Is Purinethol affected by genetics?

Yes — the active ingredient is metabolized by a gene known to vary between individuals.

Relevant genes: NUDT15, TPMT

Purinethol is affected by pharmacogenetics through the NUDT15 and TPMT genes. Your genotype for these genes can change how your body processes Purinethol, which can affect both how well it works and how well you tolerate it. The strongest evidence level on this page is Strong, based on CPIC or FDA guidelines.

What's in Purinethol

mercaptopurine affected by NUDT15, TPMT

Affected by NUDT15, TPMT · CPIC, FDA · Strong evidence

Read the full mercaptopurine genetics guide →

Mercaptopurine phenotype recommendations

Published guidance from CPIC and FDA on how mercaptopurine should be dosed or substituted based on your NUDT15, TPMT phenotype.

Phenotype	What it means	Recommendation	Evidence
Normal Function TPMT	Your body processes mercaptopurine at a normal rate. You have a typical risk of side effects, and the standard dose is appropriate for you.	CPIC Start with normal starting dose (e.g., 75 mg/m2/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment. FDA Initiate therapy with recommended starting dose.	Strong
Intermediate Function TPMT	Your body breaks down mercaptopurine more slowly than normal, which increases your risk of serious side effects like low blood cell counts. A lower starting dose is recommended.	CPIC Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m2/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m2/day or < 1.5 mg/kg/day, dose reduction may not be recommended. FDA Reduce dose based on tolerability per FDA labeling. Monitor closely for myelosuppression. More substantial reductions may be needed if intermediate for both TPMT and NUDT15.	Strong
Possible Intermediate Metabolizer TPMT	Your body may break down mercaptopurine more slowly than normal, which could increase your risk of serious side effects like low blood cell counts. A lower starting dose is recommended.	CPIC Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m2/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m2/day or < 1.5 mg/kg/day, dose reduction may not be recommended. FDA Reduce dose based on tolerability per FDA labeling. Monitor closely for myelosuppression.	Strong
Poor Function TPMT	Your body breaks down mercaptopurine very slowly, which can cause dangerously high drug levels and life-threatening side effects. A drastically reduced dose or an alternative medication is essential.	CPIC For malignancy, start with drastically reduced doses (reduce daily dose by 10-fold and reduce frequency to thrice weekly instead of daily, e.g. 10 mg/m2/day given just 3 days/week) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. FDA Drastically reduce initial dose to 10% or less of recommended dosage per FDA labeling. Consider alternative therapy. Monitor closely for myelosuppression.	Strong
Indeterminate TPMT	The impact of your genotype on response to this drug is unknown.	CPIC No recommendation. FDA Initiate therapy with recommended starting dose.	—
Not available TPMT	The impact of your genotype on response to this drug is unknown.	CPIC No recommendation. FDA Initiate therapy with recommended starting dose.	—
Normal Metabolizer NUDT15	Your body processes mercaptopurine at a normal rate based on your NUDT15 gene. You have a typical risk of side effects, and the standard dose is appropriate.	CPIC Start with normal starting dose (e.g., 75 mg/m2/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment. FDA Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer NUDT15	Your body has a reduced ability to process mercaptopurine based on your NUDT15 gene, which increases your risk of serious side effects like low blood cell counts. A lower starting dose is recommended.	CPIC Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m2/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m2/day or 1.5 mg/kg/day, dose reduction may not be recommended. FDA Reduce dose based on tolerability per FDA labeling. Monitor closely for myelosuppression. More substantial reductions may be needed if intermediate for both TPMT and NUDT15.	Strong
Possible Intermediate Metabolizer NUDT15	Your body may have a reduced ability to process mercaptopurine based on your NUDT15 gene, which could increase your risk of serious side effects like low blood cell counts. A lower starting dose is recommended.	CPIC Start with reduced starting doses (30-80% of normal dose) if normal starting dose is > or = 75 mg/m2/day or > or = 1.5 mg/kg/day (e.g. start at 25-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. If normal starting dose is already < 75 mg/m2/day or 1.5 mg/kg/day, dose reduction may not be recommended. FDA Reduce dose based on tolerability per FDA labeling. Monitor closely for myelosuppression.	Strong
Poor Metabolizer NUDT15	Your body has a greatly reduced ability to process mercaptopurine based on your NUDT15 gene, which puts you at high risk for life-threatening side effects. A drastically reduced dose or an alternative medication is essential.	CPIC For malignancy, initiate dose 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 dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For non-malignant conditions, consider alternative non-thiopurine immunosuppressant therapy. FDA Drastically reduce initial dose to 10% or less of recommended dosage per FDA labeling. Consider alternative therapy. Monitor closely for myelosuppression.	Strong
Indeterminate NUDT15	The impact of your genotype on response to this drug is unknown	CPIC + FDA Initiate therapy with recommended starting dose.	—
Not available NUDT15	The impact of your genotype on response to this drug is unknown	CPIC + FDA Initiate therapy with recommended starting dose.	—

Sources: CPIC, FDA

The gene behind the guidance

TPMT Thiopurine S-Methyltransferase

TPMT inactivates thiopurine drugs like azathioprine, mercaptopurine, and thioguanine. About 1 in 300 people of European descent has essentially no TPMT activity, and standard doses can cause life-threatening bone marrow suppression in those people within weeks. Intermediate activity affects around 10 percent of people and still requires dose reduction.

TPMT testing is one of the oldest and most established pharmacogenetic tests. Most rheumatologists, gastroenterologists, and oncologists order it before starting thiopurine therapy.

See all drugs affected by TPMT →

Browse the full drug-class: Chemotherapy agents.

Related medications

Find out how your genetics affect Purinethol

This page describes the general pharmacogenetics. A Gene2Rx report analyzes your own DNA to tell you which metabolizer group you fall into, across every medication.

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Informational only — not medical advice. Pharmacogenetic guidance describes population-level patterns; your individual response depends on many factors. Never start, stop, or change a medication without talking to your prescribing clinician.