Cytarabine

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{{DrugProjectFormSinglePage |authorTag=Alberto Plate [1] |genericName=Cytarabine |aOrAn=an |drugClass=antineoplastic agent |indicationType=treatment |indication=acute non-lymphocytic leukemia of adults and children, acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. Intrathecal administration of cytarabine injection is indicated for the prophylaxis and treatment of meningeal leukemia |hasBlackBoxWarning=Yes |adverseReactions=thrombophlebitis, rash, hyperuricemia, anal inflammation, diarrhea, loss of apetite, nauseas, stomatitis, mouth ulceration, vomiting, decreased reticulocyte count, megaloblastic anemia, decreased liver function and fever. |blackBoxWarningTitle=Black Box Warning: |blackBoxWarningBody=ConditionName:

Only physicians experienced in cancer chemotherapy should use Cytarabine Injection.

For induction therapy 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. The main toxic effect of cytarabine is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration and hepatic dysfunction.

The physician must judge possible benefit to the patient against known toxic effects of this drug in considering the advisability of therapy with cytarabine. Before making this judgment or beginning treatment, the physician should be familiar with the following text.


|fdaLIADAdult=====Acute Non-Lymphocytic Leukemia====

  • Induction: 100 mg/m2/day by continuous IV infusion (Days 1-7) or 100 mg/m2 IV every 12 hours (Days 1-7).

Meningeal Leukemia

  • Dosage: doses ranging from 5 mg/m2 to 75 mg/m2 of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment.

|offLabelAdultGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Cytarabine in adult patients. |offLabelAdultNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Cytarabine in adult patients. |offLabelPedGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Cytarabine in pediatric patients. |offLabelPedNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Cytarabine in pediatric patients. |contraindications=Cytarabine is contraindicated in those patients who are hypersensitive to the drug. |warnings=*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 of the 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 cytarabine injection containing benzyl alcohol.
  • Cases of cardiomyopathy with subsequent death has 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 this product. Benzyl alcohol has been reported to be associated with a 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.

|clinicalTrials=====Hematological Effects====

Infections

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.

Cytabarine Syndrome

Cardiovascular effects

  • Cardiomyopathy
  • Cardiovascular finding
  • Pericarditis: < 0.1% of patients develop this adverse effect, between 2 - 3 days after initiating the therapy, symptoms lasting for 1-6 weeks [1] [2] [3]. Symptoms include:
    • Chest pain
    • Dyspnea
    • Pericardial effusion
    • Pericardial friction rub
    • Pulsus paradoxus
    • Right ventricular diastolic collapse
    • ST-Segment elevation on EKG
  • Vasculitis: high-dose cytarabine causes small vessel necrotizing vasculitis[4].

Dermatological effects

Endocrine/metabolic Effects

Gastrointestinal Effects

  • Gastrointestinal tract finding: nausea and vomiting are common agh high-dosis[9]. GI bleeding has also been reported[8].
  • Pancreatitis
    • Case report of a 36-year old male in therapy for 7 days with 200mg / m2 surface area / day [11].
    • Case report of 2/30 Patients receiving cytarabine for leukemia and lymphoma in high doses (6.9 g IV every 12 hours for 11 doses and 5.25 g every 12 hours for 6 days)[12].
  • Parotiditis:
    • Case report: 2/30 patients developed parotiditis with cytarabine 200 milligrams/square meter/day in continuous infusion for 7 days [13].
  • Pseudomembranous enterocolitis
    • Case report: 2 patients who developed Pseudomembranous Enterocolitis and as a consequence, needed subtotal colectomy[14].

Hepatic Effects

Immunological Effects

Musculoeskeletal Effects

Neurologic Effects

Ophthalmic Effects

Urinary Tract Effects

  • Cystitis[31]
  • Renal failure
    • Case report: 45 year-old patient treated for hypoplastic myelodysplastic syndrome with low-dose cytarabine[32].
  • Urinary retention: its the least frequent of the urinary tract adverse effects

Respiratory Effects

Other

|PD=s |alcohol=Alcohol-Cytarabine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. }}

  1. ↑ Woods T, Vidarsson B, Mosher D, Stein JH (1999). "Transient effusive-constrictive pericarditis due to chemotherapy". Clin Cardiol. 22 (4): 316–8. PMID 10198745.
  2. ↑ Hermans C, Straetmans N, Michaux JL, Ferrant A (1997). "Pericarditis induced by high-dose cytosine arabinoside chemotherapy". Ann Hematol. 75 (1–2): 55–7. PMID 9322684.
  3. ↑ Vaickus L, Letendre L (1984). "Pericarditis induced by high-dose cytarabine therapy". Arch Intern Med. 144 (9): 1868–9. PMID 6477012.
  4. ↑ Ahmed I, Chen KR, Nakayama H, Gibson LE (1998). "Cytosine arabinoside-induced vasculitis". Mayo Clin Proc. 73 (3): 239–42. doi:10.1016/S0025-6196(11)64465-0. PMID 9511781.
  5. ↑ Graves T, Hooks MA (1989). "Drug-induced toxicities associated with high-dose cytosine arabinoside infusions". Pharmacotherapy. 9 (1): 23–8. PMID 2922357.
  6. ↑ Aktas B, Topcuoglu P, Kurt OK, Ensari A, Demirer T (2009). "Severe Henoch-Schönlein purpura induced by cytarabine". Ann Pharmacother. 43 (4): 792–3. doi:10.1345/aph.1L608. PMID 19336650.
  7. ↑ Ozkan A, Apak H, Celkan T, Yüksel L, Yildiz I (2001). "Toxic epidermal necrolysis after the use of high-dose cytosine arabinoside". Pediatr Dermatol. 18 (1): 38–40. PMID 11207969.
  8. ↑ 8.0 8.1 Slavin RE, Dias MA, Saral R (1978). "Cytosine arabinoside induced gastrointestinal toxic alterations in sequential chemotherapeutic protocols: a clinical-pathologic study of 33 patients". Cancer. 42 (4): 1747–59. PMID 709532.
  9. ↑ 9.0 9.1 Rudnick SA, Cadman EC, Capizzi RL, Skeel RT, Bertino JR, McIntosh S (1979). "High dose cytosine arabinoside (HDARAC) in refractory acute leukemia". Cancer. 44 (4): 1189–93. PMID 498009.
  10. ↑ Bensinger TA, Fahey JL, Kellon DB, Beutler E (1974). "Letter: Febrile response to cytarabine". JAMA. 229 (12): 1578. PMID 4408256.
  11. ↑ McBride CE, Yavorski RT, Moses FM, Robson ME, Solimando DA, Byrd JC (1996). "Acute pancreatitis associated with continuous infusion cytarabine therapy: a case report". Cancer. 77 (12): 2588–91. doi:10.1002/(SICI)1097-0142(19960615)77:12<2588::AID-CNCR24>3.0.CO;2-N. PMID 8640710.
  12. ↑ Siemers RF, Friedenberg WR, Norfleet RG (1985). "High-dose cytosine arabinoside-associated pancreatitis". Cancer. 56 (8): 1940–2. PMID 2411382.
  13. ↑ Cetkovský P, Koza V (1994). "Salivary glands enlargement in association with cytosine arabinoside application in patients with acute myeloid leukaemia". Eur J Cancer. 30A (11): 1727–8. PMID 7833152.
  14. ↑ Lea JW, Masys DR, Shackford SR (1980). "Typhlitis: a treatable complication of acute leukemia therapy". Cancer Clin Trials. 3 (4): 355–62. PMID 6933028.
  15. ↑ Woods WG, Dehner LP, Nesbit ME, Krivit W, Coccia PF, Ramsay NK; et al. (1980). "Fatal veno-occlusive disease of the liver following high dose chemotherapy, irradiation and bone marrow transplantation". Am J Med. 68 (2): 285–90. PMID 6986767.
  16. ↑ Berkowitz FE, Wehde S, Ngwenya ET, Greeff M, Wadee AA, Rabson AR (1987). "Anaphylactic shock due to cytarabine in a leukemic child". Am J Dis Child. 141 (9): 1000–1. PMID 3475975.
  17. ↑ Margolis D, Ross E, Miller KB (1987). "Rhabdomyolysis associated with high-dose cytarabine". Cancer Treat Rep. 71 (12): 1325–6. PMID 3690552.
  18. ↑ Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR; et al. (1999). "Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis". J Clin Oncol. 17 (10): 3110–6. PMID 10506606.
  19. ↑ Pease CL, Horton TM, McClain KL, Kaplan SL (2001). "Aseptic meningitis in a child after systemic treatment with high dose cytarabine". Pediatr Infect Dis J. 20 (1): 87–9. PMID 11176579.
  20. ↑ Baker WJ, Royer GL, Weiss RB (1991). "Cytarabine and neurologic toxicity". J Clin Oncol. 9 (4): 679–93. PMID 1648599.
  21. ↑ Grossman L, Baker MA, Sutton DM, Deck JH (1983). "Central nervous system toxicity of high-dose cytosine arabinoside". Med Pediatr Oncol. 11 (4): 246–50. PMID 6888324.
  22. ↑ 22.0 22.1 Herzig RH, Hines JD, Herzig GP, Wolff SN, Cassileth PA, Lazarus HM; et al. (1987). "Cerebellar toxicity with high-dose cytosine arabinoside". J Clin Oncol. 5 (6): 927–32. PMID 3585447.
  23. ↑ Powell BL, Zekan PJ, Muss HB, Richards F, Lyerly ES, Capizzi RL (1986). "Ara-C syndrome during low-dose continuous infusion therapy". Med Pediatr Oncol. 14 (6): 310–2. PMID 3784982.
  24. ↑ Hasle H (1990). "Cerebellar toxicity during cytarabine therapy associated with renal insufficiency". Cancer Chemother Pharmacol. 27 (1): 76–8. PMID 2245495.
  25. ↑ Smith GA, Damon LE, Rugo HS, Ries CA, Linker CA (1997). "High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency". J Clin Oncol. 15 (2): 833–9. PMID 9053511.
  26. ↑ Wolff L, Zighelboim J, Gale RP (1979). "Paraplegia following intrathecal cytosine arabinoside". Cancer. 43 (1): 83–5. PMID 282937.
  27. ↑ Luque FA, Selhorst JB, Petruska P (1987). "Parkinsonism induced by high-dose cytosine arabinoside". Mov Disord. 2 (3): 219–22. doi:10.1002/mds.870020309. PMID 3504550.
  28. ↑ Fort JA, Smith LD (1999). "Pseudotumor cerebri secondary to intermediate-dose cytarabine HCl". Ann Pharmacother. 33 (5): 576–8. PMID 10369621.
  29. ↑ Hopen G, Mondino BJ, Johnson BL, Chervenick PA (1981). "Corneal toxicity with systemic cytarabine". Am J Ophthalmol. 91 (4): 500–4. PMID 6939330.
  30. ↑ Schwartz J, Alster Y, Ben-Tal O, Lowenstein A (2000). "Visual loss following high-dose cytosine arabinoside (ARA-C)". Eur J Haematol. 64 (3): 208–9. PMID 10997890.
  31. ↑ Renert WA, Berdon WE, Baker DH (1973). "Hemorrhagic cystitis and vesicoureteral reflux secondary to cytotoxic therapy for childhood malignancies". Am J Roentgenol Radium Ther Nucl Med. 117 (3): 664–9. PMID 4511884.
  32. ↑ Tanaka M, Kanamori H, Yamaji S, Mishima A, Fujita H, Fujisawa S; et al. (1999). "Low-dose cytarabine-induced hepatic and renal dysfunction in a patient with myelodysplastic syndrome". Anticancer Drugs. 10 (3): 289–91. PMID 10327034.
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