Pyrimidine analogues
Pyrimidine analogues are a diverse group of drugs that
inhibitproduction of pyrimidine nucleotides necessary for DNA synthe-sis. They
include:
·
capecitabine
·
cytarabine
·
floxuridine
·
fluorouracil
·
gemcitabine.
Because pyrimidine analogues are poorly absorbed
when they’re given orally, they’re usually administered by other routes.
With the exception of cytarabine, pyrimidine
analogues are well distributed throughout the body, including in cerebrospinal
fluid (CSF). They’re metabolized extensively in the liver and are excret-ed in
urine. Intrathecal cytarabine may be given with or without cranial radiation to
treat CNS leukemia.
Pyrimidine analogues kill cancer cells by
interfering with the nat-ural function ofpyrimidine nucleotides. (See How pyrimidineanalogues work.)
Pyrimidine analogues may be used to treat many
tumors. Howev-er, they’re primarily indicated in the treatment of:
§ acute leukemias
§ GI tract adenocarcinomas, such as colorectal,
pancreatic, esophageal, and stomach adenocarcinomas cancers of the breast and
ovaries
§ malignant lymphomas.
No significant drug interactions occur with most of
the pyrimidine analogues; however, several drug interactions are possible with
capecitabine.
·
Antacids, when given
with capecitabine, may increase absorption of capecitabine.
·
Capecitabine can
increase the pharmacodynamic effects of warfarin, thereby increasing the risk
of bleeding.
·
Capecitabine may
increase serum phenytoin levels. (See Adverse
reactions to pyrimidine analogues.)
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