Cytarabine

Brand names: Cytosar-U®

Chemical formula:

Español:
• Citarabina, Solución para inyección

Cytarabine Solution for injection

What is this medicine?

CYTARABINE, ARA-C is a chemotherapy drug. This medicine reduces the growth of cancer cells and can suppress the immune system. It is used for treating leukemias or lymphomas. It is often given with other cancer drugs.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• bleeding problems
• infection (especially a virus infection such as chickenpox, cold sores, or herpes)
• kidney disease
• liver disease
• recent or ongoing radiation therapy
• an unusual or allergic reaction to cytarabine or ARA-C, benzyl alcohol, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

This medicine is for injection or infusion into a vein, or for injection under the skin. It may also be given into the spinal fluid. It is administered in a hospital or clinic by a doctor or health care professional.

Talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

• digoxin
• fluorocytosine
• gentamicin
• vaccines

Talk to your doctor or health care professional before taking any of these medicines:
• aspirin
• acetaminophen
• ibuprofen
• ketoprofen
• naproxen

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor for checks on your progress. This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.

In some cases, you may be given additional medicines to help with side effects. Follow all directions for their use.

Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body's ability to fight infections. Try to avoid being around people who are sick.

This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.

Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.

Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.

Do not have any vaccinations without your doctor's approval and avoid anyone who has recently had oral polio vaccine.

Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
• low blood counts - this medicine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
• signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
• signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
• signs of decreased red blood cells - unusually weak or tired, fainting spells, lightheadedness
• breathing problems
• changes in vision
• feeling faint or lightheaded, falls
• fever
• headache
• mouth sores
• neck stiffness and/or pain
• seizures
• stomach pain
• unsteady in walking
• vomiting

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
• bone pain or muscle aches and pains
• confusion
• dizziness
• feeling tired and weak
• loss of appetite
• nausea

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

This drug is given in a hospital or clinic and will not be stored at home.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

A compound of arabinose and cytosine that inhibits both DNA synthesis and the proliferation of viruses that contain DNA, used as a chemotherapeutic agent. Also called cytarabine.

An antimetabolite that inhibits DNA synthesis, and hence has antineoplastic and antiviral properties. Called also cytosine arabinoside, arabinosyl cytosine, ara-C.

Cytarabine

Systematic (IUPAC) name
4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one
Identifiers
CAS number	147-94-4
ATC code	L01BC01
PubChem	6253
DrugBank	APRD00499
ChemSpider	6017
Chemical data
Formula	C9H13N3O5
Mol. mass	243.217 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	20% oral
Protein binding	13%
Metabolism	Liver
Half life	biphasic: 10 min, 1-3 hr
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	D (USA); D (Aus)
Legal status
Routes	Injectable (intravenous injection or infusion, intrathecal, or subcutaneously)
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Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of hematological malignancies such as acute myeloid leukemia (AML) and non-Hodgkin lymphoma.^[1] It is also known as ara C.^[2]

Contents 1 History 2 Pharmacology 2.1 Mechanism 2.2 Pharmacokinetics 3 Clinical uses 4 Side Effects 5 Brand names 6 External links 7 References

History

Cytarabine was discovered in Europe in the 1960s. It was approved by the United States Food and Drug Administration in June 1969, and was initially marketed in the US by Upjohn under the trade name Cytosar-U.

Pharmacology

Mechanism

Cytosine arabinoside is an antimetabolic agent with the chemical name of 1β-arabinofuranosylcytosine. Its mode of action is due to its rapid conversion into cytosine arabinoside triphosphate, which damages DNA when the cell cycle holds in the S phase (synthesis of DNA). Rapidly dividing cells, which require DNA replication for mitosis, are therefore most affected. Cytosine arabinoside also inhibits both DNA^[3] and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis.

When used as an antiviral, cytarabine functions by inhibiting deoxycytidine use.^[4]

Cytarabine is rapidly deaminated in the body into the inactive uracil derivative and therefore is often given by continuous intravenous infusion.

Pharmacokinetics

Orally, less than 20% of a dose of cytarabine is absorbed from the gastrointestinal tract and is ineffective by this route. Subcutaneously or intramuscularly, tritium-labelled cytarabine produces peak plasma concentrations of radioactivity within 20 to 60 minutes which are considerably lower than those attained after intravenous administration. Continuous intravenous infusions produce relatively constant plasma levels in 8 to 24 hours.

Intravenous doses of cytarabine exhibit a biphasic elimination, with an initial distribution half-life of about ten minutes during which time a major portion of the drug is metabolised in the liver to the inactive metabolite uracil arabinoside. The secondary elimination half-life is longer, approximately one to three hours. Metabolism also occurs in the kidneys, gastrointestinal mucosa, granulocytes and other tissues.

Cytarabine is mainly excreted via the kidney with 70 to 80% of a dose administered by any route appearing in the urine within 24 hours; approximately 90% as the metabolite and 10% as unchanged drug.

Clinical uses

Cytarabine is mainly used in the treatment of acute myeloid leukaemia, acute lymphocytic leukaemia (ALL) and in lymphomas,^[5] where it is the backbone of induction chemotherapy. Cytarabine also possesses antiviral activity, and it has been used for the treatment of generalised herpesvirus infection. However, cytarabine is not very selective in this setting and causes bone marrow suppression and other severe side effects, so it is used mainly for the chemotherapy of hematologic cancers.

One of the unique toxicities of cytarabine is cerebellar toxicity when given in high doses.

Cytarabine is also used in the study of the nervous system to control the proliferation of glial cells in cultures, the amount of glial cells having an important impact on neurons.

Side Effects

Possible infection resulting from granulocytopenia and other impaired body defences, and hemorrhage secondary to thrombocytopenia

Toxicity: Leukopenia, Thrombocytopenia, anemia, GI disturbances, stomatitis, conjunctivitis, pneumonitis, fever, and dermatitis, Palmar-Plantar Erythrodysesthesia.

Rarely, myelopathy has been reported after high dose or frequent intrathecal Ara-C administration [Watterson J, et al. Cancer,1994;74:3034-3041].

Brand names

• Cytosar-U
• Tarabine PFS
• Depocyt (longer-lasting liposomal formulation)

External links

• MedlinePlus page on cytarabine
• ADAP drugs page on cytarabine
• BC Cancer network page on cytarabine
• Chembank entry
• Sea to Ara C An essay on the history of cytarabine.

References

1. ^ Wang WS, Tzeng CH, Chiou TJ, et al. (June 1997). "High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin's lymphoma". Jpn. J. Clin. Oncol. 27 (3): 154–7. doi:10.1093/jjco/27.3.154. PMID 9255269. http://jjco.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9255269. 
2. ^ Ogbomo H, Michaelis M, Klassert D, Doerr HW, Cinatl J (December 2008). "Resistance to cytarabine induces the up-regulation of NKG2D ligands and enhances natural killer cell lysis of leukemic cells". Neoplasia 10 (12): 1402–10. PMID 19048119. PMC 2586691. http://www.neoplasia.com/abstract.php?msid=1944. 
3. ^ Perry, Michael J. (2008). The Chemotherapy source book. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 80. ISBN 0-7817-7328-8. 
4. ^ Lemke, Thomas L.; Williams, David H.; Foye, William O. (2002). Foye's principles of medicinal chemistry. Hagerstwon, MD: Lippincott Williams & Wilkins. pp. 963. ISBN 0-683-30737-1. 
5. ^ Pigneux A, Perreau V, Jourdan E, et al. (October 2007). "Adding lomustine to idarubicin and cytarabine for induction chemotherapy in older patients with acute myeloid leukemia: the BGMT 95 trial results". Haematologica 92 (10): 1327–34. doi:10.3324/haematol.11068. PMID 18024370. http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=18024370. 

v • d • e Intracellular chemotherapeutic agents/antineoplastic agents (L01) SPs/MIs (M phase) Block microtubule assembly Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine) Block microtubule disassembly Taxanes (Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) · Epothilones (Ixabepilone) DNA replication inhibitor DNA precursors/ antimetabolites (S phase) Folic acid dihydrofolate reductase inhibitor (Aminopterin, Methotrexate, Pemetrexed) · thymidylate synthase inhibitor (Raltitrexed, Pemetrexed) Purine adenosine deaminase inhibitor (Pentostatin) halogenated/ribonucleotide reductase inhibitors (Cladribine, Clofarabine, Fludarabine) thiopurine (Thioguanine, Mercaptopurine) Pyrimidine thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur, Carmofur, Floxuridine) DNA polymerase inhibitor (Cytarabine) ribonucleotide reductase inhibitor (Gemcitabine) hypomethylating agent (Azacitidine, Decitabine) Deoxyribonucleotide ribonucleotide reductase inhibitor (Hydroxyurea) Topoisomerase inhibitors (S phase) I Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan) II Podophyllum (Etoposide, Teniposide) II+Intercalation Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) · Anthracenediones (Mitoxantrone, Pixantrone) Crosslinking of DNA (CCNS) Alkylating Nitrogen mustards: Mechlorethamine · Cyclophosphamide (Ifosfamide, Trofosfamide) · Chlorambucil (Melphalan, Prednimustine) · Bendamustine · Uramustine · Estramustine Nitrosoureas: Carmustine · Lomustine (Semustine) · Fotemustine · Nimustine · Ranimustine · Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan, Treosulfan) Aziridines: Carboquone · ThioTEPA · Triaziquone · Triethylenemelamine Alkylating-like Platinum (Carboplatin, Cisplatin, Nedaplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin) Nonclassical Hydrazines (Procarbazine) · Triazenes (Dacarbazine, Temozolomide) · Altretamine · Mitobronitol Intercalation Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) Photosensitizers/PDT Aminolevulinic acid/Methyl aminolevulinate · Efaproxiral · Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin) Other Enzyme inhibitors FI (Tipifarnib)  · CDK inhibitors (Alvocidib, Seliciclib) · PrI (Bortezomib) · PhI (Anagrelide) · IMPDI (Tiazofurine) · LI (Masoprocol) · PARP inhibitor (Olaparib) · HDAC (Vorinostat, Romidepsin) Receptor antagonists ERA (Atrasentan) · retinoid X receptor (Bexarotene) · sex steroid (Testolactone) Other/ungrouped Amsacrine · Trabectedin · retinoids (Alitretinoin, Tretinoin) · Arsenic trioxide · asparagine depleter (Asparaginase/Pegaspargase) · Celecoxib · Demecolcine · Elesclomol · Elsamitrucin · Etoglucid · Lonidamine · Lucanthone · Mitoguazone · Mitotane · Oblimersen · Temsirolimus

v • d • e DNA virus Antivirals (primarily J05, also S01AD and D06BB) Baltimore I Herpesvirus DNA synthesis inhibitor TK activated Purine analogue guanine (Aciclovir#/Valaciclovir, Ganciclovir/Valganciclovir, Penciclovir/Famciclovir) adenine (Vidarabine, Cytarabine) Pyrimidine analogue uridine (Idoxuridine, Trifluridine, Edoxudine) thymine (Brivudine) Not TK activated Foscarnet Other Docosanol · early protein (Fomivirsen) · Tromantadine HPV/MC Imiquimod/Resiquimod · Podophyllotoxin Vaccinia assembly: Rifampicin Poxviridae Methisazone Hepatitis B (VII) Nucleoside analogues/NARTIs: Entecavir · Lamivudine · Telbivudine · Clevudine Nucleotide analogues/NtRTIs: Adefovir · Tenofovir Multiple/general Nucleic acid inhibitors Cidofovir Interferon Interferon alfa-2b · Peginterferon alfa-2a Multiple/unknown Ribavirin#/Taribavirin† ErbB2/PI3K Pathway NOV-205§ · NOV-002† #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III

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