Cytarabine (HCl)

Cytarabine is an antineoplastic agent or anticancerous drug and also known as cytosine arabinoside (ara-C). Cytarabine (HCl) is analog of cytidine in which the ribose moiety has been replaced with an arabinose. It belongs to class of antimetabolite. Antimetabolites are the compounds that bear a structural similarity to a naturally occurring substance, such as vitamin, nucleoside or amino acid. Cytarabine (HCl) is effective in the treatment of different cancers such as acute granulocytic, myelomonocytic or monocytic leukemias to slow or stop the growth of abnormal or cancerous cells. Cytarabine (HCl) is used in combination with different anticancerous drugs to obtain excellent therapeutic effects and minimize unwanted effects or toxicities.

Cytarabine (HCl) is primarily indicated in conditions like Acute granulocytic leukemia, Acute leukemia, Acute Nonlymphocytic leukemia, Gliomas, Lung cancer and pancreatic cancer, Mesothelioma, Non-Hodgkin's lymphoma, Ovarian cancer, Refractory leukemia, Lymphomatous Meningitis, Meningeal leukemia

Cytarabine (HCl) is contraindicated in conditions like Hypersensitivity to the drug, Liposomal cytarabine: Active meningeal infection.

The severe or irreversible adverse effects of Cytarabine (HCl), which give rise to further complications include CNS toxicity. Cytarabine (HCl) produces potentially life-threatening effects which include Pulmonary toxicity, CNS disturbances, Diarrhea, Bleeding, Dementia, Fits, Cerebral dysfunction, Myelosuppression, which are responsible for the discontinuation of Cytarabine (HCl) therapy. The symptomatic adverse reactions produced by Cytarabine (HCl) are more or less tolerable and if they become severe, they can be treated symptomatically, these include Nausea, Abnormal LFT, Impaired renal function, Intense vomiting, Fever, Rashes, Thrombophlebitis, Anorexia, Chest pain, Neuropathy, Headache, Anemia, Leukopenia, Sepsis.

Conventional cytarabine: Potent myelosuppressant. Initiate with caution in patients with preexisting drug-induced myelosuppression. Patients must be under close medical supervision and facilities should be available for management of serious complications, possibly fatal, of myelosuppression (e.g., infection resulting from granulocytopenia, hemorrhage secondary to thrombocytopenia). (See Boxed Warning.) Risk of increased frequency of infections (e.g., viral, bacterial, fungal), as well as possible hemorrhagic complications; potentially fatal. During induction therapy, perform leukocyte and platelet counts daily. (See Dosage Modification for Toxicity under Dosage and Administration.) Perform bone marrow examinations frequently after blasts have disappeared from peripheral blood. Counts of formed elements in peripheral blood may continue to fall after drug discontinuance and reach lowest values after drug-free intervals of 12–24 days. Liposomal cytarabine: Clinically important systemic exposure to unencapsulated cytarabine unlikely following intrathecal administration. However, careful hematologic monitoring recommended since myelosuppression cannot be completely ruled out. Severe and sometimes fatal CNS, GI, and pulmonary toxicities reported following experimental dosage regimens for refractory or secondary acute leukemia or refractory non-Hodgkin’s lymphomas; differ from reactions seen with regimens employing lower dosages. Cerebral and cerebellar dysfunction (e.g., somnolence, coma, personality changes) reported; usually reversible. Reversible, acute aseptic meningitis, combined with cerebellar dysfunction, reported in at least 1 patient. Peripheral motor and sensory neuropathies have occurred occasionally. Patients with renal or hepatic impairment may be at increased risk of CNS toxicity associated with high-dose cytarabine therapy. Monitor patients receiving high-dose therapy closely for signs of central or peripheral neurotoxicity. Dosage schedule adjustment may be necessary to avoid irreversible neurologic toxicity. Severe GI ulceration (including pneumatosis cystoides intestinalis leading to peritonitis), bowel necrosis, necrotizing colitis, hepatic abscess or hepatic damage with increased hyperbilirubinemia reported. Pancreatitis reported in patients previously treated with asparaginase and those receiving high-dose cytarabine therapy. Pulmonary edema reported. Diffuse interstitial pneumonitis reported occasionally in patients receiving relatively high doses (e.g., 1 g/m 2 ) of cytarabine alone or in combination with other antineoplastic agents. A syndrome of acute respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly, which was sometimes fatal, has been reported in patients with refractory acute leukemia receiving high-dose therapy. Severe skin rash leading to desquamation has been reported rarely. Complete alopecia occurs more commonly with high-dose regimens. Fatal cardiomyopathy reported in patients receiving high-dose cytarabine in combination with cyclophosphamide in preparation for bone marrow transplantation; this cardiac toxicity may be schedule dependent. Hemorrhagic conjunctivitis and reversible corneal toxicity (e.g., keratitis) reported; may be minimized or prevented by prophylaxis with ophthalmic corticosteroid preparations. Possible systemic toxicity; carefully monitor hematologic status. Dosage adjustment of concurrently administered antineoplastic agents may be necessary. Concurrent (within a few days) IV chemotherapy or cranial/spinal irradiation and intrathecal treatment with conventional cytarabine may be associated with increased risk of neurotoxicity (e.g., spinal cord toxicity). Progressive ascending paralysis reported. Occurred in 2 children 4–6 months after intrathecal and IV therapy with conventional cytarabine at usual doses in combination with other drugs and CNS irradiation; fatal in one patient. Permanent neurologic deficits reported rarely. Observe closely for acute toxic reactions. Neurotoxicity may occur after a single dose or repeated administration; most likely to occur within 5 days of intrathecal administration. Monitor continuously and reduce subsequent doses if neurotoxicity occurs; discontinue if neurotoxicity persists. CSF flow obstruction may result in increased CSF concentrations and increased risk of neurotoxicity. (See Dosage Modification for Toxicity under Dosage and Administration.) At least 2 fatalities attributed to liposomal cytarabine have occurred. One patient died after developing encephalopathy 36 hours after receiving intraventricular liposomal cytarabine; the other patient developed focal seizures that progressed to status epilepticus and died approximately 8 weeks after the last intraventricular dose of liposomal cytarabine. Possible increased risk of adverse events in patients receiving concurrent radiation or chemotherapy. Common complication of intrathecal liposomal cytarabine; in clinical studies, generally occurred ≤48 hours after intrathecal administration. Defined in clinical studies as occurrence of any 1 of certain manifestations (i.e., neck rigidity, neck pain, meningism) or any 2 of the following: nausea, vomiting, headache, fever, back pain, or CSF pleocytosis. Administer dexamethasone to ameliorate symptoms and reduce incidence. (See Intrathecal Administration under Dosage and Administration and also Chemical Arachnoiditis in Boxed Warning.) Do not use conventional cytarabine injection solution containing benzyl alcohol in neonates. Do not use diluents containing benzyl alcohol to reconstitute or dilute conventional cytarabine for use in neonates. Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates. Do not use conventional cytarabine injection solution containing benzyl alcohol for intrathecal administration. Do not use diluents containing benzyl alcohol to reconstitute conventional cytarabine for intrathecal administration. Because of potential neurotoxicity, conventional cytarabine injection solution containing benzyl alcohol or cytarabine powder reconstituted or diluted with diluents containing benzyl alcohol should not be used for high-dose regimens. May cause fetal harm; upper and lower distal limb defects, extremity and ear deformities, low birth weight, premature delivery, and adverse hematologic effects reported. Avoid pregnancy during therapy with conventional or liposomal cytarabine; especially avoid cytarabine use during first trimester. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard. Follow-up monitoring of infants exposed to cytarabine in utero is advised. At least one case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported after IV administration of conventional cytarabine. Cytarabine syndrome reported; may manifest as fever, myalgia, bone pain, maculopapular rash, conjunctivitis, malaise, and occasionally chest pain. Generally occurs 6–12 hours after administration of conventional cytarabine. Corticosteroids are beneficial in treatment and prevention. If symptoms require treatment, consider administration of corticosteroids, as well as continuation of conventional cytarabine therapy. Nausea and vomiting are more frequent and severe following rapid IV administration of conventional cytarabine than with continuous IV infusion. Pancreatitis reported in patients receiving conventional cytarabine and in those previously treated with asparaginase. (Also see High-dose Regimens with Conventional Cytarabine under Cautions.) Hyperuricemia may occur in patients receiving conventional cytarabine because of extensive purine catabolism accompanying rapid cellular destruction. Monitor serum uric acid concentrations in patients receiving conventional cytarabine. Hyperuricemia may be minimized or prevented by adequate hydration, alkalinization of urine, and/or administration of allopurinol. Transient increases in CSF protein concentration and WBC counts reported in patients following intrathecal administration of liposomal or conventional cytarabine. Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Not known whether cytarabine is distributed into milk; discontinue nursing or the drug. Do not use conventional cytarabine injection solution or diluents containing benzyl alcohol in neonates. (See Benzyl Alcohol under Cautions.) Safety and efficacy of liposomal cytarabine not established in children. Use with caution; increased risk of CNS toxicity after high-dose therapy with conventional cytarabine because of decreased clearance. Assess hepatic function prior to and periodically during prolonged therapy. Use with caution; increased risk of CNS toxicity after high-dose therapy with conventional cytarabine because of decreased clearance. Assess renal function prior to and periodically during prolonged therapy.

Conventional cytarabine: Potent myelosuppressant. Initiate with caution in patients with preexisting drug-induced myelosuppression. Patients must be under close medical supervision and facilities should be available for management of serious complications, possibly fatal, of myelosuppression (e.g., infection resulting from granulocytopenia, hemorrhage secondary to thrombocytopenia). (See Boxed Warning.) Risk of increased frequency of infections (e.g., viral, bacterial, fungal), as well as possible hemorrhagic complications; potentially fatal. During induction therapy, perform leukocyte and platelet counts daily. (See Dosage Modification for Toxicity under Dosage and Administration.) Perform bone marrow examinations frequently after blasts have disappeared from peripheral blood. Counts of formed elements in peripheral blood may continue to fall after drug discontinuance and reach lowest values after drug-free intervals of 12–24 days. Liposomal cytarabine: Clinically important systemic exposure to unencapsulated cytarabine unlikely following intrathecal administration. However, careful hematologic monitoring recommended since myelosuppression cannot be completely ruled out. Severe and sometimes fatal CNS, GI, and pulmonary toxicities reported following experimental dosage regimens for refractory or secondary acute leukemia or refractory non-Hodgkin’s lymphomas; differ from reactions seen with regimens employing lower dosages. Cerebral and cerebellar dysfunction (e.g., somnolence, coma, personality changes) reported; usually reversible. Reversible, acute aseptic meningitis, combined with cerebellar dysfunction, reported in at least 1 patient. Peripheral motor and sensory neuropathies have occurred occasionally. Patients with renal or hepatic impairment may be at increased risk of CNS toxicity associated with high-dose cytarabine therapy. Monitor patients receiving high-dose therapy closely for signs of central or peripheral neurotoxicity. Dosage schedule adjustment may be necessary to avoid irreversible neurologic toxicity. Severe GI ulceration (including pneumatosis cystoides intestinalis leading to peritonitis), bowel necrosis, necrotizing colitis, hepatic abscess or hepatic damage with increased hyperbilirubinemia reported. Pancreatitis reported in patients previously treated with asparaginase and those receiving high-dose cytarabine therapy. Pulmonary edema reported. Diffuse interstitial pneumonitis reported occasionally in patients receiving relatively high doses (e.g., 1 g/m 2 ) of cytarabine alone or in combination with other antineoplastic agents. A syndrome of acute respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly, which was sometimes fatal, has been reported in patients with refractory acute leukemia receiving high-dose therapy. Severe skin rash leading to desquamation has been reported rarely. Complete alopecia occurs more commonly with high-dose regimens. Fatal cardiomyopathy reported in patients receiving high-dose cytarabine in combination with cyclophosphamide in preparation for bone marrow transplantation; this cardiac toxicity may be schedule dependent. Hemorrhagic conjunctivitis and reversible corneal toxicity (e.g., keratitis) reported; may be minimized or prevented by prophylaxis with ophthalmic corticosteroid preparations. Possible systemic toxicity; carefully monitor hematologic status. Dosage adjustment of concurrently administered antineoplastic agents may be necessary. Concurrent (within a few days) IV chemotherapy or cranial/spinal irradiation and intrathecal treatment with conventional cytarabine may be associated with increased risk of neurotoxicity (e.g., spinal cord toxicity). Progressive ascending paralysis reported. Occurred in 2 children 4–6 months after intrathecal and IV therapy with conventional cytarabine at usual doses in combination with other drugs and CNS irradiation; fatal in one patient. Permanent neurologic deficits reported rarely. Observe closely for acute toxic reactions. Neurotoxicity may occur after a single dose or repeated administration; most likely to occur within 5 days of intrathecal administration. Monitor continuously and reduce subsequent doses if neurotoxicity occurs; discontinue if neurotoxicity persists. CSF flow obstruction may result in increased CSF concentrations and increased risk of neurotoxicity. (See Dosage Modification for Toxicity under Dosage and Administration.) At least 2 fatalities attributed to liposomal cytarabine have occurred. One patient died after developing encephalopathy 36 hours after receiving intraventricular liposomal cytarabine; the other patient developed focal seizures that progressed to status epilepticus and died approximately 8 weeks after the last intraventricular dose of liposomal cytarabine. Possible increased risk of adverse events in patients receiving concurrent radiation or chemotherapy. Common complication of intrathecal liposomal cytarabine; in clinical studies, generally occurred ≤48 hours after intrathecal administration. Defined in clinical studies as occurrence of any 1 of certain manifestations (i.e., neck rigidity, neck pain, meningism) or any 2 of the following: nausea, vomiting, headache, fever, back pain, or CSF pleocytosis. Administer dexamethasone to ameliorate symptoms and reduce incidence. (See Intrathecal Administration under Dosage and Administration and also Chemical Arachnoiditis in Boxed Warning.) Do not use conventional cytarabine injection solution containing benzyl alcohol in neonates. Do not use diluents containing benzyl alcohol to reconstitute or dilute conventional cytarabine for use in neonates. Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates. Do not use conventional cytarabine injection solution containing benzyl alcohol for intrathecal administration. Do not use diluents containing benzyl alcohol to reconstitute conventional cytarabine for intrathecal administration. Because of potential neurotoxicity, conventional cytarabine injection solution containing benzyl alcohol or cytarabine powder reconstituted or diluted with diluents containing benzyl alcohol should not be used for high-dose regimens. May cause fetal harm; upper and lower distal limb defects, extremity and ear deformities, low birth weight, premature delivery, and adverse hematologic effects reported. Avoid pregnancy during therapy with conventional or liposomal cytarabine; especially avoid cytarabine use during first trimester. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard. Follow-up monitoring of infants exposed to cytarabine in utero is advised. At least one case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported after IV administration of conventional cytarabine. Cytarabine syndrome reported; may manifest as fever, myalgia, bone pain, maculopapular rash, conjunctivitis, malaise, and occasionally chest pain. Generally occurs 6–12 hours after administration of conventional cytarabine. Corticosteroids are beneficial in treatment and prevention. If symptoms require treatment, consider administration of corticosteroids, as well as continuation of conventional cytarabine therapy. Nausea and vomiting are more frequent and severe following rapid IV administration of conventional cytarabine than with continuous IV infusion. Pancreatitis reported in patients receiving conventional cytarabine and in those previously treated with asparaginase. (Also see High-dose Regimens with Conventional Cytarabine under Cautions.) Hyperuricemia may occur in patients receiving conventional cytarabine because of extensive purine catabolism accompanying rapid cellular destruction. Monitor serum uric acid concentrations in patients receiving conventional cytarabine. Hyperuricemia may be minimized or prevented by adequate hydration, alkalinization of urine, and/or administration of allopurinol. Transient increases in CSF protein concentration and WBC counts reported in patients following intrathecal administration of liposomal or conventional cytarabine. Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Not known whether cytarabine is distributed into milk; discontinue nursing or the drug. Do not use conventional cytarabine injection solution or diluents containing benzyl alcohol in neonates. (See Benzyl Alcohol under Cautions.) Safety and efficacy of liposomal cytarabine not established in children. Use with caution; increased risk of CNS toxicity after high-dose therapy with conventional cytarabine because of decreased clearance. Assess hepatic function prior to and periodically during prolonged therapy. Use with caution; increased risk of CNS toxicity after high-dose therapy with conventional cytarabine because of decreased clearance. Assess renal function prior to and periodically during prolonged therapy.

100 mg/sq.meter (180 (183)) As recommended. IV Inf — For 5 days. Repeated every 2 weeks total 12 doses

200 mg/sq.meter (370 (367)) 24 hourly Intra Venous — Initially for 5 days for induction per 2 weeks 70 to 200 mg/sq.meter (140 (135)) 24 hourly Intra Venous — Maintenance for 2-5 days per month

No neonatal dosage information is recorded for this medicine yet.

Cytarabine (HCl) is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementCrisantaspaseDaunorubicin (HCl)DigoxinFlucytosineFlucytosineGentamicinHydroxyurea These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Inj (reconstituted soln) use at once after preparation.