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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: November 3, 2017.



Cytarabine is a cytosine analogue and antineoplastic agent used largely in the therapy of acute leukemia. Cytarabine is associated with a low rate of transient serum enzyme and bilirubin elevations during therapy, but has only rarely been implicated in cases of clinically apparent acute liver injury with jaundice.


Cytarabine (sye tar' a been) is an nucleoside analogue (cytosine arabinoside: ara-C) which is converted intracellularly to a triphosphate, which competes with cytosine triphosphate for incorporation into RNA and DNA and acts as an inhibitor of RNA and DNA polymerase, thus blocking DNA synthesis and cell division. Cytarabine has potent activity in acute leukemia and was approved for use in the United States in 1969 and is still widely used. Current indications include initial, consolidation and maintenance therapy of acute myelogenous and other acute leukemias. Cytarabine is available in vials of 100, 500, 1000 and 2000 mg (20 mg/mL) for intravenous or intrathecal infusion generically and under the brand name Cytosar-U. Liposomal sustained release formulations are also available for intrathecal administration (DepoCyt). The dose regimen of cytarabine varies by body surface area and indication. A typical induction dose is 100 mg per meter squared by continuous intravenous infusion on days 1 to 7. Common side effects include bone marrow suppression, nausea, vomiting, oral or anal ulcers, abdominal pain, myalgias, bone pain, chest pain, conjunctivitis headache, fatigue, fever, rash and pruritus.


Serum aminotransferase elevations occur in 5% to 10% of patients on conventional doses of cytarabine and a greater proportion (9% to 75%) at higher doses. However, the serum enzyme elevations are rarely associated with symptoms and are generally self-limited and resolve rapidly, rarely requiring dose modification. Cases of clinically apparent liver injury attributed to cytarabine have been reported but are uncommon. The time to onset was usually within the first few cycles of therapy, and the pattern of serum enzyme elevations ranged from cholestatic to hepatocellular. Immunoallergic and autoimmune features were generally not present. Antineoplastic regimens, including cytarabine, have been implicated in cases of sinusoidal obstruction syndrome and peliosis, but the role of cytarabine in these reactions was unclear. Many examples of liver injury attributed to cytarabine in the literature were typical of jaundice of sepsis rather than acute hepatocellular or cholestatic injury, although high doses of cytarabine may cause hyperbilirubinemia independent of hepatic injury.

Likelihood score: C (probable cause of clinically apparent liver injury).

Mechanism of Injury

While hepatotoxicity from cytarabine may be rare, it is likely due to direct toxicity to hepatocytes. Cytarabine is metabolized in the liver via the cytochrome P450 system and production of a toxic or immunogenic intermediate may trigger liver injury.

Outcome and Management

The severity of the liver injury linked to cytarabine therapy is usually mild and self-limited. Cytarabine has been linked to cases of acute liver failure but the relationship to cytarabine has not always been clear. Cytarabine has not been linked chronic hepatitis or vanishing bile duct syndrome. The product label for cytarabine recommends "periodic checks" of bone marrow, renal and kidney function" during therapy. There is no information on cross sensitivity to hepatic injury between cytarabine and other pyrimidine analogues.

Drug Class: Antineoplastic Agents

Other Drugs in the Subclass, Pyrimidine Analogues: Azacitidine, Capecitabine, Decitabine, Floxuridine, Fluorouracil, Gemcitabine, Trifluridine/Tipracil



Cytarabine – Generic, Cytosar-U®, DepoCyt®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Cytarabine 147-94-4 C9-H13-N3-O5
Cytarabine Chemical Structure


References updated: 03 November 2017

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    (28 year old man with acute leukemia in relapse was treated with cytarabine [3 g/m2 every 12 hours for 9 doses], developing fever and jaundice [bilirubin 9.2 rising to 45 mg/dL, ALT 88 U/L, Alk P 55 U/L], followed by progressive multiorgan failure and dying within 11 days of starting therapy; autopsy showed bile stasis and centrolobular steatosis).
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    (47 year old man with AML developed jaundice with normal ALT and Alk P levels after a course of cytarabine, idarubicin and etoposide [bilirubin 1.6 on day 8 rising to 14.9 mg/dL on day 26], course complicated by sepsis and hypotension).
  • Advani AS, McDonough S, Coutre S, Wood B, Radich J, Mims M, O'Donnell M, et al. SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for elapsed/refractory acute lymphocytic leukaemia. Br J Haematol 2014; 165: 504-9. [PMC free article: PMC4209396] [PubMed: 24579885]
    (Among 35 adults with refractory ALL treated with clofarabine, cytarabine and epratuzumab [anti-CD22], the response rate was 52%, but adverse events were common, including ALT elevations above 5 times ULN in 11 patients [31%], one of whom had "hepatic failure", but there were no liver related deaths).
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    (Among 11 elderly adults with AML treated with clofarabine with low doses of cytarabine, the response rate was 27%, but the mortality rate rose to 73% at 8 weeks and one death was attributed to hepatic and renal failure).
  • Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, et al; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood 2015; 126: 1415-23. [PMC free article: PMC4624454] [PubMed: 26194764]
    (Among 27 patients with refractory Langerhans cell histiocytosis treated with two 5-day courses of cytarabine and cladribine, the major toxicities were pancytopenia and sepsis; no mention of ALT elevations or hepatotoxicity).
  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 49 [5.5%] [PMC free article: PMC4446235] [PubMed: 25754159]
    were attributed to antineoplastic agents, but none were due to cytarabine).


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