DRUGS & SUPPLEMENTS

Mercaptopurine

Name: Mercaptopurine drug & pharmaceuticals. Available Forms, Doses, Prices
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Published: 2021-11-11T10:10:10+00:00

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Mercaptopurine uses

Indications and usage
Contraindications
Warnings
Precautions
Adverse reactions
Overdosage
Dosage and administration
How supplied
References
Mercaptopurine reviews

INDICATIONS AND USAGE

Mercaptopurine tablets are indicated for maintenance therapy of acute lymphatic (lymphocytic, lymophoblastic) leukemia as part of a combination regimen. The response to this agent depends upon the particular subclassification of acute lymphatic leukemia and the age of the patient (pediatric or adult).

Mercaptopurine tablets are not effective 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.

CONTRAINDICATIONS

Mercaptopurine tablets 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 tablets should not be used in patients who have a hypersensitivity to Mercaptopurine or any component of the formulation.

WARNINGS

Mercaptopurine is mutagenic in animals and humans, carcinogenic in animals, and may increase the patient's risk of neoplasia. Cases of hepatosplenic T-cell lymphoma have been reported in patients treated with Mercaptopurine for inflammatory bowel disease. The safety and efficacy of Mercaptopurine in patients with inflammatory bowel disease have not been established.

Bone Marrow Toxicity

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 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 myelosuppressive chemotherapy as required for treatment.

Bone marrow toxicity may be more profound in patients treated with concomitant allopurinol. This problem could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalamine, or sulfasalazine.

Hepatotoxicity

Mercaptopurine is hepatotoxic in animals and humans. A small number of deaths have been reported that may have been attributed to hepatic necrosis due to administration of Mercaptopurine. Hepatic injury can occur with any dosage, but seems to occur with more frequency when doses of 2.5 mg/kg/day are exceeded. The histologic pattern of Mercaptopurine hepatotoxicity includes features of both intrahepatic cholestasis and parenchymal cell necrosis, either of which may predominate. It is not clear how much of the hepatic damage is due to direct toxicity from the drug and how much may be due to a hypersensitivity reaction. In some patients jaundice has cleared following withdrawal of Mercaptopurine and reappeared with its reintroduction.

Published reports have cited widely varying incidences of overt hepatotoxicity. In a large series of patients with various neoplastic diseases, Mercaptopurine was administered orally in doses ranging from 2.5 mg/kg to 5 mg/kg without evidence of hepatotoxicity. It was noted by the authors that no definite clinical evidence of liver damage could be ascribed to the drug, although an occasional case of serum hepatitis did occur in patients receiving 6-MP who previously had transfusions. In reports of smaller cohorts of adult and pediatric leukemic patients, the incidence of hepatotoxicity ranged from 0% to 6%. In an isolated report by Einhorn and Davidsohn, jaundice was observed more frequently (40%), especially when doses exceeded 2.5 mg/kg. Usually, clinically detectable jaundice appears early in the course of treatment (1 to 2 months). However, jaundice has been reported as early as 1 week and as late as 8 years after the start of treatment with Mercaptopurine. The hepatotoxicity has been associated in some cases with anorexia, diarrhea, jaundice and ascites. Hepatic encephalopathy has occurred.

Monitoring of serum transaminase levels, alkaline phosphatase, and bilirubin levels may allow early detection of hepatotoxicity. It is advisable to monitor these liver function tests at weekly intervals when first beginning therapy and at monthly intervals thereafter. Liver function tests may be advisable more frequently in patients who are receiving Mercaptopurine with other hepatotoxic drugs or with known pre-existing liver disease. The onset of clinical jaundice, hepatomegaly, or anorexia with tenderness in the right hypochondriuim are immediate indications for withholding Mercaptopurine until the exact etiology can be identified. Likewise, any evidence of deterioration in liver function studies, toxic hepatitis, or biliary stasis should prompt discontinuation of the drug and a search for an etiology of the hepatotoxicity.

The concomitant administration of Mercaptopurine with other hepatotoxic agents requires especially careful clinical and biochemical monitoring of hepatic function. Combination therapy involving Mercaptopurine with other drugs not felt to be hepatotoxic should nevertheless be approached with caution. The combination of Mercaptopurine with doxorubicin was reported to be hepatotoxic in 19 of 20 patients undergoing remission-induction therapy for leukemia resistant to previous therapy.

Immunosuppression

Mercaptopurine recipients may manifest decreased cellular hypersensitivities and decreased allograft rejection. Induction of immunity to infectious agents or vaccines will be subnormal in these patients; the degree of immunosuppression will depend on antigen dose and temporal relationship to drug. This immunosuppressive effect should be carefully considered with regard to intercurrent infections and risk of subsequent neoplasia.

Pregnancy

Pregnancy Category D

Mercaptopurine can cause fetal harm when administered to a pregnant woman. Women receiving Mercaptopurine in the first trimester of pregnancy have an increased incidence of abortion; the risk of malformation in offspring surviving first trimester exposure is not accurately known. In a series of 28 women receiving Mercaptopurine after the first trimester of pregnancy, 3 mothers died undelivered, 1 delivered a stillborn child, and 1 aborted; there were no cases of macroscopically abnormal fetuses. Since such experience cannot exclude the possibility of fetal damage, Mercaptopurine should be used during pregnancy only if the benefit clearly justifies the possible risk to the fetus, and particular caution should be given to the use of Mercaptopurine in the first trimester of pregnancy.

There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

PRECAUTIONS

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 effect.

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

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 the 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 inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent Mercaptopurine therapy.

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

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

Geriatric Use

Clinical studies of Mercaptopurine 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.

ADVERSE REACTIONS

The principal and potentially serious toxic effects of Mercaptopurine are bone marrow toxicity and hepatotoxicity.

Hematologic

The most frequent adverse reaction to Mercaptopurine is myelosuppression. The induction of complete remission of acute lymphatic leukemia frequently is associated with marrow hypoplasia. Patients without TPMT enzyme activity (homozygous-deficient) are particularly susceptible to hematologic toxicity, and some patients with low or intermediate TPMT enzyme activity are more susceptible to hematologic toxicity than patients with normal TPMT activity, 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 Mercaptopurine 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 Mercaptopurine 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 Mercaptopurine has been associated with skin rashes and hyperpigmentation. Alopecia has been reported.

Drug fever has been very rarely reported with Mercaptopurine. Before attributing fever to Mercaptopurine, 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.

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 Mercaptopurine tablets 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 Mercaptopurine tablets have been combined with other agents for remission maintenance. Mercaptopurine tablets 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 reduced to one-third to one-quarter of the usual dose to avoid severe toxicity.

Dosage in TPMT-Deficient Patients

Patients with inherited little or no thiopurine S-methyltransferase activity are at increased risk for severe Mercaptopurine toxicity from conventional doses of Mercaptopurine and generally require substantial dose reduction. The optimal starting dose for homozygous deficient patients has not been established.

Most patients with heterozygous TPMT deficiency tolerated recommended Mercaptopurine doses, but some required dose reduction. Genotypic and phenotypic testing of TPMT status are available.

Dosage in Renal and Hepatic Impairment

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 effect. Consideration should be given to reducing the dosage in patients with impaired hepatic function.

HOW SUPPLIED

Mercaptopurine Tablets USP

50 mg supplied as pale yellow, biconvex tablets, with product identification “54 420” on one side and a score on the other side.

NDC 0054-4581-11: Bottle of 25 tablets

NDC 0054-4581-27: Bottle of 250 tablets

Store at 20° to 25°C (68° to 77°F) Store in a dry place. Dispense in a tight, child-resistant container as defined in the USP/NF.

REFERENCES

ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society;1999:32-41.
Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety; Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of Health and Human Services. Public Health Service publication NIH 92-2621.
AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1591.
National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia. 1983;1:426-428.
Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clinicians.1983;33:258-263.
American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm.1990;47:1033-1049.
Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10002106/07 Revised August 2016

Mercaptopurine Tablets USP

NDC 0054-4581-11: Bottle of 25 tablets

Rx only

Mercaptopurine Tablets USP

NDC 0054-4581-27: Bottle of 250 tablets

Rx only

Mercaptopurine pharmaceutical active ingredients containing related brand and generic drugs:

Mercaptopurine

Mercaptopurine available forms, composition, doses:

	Price
Mercaptopurine 50 mg tablet	4.17 USD
Mercaptopurine powder	33.97 USD
Purinethol 50 mg tablet	6.09 USD
Tablets; Oral; Mercaptopurine 50 mg

Mercaptopurine destination | category:

Human:
Antineoplastic agents
Cytotoxic chemotherapy

Mercaptopurine Anatomical Therapeutic Chemical codes:

L01BB02 - Mercaptopurine

Mercaptopurine pharmaceutical companies:

References

Dailymed."MERCAPTOPURINE TABLET [WEST-WARD PHARMACEUTICALS CORP.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Mercaptopurine?

Depending on the reaction of the Mercaptopurine after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Mercaptopurine not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Mercaptopurine addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

Review

sdrugs.com conducted a study on Mercaptopurine, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Mercaptopurine consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.