General: The safe and effective use of mercaptopurine demands close monitoring of the CBC and patient clinical status. After selection of an initial dosage schedule, therapy will frequently need to be modified depending upon the patient's response and manifestations of toxicity. It is probably advisable to start with lower dosages in patients with impaired renal function, due to slower elimination of the drug and metabolites and a greater cumulative effects. 

Information for Patients: Patients should be informed that the major toxicities of mercaptopurine are related to myelosuppression, hepatotoxicity, and gastrointestinal toxicity. Patients should never be allowed to take the drug without medical supervision and should be advised to consult their physician if they experience fever, sore throat, jaundice, nausea, vomiting, signs of local infection, bleeding from any site, or symptoms suggestive of anemia. Women of childbearing potential should be advised to avoid becoming pregnant. 

Laboratory Tests: (Also see WARNINGS, Bone Marrow Toxicity) It is recommended that evaluation of the hemoglobin or hematocrit, total white blood cell count and differential count, and quantitative platelet count be obtained weekly while the patient is on therapy with mercaptopurine. Bone marrow examination may also be useful for the evaluation of marrow status. The decision to increase, decrease, continue, or discontinue a given dosage of mercaptopurine must be based upon the degree of severity and rapidity with which changes are occurring. In many instances, particularly during the induction phase of acute leukemia, complete blood counts will need to be done more frequently than once weekly in order to evaluate the effect of the therapy. If a patient has clinical or laboratory evidence of severe bone marrow toxicity, particularly myelosuppression, TPMT testing should be considered. 

TPMT Testing: Genotypic and phenotypic testing of TPMT status are available. Genotypic testing can determine the allelic pattern of a patient. Currently, 3 alleles—TPMT*2, TPMT*3A and TPMT*3C—account for about 95% of individuals with reduced levels of TPMT activity. Individuals homozygous for these alleles are TPMT deficient and those heterozygous for these alleles have variable TPMT (low or intermediate) activity. Phenotypic testing determines the level of thiopurine nucleotides or TPMT activity in erythrocytes and can also be informative. Caution must be used with phenotyping since some co-administered drugs can influence measurement of TPMT activity in blood, and recent blood transfusions will misrepresent a patient's actual TPMT activity. 

Drug Interactions: When allopurinol and mercaptopurine are administered concomitantly, the dose of mercaptopurine must be reduced to one third to one quarter of the usual dose to avoid severe toxicity. 

There is usually complete cross-resistance between mercaptopurine and thioguanine. 

The dosage of mercaptopurine may need to be reduced when this agent is combined with other drugs whose primary or secondary toxicity is myelosuppression. Enhanced marrow suppression has been noted in some patients also receiving trimethoprim-sulfamethoxazole. 

Inhibition of the anticoagulant effect of warfarin, when given with mercaptopurine, has been reported. 

As there is in vitro evidence that aminosalicylate derivatives (e.g., olsalazine, mesalazine, or sulphasalazine) inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent mercaptopurine therapy (see WARNINGS). 

Carcinogenesis, Mutagenesis, Impairment of Fertility: Mercaptopurine causes chromosomal aberrations in animals and humans and induces dominant-lethal mutations in male mice. In mice, surviving female offspring of mothers who received chronic low doses of mercaptopurine during pregnancy were found sterile, or if they became pregnant, had smaller litters and more dead fetuses as compared to control animals. Carcinogenic potential exists in humans, but the extent of the risk is unknown. 

The effect of mercaptopurine on human fertility is unknown for either males or females. 

Pregnancy: Teratogenic Effects: Pregnancy Category D. See WARNINGS section. 

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from mercaptopurine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 

Pediatric Use: See DOSAGE AND ADMINISTRATION section. 

Geriatric Use: Clinical studies of mercaptopurine therapy did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.