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CYTARABINE is a brand name for Cytarabine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Cytarabine may be used alone or in combination with other antineoplastic agents. It is indicated alone or in combination for induction of remission and/or maintenance in patients with acute myeloid leukaemia, acute non- lymphoblastic leukaemias, acute lymphoblastic leukaemias, acute lymphocytic leukaemia,…
Verbatim from this product's MHRA label. Tap a section to expand.
Posology Cytarabine Injection can be diluted with Sterile Water for Injections BP, Glucose Intravenous Infusion BP or Sodium Chloride Intravenous Infusion BP. Prepared infusions, in the recommended diluents, should be used immediately.
Alternatively, the diluted infusion fluids may be stored at 2-8°C, protected from light, but portions remaining unused after 24 hours must be discarded.
Remission Induction:
Adults Continuous dosing: The usual dose in leukaemia is 2 mg/kg by rapid intravenous injection daily for ten days. If after ten days neither therapeutic response nor toxicity has been observed, the dose may be increased to 4 mg/kg until a therapeutic response or toxicity is evident.
Daily blood counts should be taken. Almost all patients can be carried to toxicity with these doses. 5 to 1 mg/kg may be infused daily in 1-24 hours for ten days, and then at a rate of 2 mg/kg/day until toxicity is observed. Continue to toxicity or until remission occurs.
Results from one hour infusions have been satisfactory in the majority of patients.
Intermittent dosing:
Cytarabine may be given as intermittent intravenous doses of 3-5 mg/kg daily, for five consecutive days. This course of treatment can be repeated after an interval of 2 to 9 days and repeated until the therapeutic response or toxicity is exhibited.
Evidence of bone marrow improvement has been reported to occur 7-64 days after the beginning of therapy. In general, if a patient shows neither remission nor toxicity after a trial period, then cautiously administered higher doses can be administered.
Generally patients tolerate higher doses given by rapid intravenous injection rather than slow infusion. As a single agent for induction of remissions in patients with acute leukaemia, cytarabine has been given in doses of 200 mg/m2 by continuous intravenous infusion for five days at approximately 2 week intervals.
Maintenance therapy:
To maintain remission, doses of 1 mg/kg may be given intravenously or subcutaneously, once or twice weekly.
Leukemic meningitis:
The following adverse events have been reported in association with cytarabine therapy.
Frequencies are defined using the following convention:
Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data) Undesirable effects from cytarabine are dose-dependent.
Most common are gastrointestinal undesirable effects. Cytarabine is toxic to the bone marrow, and causes haematological undesirable effects.
Infections and infestations Uncommon:
Sepsis (immunosuppression) Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon: Lentigo Blood and lymphatic system disorders Common: Anaemia, megaloblastosis, leukopenia, thrombocytopenia Not known: Reticulocytopenia, neutropenia, febrile neutropenia These appear to be more evident after high doses and continuous infusions; the severity depends on the dose of the drug and schedule of administration.
Gastrointestinal disorders Common:
Dysphagia, abdominal pain, nausea, vomiting, diarrhoea, oral/anal inflammation or ulceration Uncommon: Oesophagitis, oesophageal ulceration, pneumatosis cystoides intestinalis, necrotising colitis, peritonitis Not known: Gastrointestinal haemorrhage, pancreatitis Nausea and vomiting occur and are generally more frequent following rapid IV administration than with continuous IV infusion of the drug.
4 Special warnings and precautions for use).
Nervous system disorders Common:
At high doses cerebellar or cerebral influence with deterioration of the level of consciousness, dysarthria, nystagmus Uncommon: Headache, peripheral neuropathy, paraplegia at intrathecal administration Not known: Dizziness, neuritis or neural toxicity and pain, neurotoxicity rash Eye disorders Common: Reversible haemorrhagic conjunctivitis (photophobia, burning, visual disturbance, increased lacrimation), keratitis Not known: Conjunctivitis Respiratory, thoracic and mediastinal disorders Uncommon: Pneumonia, dyspnoea, sore throat Musculoskeletal and connective tissue disorders Uncommon: Myalgia, joint pain A cytarabine syndrome (immunoallergic effect) is characterised by fever, myalgia, bone pain, occasionally chest pain, exanthema, maculopapular rash, conjunctivitis, nausea and malaise.
Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving the drug should be kept under close medical supervision. Leucocyte and platelet counts should be performed frequently and daily during induction.
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).
One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitation has been reported. This occurred immediately after intravenous cytarabine was administered. Severe and at times fatal central nervous system (CNS), gastrointestinal (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; cerebral and cerebellar dysfunction, usually reversible; somnolence; convulsion; severe gastrointestinal ulceration including pneumatises cysteroides intestinalis, leading to peritonitis; sepsis and liver abscess; and pulmonary oedema.
The risk of CNS toxicity increases if high dose cytarabine is given in combination with another CNS toxic treatment such as radiation therapy or in patients who have previously had CNS treatment as chemotherapy intrathecally. Rarely, neurological effects such as severe spinal cord toxicity even leading to necrotising encephalopathy, quadriplegia and paralysis and blindness have been reported with cytosine arabinoside and have been predominantly associated with intrathecal administration.
8). Delayed progressive ascending paralysis resulting in death has been reported in children with AML following intravenous cytarabine at conventional doses in combination with other drugs. Cytarabine has been shown to be mutagenic and carcinogenic in animals.
1. g. bone marrow aplasia), unless the benefits outweigh the risk. Degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation. During pregnancy, cytarabine should only be administrated on strict indication, where the benefits of the drug to the mother should be weighed against possible hazards to the foetus.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Therapy for established meningitis employs a wide variety of dose regimens but a recommended total daily dose not exceeding 100 mg, alternating with methotrexate is recommended. Myelosuppression, anaemia and thrombocytopenia occur almost to all patients given daily infusions or injections.
Myelosuppression is biphasic and nadirs at 7-9 and 15- 24 days. Evidence of bone marrow improvement may be expected 7-64 (mean 28) days after the beginning of treatment.
Paediatric population:
Children appear to tolerate higher doses of cytarabine than adults, and where the range of doses is given, children should receive the higher dose.
Elderly:
No data is available to suggest that a change in dose is necessary in the elderly. However, the elderly patient is more susceptible to toxic reactions and therefore particular attention should be paid to drug induced leukopenia, thrombocytopenia and anaemia.
Method of administration Cytarabine 100 mg/ml Injection is a ready to use injection and can be administered by the intravenous and subcutaneous routes. Cytarabine 100 mg/ml Injection should not be administered by the intrathecal route due to the slight hypertonicity of this formulation.
8).
It usually occurs 6-12 hours after 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.
If treatment is effective, therapy with cytarabine may be continued. Adverse effects due to high dose cytarabine treatment, other than those seen with conventional doses include: Blood and lymphatic system disorders Hematological toxicity has been seen as profound pancytopenia which may last 15-25 days along with more severe bone marrow aplasia than that observed at conventional doses.
Nervous system disorders After treatment with high doses of cytarabine, symptoms of cerebral or cerebellar influence like personality changes, affected alertness, dysarthria, ataxia, tremor, nystagmus, headache, confusion, somnolence, dizziness, coma, convulsions, etc.
appear in 8-37 % of treated patients. The incidence in elderly (>55 years) may be even higher. , radiotherapy) and alcohol abuse. CNS disturbances are in the most cases reversible. The risk of CNS toxicity increases if the cytarabine treatment, given as high dose IV, is combined with another CNS toxic treatment such as radiation therapy or high dose of a cytotoxic agent.
Eye disorders Reversible corneal lesion and haemorrhagic conjunctivitis have been described. These phenomena can be prevented or decreased by installation of corticosteroid eye drops. Gastrointestinal disorders Especially in treatment with high doses of cytarabine, more severe reactions may appear in addition to common symptoms.
Intestinal perforation or necrosis with ileus and peritonitis have been reported. Pancreatitis has also been observed after high-dose therapy. Hepatobiliary disorders Liver abscesses, hepatomegaly, Budd-Chiari-syndrome (hepatic venous thrombosis), and hyperbilirubinemia have been observed after high-dose therapy.
Respiratory, thoracic and mediastinal disorders Clinical signs as present in pulmonary oedema/ARDS may develop, particularly in high-dose therapy. The reaction is probably caused by an alveolar capillary injury. It is difficult to make an assessment of frequencies (stated as 10-26 % in different publications), since the patients usually have been in relapse where other factors may contribute to this reaction.
Reproductive system and breast disorders Amenorrhoea and azoospermia Others Following cytarabine […]
The possibility of a similar effect should be borne in mind when designing the long-term management of the patient. Cytarabine should only be used under the constant supervision by physicians experienced in therapy with cytotoxic agents.
Hyperuricemia secondary to rapid lysis of neoplastic cells may occur in patients receiving cytarabine; serum uric acid concentrations should be monitored. The physician should be prepared to use such supportive and pharmacological measures as may be necessary to control this problem.
Periodic determinations of renal and hepatic functions and bone marrow should also be performed and the drug should be used with caution in patients with impaired hepatic function. However, dosage reduction does not appear to be necessary in patients with impaired renal function.
The human liver apparently detoxifies a substantial fraction of the administered dose. The drug should be used with caution and at a reduced dose when liver function is poor. Frequent platelet and leucocyte counts are mandatory. Therapy should be suspended or modified when drug-induced bone marrow depression results in a platelet count of less than 50,000 or a polymorph nuclear count of under 1000 per mm3.
Counts may continue to fall after the therapy has been discontinued and may reach lowest values after five to seven days. Therapy may be restarted when the bone marrow appears to be recovering on successive bone marrow studies. Therapy should not wait until the normal blood values are obtained to be re- initiated.
If treatment is not resumed before blood values return to normal, the disease can get out of control. When intravenous doses are given quickly, patients may become nauseated and may vomit for several hours afterwards. The problem tends to be less severe when infused.
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.
Concurrent granulocyte-transfusion should be avoided as severe respiratory insufficiency has been reported. 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. High dose therapy Peripheral motor and sensory neuropathies after consolidation with high doses of cytarabine, daunorubicin, and asparaginase have occurred in adult patients with acute non lymphocytic leukaemia.
Patients treated with high doses of cytarabine should be observed for neuropathy since dose adjustments may be needed to avoid irreversible neurologic disorders. Severe and sometimes fatal pulmonary toxicity, adult respiratory distress syndrome, and pulmonary edema have occurred following high dose schedules with cytarabine therapy.
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. Paediatric population The safety of the drug has not been established in infants.
Excipient information Cytarabine 100 mg/ml Injection contains less than 1 mmol sodium (23 mg) in each vial, that is to say essentially ‘sodium-free’.