Marrow Toxicity), although the latter can also experience severe toxicity. Maintenance of remission generally involves multiple-drug regimens whose component agents cause myelosuppression. Anemia, leukopenia, and thrombocytopenia are frequently observed. Dosages and also schedules are adjusted to prevent life-threatening cytopenias.
Renal
Hyperuricemia and/or hyperuricosuria may occur in patients receiving Purinethol as a consequence of rapid cell lysis accompanying the antineoplastic effect. Renal adverse effects can be minimized by increased hydration, urine alkalinization, and the prophylactic administration of a xanthine oxidase inhibitor such as allopurinol. The dosage of Purinethol should be reduced to one third to one quarter of the usual dose if allopurinol is given concurrently.
Gastrointestinal
Intestinal ulceration has been reported. Nausea, vomiting, and anorexia are uncommon during initial administration, but may increase with continued administration. Mild diarrhea and sprue-like symptoms have been noted occasionally, but it is difficult at present to attribute these to the medication. Oral lesions are rarely seen, and when they occur they resemble thrush rather than antifolic ulcerations.
Miscellaneous
The administration of Purinethol has been associated with skin rashes and hyperpigmentation. Alopecia has been reported.
Drug fever has been very rarely reported with Purinethol. Before attributing fever to Purinethol, every attempt should be made to exclude more common causes of pyrexia, such as sepsis, in patients with acute leukemia.
Oligospermia has been reported.
Overdosage
Signs and symptoms of overdosage may be immediate (anorexia, nausea, vomiting, and diarrhea); or delayed (myelosuppression, liver dysfunction, and gastroenteritis). Dialysis cannot be expected to clear mercaptopurine. Hemodialysis is thought to be of marginal use due to the rapid intracellular incorporation of mercaptopurine into active metabolites with long persistence. The oral LD50 of mercaptopurine was determined to be 480 mg/kg in the mouse and 425 mg/kg in the rat.
There is no known pharmacologic antagonist of mercaptopurine. The drug should be discontinued immediately if unintended toxicity occurs during treatment. If a patient is seen immediately following an accidental overdosage of the drug, it may be useful to induce emesis.
Purinethol Dosage and Administration
Maintenance Therapy
Once a complete hematologic remission is obtained, maintenance therapy is considered essential. Maintenance doses will vary from patient to patient. The usual daily maintenance dose of Purinethol is 1.5 to 2.5 mg/kg/day as a single dose. It is to be emphasized that in pediatric patients with acute lymphatic leukemia in remission, superior results have been obtained when Purinethol has been combined with other agents (most frequently with methotrexate) for remission maintenance. Purinethol should rarely be relied upon as a single agent for the maintenance of remissions induced in acute leukemia.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Dosage with Concomitant Allopurinol
When allopurinol and mercaptopurine are administered concomitantly, the dose of mercaptopurine must be red |
