoniae infection, a lack of a prompt therapeutic response may indicate the need for re-evaluation of antibacterial therapy.
    Methotrexate: Intravenous cytarabine given concomitantly with intrathecal methotrexate may increase the risk of severe neurological adverse reactions such as headache, paralysis, coma and stroke like episodes.


    Pregnancy and Lactation

    Pregnancy: Cytarabine is known to be teratogenic in some animal species. The use of cytarabine in women who are or who may become pregnant should be undertaken only after due consideration of the potential benefits and hazards. 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.
    Breast-feeding: 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.
    This product should not normally be administered to patients who are pregnant or to mothers who are breast‑feeding.


    Overdose

    Cessation of therapy, followed by management of ensuing bone marrow depression including whole blood or platelet transfusion and antibiotics as required. There is no antidote for overdosage of cytarabine. Doses of 4.5g/m2 by intravenous infusion over 1 hour every 12 hours for 12 doses has caused an unacceptable increase in irreversible CNS toxicity and death.


    Important notes

    Storage: Powder freeze dried for solution for injection: Store below 25°C.
    Cytarabine 1g vial is to be used for preparation of a solution for single dose administration.


    Manufacturer
    Actavis, Italy S.P.S
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