Mercaptopurine tablets are indicated for maintenance therapy of acute lymphatic (lymphocytic, lymphoblastic) leukemia as part of a combination regimen.The response to this agent depends upon the particular sub-classification of acute lymphatic leukemia and the age of the patient (pediatric or adult).Mercaptopurine tablets are not effective for prophylaxis or treatment of central nervous system leukemia.Mercaptopurine tablets are not effective in acute myelogenous leukemia, chronic lymphatic leukemia, the lymphomas (including Hodgkins Disease), or solid tumors.
Mercaptopurine should not be used in patients whose disease has demonstrated prior resistance to this drug.In animals and humans, there is usually complete cross-resistance between mercaptopurine and thioguanine.Mercaptopurine should not be used in patients who have a hypersensitivity to mercaptopurine or any component of the formulation.
The most consistent, dose-related toxicity is bone marrow suppression.
This may be manifest by anemia, leukopenia, thrombocytopenia, or any combination of these.
Any of these findings may also reflect progression of the underlying disease.
In many patients with severe depression of the formed elements of the blood due to mercaptopurine, the bone marrow appears hypoplastic on aspiration or biopsy, whereas in other cases it may appear normocellular.
The qualitative changes in the erythroid elements toward the megaloblastic series, characteristically seen with the folic acid antagonists and some other antimetabolites, are not seen with this drug.
Life-threatening infections and bleeding have been observed as a consequence of mercaptopurine-induced granulocytopenia and thrombocytopenia.
Since mercaptopurine may have a delayed effect, it is important to withdraw the medication temporarily at the first sign of an unexpected abnormally large fall in any of the formed elements of the blood, if not attributable to another drug or disease process.Individuals who are homozygous for an inherited defect in the TPMT (thiopurine-S-methyltransferase) gene are unusually sensitive to the myelosuppressive effects of mercaptopurine and prone to developing rapid bone marrow suppression following the initiation of treatment.
Laboratory tests are available, both genotypic and phenotypic, to determine the TPMT status.
Substantial dose reductions are generally required for homozygous-TPMT deficiency patients (two non-functional alleles) to avoid the development of life threatening bone marrow suppression.
Although heterozygous patients with intermediate TPMT activity may have increased mercaptopurine toxicity, this is variable, and the majority of patients tolerate normal doses of mercaptopurine.
If a patient has clinical or laboratory evidence of severe toxicity, particularly myelosuppression, TPMT testing should be considered.
In patients who exhibit excessive myelosuppression due to 6-mercaptopurine, it may be possible to adjust the mercaptopurine dose and administer the usual dosage of other myelo-suppressive chemotherapy as required for treatment (see DOSAGE AND ADMINISTRATION).Bone marrow toxicity may be more profound in patients treated with concomitant allopurinol (see PRECAUTIONS: Drug Interactions and DOSAGE AND ADMINISTRATION).This problem could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine, or sulphasalazine.