Cytarabine: What is it? History, Medical Uses, Side Effects and Mechanism of Action

Also known as cytosine arabinoside (ara-C), it is a chemotherapy drug used to treat acute myeloid leukemia (AML).

As well as to treat acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin’s lymphoma.

Alternative Names for Cytarabine

It is also known as ara-C (arabinofuranosyl cytidine):

  • Cytosar-U.
  • Carabine PFS (Pfizer).
  • Deposit (liposomal formulation of longer duration).
  • Vehicle.

It is given by injection into a vein, under the skin, or spinal fluid. There is a liposomal formulation for which there is tentative evidence of better results in lymphoma involving the meninges.

Common side effects include bone marrow suppression, vomiting, diarrhea, liver problems, rash, ulcers in the mouth, and bleeding. Other serious side effects include loss of consciousness, lung disease, and allergic reactions.

Use during pregnancy can harm the baby. Cytarabine is found in the families of antimetabolite and nucleoside analog drugs. It works by blocking the function of DNA polymerase.

Cytarabine was patented in 1960 and approved for medical use in 1969. It is on the World Health Organization’s List of Essential Drugs, the most effective and safe medicines needed in a health system.


The wholesale cost in the developing world is approximately US $ 4.27 to the US $ 5.70 per 500mg vial. This dose in the UK costs the NHS around 50 pounds, while the liposomal form is 1,223.75 pounds per 50mg vial.


Cytarabine was synthesized for the first time in 1959 by Richard WalwickWalden Roberts, and Charles Dekker at the University of California, Berkeley.

It was approved by the Food and Drug Administration of the United States in June 1969 and was initially marketed in the US. UU By Upjohn under the trade name Cytosar-U.

Medical uses of cytarabine

Cytarabine is used primarily to treat acute myeloid leukemia, acute lymphocytic leukemia (ALL), and lymphomas.

Cytarabine also has antiviral activity and has been used to treat generalized herpes virus infection. However, cytarabine is not very selective in this context and causes suppression of the bone marrow and other serious side effects.

Therefore, cytosine arabinoside is not a beneficial antiviral agent in humans due to its toxic profile and is used primarily for the chemotherapy of hematologic cancers.

Cytarabine is also used in the study of the nervous system to control the proliferation of glial cells in cultures; the number of glial cells has an important impact on neurons.

Side effects

One of the unique toxicities of cytarabine is cerebellar toxicity when administered in high doses, which can cause ataxia.

Cytarabine can cause granulocytopenia and other impaired body defenses, leading to infection, and thrombocytopenia, leading to bleeding.

Toxicity: due to its toxicity, it can cause leukopenia, thrombocytopenia, anemia, gastrointestinal disorders, stomatitis, conjunctivitispneumonitis, fever, and palmoplantar erythrodysesthesia dermatitis.

Rarely myelopathy has been reported after administering a high or frequent dose of intrathecal parabiotic cytosine.

When used in protocols designated as high doses, cytarabine can cause cerebral and cerebellar dysfunction, ocular toxicity, pulmonary toxicity, severe gastrointestinal ulceration, and peripheral neuropathy.

To avoid side effects and improve therapeutic efficacy, various derivatives of these drugs (including amino acids, peptides, fatty acids, and phosphates) have been evaluated, and different administration systems.

Mechanism of action of cytarabine

The cytosine arabinoside combines a cytosine base with an arabinose sugar. It is an antimetabolic agent with the chemical name 1β-arabinofuranosilcitosina.

Certain sponges, where it was initially found, use arabinoside sugars to form a different compound (which is not part of the DNA).

The cytosine arabinoside is sufficiently similar to human cytosine deoxyribose (deoxycytidine) to be incorporated into human DNA but different enough to kill the cell.

Cytosine arabinoside interferes with DNA synthesis. Its mode of action is due to its rapid conversion into cytosine arabinoside triphosphate, which damages DNA when the cell cycle is maintained in the S phase (DNA synthesis).

Cells that divide rapidly, which require DNA replication for mitosis, are the most affected. Cytosine arabinoside also inhibits DNA and RNA polymerases and the nucleotide reductase enzymes necessary for DNA synthesis.

Cytarabine is the first in a series of anti-cancer drugs that alter the sugar component of nucleosides.

Cytarabine is often administered by continuous intravenous infusion, which follows a biphasic elimination: an initial rapid clearance rate followed by a slower analog rate. Cytarabine is transported to the cell mainly by hENT-1.

Then it is monophosphorylated by deoxycytidine kinase, and finally, cytarabine-5′-triphosphate, the active metabolite incorporated into DNA during DNA synthesis.

Several resistance mechanisms have been reported. Cytarabine is rapidly deaminated by cytidine deaminase in serum in the inactive uracil derivative.

Cytarabine-5′-monophosphate is deaminated by deoxycytidylatoaminase, which leads to the inactive uridine-5′-monophosphate analog. Cytarabine-5′-triphosphate is a substrate for SAMDH1.

In addition, SAMHD1 has been shown to limit the effectiveness of cytarabine efficacy in patients. When used as an antiviral, cytarabine-5′-triphosphate works by inhibiting viral DNA synthesis. Cytarabine can inhibit herpes virus and vaccinia virus replication in cells during tissue culture.

However, treatment with cytarabine alone was adequate for herpesvirus infection in a murine model.