Mercaptopurine: Pediatric drug information

For additional information see "Mercaptopurine: Drug information" and "Mercaptopurine: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Purixan

Brand Names: Canada

Purinethol

Therapeutic Category

Antineoplastic Agent, Antimetabolite;
Antineoplastic Agent, Purine

Dosing: Pediatric

Dosage guidance:

Safety: Consider testing for thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency, patients with minimal or no TPMT activity are at increased risk for severe toxicity at conventional mercaptopurine doses and generally require dose reduction (see "Dosage Adjustment for TPMT or NUDT15 Deficiency" below). Pediatric doses presented as mg/m² and mg/kg; use caution.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL): Limited data available; multiple regimens/protocols reported; refer to specific protocols.

Standard risk (Ref): Children 1 to <10 years: Consolidation, Interim Maintenance I and Maintenance: Oral: 75 mg/m² once daily, frequency and duration dependent on protocol phase (in combination with vincristine, steroid, and methotrexate [oral and/or intrathecal]). Maintenance cycles are repeated for a total duration of 2 years (females) and 3 years (males) from the start of Interim Maintenance I. During Maintenance, oral methotrexate and mercaptopurine are adjusted to maintain a target ANC goal (generally 1,000 to 2,000/mm³; varies based on protocol).

High risk (Ref):

Children and Adolescents:

Consolidation: Oral: 60 mg/m² once daily on days 1 to 14 and 29 to 42 of a 56-day cycle (in combination with cyclophosphamide, cytarabine, vincristine, pegaspargase, and intrathecal methotrexate).

Interim Maintenance 1 and 2: Oral: 25 mg/m² once daily on days 1 to 56 (in combination with vincristine, high-dose methotrexate, and intrathecal methotrexate).

Maintenance phase: Oral: 75 mg/m² once daily on days 1 to 84 of an 84-day cycle (in combination with vincristine, steroid, oral methotrexate, and intrathecal methotrexate). Maintenance cycles duration: 2 to 3 years (refer to specific protocol). During Maintenance, the oral methotrexate and mercaptopurine are titrated to a target ANC goal (generally 1,000 to 2,000/mm³; varies based on protocol).

Acute promyelocytic leukemia

Acute promyelocytic leukemia (APL): Limited data available; multiple regimens reported:

Combination with tretinoin: Maintenance phase: Children and Adolescents ≤14 years: Oral: 100 mg/m²/day for 14 days of a 28-day cycle in combination with tretinoin. Cycles were repeated every 28 days for 2 years (Ref).

Combination with tretinoin and methotrexate:

Kutny 2017: AAML0631: Maintenance phase: Children ≥2 years and Adolescents: Oral: 50 mg/m²/day for 9 cycles of 12 weeks in combination with methotrexate and tretinoin.

Ortega 2005: PETHEMA Group: Maintenance phase: Children and Adolescents <17 years: Oral: 50 mg/m²/day for 2 years in combination with methotrexate and tretinoin. Doses of mercaptopurine and methotrexate were decreased by 50% if the WBC count was <3,500 cells/mm³ and discontinued for WBC <2,500/mm³.

Powell 2010: North American Leukemia Intergroup Study C9710: Maintenance phase: Adolescents ≥15 years: Oral: 60 mg/m²/day for 1 year in combination with tretinoin and methotrexate.

Crohn disease, remission maintenance

Crohn disease, remission maintenance: Limited data available: Children and Adolescents: Oral: 1 to 1.5 mg/kg/day (Ref).

Hepatitis, autoimmune

Hepatitis, autoimmune (alternative agent): Limited data available: Note: Use should be reserved for patients not responsive or intolerant of other therapies (Ref).

Children and Adolescents: Oral: Initial: 0.5 to 1 mg/kg/day; monitor serum levels and adjust dose accordingly; a higher dose of 1.5 mg/kg/day has also been suggested (Ref).

Ulcerative colitis, remission maintenance

Ulcerative colitis, remission maintenance: Limited data available: Children and Adolescents: Oral: 1 to 1.5 mg/kg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment in TPMT and/or NUDT15 deficiency: Limited data available:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (Ref):

Normal TPMT or NUDT15 activity (wild type): No initial dosage adjustment necessary; adjust dose based on condition being treated. Allow at least 2 weeks after each dosage adjustment to reach steady state. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on mercaptopurine compared to other agents.

TPMT intermediate or possible intermediate metabolizer or NUDT15 intermediate or possible intermediate metabolizer: Initiate mercaptopurine with the dose reduced to 30% to 80% of the usual dose and adjust dose based on the degree of myelosuppression and condition being treated. Allow 2 to 4 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy). If the starting dose is already below the normal recommended dose, dose reduction may not be recommended.

TPMT poor metabolizer:

• When used for malignancy, initiate mercaptopurine at a drastically reduced dose (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times a week). Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).

• When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.

NUDT15 poor metabolizer:

• When used for malignancy, initiate mercaptopurine at 10 mg/m²/day. Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state. If myelosuppression occurs, the focus should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).

• When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy.

Manufacturer's labeling:

Heterozygous deficiency (intermediate activity): Reduce the dose based on tolerability; most patients with heterozygous deficiency of TPMT or NUDT15 tolerate recommended doses, although some require dosage reduction. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.

Homozygous deficiency (low or deficient activity): Reduce the mercaptopurine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents:

CrCl ≥50 mL/minute: No adjustment required (Ref).

CrCl <50 mL/minute: Initiate with the lowest recommended starting dose or increase the dosing interval to every 36 to 48 hours to avoid accumulation in patients with renal impairment adjust dose to maintain desirable ANC level and for adverse reactions (Ref).

Hemodialysis: Administer every 48 hours (Ref).

Continuous ambulatory peritoneal dialysis (CAPD): Administer every 48 hours (Ref).

Continuous renal replacement therapy (CRRT): Administer every 48 hours (Ref).

Dosing: Liver Impairment: Pediatric

Children and Adolescents:

Hepatic impairment at baseline: Initiate with the lowest recommended starting dose; adjust dose to maintain desirable ANC level and for adverse reactions.

Hepatotoxicity during treatment: Withhold therapy.

Dosing: Adult

(For additional information see "Mercaptopurine: Drug information")

Dosage guidance:

Safety: Consider testing for thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency; patients with TPMT or NUDT15 deficiency are at increased risk for severe toxicity at conventional mercaptopurine doses and generally require dose reduction (see Dosage adjustment for TPMT and/or NUDT15 deficiency below) (Ref).

Clinical considerations: Refer to the protocol or institutional guidance for additional details of off-label dosing.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL): Maintenance: Oral: 1.5 to 2.5 mg/kg once daily (50 to 75 mg/m² once daily); continue based on blood counts or

Off-label ALL dosing (combination chemotherapy; refer to specific reference for combinations):

CALGB 8811/9111:

Early intensification (two 4-week courses): Oral: 60 mg/m²/day on days 1 to 14 of each 28-day cycle (Ref).

Interim maintenance (12-week course): Oral: 60 mg/m²/day on days 1 to 70 of an 84-day cycle (Ref).

Maintenance (prolonged): Oral: 60 mg/m²/day; continue for 2 years from diagnosis (Ref).

AALL0232: Patients ≤30 years of age:

Consolidation: Oral: 60 mg/m² once daily on days 1 to 14 and 29 to 42 of a 56-day cycle (in combination with cyclophosphamide, cytarabine, vincristine, pegaspargase, and intrathecal methotrexate) (Ref).

Interim maintenance 1 and 2: Oral: 25 mg/m² once daily on days 1 to 56 (in combination with vincristine, high-dose methotrexate, and intrathecal methotrexate) (Ref).

Maintenance phase: Oral: 75 mg/m² once daily on days 1 to 84 of an 84-day cycle (in combination with vincristine, steroid, oral methotrexate, and intrathecal methotrexate). Maintenance cycles are repeated for a total duration of 2 years (females) and 3 years (males) from the start of Interim Maintenance I. During Maintenance, the mercaptopurine (and oral methotrexate) dose may be titrated to target ANC and platelet count goals (Ref).

CALGB 10403 regimen: Patients <40 years of age:

Remission consolidation (course II): Oral: 60 mg/m² once daily on days 1 to 14 and 29 to 42 of remission consolidation course II (in combination with cyclophosphamide, cytarabine, vincristine, pegaspargase, and intrathecal methotrexate) (Ref).

Maintenance phase (course V): Oral: 75 mg/m² once daily on days 1 to 84 of an 84-day cycle (in combination with vincristine, dexamethasone, oral methotrexate, and intrathecal methotrexate). Maintenance cycles are repeated for a total duration of 2 years (females) and 3 years (males) from the start of interim maintenance (course III) (Ref).

E2993 regimen: Patients <60 years of age:

Induction phase 2 (weeks 5 to 8): Oral: 60 mg/m² once daily on days 1 to 28 of a 28-day cycle (in combination with cyclophosphamide, cytarabine, and intrathecal methotrexate) (Ref).

Maintenance phase: Oral: 75 mg/m² once daily (in combination with vincristine, prednisone, and methotrexate); continue until 2.5 years from the start of intensification therapy (Ref).

GRAALL-2005: Patients <60 years of age:

Consolidations 1, 2, and 3 (methotrexate blocks): Oral: 60 mg/m² once daily on days 15 to 21 (in combination with methotrexate, vincristine, and asparaginase) in the methotrexate blocks of consolidations 1, 2, and 3 (Ref).

CNS prophylaxis (between the end of consolidation 3 and prior to maintenance therapy initiation): Oral: 60 mg/m² once daily beginning after the end of consolidation 3 (in combination with CNS irradiation); adjust dose according to blood counts (Ref).

Maintenance phase: Oral: 60 mg/m² once daily (in combination with vincristine, prednisone, and weekly methotrexate) beginning 1 to 2 weeks after CNS irradiation and continue for 2 years; adjust dose based on blood counts (Ref).

Hyper-CVAD regimen:

Maintenance phase: Oral: 50 mg three times daily (in combination with methotrexate, vincristine, and prednisone); continue for 2 years (Ref).

E1910 regimen (multiagent combination chemotherapy + blinatumomab): Patients 30 to 70 years of age:

Consolidation (cycle 5): Oral: 60 mg/m² once daily on days 29 to 42 (in combination with daunorubicin, vincristine, dexamethasone, intrathecal methotrexate, cyclophosphamide, cytarabine, ± rituximab) of a 42-day cycle (Ref).

Maintenance phase: Oral: 75 mg/m² once daily (in combination with vincristine, prednisone, intrathecal methotrexate, and oral/IV methotrexate); continue for 2.5 years from the start of the intensification phase (Ref).

PETHEMA ALL-96: Patients ≤30 years of age:

Consolidation 1: Oral: 50 mg/m² once daily on days 1 to 7 (in combination with methotrexate, teniposide, cytarabine, and triple intrathecal therapy) of a 56-day cycle (Ref).

Maintenance phase: Oral: 50 mg/m² once daily (in combination with weekly methotrexate and every-4-week reinductions with vincristine, prednisone, asparaginase, and triple intrathecal therapy) for 1 year (until week 52), followed by 50 mg/m² once daily (in combination with methotrexate) for 1 year (weeks 53 to 104) (Ref).

Protocol 8707 (Linker regimen): Patients <60 years of age:

Consolidation (1C, 2C, and 3C): Oral: 75 mg/m² once daily on days 1 to 28 of a 28-day cycle (in combination with methotrexate) of consolidation cycles 1C, 2C, and 3C (Ref).

Maintenance phase: Oral: 75 mg/m² once daily (in combination with weekly methotrexate); continue until in complete remission for 30 months (Ref).

Acute promyelocytic leukemia, maintenance

Acute promyelocytic leukemia, maintenance (off-label use):

APL93 regimen:

Maintenance phase: Oral: 90 mg/m²/day (in combination with tretinoin and methotrexate) for 2 years (Ref).

APML4 regimen:

Maintenance phase: Oral: 50 to 90 mg/m²/day on days 15 to 90 every 90 days (in combination with tretinoin and methotrexate) for 8 cycles (2 years); begin 3 to 4 weeks after consolidation cycle 2 (Ref).

APL 2000 regimen:

Maintenance phase: Oral: 50 mg/m²/day (in combination with tretinoin and methotrexate) for 2 years (Ref).

C9710 regimen:

Maintenance phase: Oral: 60 mg/m²/day (in combination with tretinoin and methotrexate); continue for 1 year (Ref).

Crohn disease

Crohn disease (off-label use):

Maintenance of remission: Oral: 0.75 to 1.5 mg/kg/day (Ref).

Management after surgical resection: Note: For patients at high risk of recurrence (eg, smoker, perforating disease or previous resection) (Ref).

Oral: 1 mg/kg/day (round to the nearest 25 mg) (Ref) or 1.5 mg/kg/day (in combination with metronidazole) (Ref).

Lymphoblastic lymphoma

Lymphoblastic lymphoma, maintenance (off-label use): Maintenance (prolonged): Oral: 50 mg 3 times daily for 2 years (Ref).

Ulcerative colitis, remission maintenance

Ulcerative colitis, remission maintenance (off-label use): Oral: 1 to 1.5 mg/kg/day (Ref).

Dosage adjustment for TPMT and/or NUDT15 deficiency:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (Ref):

**Recommended Mercaptopurine Dosage Modifications for *TPMT* and/or *NUDT15* Deficiency**
TPMT/NUDT15 phenotype	Mercaptopurine starting dose	Mercaptopurine dose adjustment
^aRelling 2019.
^bCPIC Guideline for Thiopurine and TPMT and NUDT15 March 2024 update. CPIC guidelines (including updates) are located at: https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/.
TPMT normal metabolizer OR NUDT15 normal metabolizer	Follow instructions for the specific determinate phenotype: Utilize the more stringent determinate phenotype for dosage modification (eg, if TPMT normal metabolizer and NUDT15 poor metabolizer, follow instructions for NUDT15 poor metabolizer).
TPMT normal metabolizer AND NUDT15 normal metabolizer	No initial dosage adjustment necessary.^a	Adjust dose based on the condition being treated. Allow at least 2 weeks to reach steady state after each dose adjustment. For patients receiving combination therapy, dosage adjustments (of all agents) should be made without any emphasis on mercaptopurine compared to other agents.^a
TPMT intermediate metabolizer or possible intermediate metabolizer OR NUDT15 intermediate metabolizer or possible intermediate metabolizer	Normal starting dose ≥75 mg/m²/day or ≥1.5 mg/kg/day: Initiate mercaptopurine with a reduced starting dose (30% to 80% of the normal dose).^a Normal starting dose <75 mg/m²/day or <1.5 mg/kg/day: Dose reduction may not be recommended.^a Note: Follow instructions for the specific determinate phenotype: Utilize the more stringent determinate phenotype for dosage modification (eg, if TPMT intermediate metabolizer and NUDT15 poor metabolizer, follow instructions for NUDT15 poor metabolizer).	Adjust dose based on the degree of myelosuppression and the condition being treated. Allow 2 to 4 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).^a
TPMT intermediate metabolizer or possible intermediate metabolizer AND NUDT15 intermediate metabolizer or possible intermediate metabolizer	Normal starting dose ≥75 mg/m²/day or ≥1.5 mg/kg/day: Initiate mercaptopurine with a reduced starting dose (20% to 50% of the normal dose).^b Normal starting dose <37.5 mg/m²/day or <0.75 mg/kg/day: Dose reduction may not be recommended.^b	Adjust dose based on the degree of myelosuppression and the condition being treated. Allow 2 to 4 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).^b
TPMT poor metabolizer	Nonmalignant conditions: Consider alternative (non-thiopurine) immunosuppressant therapy.^a Malignant conditions: Initiate mercaptopurine with a drastically reduced dose (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times a week [eg, 10 mg/m²/day 3 times a week]).^a	Adjust dose based on the degree of myelosuppression and the condition being treated. Allow 4 to 6 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).^a
NUDT15 poor metabolizer	Nonmalignant conditions: Consider alternative (non-thiopurine) immunosuppressant therapy.^a Malignant conditions: Initiate mercaptopurine with the starting dose reduced to 10 mg/m²/day.^a	Adjust doses of mercaptopurine based on the degree of myelosuppression and the condition being treated. Allow 4 to 6 weeks to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing the mercaptopurine dose over other agents (depending on concomitant therapy).^a
TPMT indeterminate AND NUDT15 indeterminate	Consider evaluating TPMT erythrocyte activity to assess phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.^b
TPMT indeterminate OR NUDT15 indeterminate	Follow instructions above for the specific determinate phenotype. If TPMT indeterminate, consider evaluating TPMT erythrocyte activity to assess phenotype. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.^b

Manufacturer's labeling:

Homozygous deficiency (low or deficient activity): Reduce the mercaptopurine dose to 10% of the usual dose or lower for homozygous deficiency in either TPMT or NUDT15.

Missed dose: If a dose is missed, continue with the next scheduled dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

CrCl <50 mL/minute: Initiate with the lowest recommended starting dose or increase the dosing interval to every 36 to 48 hours to avoid accumulation in patients with renal impairment; adjust dose to maintain desirable ANC level and for adverse reactions.

Dosing: Liver Impairment: Adult

Altered liver function at baseline: Initiate with the lowest recommended starting dose; adjust dose to maintain desirable ANC level and for adverse reactions.

Acute hepatotoxicity during treatment: Withhold mercaptopurine therapy.

Intrahepatic cholestasis of pregnancy during treatment: Discontinue mercaptopurine therapy.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Skin rash (5% to 20%)

Gastrointestinal: Anorexia (5% to 20%), diarrhea (5% to 20%), nausea (5% to 20%), vomiting (5% to 20%)

Hematologic & oncologic: Bone marrow depression (>20%, including anemia, lymphocytopenia, neutropenia, thrombocytopenia)

Nervous system: Malaise (5% to 20%)

1% to 10%:

Dermatologic: Hyperpigmentation (<5%), urticaria (<5%)

Endocrine & metabolic: Hyperuricemia (<5%)

Gastrointestinal: Oral lesion (<5%), pancreatitis (<5%)

Hepatic: Hyperbilirubinemia (<5%), increased serum transaminases (<5%)

Infection: Infection (<5%)

Frequency not defined:

Dermatologic: Alopecia

Gastrointestinal: Cholestasis, sprue-like symptoms, ulcerative bowel lesion

Genitourinary: Oligospermia

Hematologic & oncologic: Granulocytopenia, leukopenia, metastases (secondary)

Hepatic: Ascites, hepatic encephalopathy, hepatic fibrosis, hepatic injury, hepatic necrosis, hepatomegaly, hepatotoxicity, intrahepatic cholestasis, jaundice, toxic hepatitis

Immunologic: Immunosuppression

Renal: Nephrotoxicity

Respiratory: Pulmonary fibrosis

Postmarketing:

Cardiovascular: Portal hypertension

Dermatologic: Erythema nodosum, skin photosensitivity

Endocrine & metabolic: Hypoglycemia, pellagra

Miscellaneous: Drug fever

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to mercaptopurine or any component of the formulation; patients whose disease showed prior resistance to mercaptopurine; immunizations with live organism vaccines.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Dose-related leukopenia, thrombocytopenia, and anemia are common; however, may also be indicative of disease progression. Hematologic toxicity may be delayed. Bone marrow may appear hypoplastic (could also appear normal). Monitor blood counts; dose may require modification for severe neutropenia or thrombocytopenia. Monitor for bleeding (due to thrombocytopenia) or infection (due to neutropenia). Profound severe or repeated hematologic toxicity may be indicative of thiopurine methyltransferase (TPMT) deficiency or nudix hydrolase 15 (nucleotide diphosphatase [NUDT15]) deficiency (see “TPMT or NUDT15 deficiency” below); patients who are homozygous for TPMT or NUDT15 deficiency may require substantial dosage reductions. TPMT genotyping or phenotyping or NUDT15 genotyping can identify patients with reduced TPMT or NUDT15 enzyme activity.

• Hepatotoxicity: Hepatotoxicity has been reported, including jaundice, ascites, pruritus, hepatic necrosis (may be fatal), intrahepatic cholestasis (including intrahepatic cholestasis of pregnancy), parenchymal cell necrosis, and/or hepatic encephalopathy; may be due to direct hepatic cell damage or hypersensitivity. While hepatotoxicity or hepatic injury may occur at any dose, dosages exceeding the recommended dose are associated with a higher incidence. Signs of jaundice generally appear early in treatment, after ~1 to 2 months (range: 1 week to 8 years) and may resolve following discontinuation; recurrence with rechallenge has been noted.

• Immunosuppression: Mercaptopurine is immunosuppressive; immune responses to infections may be impaired and the risk for infection is increased. Common signs of infection, such as fever and leukocytosis may not occur; lethargy and confusion may be more prominent signs of infection.

• Macrophage activation syndrome: Macrophage activation syndrome (MAS), also known as hemophagocytic lymphohistiocytosis, is a life-threatening disorder which may develop in patients with autoimmune disorders (particularly inflammatory bowel disease); mercaptopurine use for the treatment of autoimmune conditions (off-label use) may cause increased susceptibility to MAS. Discontinue mercaptopurine if MAS develops or is suspected. Monitor; promptly treat infections such as Epstein-Barr virus (EBV) and cytomegalovirus (which are known triggers for MAS).

• Photosensitivity: Minimize sun exposure due to possible photosensitivity.

• Secondary malignancy: Immunosuppressive agents, including mercaptopurine, are associated with the development of lymphoproliferative disorders and other malignancies. In an analysis of T-cell lymphomas associated with TNF blockers (with or without thiopurines) for the treatment of rheumatoid arthritis, Crohn disease, ulcerative colitis, or ankylosing spondylitis (off-label uses for thiopurines), an increase in the incidence of T-cell lymphomas, most commonly mycosis fungoides/Sézary syndrome and hepatosplenic T-cell lymphoma (HSTCL) was reported (Deepak 2013). HSTCL is a rare white blood cell cancer that is usually fatal. Most HSTCL cases occurred in patients treated with a combination of TNF blockers and thiopurines, although cases of HSTCL also occurred in patients receiving azathioprine or mercaptopurine monotherapy. Skin cancers (melanoma and non-melanoma), Kaposi and non-Kaposi sarcomas, and uterine cervical cancer in situ have been reported in patients receiving immunosuppressive treatment (including mercaptopurine); risk of development may be related to the degree and duration of immunosuppression. Partial regression of lymphoproliferative disorders may occur upon therapy discontinuation. Regimens containing multiple immunosuppressants increase the risk of EBV-associated lymphoproliferative disorders; use with caution.

Disease-related concerns:

• TPMT or NUDT15 deficiency: Patients with reduced TPMT or NUDT15 activity have a higher risk of severe myelosuppression with usual doses of thiopurines (eg, mercaptopurine, azathioprine, thioguanine) and may require substantial thiopurine dose reductions. Individuals who are TPMT homozygous or compound heterozygous deficient are at very high risk for severe myelosuppression (Relling 2019). TPMT genotyping or phenotyping and NUDT15 genotyping may assist in identifying patients at risk for developing toxicity. Consider testing for NUDT15 and TPMT deficiency in patients who experience severe bone marrow toxicities or repeated myelosuppressive episodes. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received recent blood transfusions. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes (Relling 2019) recommends reduced initial doses for TPMT and NUDT15 intermediate (and possible intermediate) metabolizers (with dosage adjustments based on myelosuppression). For TPMT and NUDT15 poor metabolizers, CPIC guideline recommends considering alternative nonthiopurine agents for nonmalignant conditions and drastically reduced doses if used to treat malignancy. Genetic TPMT deficiency is the primary cause of thiopurine intolerance in Europeans and Africans; NUDT15 risk alleles are associated with a majority of thiopurine intolerance in Asians and are also common in Hispanics (Relling 2019).

Special populations:

• Pediatric: Cases of symptomatic hypoglycemia have been reported in children receiving mercaptopurine for the treatment of ALL; cases were reported in children less than 6 years of age or with a low body mass index.

Other warnings/precautions:

• Error-prone terms: To avoid potentially serious dosage errors, the terms “6-mercaptopurine” or “6-MP” should be avoided; use of these terms has been associated with six-fold overdosages.

• Vaccines: Immune response to vaccines may be diminished. Live virus vaccines impose a risk for infection.

Warnings: Additional Pediatric Considerations

The development of secondary hemophagocytic lymphohistiocytosis (HLH), a rare and frequently fatal activation of macrophages which causes phagocytosis of all bone marrow blood cell lines, is increased (100-fold) in pediatric patients diagnosed with inflammatory bowel disease; this risk is further increased with concomitant thiopurine (ie, azathioprine, mercaptopurine) therapy, Epstein-Barr virus, or other possible infections; if patient presents with fever (at least 5 days), cervical lymphadenopathy, and lymphopenia, discontinue immunosuppressive therapy and further diagnostic evaluation for HLH should be performed; diagnostic delay associated with increased mortality (Biank 2011).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Oral:

Purixan: 2000 mg/100 mL (100 mL) [contains aspartame, methylparaben, propylparaben]

Generic: 2000 mg/100 mL (100 mL)

Tablet, Oral:

Generic: 50 mg

Generic Equivalent Available: US

Yes

Pricing: US

Suspension (Mercaptopurine Oral)

2000 mg/100 mL (per mL): $16.33

Suspension (Purixan Oral)

2000 mg/100 mL (per mL): $17.19

Tablets (Mercaptopurine Oral)

50 mg (per each): $4.09 - $8.18

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Purinethol: 50 mg

Generic: 50 mg

Extemporaneous Preparations

50 mg/mL oral suspension:

A 50 mg/mL oral suspension may be prepared in a vertical flow hood with tablets and a mixture of sterile water for injection (SWFI), simple syrup, and cherry syrup. Crush thirty 50 mg tablets in a mortar and reduce to a fine powder. Add ~5 mL SWFI and mix to a uniform paste; then add ~10 mL simple syrup; mix while continuing to add cherry syrup to make a final volume of 30 mL; transfer to a calibrated bottle. Label "shake well" and "caution chemotherapy". Stable for 35 days at room temperature.

Aliabadi HM, Romanick M, Desai, S, et al. Effect of buffer and antioxidant on stability of a mercaptopurine suspension. Am J Health Syst Pharm. 2008;65(5):441-447.18281736

Administration: Pediatric

Oral: Administer at the same time(s) each day, preferably on an empty stomach (Ref); avoid concomitant milk products if possible (Ref).

Acute lymphoblastic leukemia (ALL): Administration in the evening has demonstrated superior outcome; administration with food did not significantly affect outcome (Ref).

If adherence is limited by administering on an empty stomach in the evening or by avoiding concomitant milk products, simplification of administration (eg, take with food/dairy without regard to time of day) should be considered. In adherent patients (taking mercaptopurine regularly), no association was seen between risk of ALL relapse and mercaptopurine ingestion habits; there was also no association noted with red cell thioguanine nucleotide (TGN) levels and administration with food, dairy, or time of day (Ref).

Suspension: Shake well for at least 30 seconds to ensure suspension is mixed thoroughly (suspension is viscous). Measure dose with an oral dosing syringe (a 1 mL and a 5 mL oral dosing syringe are supplied by the manufacturer) to assure proper dose is administered. If oral syringe is intended to be re-used, wash with warm soapy water and rinse well (hold syringe under water and move plunger several times to ensure inside of syringe is clean); allow to dry completely. Patients and caregivers should be trained on appropriate measuring and administration, handling, storage, disposal, cleanup of accidental spills, and proper cleaning of oral dosing syringe. Use within 8 weeks after opening.

Administration: Adult

Oral: Administer at the same time(s) each day. Administer preferably on an empty stomach (Ref); avoid concomitant milk products if possible (Ref). The manufacturer recommends taking consistently either with or without food.

Suspension: Shake vigorously for at least 30 seconds to ensure suspension is mixed thoroughly (suspension is viscous). Attach the bottle adaptor into the neck of the bottle (do not remove after insertion). Measure dose with an oral dosing syringe (a 1 mL and a 5 mL oral dosing syringe are supplied by the manufacturer) to assure proper dose is administered. If oral syringe provided by the manufacturer is intended to be reused, wash with warm soapy water and rinse well (hold syringe under water and move plunger several times to ensure inside of syringe is clean); allow to dry completely. Patients and caregivers should be trained on appropriate measuring and administration, handling, storage, disposal, cleanup of accidental spills, and proper cleaning of oral dosing syringe. Use within 8 weeks after opening.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Storage/Stability

Tablets: Store at 20°C to 25°C (68°F to 77°F). Store in a dry place.

Suspension: Store at 15°C to 25°C (59°F to 77°F). Do not store above 25°C (77°F). Store in a dry place. Use within 8 weeks after opening. Storage information at refrigerated temperature may be available; contact product manufacturer to obtain current recommendations.

Use

Maintenance treatment of acute lymphoblastic leukemia (ALL) in combination with other agents (eg, methotrexate) (FDA approved in pediatric patients [age not specified] and adults); has also been used for maintenance of remission of inflammatory bowel diseases, treatment of autoimmune hepatitis and acute promyelocytic leukemia (APL).

Medication Safety Issues

Sound-alike/look-alike issues:

Mercaptopurine may be confused with methotrexate

Purinethol [DSC] may be confused with propylthiouracil

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral; immunosuppressant agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

International issues:

Mercaptopurine may be confused with mercaptamine [multiple international markets]

Other safety concerns:

To avoid potentially serious dosage errors, the terms “6-mercaptopurine” or “6-MP” should be avoided; use of these terms has been associated with sixfold overdosages.

Azathioprine is metabolized to mercaptopurine; concurrent use of these commercially-available products has resulted in profound myelosuppression.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Thiopurine Analogs. 5-Aminosalicylic Acid Derivatives may increase active metabolite exposure of Thiopurine Analogs. Specifically, exposure to the active 6-thioguanine nucleotides (6-TGN) may be increased. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Allopurinol: May increase serum concentration of Mercaptopurine. Allopurinol may also promote formation of active thioguanine nucleotides. Management: Reduce the mercaptopurine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Risk D: Consider Therapy Modification

Anti-TNF Agents: May increase adverse/toxic effects of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

AzaTHIOprine: May increase myelosuppressive effects of Mercaptopurine. Risk X: Avoid

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

DOXOrubicin (Conventional): May increase hepatotoxic effects of Mercaptopurine. Risk C: Monitor

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Febuxostat: May increase serum concentration of Mercaptopurine. Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Methotrexate: May increase serum concentration of Mercaptopurine. Conversely, intracellular concentrations of thioguanine nucleotides may be decreased with the combination. Risk C: Monitor

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor

Sulfamethoxazole: May increase myelosuppressive effects of Mercaptopurine. Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Trimethoprim: May increase myelosuppressive effects of Mercaptopurine. Risk C: Monitor

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Vitamin K Antagonists: Mercaptopurine may decrease anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Reproductive Considerations

Verify pregnancy status prior to initiating therapy in patients who could become pregnant.

Mercaptopurine is approved for use as part of combination maintenance therapy for acute lymphoblastic leukemia. Product labeling recommends patients who could become pregnant use effective contraception during mercaptopurine treatment and for 6 months after the last mercaptopurine dose. Patients with partners who could become pregnant should be advised to use effective contraception during therapy and for 3 months after the last dose of mercaptopurine.

Mercaptopurine is also used (off label) for the treatment of ulcerative colitis and Crohn disease; monotherapy use for these indications may be continued in patients planning a pregnancy (Bermejo 2018). Mercaptopurine does not decrease fertility in patients with inflammatory bowel disease (AGA [Mahadevan 2019]; Bermejo 2018).

Pregnancy Considerations

The 6-methylmercaptopurine (6-MMP) and 6-thioguanine (6-TGN) metabolites can be detected in cord blood following maternal use during pregnancy. Infant serum concentrations were undetectable by 6 weeks of age in one study (Flanagan 2021).

Mercaptopurine may be associated with adverse fetal outcomes. An increased risk of miscarriage has been noted with mercaptopurine administration during the first trimester; adverse events, including miscarriage and stillbirth, have also been noted with second and third trimester use. An increased risk of stillbirth, preterm birth, and infants large for gestational age may be observed with maternal use of thiopurines (Meyer 2021).

Intrahepatic cholestasis of pregnancy (ICP) has been associated with thiopurine use. In one study, patients with a metabolite ratio of 6-MMP to 6-TGN >11 (referred to as thiopurine shunting) was associated with the risk of ICP (Prentice 2024). The pharmacokinetic properties of thiopurines may be altered by pregnancy. A decrease in 6-TGN and an increase in 6-MMP was observed in the second trimester (Flanagan 2021). Closely monitor liver transaminases and thiopurine metabolites during pregnancy. Split dosing (taking half the total daily dose every 12 hours) may also prevent shunting (Prentice 2024). Patients with symptoms of ICP and elevated bile acid levels should discontinue treatment. Symptoms improve after the thiopurine is discontinued (FDA 2024).

Mercaptopurine is approved for use as part of combination therapy for acute lymphoblastic leukemia. Data are available following use for leukemia during pregnancy; outcomes may be influenced by concomitant medications (NTP 2013; Ticku 2013).

Mercaptopurine is also used (off label) for the treatment of ulcerative colitis and Crohn disease. The risk of adverse fetal events is decreased with monotherapy. In addition, maternal use to maintain remission may improve pregnancy outcomes. Patients with inflammatory bowel disease who are on maintenance therapy with mercaptopurine monotherapy may continue treatment during pregnancy. Initiating treatment during pregnancy is not recommended. Combination therapy is also not recommended (AGA [Mahadevan 2019]; Puchner 2019; Restellini 2020).

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Peccatori 2013).

Monitoring Parameters

For use in leukemia: CBC with differential (weekly initially, although clinical status may require increased frequency), bone marrow exam (to evaluate marrow status), LFTs (weekly initially, then monthly; monitor more frequently if on concomitant hepatotoxic agents), renal function, urinalysis; consider thiopurine S-methyltransferase (TPMT) genotyping to identify TPMT defect (if severe toxicity occurs).

For use in inflammatory bowel disease: TPMT genotyping before initiation. Monitor CBC with differential and liver function tests at baseline then every 1 to 2 weeks for 1 month, then monthly for 3 months, followed by monitoring every 3 months throughout the course of therapy. Monitor for signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) (ECCO/ESPGHAN [Turner 2018]; ECCO/ESPGHAN [van Rheenen 2020]).

Mechanism of Action

Mercaptopurine is a purine antagonist which inhibits DNA and RNA synthesis; acts as false metabolite and is incorporated into DNA and RNA, eventually inhibiting their synthesis; specific for the S phase of the cell cycle

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Variable and incomplete (~50% of a dose is absorbed); C_max of suspension is 34% higher than the tablet.

Distribution: V_d: ~0.9 L/kg; CNS penetration is poor.

Protein binding: ~19%.

Metabolism: Hepatic and in GI mucosa; hepatically via xanthine oxidase and methylation via thiopurine methyltransferase to sulfate conjugates, 6-thiouric acid, and other inactive compounds; first-pass effect.

Half-life elimination: Suspension: Median: 1.3 hours (range: 0.9 to 5.4 hours).

Time to peak, serum: Suspension: Median: Children: 1 to 3 hours, Adults: 0.75 hours (range: 0.33 to 2.5 hours).

Excretion: Urine (46% as mercaptopurine and metabolites).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Kidney function impairment may result in slower elimination of parent drug and metabolites, and a greater cumulative effect.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Purinethol;
(AR) Argentina: Mercaptopurina | Puri nethol | Purinethol | Varimer;
(AT) Austria: Puri nethol | Xaluprine;
(AU) Australia: Allmercap | Mercaptopurine link | Purinethol;
(BD) Bangladesh: Purinethol;
(BE) Belgium: Puri nethol;
(BG) Bulgaria: Puri nethol;
(BR) Brazil: Purinethol;
(CH) Switzerland: Puri nethol;
(CL) Chile: Mercaptopurina | Purinethol;
(CO) Colombia: Empurine | Kapto | Purinethol;
(CZ) Czech Republic: Puri nethol | Xaluprine;
(DE) Germany: Medipurin | Mercaptopurin holsten | Puri nethol | Purinethol | Xaluprine;
(DO) Dominican Republic: Merpurine | Purinethol;
(EC) Ecuador: Mercaptopurina | Varimer;
(EE) Estonia: Merkaptopurin | Puri nethol | Xaluprine;
(EG) Egypt: Purinethol;
(ES) Spain: Mercaptopurina | Mercaptopurina silver | Mercaptopurina tillomed;
(FI) Finland: Mercaptopurin orion | Merkaptopurin | Puri nethol | Xaluprine;
(FR) France: Mercaptopurine Dci | Purinethol | Xaluprine;
(GB) United Kingdom: Hanixol | Puri nethol | Xaluprine;
(GR) Greece: Mercaptopurin | Mercaptopurinum | Puri nethol | Xaluprine;
(HK) Hong Kong: Allmercap mercaptopurine | Puri nethol;
(HU) Hungary: Purinethol | Xaluprine;
(IE) Ireland: Puri nethol | Xaluprine;
(IL) Israel: Puri nethol;
(IN) India: 6 mp | Captomer | Empurine | Puri nethol | Purinetone;
(IT) Italy: Purinethol | Xaluprine;
(JO) Jordan: Purinethol;
(JP) Japan: Classen | Pro;
(KE) Kenya: Purinethol;
(KR) Korea, Republic of: Catoprine | Purinethol | Purinetone | Union mercaptopurine;
(LB) Lebanon: Puri nethol;
(LT) Lithuania: Mercaptopurin | Merkaptopurin | Puri nethol | Xaluprine;
(LU) Luxembourg: Puri nethol;
(LV) Latvia: Merkaptopurin | Puri nethol | Purinethol;
(MA) Morocco: Purinethol;
(MX) Mexico: Mercaptopurina | Purinethol;
(MY) Malaysia: Empurine | Puri nethol;
(NL) Netherlands: Mercaptopurine bmodesto | Puri nethol | Purinethol | Xaluprine;
(NO) Norway: Puri nethol | Purimmun | Xaluprine;
(NZ) New Zealand: Allmercap | Purinethol;
(PE) Peru: Mervitae | Purinethol | Varimer;
(PH) Philippines: Capmerin | Empurine | Purinethol;
(PK) Pakistan: Mercaprine;
(PL) Poland: Mercaptopurin | Purinethol | Xaluprine;
(PR) Puerto Rico: Purinethol;
(PT) Portugal: Mercaptopurina;
(PY) Paraguay: Mercaptopurina d.a. carrion | Purinethol | Varimer;
(QA) Qatar: Puri-Nethol | Xaluprine;
(RU) Russian Federation: Mercaptopurin | Mercaptopurine nativ | Puri nethol;
(SA) Saudi Arabia: Purinethol;
(SE) Sweden: Merkaptopurin ebb | Puri nethol | Purimmun | Purinethol | Xaluprine;
(SG) Singapore: Purinethol | Purinetone;
(SI) Slovenia: Purinethol | Xaluprine;
(SK) Slovakia: Puri nethol | Xaluprine;
(SR) Suriname: Puri nethol;
(TH) Thailand: Empurine | Puri nethol | Purinetone;
(TN) Tunisia: Purinethol;
(TR) Turkey: Mercaptopurin | Merpurin | Purinethol;
(TW) Taiwan: Merkaptopurine | Merpurine | Puri nethol;
(UA) Ukraine: Mercaptopurin | Merkaptopurine | Puri nethol;
(UY) Uruguay: Puri nethol | Purinethol;
(ZA) South Africa: Purinethol

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Mercaptopurine: Pediatric drug information