Mercaptopurine (mercaptopurine)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Mercaptopurine, a purine antagonist, is an antineoplastic agent and immunosuppressant.
Mercaptopurine, a purine analog, is a nucleoside metabolic inhibitor. The drug undergoes intracellular transport and activation to form metabolites including thioguanine nucleotides (TGNs). Incorporation of TGNs into DNA or RNA results in cell-cycle arrest and cell death.
TGNs and other mercaptopurine metabolites are also inhibitors of de novo purine synthesis and purine nucleotide interconversions. Mercaptopurine is cytotoxic to proliferating cancer cells in vitro and has antitumor activity in mouse tumor models. It is not known which of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death.
Mercaptopurine is also an immunosuppressant that inhibits the primary immune response.
Following a single oral dose of mercaptopurine 50mg under fasted conditions in healthy individuals, the peak plasma concentration was 69 ng/mL. Food has been shown to decrease the exposure of mercaptopurine. Plasma protein binding is approximately 19% over the concentration range 10-50 mcg/mL (a concentration achieved only by IV administration of mercaptopurine at doses >5-10mg/kg).
There isnegligible entry of mercaptopurine into the cerebrospinal fluid. Mercaptopurine is inactivated via 2 major pathways. One is thiol methylation, which is catalyzed by the polymorphic enzyme thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-mercaptopurine.
The second inactivation pathway is oxidation, which is catalyzed by xanthine oxidase. The product of oxidation is the inactive metabolite 6-thiouric acid. Mercaptopurine is excreted principally in the urine as unchanged drug and metabolites within the first 24 hours.
The elimination half-life is less than 2 hours following a single oral dose.
USES: This medication is used to treat a certain type of cancer (acute lymphocytic leukemia). It is a chemotherapy drug that works by slowing or stopping the growth of cancer cells. Talk to the doctor about the risks and benefits of mercaptopurine, especially when used by children and young adults.
Generic name: mercaptopurine
Pronunciation: (mer-KAP-toe-PURE-een)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Mercaptopurine
Indications
The following indications are listed for Mercaptopurine:
- Acute Lymphoid Leukemia
Also known as: Acute Lymphatic Leukemia, Acute Lymphocytic Leukemia, Acute Lymphogenous Leukemia, Lymphoblastic Leukemia.
Dosing
TPMT intermediate or TPMT possible intermediate metabolizer:CPIC guidelines recommend to start withreduced doses of mercaptopurine(30-80% of normal dose) if starting dose is >=75 mg/m2/day or >=1.5 mg/kg/day (e.g., start at 22.5-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust doses based on degree of myelosuppression and disease specific guidelines. Allow 2-4 weeks to reach steady state after each dosage adjustment. If myelosuppression occurs,emphasis should be on reducing the dosage ofmercaptopurine over other agents, depending on other therapy. If thenormal starting dose is already <75 mg/m2/day or <1.5 mg/kg/day,dosage reduction may not be recommended.
TPMT poor metabolizer: For malignancy, CPIC guidelines state to start with drastically reduced doses of mercaptopurine(reduce daily doseby 10-fold and reduce frequency to three times weekly instead of daily(e.g., 10 mg/m2/day given just 3 days/week) and adjust doses based on degree of myelosuppression and disease specific guidelines. Allow 4-6 weeks to reach steady state after each dosage adjustment. If myelosuppression occurs, an emphasis should be on reducing the dosage ofmercaptopurine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy.
NUDT15 intermediate or NUDT15 possible intermediate metabolizer:Start with reduced mercaptopurinedoses (30-80% of normal dose) if normal starting doseis >=75 mg/m2/day or >=1.5 mg/kg/day (e.g., start at 22.5-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust dosesbased on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady state after each dosage adjustment. If myelosuppression occurs,emphasis should be on reducing mercaptopurine over other agents, depending on other therapy. If thenormal starting dose is already <75 mg/m2/day or <1.5 mg/kg/day, dosage reduction may not berecommended.
NUDT15 poor metabolizer: For malignancy, CPIC guidelines state to initiate the mercaptopurinedose at 10 mg/m2/day and adjust dose based on myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dosage adjustment. If myelosuppression occurs,emphasis should be on reducing the dosage ofmercaptopurine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy.
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Drug interactions
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There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
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There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and effectiveness of mercaptopurine have not been established in pediatric patients, but useof the drug in pediatrics is supported by evidence from the published literature andclinical experience.
Symptomatic hypoglycemia has been reported in pediatric patientswith ALL receiving mercaptopurine. Reported cases were in patients <6 yearsof age or those with a low body mass index.
Mercaptopurine can cause fetal harm when administered to a pregnant woman. Advise pregnant women of thepotential risk to a fetus.
Women receiving mercaptopurine in the first trimester of pregnancy have an increasedincidence of miscarriage; the risk of malformation in offspring surviving first trimesterexposure is not known. In a series of 28 women receiving mercaptopurine after the firsttrimester of pregnancy, 3 died prior to delivery, 1 delivered a stillborn child, and1 aborted; there were no cases of macroscopically abnormal fetuses.
In animal studies, mercaptopurine was embryo-lethal and teratogenic in several animal species (rat,mouse, rabbit, and hamster) at doses less than the recommended human dose.
There are no data on the presence of mercaptopurine or its metabolites in human milk,the effects on the breastfed child, oreffects on milk production. Because of thepotential for serious adverse reactions in the breastfed child, advise women not tobreastfeed during treatment with mercaptopurine and for 1 week after the final dose.
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.
Clinical studies of mercaptopurine did not include sufficient numbers of patients>=65 years of age to determine whether they respond differently from younger patients. Otherreported clinical experience has not identified differences in responses between theelderly and younger patients.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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